User:Patelurology2/Metabolic syndrome, hypertension, dementia, drug therapy, interactions, side effects, pathophysiology

Formation of Beta Amyloid
Aβ is formed after sequential cleavage of the amyloid precursor protein, a transmembrane glycoprotein of undetermined function. APP can be processed by α-, β- and γ-secretases; Aβ protein is generated by successive action of the β and γ secretases. The γ secretase, which produces the C-terminal end of the Aβ peptide, cleaves within the transmembrane region of APP and can generate a number of isoforms of 39-43 amino acid residues in length. The most common isoforms are Aβ40 and Aβ42; the shorter form is typically produced by cleavage that occurs in the endoplasmic reticulum, while the longer form is produced by cleavage in the trans-Golgi network. The Aβ40 form is the more common of the two, but Aβ42 is the more fibrillogenic and is thus associated with disease states. Mutations in APP associated with early-onset Alzheimer's have been noted to increase the relative production of Aβ42, and thus one suggested avenue of Alzheimer's therapy involves modulating the activity of β and γ secretases to produce mainly Aβ40.

disease: progress, problems and perspectives
 * Clearance of amyloid-beta in Alzheimer’s

Metabolism & Transport of β Amyloid fragments
Potential Role of Endogenous and Exogenous Ab Binding Molecules in Ab Clearance and Metabolism
 * Study indicates that intrasynaptic oAβ42, but not oAβ40, acutely inhibits transmission at the squid giant synapse. This inhibition is molecularly tied to a cascade of events involving CK2 activation and the rapid clathrin-independent endocytosis pathway. The reduction of FAT induced by oAβ42 showed in the accompanying article, in combination with our results showing a dramatic acute inhibition of synaptic transmission after intrasynaptic injection of oAβ42, represent novel findings concerning AD synaptic failure now clearly associated with a reduction of synaptic vesicle pools and transmitter release.
 * Synaptic transmission block by presynaptic injection of oligomeric amyloid beta - oAβ42, but not oAβ40 or extracellular oAβ42
 * Effective therapeutic intervention in progressive neurological disorders depends on a clear understanding of the molecular mechanisms associated with the disease in question. In this manuscript we have shown that dysregulation of CK2 by oAβ is capable of inhibiting the vital neuronal process of FAT. Therefore, we propose that pharmacological regulation of CK2 activity represents a promising target for therapeutic intervention in AD, particularly when combined with treatments that help manage GSK3 activity as well.Disruption of fast axonal transport is a pathogenic mechanism for intraneuronal amyloid beta

ACE Inhibitors
Examples=

ACE inhibitors can be divided into three groups based on their molecular structure:

Sulfhydryl-containing agents

 * Captopril (trade name Capoten), the first ACE inhibitor
 * Zofenopril

Dicarboxylate-containing agents
This is the largest group, including:


 * Enalapril (Vasotec/Renitec)
 * Ramipril (Altace/Tritace/Ramace/Ramiwin)
 * Quinapril (Accupril)
 * Perindopril (Coversyl/Aceon)
 * Lisinopril (Lisodur/Lopril/Novatec/Prinivil/Zestril)
 * Benazepril (Lotensin)

Phosphonate-containing agents

 * Fosinopril (Monopril) is the only member of this group

Naturally occurring
Casokinins and lactokinins are breakdown products of casein and whey that occur naturally after ingestion of milk products, especially cultured milk. Their role in blood pressure control is uncertain. The tripeptides Val-Pro-Pro and Ile-Pro-Pro produced by the probiotic Lactobacillus helveticus have been shown to have ACE-inhibiting and antihypertensive functions.

Blood Brain Barrier, ACE & ACE Inhibitors, Dementia
Further, functionally can be grouped according to ability to cross Blood Brain Barrier- implication currently being studied for ability to affect dementia. List:

BBB Crossing ACE
 * Lisinopril
 * Perindropril
 * Ramipril
 * Trandolapril
 * Captopril
 * Fosinopril

BBB Non Crossing ACE
 * Benzapril
 * Enalapril
 * Moexipril
 * Imidapril

Other Antihypertensives, and even all ACE Inhibitors, possibly indirectly via RAAS feedback some of the effects on dementia and related complex - Construct: deemntia and BP dynamics and possibly incorporating known circadian rythm affecting Beta amyloid.

Choosing an ACE Inhibitor
Several ACE inhibitors are on the market. Here is a list of some by generic name followed by brand name(s).
 * benazepril (Lotensin)
 * captopril (Capoten)
 * enalapril (Lexxel, Vaseretic, Vasotec)
 * fosinopril (Monopril)
 * lisinopril (Prinivil, Prinzide, Zestoretic, Zestril)
 * moexipril (Univasc)
 * quinapril (Accupril)
 * ramipril (Altace)
 * trandolapril (Mavik, Tarka)


 * .Even hydrophilic ACE inhibitors can result in marked inhibition of brain ACE inside the BBB but that different brain structures show variable inhibition
 * Perindopril improved learning and memory in AD rats, which correlated with decreased ACE activity and delayed AD


 * BBB crossing ACE inhibitors/Centrally active ACE inhibitors include
 * captopril (Capoten, Bristol-Myers Squibb)
 * fosinopril (Monopril, Bristol-Myers Squibb)
 * ramipril (Altace, King Pharmaceuticals)
 * trandolapril (Mavik, Abbott Laboratories, Tarka)
 * lisinopril (Prinivil, Prinzide, Zestoretic, Zestril)
 * Perindropril


 * BBB Non Crossing/ Non–centrally active ACE inhibitors include
 * benazepril (Lotensin, Novartis Pharmaceuticals)
 * enalapril (Vasotec, Merck ,Lexxel )
 * moexipril (Univasc, Schwarz Pharma)
 * quinapril (Accupril, Pfizer)
 * Imidapril

Benefical Role of Centrally Acting ACE Inhibitors in Congestive Heart Failure

 * Benefical Role of Centrally Acting ACE Inhibitors in Congestive Heart Failure
 * Critically important contribution of the brain renin-angiotensin system to the pathophysiology of congestive heart failure.
 * ALDO of adrenal origin enters the hypothalamus in direct proportion to plasma levels and suggest that ALDO contributes to the upregulation of hypothalamic RAS activity and sympathetic drive in heart failure.
 * Sympathetic neuronal regulation of the heart in aging and heart failure Sympathetic nervous system in the failing heart and the healthy, aging heart, and consider whether the sympathetic activation accompanying aging may, perhaps, underlie and contribute to the neural pathophysiology of heart failure.... conclusion, on balance, that this proposition is not supported by the available evidence.

Dynamics & Flux Between Amyloid β fragments Beta amyloid & Blood Pressure & Autonomous System-  Dementia as a Case Study

 * Brain has ACE enzyme which takes part in local RAAS and converts Aβ42 (  plaquogenic ) to  Aβ40( more soluble and removal ) forms of  Beta amyloid ; latter is prdominentally a function of N domain portion on the ACE enzyme; Inhibition of ACE with ACE Inhibitors, especially Blood Brain Barrier crossing and with preferentially select N terminal activity would cause accumulation of  Aβ42 which is plaquogenic causing progression of dementia; preferential C domain active BBB crossing ACE would linkely have less of this latter effect.
 * ACE inhibitors vs ACE for and against dementia
 * Whether plaque is dementic environment or the downstream small fragment generated by the action of ACE are inflammatory and hence dementic an environment, is the question!

Angiotensin II Inhibitors and Dementia
<!--- 	  Unifying hypothesis Top Abstract Do diuretics have a... Diuretics in combination therapy Beta-blockers Calcium antagonists Angiotensin II receptor blockers... Angiotensin-converting enzyme... Unifying hypothesis Experimental evidence Conclusions References Our brief review seems to indicate that even though they lower BP to a similar extent, not all antihypertensive drug classes are equal in their cerebroprotective effect. This seems to hold true in hypertensive patients with a low incidence of coronary artery disease, such as in CAPPP, PATS, and PROGRESS. Specifically, diuretics, calcium antagonists, and ARBs, which increase angiotensin II formation (by stimulating renin secretion through sodium depletion [32], sympathetic activation [33,34], or blunting of the negative feedback [32], respectively) seem to have an edge over ACE inhibitors and beta-blockers, which decrease angiotensin II formation. The contrast between these drug classes that have an opposite effect on angiotensin II formation seems to be particularly important in low-renin populations, such as in hypertensive African Americans (32), in whom in ALLHAT (11,13) the stroke risk with lisinopril was 40% higher than that with chlorthalidone, which is unlikely to be related to the 4-mm Hg difference in SBP. In their hypothesis, Brown and Brown (1) suggested that the vasoconstrictive effect of angiotensin II in the proximal cerebral arteries could prevent Charcot-Bouchard aneurysms from rupturing. However, this AT1 receptor-mediated vasoconstrictive effect could only explain prevention of hemorrhagic but not ischemic strokes. To explain the reduction in ischemic strokes, which are far more prevalent, we further postulate that activation of the AT2 receptors by drugs that generate elevated levels of angiotensin II facilitates the recruitment of collateral vessels and increases neuronal resistance to anoxia. Conclusions Top Abstract Do diuretics have a... Diuretics in combination therapy Beta-blockers Calcium antagonists Angiotensin II receptor blockers... Angiotensin-converting enzyme... Unifying hypothesis Experimental evidence Conclusions References Recent trials have documented better stroke protection with diuretics, calcium antagonists, and ARBs compared with ACE inhibitors and beta-blockers. Clinical and experimental observations support the concept that this reduction of strokes may be mediated by AT2 receptors in small cerebral arteries. For any given fall in arterial pressure, drugs that activate these receptors have been shown to be more beneficial than drugs that are devoid of such activation (at least in patients with a low incidence of cardiac complications). As with all hypotheses, the Emmenthal cheese principle applies—it looks good, it smells good, it tastes good, but it has large holes! However, stroke is the most devastating consequence of hypertensive cardiovascular disease, and its prevention is the foremost goal of antihypertensive therapy. Our hypothesis of cerebroprotection by AT2 receptor activation should be thoroughly tested by a head-to-head comparison of an ARB and an ACE inhibitor in a patient population at high risk of cerebrovascular disease.

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<!--- Angiotensin II Receptor Blocker (ARB)

Click here for why I feel that Micardis® (telmisartan) should be the first line treatment for hypertension.

Related Topics:

Hypertension / pulse pressure / hardening of the arteries / angiotensin II receptor blockers (ARBs) / ace inhibitors / alpha blockers / calcium channel blockers / diuretics / beta blockers / Renin Inhibitors / Vanlev (omapatrilat) / aldosterone blockers / dihydropyridine (DHP) calcium antagonist / first line treatment for hypertension

Popular ARBs:

Cozaar® (losartan) / Diovan® (valsartan) Avapro® (irbesartan) / Atacand® (candesartan) / Micardis® (telmisartan) / Benicar (olmesartan)

News & Research:

Angiotensin-II Receptor Antagonists: Their Place in Therapy - American Academy of Family Physicians Neuroendocrine characterization and anorexigenic effects of telmisartan in diet- and glitazone-induced weight gain - Metabolism. 2009 Sep 28 - "Telmisartan prevents weight gain and decreases food intake in models of obesity and in glitazone-treated rodents" - Note: That might be another reason for using telmisartan as a first line treatment for hypertension. Valsartan Reduces Morbidity And Mortality In Japanese Patients With High Risk Hypertension: Results From The KYOTO HEART Study - Science Daily, 9/1/09 Cognitive Deficit in Amyloid-{beta}-Injected Mice Was Improved by Pretreatment With a Low Dose of Telmisartan Partly Because of Peroxisome Proliferator-Activated Receptor-{gamma} Activation - Hypertension. 2009 Jul 27 - "Taken together, our findings suggest that even a low dose of telmisartan had a preventive effect on cognitive decline in an Alzheimer disease mouse model, partly because of PPAR-gamma activation" Achieving blood pressure goals: should angiotensin II receptor blockers become first-line treatment in hypertension? - J Hypertens. 2009 Jul;27 Suppl 5:S9-14 - "Recently, the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) study established that telmisartan reduces morbidity and mortality in a broad cross-section of patients at high risk for heart and vascular events, to an extent similar to that of the angiotensin-converting enzyme inhibitor ramipril. In addition, ONTARGET demonstrated that telmisartan is somewhat better tolerated than ramipril. Attributes such as effective blood pressure lowering, tolerability and convincing outcomes data mean that ARBs satisfy the requirements for first-line antihypertensive agents" Effects of angiotensin II receptor blockers on diabetic nephropathy - J Hypertens. 2009 Jul;27 Suppl 5:S15-21 - "Key beneficial effects of ARBs and ACE inhibitors throughout the kidney disease continuum are primarily explained by blood pressure lowering effects and partially by their direct blockade of angiotensin II. Recent studies have shown that telmisartan, an ARB with high lipophilicity and the longest half-life compared with other ARBs, provides benefits on markers of cardiovascular risk, that is, microalbuminuria and slowing of early-stage nephropathy" Clinical evidence from ONTARGET: the value of an angiotensin II receptor blocker and an angiotensin-converting enzyme inhibitor - J Hypertens. 2009 Jul;27 Suppl 5:S23-9 - "Telmisartan was better tolerated than ramipril in this high-risk population: notably, the incidence of cough and angioedema was significantly lower with telmisartan alone. Thus, telmisartan provides comparable efficacy to ramipril with less adverse events, which may encourage patient compliance" Liver Disease 'Shrunk' By Blood-pressure Drug - Science Daily, 6/2/09 - "analysed a small clinical trial of losartan, a drug normally prescribed for hypertension, on 14 patients in Spain, who had Hepatitis C ... Half of the patients in the trial saw the scars in their liver shrink allowing the organ to repair itself ... Researchers believe that the drug blocks the signalling pathway so that the liver myofibroblasts die, removing the source of scar tissue. As the scar tissue breaks up, the damaged area of the liver is repaired by the body" Breast Cancer Gene Can Be Blocked By Blood Pressure Drug - Science Daily, 6/1/09 - "The gene, called AGTR1, caused normal breast cells to behave like cancer cells. This behavior was reversed by treatment with the blood pressure drug losartan. Tumors in mice that expressed AGTR1 shrunk by 30 percent eight weeks after treatment with losartan" Telmisartan Increases the Permeability of Endothelial Cells through Zonula Occludens-1 - Biol Pharm Bull. 2009 Mar;32(3):416-20 - "telmisartan but not valsartan downregulated ZO-1 mRNA and protein levels, disrupted the distribution of ZO-1 in cultured endothelial cells, and increased the permeability of endothelial cells in a dose-dependent manner ... telmisartan disrupts the continuous pericellular distribution of ZO-1, downregulates the expression of ZO-1 in endothelial cells, and increases the permeability of endothelial cells at least partly through PI3K and the peroxisome proliferator-activated receptor gamma-dependent pathway" Antihypertensive efficacy of telmisartan vs ramipril over the 24-h dosing period, including the critical early morning hours: a pooled analysis of the PRISMA I and II randomized trials - J Hum Hypertens. 2009 Feb 19 - "The adjusted mean treatment differences in the last 6-h mean ambulatory SBP/DBP were -5.8/-4.2 mm Hg after 8 weeks and -4.1/-3.0 mm Hg after 14 weeks, in favour of telmisartan (P<0.0001 for all four comparisons). Secondary end point results, including the mean 24-h ambulatory BP monitoring, day- and night-time BP and 24-h BP load, also significantly favoured telmisartan (P<0.0001). Both treatments were well tolerated; adverse events, including cough, were less common with telmisartan. These findings suggest that telmisartan is more effective than ramipril throughout the 24-h period and during the EMBPS; this may be attributable to telmisartan's long duration of effect, which is sustained throughout the 24-h dosing period" - Click here for why I feel telmisartan should be a first line treatment for hypertension. See telmisartan at OffshoreRX.com. Telmisartan induces proliferation of human endothelial progenitor cells via PPARgamma-dependent PI3K/Akt pathway - Atherosclerosis. 2008 Dec 31 - "since endothelial progenitor cells (EPCs) are thought to play a critical role in ischemic diseases, we investigated effects of telmisartan on proliferation of EPCs ... These findings suggest that telmisartan might contribute to endothelial integrity and vasculogenesis in ischemic regions by increasing numbers of EPCs" Hypertension Drug Dramatically Reduces Proteinuria In Kidney Disease Patients - Science Daily, 2/22/09 - "patients taking 128 mg of candesartan experienced more than a 33% reduction in proteinuria compared with those receiving 16 mg candesartan by the end of the study. This reduction was in addition to the reduction in proteinuria that the patients would have had when they first started taking candesartan at 16 mg daily" Telmisartan improves insulin resistance in high renin nonmodulating salt-sensitive hypertensives - J Hypertens. 2008 Dec;26(12):2393-8 - "Nonmodulating (NMHT) is a high-renin subtype of salt sensitive hypertension, which additionally develops insulin resistance and oxidative stress. Conversely, modulating hypertensives (MHT) normally regulates renal hemodynamics after high sodium intake without metabolic impairment ... In NMHT, telmisartan, after 3 months treatment, significantly reduced fasting and 120 min insulinemia (fasting: 8.4 +/- 2, 120 min: 25 +/- 10 muU%; P < 0.01) compared either to basal values or ramipril treatment. Similarly, only in NMHT, compared with basal values and ramipril treatment, telmisartan improved the HOMA-IR index in both MHT (2.76 +/- 0.16 to 2.24 +/- 0.18, P < 0.05) and NMHT (from: 4.4 +/- 1 to 2.3 +/- 0.7) and triglyceride plasma levels (MHT: from 139 +/- 1.85 to 122 +/- 2.4 mg%, P < 0.05; NMHT: from: 223 +/- 12 to 146 +/- 10 mg%, P < 0.01). Finally, highly sensitive C-protein-reactive protein values were higher in NMHT (0.33 +/- 0.07 mg.dl) than in MHT (0.14 +/- 0.06 mg.dl; P < 0.01). Both treatments reduced highly sensitive C-protein-reactive protein in NMHT. (ramipril from 0.32 +/- 0.05 mg.dl to 0.26 +/- 0.06 m.dl (P < 0.05) and telmisartan from 0.34 +/- 0.05+/- to 0.20 +/- 0.05 mg.dl (P < 0.01). CONCLUSION: Our data suggest that the improvement of the insulin sensitivity by telmisartan, instead of a similar effect on blood pressure shown by both drugs, could be ascribed to the PPAR agonistic action of telmisartan. This opens an interesting therapeutic approach for patients with hypertension and altered glycemic metabolism" Telmisartan prevents aneurysm progression in the rat by inhibiting proteolysis, apoptosis and inflammation - J Hypertens. 2008 Dec;26(12):2361-73 - "The angiotensin II type 1 receptor antagonist, telmisartan, prevents abdominal aortic aneurysm progression independently of blood pressure reduction by inhibiting proteolysis, apoptosis and inflammation in aortic tissue" Angiotensin II type 2 receptor blockade increases bone mass - J Biol Chem. 2008 Nov 11 - "Treatment with AT2 receptor blocker significantly enhanced the levels of bone mass and this effect was based on the enhancement of osteoblastic activity as well as the suppression of osteoclastic activity in vivo" Effects of Telmisartan and Ramipril on Adiponectin and Blood Pressure in Patients with Type 2 Diabetes - Am J Hypertens. 2008 Oct 30 - "There was a significant increase in adiponectin levels in the telmisartan (0.68 (95% confidence interval (CI), 0.27 to 1.10) microg/ml, P < 0.01) but not in the ramipril group" - See my adiponectin page. An increase in adiponectin is a good thing. Telmisartan versus angiotension-converting enzyme inhibitors in the treatment of hypertension: a meta-analysis of randomized controlled trials - J Hum Hypertens. 2008 Nov 6 - "Telmisartan had fewer drug-related adverse events than enalapril (RR 0.57, 95% CI 0.44-0.74), ramipril (RR 0.44, 95% CI 0.26-0.75), lisinopril (RR 0.70, 95% CI 0.56-0.89) and perindopril (RR 0.52, 95% CI 0.28-0.98). The meta-analysis indicates that telmisartan provides a superior BP control to ACEIs (enalapril, ramipril and perindopril) and has fewer drug-related adverse events and better tolerability in hypertensive patients" - Click here for reasons telmisartan might be a first line treatment. Beneficial Effects of Combination Therapy with Angiotensin II Receptor Blocker and Angiotensin-Converting Enzyme Inhibitor on Vascular Endothelial Function - Hypertens Res. 2008 Aug;31(8):1603-10 - "these results suggest that the angiotensin I-converting enzyme inhibitor perindopril is superior to the calcium channel blocker amlodipine for reducing vascular endothelial dysfunction when co-administered with angiotensin receptor blockers in patients with essential hypertension" Angiotensin receptor blockers in the treatment of NASH/NAFLD: Could they be a first-class option? - Adv Ther. 2008 Oct 29 - "Nonalcoholic fatty liver disease (NAFLD) ... nonalcoholic steatohepatitis (NASH) ... In our opinion there are two major advantages of ARBs that make them a possible therapeutic option for treating NASH and MS: their specific antihypertensive effect, and their impact on liver fibrosis. In light of this, and based on the current evidence (including existent human studies), we can speculate that some ARBs like telmisartan, candesartan, and losartan can be beneficial in treating NASH/NAFLD and its consequences, and further larger controlled clinical trials will bring consistent data into this field" Association of ACE Inhibitors and Angiotensin Receptor Blockers With Keratinocyte Cancer Prevention in the Randomized VATTC Trial - oncologystat.com, 9/3/08 - "squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs) ... Time to new BCC was 2.5 years for ACE inhibitor or ARB users and 2.2 years for nonusers. The absolute incidence rate of BCCs per 1000 patient-years was lower among ACE inhibitor/ARB users than nonusers (154 vs 233; unadjusted incidence rate ratio [IRR] = 0.66 ... Time to new SCC was 2.9 years for ACE inhibitor or ARB users and 2.6 years for nonusers. The absolute incidence rate of BCCs per 1000 patient-years was lower among ACE inhibitor/ARB users than nonusers (83 vs 141; unadjusted IRR = 0.58" Effects of telmisartan on adiponectin levels and body weight in hypertensive patients with glucose intolerance - Metabolism. 2008 Oct;57(10):1473-8 - "Telmisartan decreased body weight while increasing serum adiponectin levels in hypertensive patients with glucose intolerance. Candesartan did not achieve similar improvements in these patients. Among ARBs, telmisartan may have a larger impact on obesity-related diseases that can lead to cardiovascular disorders" Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial - Lancet. 2008 Aug 29 - "Telmisartan was well tolerated in patients unable to tolerate ACE inhibitors. Although the drug had no significant effect on the primary outcome of this study, which included hospitalisations for heart failure, it modestly reduced the risk of the composite outcome of cardiovascular death, myocardial infarction, or stroke" Medication To Lower Blood Pressure Reduces Outcome Of Cardiovascular Death, Heart Attack Or Stroke, Study Suggests - Science Daily, 8/31/08 - "Telmisartan reduced the outcome of cardiovascular death, heart attack, stroke or hospitalization for heart failure by a relative eight per cent ... However, when the outcome included cardiovascular death, heart attack or stroke (and not hospitalization for heart failure), telmisartan reduced that outcome by a significant 13 per cent" Angiotensin Inhibitors And Receptor Blockers Linked To Lower Risk Of Nonmelanoma Skin Cancer - Science Daily, 8/28/08 - "The group taking either an ACE inhibitor or ARBs had a 39 percent relative reduction in incidence of basal cell cancer and a 33 percent relative reduction in squamous cell cancers compared with nonusers" Comparison of the effects of telmisartan and olmesartan on home blood pressure, glucose, and lipid profiles in patients with hypertension, chronic heart failure, and metabolic syndrome - Hypertens Res. 2008 May;31(5):921-9 - "telmisartan had more beneficial effects on glucose and lipid profiles in patients with relatively high HbA1c, serum total and low-density lipoprotein cholesterol, and triglyceride levels. Therefore, we concluded that telmisartan was more beneficial than olmesartan for controlling blood pressure in the early morning, as well as for improving glucose and lipid profiles in patients with hypertension, chronic heart failure, and metabolic syndrome" - Click here for why I feel that telmisartan should be the first line treatment for hypertension. Telmisartan prevented cognitive decline partly due to PPAR-gamma activation - Biochem Biophys Res Commun. 2008 Aug 17 - "Pretreatment with a non-hypotensive dose of telmisartan significantly inhibited such cognitive decline. Interestingly, co-treatment with GW9662, a PPAR-gamma antagonist, partially inhibited this improvement of cognitive decline. Another ARB, losartan, which has less PPAR-gamma agonistic effect, also inhibited Abeta-injection-induced cognitive decline; however the effect was smaller than that of telmisartan and was not affected by GW9662. Immunohistochemical staining for Abeta showed the reduced Abeta deposition in telmisartan-treated mice. However, this reduction was not observed in mice co-administered GW9662. These findings suggest that ARB has a preventive effect on cognitive impairment in Alzheimer disease, and telmisartan, with PPAR-gamma activation, could exert a stronger effect" The angiotensin II receptor blocker telmisartan improves insulin resistance and has beneficial effects in hypertensive patients with type 2 diabetes and poor glycemic control - Diabetes Res Clin Pract. 2008 Aug 8 - "The telmisartan significantly improved HOMA-IR in hypertensive patients and also significantly decreased HbA1c in type 2 diabetic patients especially in the patients with poor glycemic control (HbA1c>==8.0%). These results indicate that telmisartan improves insulin resistance and gives beneficial effects in hypertensive patients with type 2 diabetes and a poor glycemic control" The angiotensin II receptor blocker telmisartan improves insulin resistance and has beneficial effects in hypertensive patients with type 2 diabetes and poor glycemic control - Diabetes Res Clin Pract. 2008 Aug 8 - "The telmisartan significantly improved HOMA-IR in hypertensive patients and also significantly decreased HbA1c in type 2 diabetic patients especially in the patients with poor glycemic control (HbA1c>==8.0%). These results indicate that telmisartan improves insulin resistance and gives beneficial effects in hypertensive patients with type 2 diabetes and a poor glycemic control" - Just another reason I feel that telmisartan should be the first line treatment for hypertension. Click here for other reasons. See telmisartan at OffshoreRX.com. Angiotensin Receptor Blockers Are Lower Incidence, Progression Of Alzheimer's Disease - Science Daily, 7/27/08 - "Researchers at Boston University School of Medicine (BUSM) have, for the first time, found that angiotensin receptor blockers (ARBs)—a particular class of anti-hypertensive medicines—are associated with a striking decrease in the occurrence and progression of dementia" Telmisartan but not candesartan affects adiponectin expression in vivo and in vitro - Hypertens Res. 2008 Apr;31(4):601-6 - "the changes in serum adiponectin and plasma glucose over 3 months were significantly greater in the telmisartan group than in the candesartan group. In vitro, although the protein level of adiponectin was not significantly elevated, the mRNA expression of adiponectin was elevated 1.5-fold by telmisartan in 3T3-L1 adipocytes. Our findings suggest that telmisartan may have beneficial effects in type 2 diabetes beyond its antihypertensive effect" - I've been saying that telmisartan should be the first line treatment for hypertension for some time now if natural methods such as coenzyme Q10 don't work. Telmisartan, an Angiotensin II Type 1 Receptor Blocker, Improves Coronary Microcirculation and Insulin Resistance among Essential Hypertensive Patients without Left Ventricular Hypertrophy - Hypertens Res. 2008 Apr;31(4):615-22 - "Coronary flow velocity reserve (CFVR) ... CFVR was improved in the telmisartan group (2.4+/-0.4 to 2.9+/-0.4; p<0.01), but there was no difference in the nifedipine group (2.5+/-0.3 to 2.5+/-0.3; n.s.). HOMA-IR was improved in the telmisartan group (3.1+/-1.1 to 1.6+/-0.7; p<0.01), but there was no difference in the nifedipine group (2.8+/-1.1 to 2.4+/-0.7; n.s.). In conclusion, this study demonstrates that antihypertensive therapy with telmisartan, but not nifedipine, has a beneficial effect on coronary microcirculation and insulin resistance among essential hypertensive patients" Microalbuminuria Reduction with Telmisartan in Normotensive and Hypertensive Japanese Patients with Type 2 Diabetes: A Post-Hoc Analysis of the Incipient to Overt: Angiotensin II Blocker, Telmisartan, Investigation on Type 2 Diabetic Nephropathy (INNOVATION) Study - Hypertens Res. 2008 Apr;31(4):657-64 - "The patients treated with either dose of telmisartan showed lower transition rates from microalbuminuria to overt nephropathy compared to the placebo group. In addition, more patients on telmisartan reverted to normoalbuminuria (UACR<30 mg/g creatinine): 15.5% of the 40 mg group, 19.6% of the 80 mg group, and 1.9% of the placebo group ... Side effects did not differ among the groups. The present study demonstrates that telmisartan prevents the progression of microalbuminuria (in some cases induces remission of albuminuria) in normotensive Japanese patients with type 2 diabetes. Telmisartan is shown to be safe and well tolerated in these patients" Effect of irbesartan on erectile function in patients with hypertension and metabolic syndrome - Int J Impot Res. 2008 Jul 3 - "Erectile function increased significantly (P<0.0001) after 6 months of treatment with irbesartan, irrespective of dosage and independent of additional treatment with hydrochlorothiazide. Prevalence of ED declined to 63.7% from 78.5% at baseline, along with a significant increase in orgasmic function (P<0.001) and intercourse satisfaction (P<0.001). Treatment with irbesartan alone, as well as in combination with hydrochlorothiazide is associated with an improvement of sexual desire, frequency of sexual contacts and erectile function in hypertensive patients with the metabolic syndrome. These results suggest a beneficial role of angiotensin receptor antagonists in the treatment of metabolic syndrome, and ED" - Note: I've been suggesting telmisartan (an ARB) for some time as the first line treatment for hypertension. See telmisartan at OffshoreRX. Hypertension Treatment Effective In Reversing Vascular Damage, Study Suggests - Science Daily, 6/17/08 - "A hypertension medication called olmesartan medoxomil is effective in reversing the narrowing of the arteries that occurs in patients with high blood pressure ... After one year of treatment, olmesartan medoxomil improved the artery abnormalities in high blood pressure patients and returned arterial architecture to normal levels. This was not seen with the atenolol" Telmisartan is more effective than losartan in reducing proteinuria in patients with diabetic nephropathy - Kidney Int. 2008 May 21 - "telmisartan is superior to losartan in reducing proteinuria in hypertensive patients with diabetic nephropathy, despite a similar reduction in blood pressure" - Just one more reason I feel telmisartan should be the first line treatment for hypertension if natural methods such as coenzyme Q10 don't work. See telmisartan at OffshoreRX.com. Effects of Angiotensin Converting Enzyme Inhibitor and Angiotensin II Receptor Antagonist Combination on Nitric Oxide Bioavailability and Atherosclerotic Change in Watanabe Heritable Hyperlipidemic Rabbits - Hypertens Res. 2008 Mar;31(3):575-84 - "1) vehicle (control), 2) the ACEI enalapril (E: 3 mg/kg/day), 3) the ARB losartan (L: 30 mg/kg/day) and 4) enalapril (1.5 mg/kg/day) + losartan (15 mg/kg/day) (E+L). Intra-aortic infusion of ACh produced an increase in plasma NO concentration, which was significantly greater with all the drug treatments than with the control. E increased ACh-induced NO significantly more than L (by 6.9 nmol/L, and 4.7 nmol/L, respectively). E+L increased ACh-induced NO by 9.5 nmol/L, significantly more than either E or L ... the combined treatment with an ACEI and an ARB may have additive protective effects on endothelial function as well as atherosclerotic change" Angiotensin-Converting Enzyme Inhibitors, Angiotensin Receptor Blockers, or Both for Patients With Proteinuria? A Best Evidence Review - Medscape, 5/20/08 - "Most significantly, the addition of ACEIs to ARBs reduced proteinuria to a greater degree than ARBs alone (ratio of means 0.76 at 1 to 4 months and 0.75 at 5 to 12 months). Combination therapy was also superior to treatment with ACEIs alone ... The 2 important conclusions that can be drawn from this meta-analysis are that ARBs are not superior to ACEIs in improving proteinuria, and that the combination of these 2 treatments appears superior in this outcome compared with either treatment alone ... Two of the biggest safety concerns regarding the combination therapy include the risks for hyperkalemia and acute worsening of renal function. A review of the literature, however, suggests that these risks may not be significantly worse with combination treatment vs monotherapy" Telmisartan increases fatty acid oxidation in skeletal muscle through a peroxisome proliferator-activated receptor-gamma dependent pathway - J Hypertens. 2008 Jun;26(6):1209-1215 - "telmisartan may increase energy expenditure and protect against dietary induced obesity and features of the metabolic syndrome at least in part by increasing muscle fatty acid oxidation through activation of peroxisome proliferator-activated receptor-gamma" Meta-analysis of Randomized Controlled Trials Comparing Telmisartan With Losartan in the Treatment of Patients With Hypertension - Am J Hypertens. 2008 May;21(5):546-52. Epub 2008 Mar 20 - "In comparison with losartan, telmisartan provides superior control of BP and has no association with increased risk of adverse events" Valsartan Improves Arterial Stiffness in Type 2 Diabetes Independently of Blood Pressure Lowering - Hypertension. 2008 Apr 21 - "Increased arterial stiffness, as estimated from aortic pulse wave velocity (Ao-PWV), and albuminuria are independent predictors for cardiovascular disease in type 2 diabetes mellitus (T2DM) ... Ao-PWV showed a significantly greater reduction, mean (95% CI), -0.9 m/s (-1.4 to -0.3) for valsartan/HCTZ compared to amlodipine (P=0.002). AER fell significantly only with Val/HCTZ from 30.8(20.4, 46.5) to 18.2(12.5, 26.3) mcg/min, (P=0.01) with between treatment difference in favor of Val/HCTZ of -15.3mcg/min" - Telmisartan, another ARB and my first line plug, will decrease arterial stiffness also. See: Angiotensin II Antagonist Telmisartan Fights Stiffening Arteries In Hypertensive Diabetics - Doctor's Guide, 4/6/01 - "not only effectively lowered blood pressure compared with placebo, but also significantly decreased arterial stiffness" - See telmisartan at OffshoreRX. Blood Pressure Drugs Halt Pancreatic Cancer Cell Growth, Researchers Find - Science Daily, 4/14/08 - "one type of pressure-lowering drug called an angiotensin receptor blocker inhibits pancreatic cancer cell growth and causes cell death" Effects of telmisartan, a unique angiotensin receptor blocker with selective peroxisome proliferator-activated receptor-gamma-modulating activity, on nitric oxide bioavailability and atherosclerotic change - J Hypertens. 2008 May;26(5):964-972 - "In addition to a class effect of ARBs, telmisartan may have additional effects on nitric oxide bioavailability and atherosclerotic change through its PPARgamma-mediated effects in genetically hyperlipidemic rabbits" - Just one more reason to consider telmisartan as a first line treatment for hypertension. See telmisartan at OffshoreRX.com. Telmisartan, an Angiotensin II Type 1 Receptor Blocker, Inhibits Advanced Glycation End-product (AGE)-elicited Hepatic Insulin Resistance via Peroxisome Proliferator-activated Receptor-gamma Activation - J Int Med Res. 2008 Mar-Apr;36(2):237-43 - "Candesartan, another ARB, did not affect AGEs-induced serine phosphorylation of IRS-1 at serine-307 residues in Hep3B cells. Our study suggests that telmisartan could improve AGE-elicited insulin resistance in Hep3B cells by inhibiting serine phosphorylation of IRS-1, at least in part, via activation of PPAR-gamma" - Note: That might be another reason for considering telmisartan as a first line treatment for hypertension. See telmisartan at OffshoreRX.com. Telmisartan, Ramipril, or Both in Patients at High Risk for Vascular Events - N Engl J Med. 2008 Mar 31 - "Telmisartan was equivalent to ramipril in patients with vascular disease or high-risk diabetes and was associated with less angioedema. The combination of the two drugs was associated with more adverse events without an increase in benefit" - Yeah but if you have to go with two drugs it sure seems like it's the least of all the evils regarding side effects. See telmisartan at OffshoreRX.com. ONTARGET: ARB Similar to ACE - Medscape, 3/31/08 - "The angiotensin receptor blocker (ARB) telmisartan (Micardis, Boehringer Ingelheim) was "noninferior" to the ACE inhibitor ramipril in patients with vascular disease or high-risk diabetes in the landmark ONTARGET trial" New Blood Pressure Medication Has Fewer Side Effects, Global Study Suggests - Science Daily, 3/31/08 - "The study found a new drug telmisartan is as effective as the popular drug ramipril in reducing cardiovascular death in high risk patients and it has fewer side effects" - I've been plugging telmisartan for some time now. Click here. See telmisartan at OffshoreRX.com. Telmisartan treatment decreases visceral fat accumulation and improves serum levels of adiponectin and vascular inflammation markers in Japanese hypertensive patients - Hypertens Res. 2007 Dec;30(12):1205-10 - "telmisartan treatment was associated with an improvement of vascular inflammation, reductions in visceral fat and increases in serum adiponectin" Angiotensin II receptor blocker inhibits tumour necrosis factor-alpha-induced cell damage in human renal proximal tubular epithelial cells - Nephrology (Carlton). 2008 Mar 5 - "The present study demonstrates that TNF-alpha induces renal tubular cell damage in RPTEC and AT1/AT2 receptor blockers showed cytoprotective effects probably via at least partly different mechanism" Treatment of hypertension in individuals with the cardiometabolic syndrome: role of an angiotensin II receptor blocker, telmisartan - Expert Rev Cardiovasc Ther. 2008 Mar;6(3):289-303 - "Concerning drug treatment of hypertension associated with other cardiometabolic risk factors, many results of head-to-head studies have demonstrated a reduction in new-onset Type 2 diabetes in hypertensive patients treated with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, when compared with conventional antihypertensive therapy. The explanations of the different actions of both these drugs include several mechanisms related to pancreatic insulin release and insulin sensitivity improvement. Another mechanism by which the inhibition of the renin-angiotensin system may improve insulin sensitivity is through the partial peroxisome proliferator-activated receptor-gamma agonism of telmisartan. For that reason, telmisartan has been considered by some experts to be an antihypertensive agent that is particularly useful in the treatment of hypertension associated with cardiometabolic risk factors" Reduced incidence of new-onset atrial fibrillation with angiotensin II receptor blockade: the VALUE trial - J Hypertens. 2008 Mar;26(3):403-411 - "These findings suggest that angiotensin II receptor blockers may result in greater benefits than calcium antagonists in hypertensive patients at risk of new-onset AF" Effects of angiotensin II type 1-receptor blockade on retinal endothelial function - J Hypertens. 2008 Mar;26(3):516-22 - "AT1-receptor blockade with irbesartan improves endothelial function of the retinal vasculature, taken as a model of cerebral circulation" Effect of Telmisartan on Nitric Oxide-Asymmetrical Dimethylarginine System. Role of Angiotensin II Type 1 Receptor and Peroxisome Proliferator Activated Receptor {gamma} Signaling During Endothelial Aging - Hypertension. 2008 Feb 4 - "Telmisartan, in addition to blocking angiotensin (Ang) II type 1 receptor (AT1R), activates peroxisome proliferator activated receptor gamma (PPARgamma) signaling that interferes with nitric oxide (NO) system. Because aging of endothelial cells (ECs) is hallmarked by a reduction in NO synthesis, we hypothesized that telmisartan increases NO formation by regulated asymmetrical dimethylarginine (ADMA)-dimethylarginine dimethylaminohydrolase (DDAH)-system through blocking AT1R and activating PPARgamma signaling ... During the process of aging, PPARgamma protein expression decreased significantly, whereas the expression of AT1R increased. Telmisartan reversed these effects and dose-dependently decreased reactive oxygen species and 8-iso-prostaglandin (PG) F2alpha formation ... telmisartan mainly by activating PPARgamma signaling can alter the catabolism and release of ADMA as an important cardiovascular risk factor. We therefore propose that telmisartan translationally and posttranslationally upregulated DDAH expression via activation of PPARgamma signaling, causing ADMA to diminish and increase NO synthesis sufficient to delay senescence" Establishing A New Option for Target-organ Protection: Rationale for ARB Plus ACE Inhibitor Combination Therapy - Am J Hypertens. 2008 Jan 24 - "Combination therapy targeting RAS activation may reduce target-organ damage and provide superior blood pressure (BP) control; combining angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) represents one possible approach" ACE Inhibitors or ARBs in Hypertension? In Chronic Kidney Disease? - Medscape, 1/17/07 - "ARBs and ACE inhibitors were similarly effective at lowering proteinuria, ARBs were more effective than calcium-channel blockers, and a combination of ARBs and ACE inhibitors was more effective than either agent alone" The effect of losartan on hemoglobin concentration and renal outcome in diabetic nephropathy of type 2 diabetes - Kidney Int. 2007 Dec 19 - "Compared with placebo, losartan treatment was associated with a significant decrease of hemoglobin, with the largest between-group difference at 1 year. After adjustment, there were significant relative risk reductions for losartan compared with placebo for ESRD and for ESRD or death regardless of the baseline hemoglobin even in those patients with a baseline hemoglobin below 120 g l(-1). Hence, the renoprotective properties of losartan were maintained despite a significant lowering of the hemoglobin concentration" Sustained Tubulo-interstitial Protection in SHRs by Transient Losartan Treatment: An Effect of Decelerated Aging? - Am J Hypertens. 2008 Jan 10 - "Transient losartan treatment reduces cell-turnover not only acutely but also for a prolonged period after drug withdrawal. This results in the long-term in reduced aging and attenuated tubulo-interstitial damage, suggesting there exists a modulating effect of angiotensin II (ANGII)-antagonism on long-term cell turnover" - Note: Losartan is an ARB. I would think that telmisartan (also and ARB and my recommendation for hypertension) would give the same effect. ACE Inhibitors vs ARBs in HTN and in CKD - Medscape, 1/4/08 - "In the setting of chronic kidney disease (CKD), concludes the other study, which is a meta-analysis, ACE inhibitor and ARB monotherapy are similarly effective at reducing proteinuria, but a combination of the two angiotensin-2-suppressing drugs works better than either agent individually [2]. But a blanket recommendation to combine them would be premature, according to the authors, because there is little evidence that the combination would improve clinical outcomes over monotherapy, and the safety of such combination therapy is largely undefined" Anti-atherosclerotic properties of telmisartan in advanced atherosclerotic lesions in apolipoprotein E deficient mice - Atherosclerosis. 2007 Dec 17 - "These data suggest that chronic inhibition of the RAS by telmisartan prevails in reducing advanced atherosclerosis and promoting plaque stability over ramipril, possibly through the reduced activity of the pro-inflammatory transcription factors NFkappaB and Egr-1 and through the activation of PPARgamma" Blood Pressure Drug Telmisartan Shows Powerful Activity Against Stroke, Study Suggests - Science Daily, 12/17/07 - "83 percent of rats given no medication showed signs of stroke, as did 56 percent of rats given ramipril alone. However, no strokes were noted in the telmisartan-only or the telmisartan/ramipril combo groups ... Telmisartan's ability to easily pass through the blood-brain barrier (something ramipril cannot do) is likely behind the neuroprotective effect noted in the study" Effect of the Angiotensin Receptor Blocker Irbesartan on Metabolic Parameters in Clinical Practice: the DO-IT Prospective Observational Study - Cardiovasc Diabetol. 2007 Nov 27;6(1):36 - "Six months of irbesartan therapy decreased systolic blood pressure by 14% (157.4+/-14.7 vs. 135.0+/-10.7 mmHg) and diastolic blood pressure by 13% (92.9+/-9.2 vs. 80.8+/-6.8 mmHg). This was associated with a decrease in body weight (-2.3%), fasting glucose (-9.5%), HbA1c (-4.6%), LDL-cholesterol (-11%), triglycerides (-16%) and gamma-GT (-12%) and an increase in HDL-cholesterol (+5%)" Renoprotective effect of the addition of losartan to ongoing treatment with an Angiotensin converting enzyme inhibitor in type-2 diabetic patients with nephropathy - Hypertens Res. 2007 Oct;30(10):929-35 - "During the 12-month treatment, addition of losartan or addition of an ACE-I to the treatment protocol reduced systolic blood pressure (SBP) by 10% and 12%, diastolic blood pressure (DBP) by 7% and 4%, and urinary albumin excretion by 38% and 20% of the baseline value, respectively. However, the effects on both BP and urinary albumin were not significantly different between the two therapies. In conclusion, addition of losartan or an ACE-I to an ongoing treatment with an ACE-I, or addition of an ACE-I to ongoing treatment with a conventional antihypertensive were equally effective at reducing the urinary albumin excretion and BP, and provided renal protection in patients with type-2 diabetic nephropathy" Systematic Review: Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers for Treating Essential Hypertension - Ann Intern Med. 2007 Nov 5 - "Available evidence shows that ACE inhibitors and ARBs have similar effects on blood pressure control, and that ACE inhibitors have higher rates of cough than ARBs. Data regarding other outcomes are limited" High-Dose Candesartan Reduces Persistent Proteinuria - Doctor's Guide, 11/6/07 Candesartan Improves Outcomes in Diabetes, Kidney Patients - Doctor's Guide, 11/8/07 - "new onset diabetes occurred in just 1.1% of the 1,024 patents on candesartan compared with 2.9% of the patients treated with other blood pressure lowering medications that did not include angiotensin receptor blockers ... "We observed that treatment with candesartan reduced that risk by 63% (P =.027)," he said during a press briefing. He also noted that patients on candesartan had fewer adverse events than the 1,025 patients who received standard therapy" - I would have liked to see telmisartan (also an ARB) in this study. Common Medications Provide Equal Blood Pressure Control - Doctor's Guide, 11/2/07 - "Two common classes of blood pressure medications – angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) – are equally effective at controlling high blood pressure ... ACEIs are slightly more likely than ARBs to cause a harmless but persistent dry cough ... If left untreated, high blood pressure can cause catastrophic health problems: the heart may enlarge, which can lead to heart failure; small bulges --aneurysms -- may form in blood vessels, including the aorta (the main artery to the heart) and others in the brain, legs, and intestines; blood vessels in the kidney may narrow, causing kidney failure; blood vessels in the eyes may burst or bleed, possibly leading to blindness; and arteries throughout the body may "harden" faster, potentially leading to heart attack or stroke" Renoprotection provided by losartan in combination with pioglitazone is superior to renoprotection provided by losartan alone in patients with type 2 diabetic nephropathy - Kidney Blood Press Res. 2007;30(4):203-11 - "Renoprotection conferred by losartan combined with pioglitazone is superior to that conferred by losartan alone in subjects with type 2 diabetic nephropathy. The combination is generally well tolerated" Drugs For Hypertension May Help Prevent And Treat Alzheimer's Disease - Science Daily, 10/26/07 - "mice genetically determined to develop Alzheimer's disease beta-amyloid production and subsequent cognitive deterioration, significantly benefit from the treatment with the anti-hypertensive agent Valsartan, found to pharmacologically prevent beta-amyloid production in the brain even when delivered to Alzheimer's disease mice at doses 3-4 fold lower than the minimal equivalent dose prescribed for the treatment of hypertension in humans. Other anti-hypertension drugs with beneficial results included Propranolol HCI, Carvedilol, Losartan, Nicardipine HCI, Amiloride HCI and Hydralazine HCI" - Note: I'm big on Micardis (telmisartan). Valsartan and losartan (generic names so they shouldn't have been capitalized) are also ARBs. I'm wondering if telmisartan was in the study. Do ACE inhibitors and ARBs mix well? Analysis urges caution - theheart.org, 10/10/07 - "patients receiving both an ACE inhibitor and an ARB were more likely not to comply with therapy due to side effects, which included hypotension, cough, angioedema, worsening renal function as defined by a change in serum creatinine >0.5 mg/dL, hyperkalemia as defined by serum potassium level changes >5.5 mEq/L, and symptomatic hypotension" Adverse Effects of Combination Angiotensin II Receptor Blockers Plus Angiotensin-Converting Enzyme Inhibitors for Left Ventricular Dysfunction: A Quantitative Review of Data From Randomized Clinical Trials - Arch Intern Med. 2007 Oct 8;167(18):1930-6 - "there were significant increases in worsening renal function (RR, 2.17 [95% CI, 1.59-2.97] and RR, 1.61 [95% CI, 1.31-1.98], respectively), hyperkalemia (RR, 4.87 [95% CI, 2.39-9.94] and RR, 1.33 [95% CI, 0.90-1.98], respectively" Prevention of stroke in patients with hypertension - Am J Cardiol. 2007 Aug 6;100(3A):17J-24J - "In contrast to angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers (ARBs) provide consistent benefits in stroke protection beyond blood pressure lowering. The ARB telmisartan has a particularly interesting profile for stroke management. Selective angiotensin II type 1 receptor blockade and 24-hour blood pressure control with telmisartan provide the potential for improved stroke prevention" Rationale for double renin-angiotensin-aldosterone system blockade - Am J Cardiol. 2007 Aug 6;100(3A):25J-31J - "The clinical benefits of both angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) extend beyond blood pressure reduction to encompass tissue-protective effects in target organs, such as the heart, vasculature, and kidneys, that underlie the reductions in cardiovascular mortality and morbidity seen in large outcome trials. However, these effects are achieved by different mechanisms. ACE inhibitors reduce circulating and tissue angiotensin II levels and potentiate the beneficial effects of bradykinin, including generation of nitric oxide (NO). By contrast, the protective effects of ARBs are owing to the blockade of the angiotensin II type 1 (AT(1)) receptors and possibly also to the stimulation of angiotensin II type 2 (AT(2)) receptors, again resulting in NO release. In addition, some ARBs, such as telmisartan, are selective activators of peroxisome proliferator-activated receptor-gamma (PPAR-gamma), thereby increasing insulin sensitivity. In contrast to other PPAR-gamma ligands, such as the thiazolidinediones, activation of this receptor by telmisartan does not result in weight gain. The complementary mechanisms of action of ACE inhibitors and ARBs create a rationale for combination therapy in high-risk patients" Angiotensin receptor blockers versus angiotensin-converting enzyme inhibitors: where do we stand now? - Am J Cardiol. 2007 Aug 6;100(3A):38J-44J - "Both classes of agent can prevent or reverse endothelial dysfunction and atherosclerosis, thereby potentially reducing the risk of cardiovascular events. Such a reduction has been shown with ACE inhibitors in patients with coronary artery disease, but no such data are currently available for ARBs. Both ACE inhibitors and ARBs have been shown to reduce damage in target organs, such as the heart and kidney, and to decrease cardiovascular mortality and morbidity in patients with congestive heart failure" New opportunities in cardiovascular patient management: a survey of clinical data on the combination of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers - Am J Cardiol. 2007 Aug 6;100(3A):45J-52J - "Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) differ in their actions on the renin-angiotensin-aldosterone system (RAAS). ACE inhibitors prevent the formation of angiotensin II, although angiotensin II may still be generated by alternative pathways. However, ACE inhibitors interrupt bradykinin breakdown, which in turn potentially enhances nitric oxide and prostacyclin mechanisms. In contrast, ARBs selectively prevent the binding of angiotensin II to the angiotensin type 1 (AT(1)) receptor while leaving the potentially beneficial effects of the AT(2) receptor unaffected. The supposition is that dual blockade of the RAAS effectively overcomes the harmful effects of angiotensin II mediated by the AT(1) receptor while offering the additional effects of the ACE inhibitor" Telmisartan Improves Endothelial Function and Nitrate Tolerance in Patients With Coronary Artery Disease and the Metabolic Syndrome - Doctor's Guide, 9/11/07 - "Telmisartan is mainly an angiotensin II receptor blocker, but recently it has [shown] antioxidant effects and insulin resistance improvement effects ... After 4 weeks of treatment, the endothelium-dependant measure of flow-mediated dilatation was significantly increased in the telmisartan group (P <.01, vs control group), indicating improvements in endothelial dysfunction with telmisartan" ACE-I/ARB treatment in type 1 diabetes patients with albuminuria is associated with lower odds of progression of coronary artery calcification - J Diabetes Complications. 2007 Sep-Oct;21(5):273-9 - "coronary artery calcification (CAC) ... In backward logistic regression, presence of albuminuria at baseline predicted progression of CAC among subjects not treated with ACE-I/ARB [odds ratio=4.06 ... Among the subjects with albuminuria, the odds of progression was 62% lower (95% CI=88% decrease to 23% increase; P=.106) in those treated with ACE-I/ARB ... Albuminuria is a significant independent risk factor for CAC progression in young type 1 diabetes patients asymptomatic for CAD, and ACE-I/ARB treatment is associated with substantially lower odds of CAC progression" Heart Damage Can Be Reversed with Early Treatment - Science Daily, 8/27/07 - "During the first six months of the study, 38 subjects received a placebo, and the other 38 subjects took 160mg of Valsartan, a drug that blocks a hormone that is detrimental to the blood vessels and the heart. During the next six months, both groups took Valsartan ... Those who took the drug for the first six months significantly reduced their Rasmussen Disease Score compared with those who took the placebo. At the 12-month mark -- after both groups were taking the drug -- every patient showed better Rasmussen Disease Scores, effectively demonstrating that Valsartan can slow progression and even reverse early cardiovascular disease in asymptomatic high-risk patients" Telmisartan, an Angiotensin II Type 1 Receptor Blocker, Inhibits Advanced Glycation End-product (AGE)-induced Monocyte Chemoattractant Protein-1 Expression in Mesangial Cells Through Downregulation of Receptor for AGEs via Peroxisome Proliferator-activated Receptor-gamma Activation - J Int Med Res. 2007 Jul-Aug;35(4):482-9 - "Candesartan, an Ang II type 1 receptor blocker, did not suppress AGEs-induced superoxide generation. Telmisartan and the antioxidant, N-acetylcysteine, completely inhibited AGEs-induced MCP-1 overproduction by mesangial cells" Vitamin C 'benefits diabetics' - BBC News, 6/28/07 - "Vitamin C neutralises free radicals, while Telmisarten stimulates the natural removal of the molecules by cells" Telmisartan Staves Off Overt Diabetic Nephropathy - Medscape, 6/27/07 - "During a mean follow-up of 1.3 years, transition rates to overt nephropathy were significantly lower with telmisartan 40 mg (22.6%) and telmisartan 80 mg (16.7%) than with placebo (49.9%)" Angiotensin Receptor Blockers: Benefits Beyond Blood Pressure Lowering? - Medscape, 6/26/07 - "I would say that at this time, both ACE inhibitors and ARBs can be said to be useful in preventing or delaying progression of nondiabetic patients into type 2 diabetes" Baseline Glycaemic Control Has No Effect on Telmisartan-Related Improvements in Diabetics With Nephropathy - Doctor's Guide, 6/25/07 - "Chronic telmisartan treatment may slow the progression of renal disease in patients with type 2 diabetes and diabetic nephropathy, irrespective of baseline glycaemic control" Telmisartan May Help Preserve Renal Function in Patients With Hypertension, Diabetes - Medscape, 6/1/07 - "In patients with hypertension and type 2 diabetes, telmisartan and ramipril both may help preserve cardiovascular and renal function by increasing nitric oxide (NO) activity of the renal endothelium" The Differential Effects of Angiotensin II Type 1 Receptor Blockers on Microalbuminuria in Relation to Low-Grade Inflammation in Metabolic Hypertensive Patients - Am J Hypertens. 2007 May;20(5):565-72 - "There was a significant increase in high molecular weight adiponectin in the telmisartan group ... The reductions of microalbuminuria and high-sensitivity C-reactive protein (hs-CRP) were significant in the telmisartan group" Telmisartan-Hydrochlorothiazide Outperforms Valsartan-Hydrochlorothiazide for Blood Pressure Reduction - Doctor's Guide, 5/29/07 - "The change in diastolic blood pressure was -18.2 mmHg for the telmisartan-hydrochlorothiazide group and -17.0 mmHg for the valsartan-hydrochlorothiazide group. The change in systolic blood pressure was -24.6 mmHg and -22.5 for the two groups, respectively" Telmisartan Reduces Proteinuria More Than Losartan - Doctor's Guide, 5/28/07 - "Our findings suggest that at similar levels of blood pressure control, telmisartan may confer greater protection against progression to end-stage renal disease" Metabolic effects of telmisartan and irbesartan in type 2 diabetic patients with metabolic syndrome treated with rosiglitazone - J Clin Pharm Ther. 2007 Jun;32(3):261-8 - "Telmisartan seemed to improve glycaemic and lipid control and metabolic parameters of the metabolic syndrome better than irbesartan" Combination therapy with an ACE inhibitor and an angiotensin receptor blocker for diabetic nephropathy: a meta-analysis - Diabet Med. 2007 May;24(5):486-93 - "This meta-analysis suggests that ACEI + ARB reduces 24-h proteinuria to a greater extent than ACEI alone. This benefit is associated with small effects on GFR, serum creatinine, potassium and blood pressure" The effect of telmisartan and ramipril on early morning blood pressure surge: a pooled analysis of two randomized clinical trials - Blood Press Monit. 2007 Jun;12(3):141-147 - "Telmisartan significantly reduced the early morning systolic blood pressure surge compared with ramipril" Angiotensin II receptor blockers downsize adipocytes in spontaneously type 2 diabetic rats with visceral fat obesity - Am J Hypertens. 2007 Apr;20(4):431-6 - "adipocyte downsizing was significantly greater with telmisartan compared to valsartan. The likely mechanism for this difference was thought to be the PPAR-gamma-mediated action of telmisartan" Combination ACE inhibitor and angiotensin receptor blocker therapy - future considerations - J Clin Hypertens (Greenwich). 2007 Jan;9(1):78-86. - "The individual gains seen with each of these drug classes have led to speculation that their combination might offer additive if not synergistic outcome benefits. The foundation of this hypothesis, although biologically possible, has thus far not been sufficiently well proven to support the everyday use of these 2 drug classes in combination. Additional outcomes trials, which are currently proceeding to their conclusion, may provide the necessary proof to support an expanded use of these 2 drug classes in combination" Treating the metabolic syndrome - Expert Rev Cardiovasc Ther. 2007 May;5(3):491-506 - "appropriate treatment of MS components often requires pharmacologic intervention with insulin-sensitizing agents, such as metformin and thiazolidinediones, while statins and fibrates, or angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are the first-line lipid-modifying or antihypertensive drugs" Novel ARB Provides Greater Reductions in Proteinuria in Diabetics With Overt Nephropathy - Medscape, 5/22/07 - "One year of treatment with the novel angiotensin receptor blocker (ARB) telmisartan provided greater reductions in proteinuria when compared with losartan, a drug approved for the treatment of diabetic nephropathy to prevent renal-disease progression" Valsartan Cuts C-Reactive Protein Levels in Prediabetics - Doctor's Guide, 5/22/07 - "In diabetic patients with abdominal obesity, after 16 weeks of hydrochlorothiazide therapy, median hsCRP values were increased 16% (4.9 vs 3.7 mg/L at baseline, P <.05) but decreased 9% in patients on valsartan (3.7 vs 4.1 mg/L at baseline, P <.05) and 5% in patients on combination therapy" Valsartan Is a Prudent Choice in Young Hypertensives - Doctor's Guide, 5/21/07 ARBs for the Treatment of Heart Failure: A Class Effect? - Medscape, 5/15/07 - "Our results suggest that all ARBs are not equivalent. Valsartan, irbesartan, and candesartan were all associated with better survival rates when compared with losartan. The comparison for telmisartan was not statistically significant, possibly because this group included the smallest number of patients. In addition, there are no data from randomized trials on the effect of telmisartan on mortality in patients with heart failure" Angiotensin II receptor blockers for the treatment of heart failure: a class effect? - Pharmacotherapy. 2007 Apr;27(4):526-34 - "Elderly patients with heart failure who were prescribed losartan had worse survival rates compared with those prescribed other commonly used ARBs" Metabolic effects of telmisartan and irbesartan in type 2 diabetic patients with metabolic syndrome treated with rosiglitazone - J Clin Pharm Ther. 2007 Jun;32(3):261-8 - "Telmisartan seemed to improve glycaemic and lipid control and metabolic parameters of the metabolic syndrome better than irbesartan. These differences could be relevant in the choice of therapy for this condition and diabetes" Effect of antihypertensive agents on plasma adiponectin levels in hypertensive patients with metabolic syndrome - Nephrology (Carlton). 2007 Apr;12(2):147-53 - "Ramipril and valsartan increased the plasma adiponectin levels significantly higher than the other regimens" Effects of telmisartan on fat distribution in individuals with the metabolic syndrome - J Hypertens. 2007 Apr;25(4):841-8 - "The visceral fat area, determined by abdominal computed tomography scan, was reduced in the telmisartan group after 24 weeks' treatment" Telmisartan shows an equivalent effect of vitamin C in further improving endothelial dysfunction after glycemia normalization in type 1 diabetes - Diabetes Care. 2007 Apr 24 - "Combining insulin and vitamin C normalized endothelial dysfunction and decreased oxidative stress to normal level. Telmisartan significantly improved basal endothelial function and decreased nitrotyrosine plasma levels. In patients treated with Telmisartan a near normalization of both flow mediated vasodilation and oxidative stress was achieved when glycemia was normalized, while adding vitamin C infusion did not show further effect on endothelial function or nitrotyrosine plasma levels" The effects of telmisartan and amlodipine on metabolic parameters and blood pressure in type 2 diabetic, hypertensive patients - J Renin Angiotensin Aldosterone Syst. 2006 Dec;7(4):243-6 - "Group A: rosiglitazone (RSG) 4 mg + Telm 80 mg; Group B: RSG 4 mg + Aml 10 mg ... Lower values of glucose, HbA1C, HOMA index and higher adiponectin levels were observed in Group A compared to Group B ... insulin sensitivity may confer make Telm particularly suitable in the treatment of the metabolic syndrome" ACE Inhibitors Provide Greater Heart Protection - Science Daily, 4/22/07 - "Our research evaluated the effects of both drugs, and found that they both provided comparable blood pressure reduction. However, ACE inhibitors reduced the risk of coronary heart disease in patients by a further 9%. This so-called blood pressure-independent effect was not seen for ARBs" FDA Panel Favors First-Line Use of Irbesartan/HCTZ Combo - Medscape, 4/19/07 - "The US FDA Cardiovascular and Renal Drugs Advisory Committee recommended extended use of the combination product irbesartan plus hydrochlorothiazide (Avalide, Bristol-Myers Squibb) for the first-line treatment of hypertension" - Yeah, if you can get by the side effects of hydrochlorothiazide plus the increased chance of diabetes. Irbesartan is a ARB and hydrochlorothiazide is a diuretic. I'm not a doctor and here I am criticizing those who are but I still feel that telmisartan (a ARB)/ramipril (a ACE inhibitor) should be the first time treatment. Click here for the research. Some doctors claim you can't mix a ARB with an ACE inhibitor but I couldn't find any evidence of that. Treating hypertension in the patient with overt diabetic nephropathy - Semin Nephrol. 2007 Mar;27(2):182-94 - "The renoprotective and proteinuria-decreasing effects of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers recommend these agents as the standard of care in type 2 diabetic nephropathy" The effects of irbesartan and telmisartan on metabolic parameters and blood pressure in obese, insulin resistant, hypertensive patients - J Endocrinol Invest. 2006 Dec;29(11):957-61 - "The greater impact on the improvement of the metabolic profile showed by telmisartan and the inverse correlation between adiponectin levels and blood pressure may be partly due to the action as partial PPARgamma agonist displayed by telmisartan" Effect of inhibition of the Renin-Angiotensin system on development of type 2 diabetes mellitus (meta-analysis of randomized trials) - Am J Cardiol. 2007 Apr 1;99(7):1006-12. Epub 2007 Feb 16 - "In ACE inhibitor trials, the odds of developing DM were reduced by 28% (OR 0.72, 95% CI 0.63 to 0.84, p <0.001), and in the 5 ARB studies, there was a 27% reduction (OR 0.73, 95% CI 0.64 to 0.84, p <0.001) in the odds. In conclusion, evidence accumulated to date indicates that inhibition of the renin-angiotensin system may contribute to the prevention of DM" Effect of losartan, compared with atenolol, on endothelial function and oxidative stress in patients with type 2 diabetes and hypertension - J Hypertens. 2007 Apr;25(4):785-791 - "losartan significantly improved endothelial function in type 2 diabetes patients with hypertension compared with atenolol. This must be independent of the blood pressure-lowering effect of losartan and is probably caused by an antioxidative effect of the angiotensin receptor blocker" Telmisartan and irbesartan therapy in type 2 diabetic patients treated with rosiglitazone: effects on insulin-resistance, leptin and tumor necrosis factor-alpha - Hypertens Res. 2006 Nov;29(11):849-56 - "The decrease in HbA1c and FPG at 12 months was statistically significant only in the telmisartan group" Angiotensin receptor blockade in diabetic renal disease-Focus on candesartan - Diabetes Res Clin Pract. 2007 Mar 3 - "In patients with type 2 diabetes and varying degrees of albuminuria, treatment with candesartan 8-32mg daily was shown to reduce urinary albumin excretion (UAE) by up to 60%. When given in addition to an ACE inhibitor (dual blockade), reductions in UAE of 25-35% relative to ACE inhibitor monotherapy have been found" Impact of Telmisartan Versus Ramipril on Renal Endothelial Function in Patients with Hypertension and Type 2 Diabetes - Diabetes Care. 2007 Mar 2 - "In patients with type 2 diabetes telmisartan and ramipril both increased NO activity of the renal endothelium significantly that in turn may support the preservation of cardiovascular and renal function" Angiotensin type-1 receptor blockade with losartan increases insulin sensitivity and improves glucose homeostasis in subjects with type 2 diabetes and nephropathy - Nephrol Dial Transplant. 2007 Feb 17 - "Fasting blood glucose, HbA1c, AUC glucose, and urinary protein values were significantly decreased in the losartan group as compared with the amlodipine group (P < 0.05). Furthermore, C-peptide concentrations, the insulin sensitivity index, and the insulin-to-glucose ratio were significantly increased after 3 months of therapy with losartan as compared to amlodipine" The effects of irbesartan and telmisartan on metabolic parameters and blood pressure in obese, insulin resistant, hypertensive patients - J Endocrinol Invest. 2006 Dec;29(11):957-61 - "Group A (23) was submitted to irbesartan 150 mg/day, Group B (23) to telmisartan 80 mg/day for 6 months ... Both irbesartan or telmisartan reduced blood pressure and ameliorated the insulin sensitivity, with increased adiponectin values; in Group B, the amelioration of metabolic parameters was greater than in Group A" Telmisartan improves lipid metabolism and adiponectin production but does not affect glycemic control in hypertensive patients with type 2 diabetes - Adv Ther. 2007 Jan-Feb;24(1):146-53 - "Triglyceride levels were significantly decreased, however, and adiponectin levels were significantly increased" Telmisartan reduced blood pressure and HOMA-IR with increasing plasma leptin level in hypertensive and type 2 diabetic patients - Diabetes Res Clin Pract. 2007 Jan 18 - "Fasting IRI and HOMA-IR were significantly decreased after Telmisartan treatment, suggesting the improved insulin sensitivity" The effect of telmisartan on glucose and lipid metabolism in nondiabetic, insulin-resistant subjects - Metabolism. 2006 Sep;55(9):1149-54 - "in insulin-resistant persons 12 weeks of telmisartan result in a significant improvement in glucose metabolism with a predominant improvement in beta-cell function" Blood Pressure Drugs Could Help Halt Pancreatic Cancer Spread, Researchers Find - Science Daily, 12/8/06 - "two types of pressure-lowering drugs -- ACE inhibitors and AT1R blockers -- may help reduce the development of tumor-feeding blood vessels, a process called angiogenesis. Such drugs, they say, may become part of a novel strategy to control the growth and spread of cancer ... In the test tube, Ang II significantly enhanced VEGF production in AT1R-positive cells. Captopril and losartan both blocked this effect" Study Shows Valsartan Reduced Urinary Protein Excretion in Patients with Type 2 Diabetes and High Blood Pressure - Doctor's Guide, 11/20/06 - "In patients with high blood pressure and type 2 diabetes, the blood pressure-lowering medication Diovan® (valsartan) significantly reduced urinary protein excretion, with high doses providing the greatest sustained reduction" 24-hour urine protein - Medline Plus - "Increased urinary protein is usually measured when glomerular disease is suspected. The deterioration in the integrity of the glomerulus allows albumin to permeate in large quantities. Glomerular disease, such as nephrotic syndrome may result in urine protein (mostly urine albumin) of greater than 3.5 gm/day. So-called microalbuminuria with urine albumin levels of 30 to 200 mg/day is considered an early sign of diabetic nephropathy." Improved insulin sensitivity with the angiotensin II-receptor blocker losartan in patients with hypertension and other cardiovascular risk factors - J Hum Hypertens. 2006 Sep 21 - "angiotensin II-receptor blockade with losartan improves glucose metabolism at the cellular level beyond what can be expected by the vasodilatation and blood pressure reduction alone" Effect of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Type 1 Receptor Blockers on the Rate of New-Onset Diabetes Mellitus: A Review and Pooled Analysis - Pharmacotherapy. 2006 Sep;26(9):1297-306 - "The combined occurrence of new-onset diabetes in all 13 studies was 2249 cases among 31,283 patients (7.2%) in the ACE inhibitor or ARB group versus 3230 cases among 35,988 patients (9.0%) in the control group" Cardiovascular Events Reduced in Japanese JIKEI Study With Valsartan - Doctor's Guide, 9/5/06 - "Blood pressure control was equal in both arms of the study, but the difference in outcomes was substantial and there were significant decreases in cardiovascular events with valsartan, specifically stroke, bouts of angina, heart failure and the need for hospitalization due to cardiac events" Short-term administration of an angiotensin-receptor antagonist in patients with impaired fasting glucose improves insulin sensitivity and increases free IGF-I - Eur J Endocrinol. 2006 Aug;155(2):293-6 - "received 100 mg losartan during 8 weeks ... After the treatment period, the HOMA score for insulin resistance had decreased from 5.3 +/- 1.1 to 3.7 +/- 0.9 (P = 0.004) and the 2-h CIGMA score from 23.4 +/- 3.1 to 15.9 +/- 2.1 (P = 0.07). The serum levels of free IGF-I had increased from 57 +/- 18.8 to 134 +/- 31.3 pmol/l" - Does that mean you can more than double you IGF-1 just by taking an ARB instead of hGH? I don't know. See losartan at OffshoreRX.com. - Ben Renal and vascular protective effects of telmisartan in patients with essential hypertension - Hypertens Res. 2006 Aug;29(8):567-72 - "telmisartan is more effective at protecting renal function and vascular endothelial function, and at improving arteriosclerosis than the calcium channel blocker in patients with essential hypertension" ACE Inhibitors and Angiotensin Receptor Antagonists and the Incidence of New-Onset Diabetes Mellitus : An Emerging Theme - Drugs. 2006;66(9):1169-1177 - "These trials have demonstrated an approximately 15-30% reduction in the new onset of diabetes in those receiving ACE inhibitors and ARBs when compared with placebo or other active therapy" Angiotensin Receptor Blocker Added to Previous Antihypertensive Agents on Arteries of Diabetic Hypertensive Patients - Hypertension. 2006 Jun 19 - "After 1 year of treatment, resistance artery media:lumen ratio decreased in the valsartan group (7.9+/-0.5% after versus 9.8+/-0.6% before; P<0.05) but not in the atenolol-treated group" Incidence of Atrial Fibrillation Significantly Reduced by Candesartan Cilexetil Therapy in Heart Failure Patients - Doctor's Guide, 7/5/06 Telmisartan Provides Superior, Powerful Blood Pressure Reduction From Morning to Morning Compared to Other Leading ARBS - Doctor's Guide, 6/15/06 - "telmisartan provides superior, powerful blood pressure reduction from morning to morning compared to other leading angiotensin II receptor blockers" Valsartan the First Blood Pressure Medication in a Large-Scale Clinical Trial to Lower C-Reactive Protein, an Important Marker of Inflammation - Doctor's Guide, 5/26/06 - "The median change in hsCRP from baseline after six weeks in the Diovan group was -0.12 mg/L compared to +0.05 mg/L in the Diovan HCT group, representing a difference between the treatment groups of 13.3%" Valsartan Lowers C-reactive Protein Levels; Combination Doesn't - Doctor's Guide, 5/19/06 - "Paradoxically, adding a diuretic to valsartan (Diovan) allows even more patients to reach blood pressure goals -- but appears to raise levels of C-reactive protein ... the monotherapy patients achieved an 8.9% reduction while the combination patients experienced a 4.4% increase" Reduced Diabetes Likelihood in Hypertensives Starting Valsartan Treatment - Doctor's Guide, 5/18/06 - "Over a mean follow-up of 4.2 years, the risk of diabetes was 11.5% for valsartan versus 14.5% for amlodipine; the odds ratio was 0.77 in favor of valsartan" New treatment strategies for patients with hypertension and insulin resistance - Am J Med. 2006 May;119(5 Suppl 1):S24-30 - "older antihypertensive agents such as thiazide diuretics and beta-blockers have potentially adverse effects on glucose and lipid metabolism and may even the exacerbate the metabolic syndrome and increase risk of type 2 diabetes ... Evidence is accumulating that telmisartan, in addition to blocking the angiotensin II type 1 receptor, activates the peroxisome proliferator-activated receptor (PPAR)-gamma a well-known target for treatment of the metabolic syndrome and diabetes ... the ability of telmisartan both to activate PPAR-gamma and to block the angiotensin receptor may provide added value not only in the treatment of the metabolic syndrome and prevention of type 2 diabetes but also in prevention and treatment of atherosclerotic cardiovascular disease" Telmisartan: The ACE of ARBs? - Sharma 47 (5): 822 -- Hypertension, 3/27/06 - "telmisartan also reduced weight gain, increased total energy expenditure, and increased expression of key mitochondrial enzymes (cyclooxygenase-1 and mitochondrial transcription factor A) in skeletal muscle" New Drug Delays High Blood Pressure - WebMD, 3/14/06 - "the blood-pressure-lowering drug Atacand may be able to delay the development of full-blown hypertension among people whose blood pressure is slightly high ... taking the drug for two years appeared to prime the body to keep blood pressure in check, even when the person stopped the drug for another two years" ACE Inhibitors and ARBs vs. Other Antihypertensives - Medscape, 3/9/06 - "When diabetics and nondiabetics were analyzed together, ACE inhibitors or ARBs were significantly more effective than other antihypertensives in reducing ESRD incidence, serum creatinine levels, and albuminuria, but they had no significant effect on preventing doubling of serum creatinine or reduction in GFR. In diabetics, ACE inhibitors or ARBs were significantly more effective than other antihypertensives only in reducing albuminuria; in nondiabetics, ACE inhibitors or ARBs were more effective than other agents only in reducing albuminuria and serum creatinine levels" Blood pressure control in eldery hypertension - Nippon Rinsho. 2006 Jan;64(1):75-80 - "Because ACE inhibitors/ARBs or Ca blockers increase insulin sensitivity, these drugs should be used as the first choice in cases of elderly hypertensive patients complicated with diabetes mellitus" Valsartan Inhibits Platelets (VIP) Trial - Medscape, 2/3/06 Addition of an angiotensin receptor blocker to full-dose ACE-inhibition: controversial or common sense? - Eur Heart J. 2005 Nov;26(22):2361-7 - "combination of a full-dose ACE-inhibitor and an ARB can be a rational choice in selected patients" - [full article] Olmesartan Improves Insulin Resistance in Chronic Kidney Disease Patients - Doctor's Guide, 11/15/05 Titration-Extension Study Shows Losartan-Based Treatment Significantly Reduced Blood Pressure in Real-Life Practice Settings - Doctor's Guide, 10/24/05 A Debate on the Metabolic Syndrome: Evolving Challenges and Controversies - Medscape, exp. 8/31/07 - "Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are first-line treatments for hypertensive albuminurics with the metabolic syndrome" Preliminary Studies Suggest Potential Metabolic Effects of Micardis (Telmisartan) - Doctor's Guide, 9/9/05 - "The Micardis molecule is structurally similar to the PPAR-gamma activator, pioglitazone,3 which has been approved for the treatment of type 2 diabetes.7 Micardis partially activates PPAR-gamma resulting in metabolic effects that differentiate it from other ARBs, according to preclinical data.1-4 These data demonstrate that Micardis has a beneficial effect on insulin resistance and blood lipids, independent of its effect on the renin-angiotensin-aldosterone system" Angiotensin-converting enzyme inhibitors or Angiotensin receptor blockers for prevention of type 2 diabetes a meta-analysis of randomized clinical trials - J Am Coll Cardiol. 2005 Sep 6;46(5):821-6 - "ACE inhibitors and ARBs were associated with reductions in the incidence of newly diagnosed diabetes by 27% and 23%, respectively, and by 25% in the pooled analysis ... The use of an ACE inhibitor or ARB should be considered in patients with pre-diabetic conditions such as metabolic syndrome, hypertension, impaired fasting glucose, family history of diabetes, obesity, congestive heart failure, or coronary heart disease" Comparison of the effects of valsartan and felodipine on plasma leptin and insulin sensitivity in hypertensive obese patients - Hypertens Res. 2005 Mar;28(3):209-14 - "These results suggest that in hypertensive obese subjects, treatment with valsartan might offer an advantage over treatment with felodipine, since valsartan may help to improve obesity-related disorders in addition to lowering BP" Strategies to Prevent Type 2 Diabetes - Medscape, 8/8/05 - "Valsartan reduced the incidence of new-onset diabetes by 23% ... Traditional beta-blockers worsen insulin sensitivity and increase the risk of developing new diabetes" FDA Approves Diovan (Valsartan) to Reduce Cardiovascular Death in Heart Attack Survivors at High Risk - Doctor's Guide, 8/4/05 - "was a rigorous comparison of Diovan vs. captopril, an ACE inhibitor, vs. the combination of both ... Diovan was reported to improve survival and reduce cardiovascular events including recurrent heart attack and hospitalizations for heart failure in these patients" Antihypertensive, cardiovascular, and pleiotropic effects of angiotensin-receptor blockers - Curr Opin Nephrol Hypertens. 2005 Sep;14(5):435-41 - "it has been shown that treatment with ARBs prevents the development of type 2 diabetes ... ARBs are first-line agents for the treatment of hypertension and cardiovascular diseases. Blocking the renin-angiotensin system with these agents has special advantages due to specific vascular and antiatherosclerotic effects, which contribute to a better cardiovascular and renal protection in patients at risk from or with cardiovascular disease" Stabilization and Regression of Albuminuria in Chinese Patients With Type 2 Diabetes: A One-year Randomized Study of Valsartan Versus Enalapril - Adv Ther. 2005 Mar-Apr;22(2):155-62 - "enalapril and valsartan both reduced blood pressure and albuminuria to a similar extent ... Fewer adverse events were reported with valsartan" Atacand Therapy Can Reduce Risk of Diabetes in Heart Failure Patients - Doctor's Guide, 7/4/05 - "Six percent of patients in the candesartan group were newly diagnosed with diabetes during the study period (median 3.1 year), compared to 7.4% in the placebo group" Effects of irbesartan on intracellular antioxidant enzyme expression and activity in adolescents and young adults with early diabetic angiopathy - Diabetes Care. 2005 Jul;28(7):1690-7 - "Adolescents and young adults with early signs of diabetic angiopathy have defective intracellular antioxidant enzyme production and activity. Treatment with irbesartan can substantially improve the activity and production of these enzymes in skin fibroblasts" Effects of Valsartan Compared to Amlodipine in Prevention of Type 2 Diabetes in High-Risk Hypertensive Patients: Presented at EMH - Doctor's Guide, 6/24/05 - "Valsartan is significantly superior to amlodipine for prevention of new-onset type-2 diabetes in high-risk patients with hypertension" Administration Time-Dependent Efficacy of Valsartan-Atorvastatin Combination in Hyperlipidaemic Patients With Essential Hypertension: Presented at EMH - Doctor's Guide, 6/22/05 - "160-mg/day dose of valsartan ... 10 mg/day of atorvastatin ... combination treatment significantly improved systolic/diastolic blood pressure levels (SBP/DBP) compared to monotherapy (17.1/10.7 vs. 13.9/9.6 mm Hg; P = .027). The same benefit was seen in terms of pulse pressure (6.4 vs. 4.3 mm Hg ... there were large significant increases in efficacy seen with the valsartan/atorvastatin combination dosed at night versus morning (SBP, 23.5 vs. 11.0 mm Hg; DBP, 15.9 vs. 6.8 mm Hg; pulse pressure, 7.8 vs. 4.1 mm Hg" Valsartan Significant Better Than Amlodipine for Improving Long-term Heart-rate Variability in Patients With LVH: Presented at EMH - Doctor's Guide, 6/20/05 Irbesartan/Hydrochlorothiazide Helps Patients with Metabolic Syndrome and Poorly Controlled Hypertension: Presented at ADA - Doctor's Guide, 6/14/05 Novartis Receives EU Marketing Authorization for Diovan to Treat People With Heart Failure - Doctor's Guide, 6/13/05 Fixed-Dose Valsartan Gets Patients to Goal After Other Angiotensin Receptor Blocker Fixed-Dose Failures - Doctor's Guide, 5/25 - "Valsartan was deemed statistically better than either of the two initial drugs" Comparison of the effects of ramipril versus telmisartan in reducing serum levels of high-sensitivity C-reactive protein and oxidized low-density lipoprotein cholesterol in patients with type 2 diabetes mellitus - Am J Cardiol. 2005 Jun 1;95(11):1386-8 - "All regimens were associated with a significant reduction of C-reactive protein and oxidized low-density lipoprotein cholesterol serum levels" Patients Who Fail Anti-Hypertensive Monotherapy Respond to Fixed-Dose Combination of Irbesartan/Hydrochlorothiazide - Doctor's Guide, 5/19/05 FDA Approves Atacand (Candesartan Cilexetil) For Use With An Ace Inhibitor In The Treatment Of Heart Failure - Doctor's Guide, 5/19/05 Telmisartan Superior to Ramipril in Preventing Morning Blood Pressure Rise - Doctor's Guide, 5/19/05 - "Reductions were greater and statistically significant in the highest quartile (34 mmHg), in whom telmisartan reduced systolic surge by 12.4 mmHg and ramipril by 7.1 mmHg" Valsartan Reduces Chance of Diabetes in High-Risk Hypertensive Patients - Doctor's Guide, 5/19/05 - "patients taking valsartan had a 23% lower risk of developing diabetes during the four or more years of the study. The two drugs had previously been shown to be roughly equivalent in reducing the risk of heart attack and stroke" - See valsartan at OffshoreRX.com. Combo Drug Controls Hypertension In Hard-to-treat Patients - Science Daily, 5/18/05 - "the combination pill of irbesartan (an angiotensin II receptor blocker) and a diuretic, hydrochlorothiazide ... the participants' systolic blood pressure (the top number) dropped an average of 21.5 points, from 154.4 to 132.9 points. Their diastolic blood pressure (the bottom number) fell an average of 10.4 points, from 91.3 to 80.9" - Yeah, but what about impotence from the diuretic? Bedtime Dosing of Atorvastatin and Valsartan Together Improves Overall Anti-Hypertensive Effects - Doctor's Guide, 5/17/05 - "When valsartan was dosed by itself during the day, patients averaged a 9 mmHg fall in systolic blood pressure; daytime dosing of both valsartan and atorvastatin resulted in a 17 mmHg reduction in the 24-hour mean of systolic and diastolic BP" Blood Pressure Linked to Erectile Dysfunction - WebMD, 5/16/05 - "Men on older high blood pressure medications (diuretics, beta-blockers) had higher rates and more severe erectile dysfunction than men on newer medications (calcium antagonists, ACE inhibitors, angiotensin II receptor blockers)" ACE Inhibitors or ARBs for Prevention of Type 2 Diabetes: A Meta-analysis of Randomized Clinical Trials - Medscape, 4/18/05 - "the use of valsartan reduced the incidence of new-onset type 2 diabetes by 23%" The Effects of Losartan Compared to Atenolol on Stroke - Medscape, 4/14/05 - "these data suggest that losartan-based treatment reduces CV complications, primarily stroke, when compared to atenolol-based treatment for patients with ISH and high CV risk" FDA Approves Hyzaar (Losartan Potassium-Hydrochlorothiazide) Fixed-Dose Combination - Doctor's Guide, 4/14/05 Evidence-Based Treatment of Hypertension: What's the Role of Angiotensin II Receptor Blockers? - Medscape, 4/8/05 - "The ARBs are highly effective in lowering blood pressure and reducing cardiovascular mortality. They also appear to provide additional renal protection in patients with diabetes, and this effect is independent of their effect on blood pressure. Combinations of ARBs with drugs from other classes such as ACE inhibitors have been found to be highly effective; they may permit lower doses of ACE inhibitors to be used than in monotherapy, which may lower the incidence of dose-related adverse effects. The ARBs themselves are very well tolerated and are not associated with the side-effects known to cause compliance problems with beta blockers, ACE inhibitors and calcium channel blockers such as impotence, dry cough and peripheral oedema" New Data Shows Telmisartan (Micardis/Pritor) Provides Effective and Well-Tolerated Blood Pressure Lowering in Chronic Kidney Disease Patients - Doctor's Guide, 4/4/05 Angiotensin II Receptor Blockers: A New Lease of LIFE? - Medscape, 10/26/04 Losartan and Irbesartan Comparable in Efficacy for Blood Pressure Lowering - Doctor's Guide, 10/8/04 Study Findings Add Further Weight to Effectiveness of Atacand (Candesartan Cilexetil) in Treating Heart Failure - Doctor's Guide, 9/3/04 Both ACE Inhibitors and ARBs Slow Renal Decline in Type 2 Diabetes - Medscape, 8/31/04 - "the angiotensin-converting enzyme (ACE) inhibitor enalapril and the angiotensin-receptor blocker (ARB) telmisartan were equally effective in slowing kidney damage in people with type 2 diabetes, hypertension, and nephropathy" DETAIL Results Show Telmisartan Not Inferior to Enalapril in Renal Protection of Diabetics - Doctor's Guide, 8/31/04 Erythema Multiforme Associated with Candesartan Cilexetil - Medscape, 7/29/04 Antihypertensive Effect of Valsartan Appears Safely Enhanced By Doubling Conventional Dosage - Doctor's Guide, 7/9/04 Valsartan Appears More Effective Than Telmisartan in Patients With Essential Hypertension - Doctor's Guide, 6/25/04 - "At the end of the study, the 24-hour mean BP was statistically lower in the valsartan-treated group compared to telmisartan-treated group" Amlodipine More Effective for Blood Pressure Reduction but Confers Similar Cardiac Outcomes to Valsartan Therapy - Doctor's Guide, 6/18/04 Significant Reduction in Left Ventricular Mass Index, Reactive Oxygen Species Formation and C-Reactive Protein With Valsartan Treatment - Doctor's Guide, 6/18/04 - "Despite very similar effects on BP, there was a significantly higher reduction in LVMI with valsartan compared with amlodipine ... In the valsartan group, CRP levels were significantly reduced" Telmisartan Associated with Greater Left Ventricular Hypertrophy Regression Than Carvedilol - Doctor's Guide, 6/17/04 - "The angiotensin II receptor blocker telmisartan produces significantly greater left ventricular hypertrophy (LVH) regression than does the beta blocker carvedilol in hypertensive patients" Newer Drug Helps Prevent Heart Attack - HealthDay, 6/17/04 - "people taking valsartan had much lower rates of admission to hospital for heart failure. And fewer people in the valsartan group (13 percent) developed type 2 diabetes than those in the amlodipine group (16 percent)" Telmisartan 40 or 80 mg/Hydrochlorothiazide 12.5 mg Fixed –Dose Combinations Can Thwart Early Morning Blood Pressure Surge - Doctor's Guide, 6/15/04 Benicar (Olmesartan Medoxomil) and Benicar HCT (Olmesartan Medoxomil/Hydrochlorothiazide) Therapies Achieve Blood Pressure Goals in Hypertension - Doctor's Guide, 5/26/04 - "at the usual recommended starting doses, approximately twice as many patients treated with Benicar achieved goal blood pressure of less than 140/90 mm Hg compared to Cozaar®(losartan potassium) and Diovan® (valsartan), the two most commonly prescribed angiotensin II receptor blockers (ARBs)" Maximum Dose of Valsartan Appears More Effective than Telmisartan in Lowering Ambulatory Blood Pressure and Pulse Pressure Over 24 hours - Doctor's Guide, 5/25/04 - "the blood pressure reduction in the 24-hour mean was significantly larger for valsartan 160 mg (18.6 and 12.1 mm Hg for systolic and diastolic blood pressure, respectively) than for telmisartan 80 mg (10.8 and 8.4 mm Hg" Losartan Preserves Cerebral Blood Flow in Hypertensive Patients With a History of Stroke - Doctor's Guide, 5/19/04 Atacand (Candesartan Cilexetil) Appears More Effective Than Cozaar (Losartan) at Lowering Blood Pressure - Doctor's Guide, 5/10/04 - "Candesartan was shown to lower systolic and diastolic blood pressure by 2 to 3 mm Hg on average more than losartan potassium when measured at the time of either peak or trough effect" Valsartan May Produce Lower Ambulatory Heart Rate, Greater Lowering of Daytime Systolic Blood Pressure than Amlodipine in Elderly Patients with Systolic Hypertension - Doctor's Guide, 5/6/04 Telmisartan Safe, Effective for the Treatment of Isolated Systolic Hypertension - Doctor's Guide, 5/4/04 Left Ventricular Mass Index Reduced with Low-Dose Valsartan in Patients with Type 2 Diabetes - Doctor's Guide, 4/15/04 Telmisartan Lowers Early Morning Blood Pressure in Patients With Hypertension More Effectively Than Does Valsartan - Doctor's Guide, 4/12/04 - "telmisartan reduced BP during the last 6 h of the dosing period more effectively than did valsartan (-11/-7.6 ± 0.8/0.6 mm Hg vs. -8.7/-5.8 ± 0.8/0.6 mm Hg" Losartan-Based Treatment Appears More Effective In Reducing Strokes In Hypertensives Than Atenolol-Based Treatment - Doctor's Guide, 4/1/04 Telmisartan Safe, Effective for Treatment of Hypertension in a Diverse Population - Doctor's Guide, 3/5/04 Irbesartan More Cost and Survival Effective than Amlodipine in Canadian Patients with Diabetic Neuropathy and Hypertension - Doctor's Guide, 3/4/04 Telmisartan Appears to Offer Additional Benefit to Antihypertensive Regimens - Doctor's Guide, 1/22/04 ARB, ACE Inhibitor, or Both After MI in High-Risk Patients? - Medscape, 1/9/04 Telmisartan Reduces Blood Pressure and Left Ventricular Mass Index in Patients with Hypertension - Doctor's Guide, 1/7/04 - "Telmisartan was significantly more effective in reducing blood pressure and left ventricular mass index (LVMI) than was hydrochlorothiazide in patients with mild-to-moderate hypertension ... Reducing LVM is a primary objective to managing hypertension because of the increased risk of cardiovascular morbidity and mortality associated with increases in LVM" Reduction in Left Ventricular Mass Due to Irbesartan Correlates With Increased Angiotensin II Levels - Doctor's Guide, 12/9/03 Persistent Renoprotection After Irbesartan Withdrawal in Hypertensive Type 2 Diabetics - Doctor's Guide, 11/18/03 Teveten (Eprosartan Mesylate) Effectively Lowers Systolic Blood Pressure, Pulse Pressure in Isolated Systolic Hypertension - Doctor's Guide, 11/14/03 Valsartan Shown as Effective as Captopril for Post-Heart Attack Treatment - Doctor's Guide, 11/10/03 Two Heart Drugs [ARBs & ACE Inhibitors] Found Equally Effective - HealthDay, 11/10/03 - "Overall survival in both groups and among patients who got combined therapy was better than 80 percent ... The incidence of side effects such as cough, taste disturbance and rash was higher among those given both drugs together, and people getting the combined treatment were more likely to stop taking the medications ... valsartan is "a safe and equally effective alternative" for patients who have problems with ACE inhibitor treatment, Mann writes. People with kidney problems, for instance, are usually kept away from these drugs" Irbesartan More Effective Than Amlodipine in Reducing Left Ventricular Mass Index - Doctor's Guide, 11/4/03 - "Several studies have established that LVH is a powerful BP-independent cardiovascular risk factor; however, not all antihypertensive drugs can reverse LVH ... After 3 months, echocardiographically estimated LVMI decreased by 23.2% in the irbesartan-treated patients and 11.4% in the amlodipine-treated patients" Losartan Improves Cognitive Function in Elderly Hypertensive Patients - Doctor's Guide, 10/31/03 - "Patients receiving losartan showed significant improvement in both memory tests, while those receiving atenolol did not shown a difference with treatment. Losartan treatment was associated with a 2.2 point increase in word list memory score and a 2.1 point increase in the word list recall score ... Notably, a greater number of adverse events were reported in patients given atenolol than in those given losartan (31 vs. 8 events)" Telmisartan And Lisinopril Appear Equally Effective In Reducing Blood Pressure and Pulse Pressure - Doctor's Guide, 10/10/03 - "For both TPR and SI measurement techniques, no differences were detected between the two drugs in their effects on systolic and diastolic BP" Renin-Angiotensin System Blockade Produces Multiple Benefits Independent of Blood Pressure Reduction - Doctor's Guide, 9/29/03 - "According to the authors, ACE inhibitors and ARBs, at least in higher- or moderate-risk individuals, "show advantages that are additional to the reduction in blood pressure that they achieve ... We still await new and forthcoming data as to whether the better-tolerated ARBs have benefits equivalent to those of the ACE inhibitors, for which there are now numerous data ... We also await data on the combination of both these classes of drugs, particularly with respect to safety" Candesartan More Effective Than ACE Inhibition Post-Myocardial Infarction - Doctor's Guide, 9/29/03 Losartan Reduces Hospitalizations in Diabetic Heart-Failure Patients - Doctor's Guide, 9/29/03 Drugs Blocking the Renin-Angiotensin System Offer Advantages Beyond Lowering Blood Pressure - Doctor's Guide, 9/15/03 - "According to the authors, ACE inhibitors and ARBs, at least in higher- or moderate-risk individuals, "show advantages that are additional to the reduction in blood pressure that they achieve" High Doses of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Required for Maximum Renoprotection - Doctor's Guide, 9/12/03 - "angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) can have significant renoprotective effects, in addition to known antihypertensive benefits ... The optimal dose and strategy for renoprotection using ACEI and ARBs should be guided by titrating to the maximum antiproteinuric effect ... For patients who maintain elevated proteinuria despite high dose monotherapy, they recommend combined use of ACE inhibitors and ARBs" Brain Natriuretic Peptide Changes Are Predictive of Valsartan Treatment Success in Heart Failure - Doctor's Guide, 9/9/03 CHARM Trials Demonstrate Add-On Benefit of Candesartan for Heart Failure - Doctor's Guide, 9/3/03 Effect of losartan on sudden cardiac death in people with diabetes: data from the LIFE study - Lancet. 2003 Aug 23;362(9384):619-20 - "In the losartan group, five (6%) of 86 patients with diabetes and atrial fibrillation during the trial died of sudden cardiac death compared with nine (2%) of 500 in those without atrial fibrillation. The respective figures for the atenolol group were 14 (13%) of 105 and 16 (3%) of 504. Our results suggest losartan affords better protection against cardiac death from arrhythmias for patients with diabetes mellitus than does atenolol" Renin-Angiotensin System Blockers Offers Added Benefits Beyond Blood-Pressure Lowering For Hypertensives - Doctor's Guide, 8/28/03 - "Emerging data on newer drugs that block the renin-angiotensin system, such as the angiotension II type 1 receptor blockers (ARBs) and angiotension-converting enzyme (ACE) inhibitors, indicate added benefits such as reduced mortality, strokes, and myocardial infarction along with decreased blood pressure" Losartan Superior to Atenolol For Reducing Cardiac Death From Arrhythmias In Hypertensive Diabetics - Doctor's Guide, 8/21/03 Losartan More Effective Than Atenolol in Preventing Morbidity and Mortality in Low-Risk Hypertensive Patients - Doctor's Guide, 8/21/03 - "Losartan appears to be more effective than atenolol in preventing cardiovascular morbidity and death - especially fatal and non-fatal stroke - in patients with hypertension but without clinically evident vascular disease. Furthermore, the effect appears to be independent of blood pressure reduction ... In addition, incident diabetes occurred less often in patients treated with losartan" Losartan Causes Greater Regression of Left Ventricular Hypertrophy Compared to Atenolol - Doctor's Guide, 8/8/03 Early Intervention with Atacand (Candesartan) Improves Outcome for Patients with Acute Ischaemic Stroke - Doctor's Guide, 7/28/03 ACE Inhibitors Prevent Diabetes and Cardiovascular Disease by Multiple Mechanisms - Doctor's Guide, 7/25/03 - "ACE inhibitors inhibit the conversion of angiotensin I to angiotensin II ... Angiotensin II increases the production of reactive oxygen species and has several vasoconstrictive effects, including opposition of the vasorelaxant actions of nitric oxide and stimulation of plasminogen activator inhibitor-1 ... Angiotensin II, furthermore, increases arterial stiffness by a variety of mechanisms ... fewer studies have evaluated the effects of angiotensin receptor blockers (ARBs), although these agents may also exert beneficial effects and may act synergistically with ACE inhibitors ... The authors note that, regarding the role of ACE inhibitors in diabetic renal disease, with the exception of ARBs, ACE inhibitors "have been shown to be more effective in reducing proteinuria than any other antihypertensive agents." Telmisartan Effective and Well-tolerated for Renal Failure Patients - Doctor's Guide, 6/20/03 FDA Grants Marketing Approval for Benicar HCT (Olmesartan Medoxomil-Hydrochlorothiazide) Treatment For Hypertension - Doctor's Guide, 6/9/03 Fenofibrate, Losartan Show Additive Benefits with Anti-hyperuricaemic Agents in Gout Patients - Doctor's Guide, 6/4/03 Telmisartan Improves Quality of Life Measurements in Hypertensive Patients - Doctor's Guide, 5/30/03 - "The angiotensin II receptor blocker telmisartan appears to enhance the quality of life for patients who are being treated for high blood pressure ... the scores increased from 77 at baseline to an average of 82.2" Losartan Treatment Effect is Boosted by DASH Diet - Doctor's Guide, 5/26/03 - "For patients receiving losartan, systolic and diastolic blood pressure was significantly reduced from baseline on the control diet (-6.7 + 1.5/-3.7 + 1.0 mm Hg, P < .05), with an even greater effect evident for the DASH diet (-1.7 + 1.5/-6.9 + 1.0 mm Hg, P < .05) ... A reduction in systolic blood pressure in patients receiving placebo occurred on the DASH diet (-5.3 + 1.5 mm Hg, P < .05). No other significant changes to blood pressure levels were observed" - [Abstract] Angiotensin II Receptor Blockers Effective, Better Tolerated than Calcium Channel Blockers in Elderly Patients - Doctor's Guide, 5/21/03 - "Valsartan and amlodipine are both highly effective in controlling blood pressure in patients with isolated systolic hypertension ... However, valsartan offers a significant tolerability advantage as it shows a reduced risk of developing adverse events" Olmesartan Medoxomil Has Equal Efficacy and Safety in Hypertensive Men and Women - Doctor's Guide, 5/21/03 Hypertensive Patients Respond to Telmisartan Titration in Community-Based Trial - Doctor's Guide, 5/20/03 Eprosartan Mesylate Shows Benefits in Elderly with Isolated Systolic Hypertension - Doctor's Guide, 5/20/03 Valsartan Appears to Improve Sexual Function in Men and Women with Hypertension - Doctor's Guide, 5/18/03 - "Men and women being treated with the angiotensin II receptor blocker valsartan for mild-to-moderate hypertension appear to show improvements in sexual function and desire" Patients Respond to Up-titration of Olmesartan - Doctor's Guide, 5/18/03 Candesartan Effectively Reduces Blood Pressure in Elderly Hypertensives - Doctor's Guide, 5/12/03 - "Active anti-hypertensive treatment was given to most patients (84%) in the control group ... A first major cardiovascular event occurred in 242 candesartan patients and in 268 controls. The risk reduction with candesartan was 10.9%. Candesartan-based treatment reduced non-fatal stroke by 27.8% and all stroke by 23.6%" - [Abstract] Eplerenone Superior To Losartan In Black Patients With Hypertension - Doctor's Guide, 4/14/03 Candesartan Improves Congestive Heart Failure - Doctor's Guide, 4/11/03 LIFE Sub-Study Finds Losartan Superior To Atenolol In Atrial Fibrillation - Doctor's Guide, 4/4/03 Basal Nitric Oxide Production, Release Improved By AT(1) Receptor Blockade With Valsartan - Doctor's Guide, 2/19/03 Which Blood Pressure Drug Is Best? - HealthDay, 2/12/03 Amlodipine Appears To Provide Greater Reduction In Blood Pressure Than Does Losartan - Doctor's Guide, 2/6/03 - "Diastolic blood pressure equal to or below 90 mm Hg was achieved by 43.6% of the amlodipine patients and 42.3% of the losartan patients. Seventy-one percent of the amlodipine and 81% of the losartan patients who continued treatment with the original dose reached blood pressure goals ... However, among those patients who required dosage adjustments, a significantly higher number of amlodipine patients reached blood pressure goals. Fifty-nine percent of the amlodipine patients compared with 42%" BP Drug Cozaar Also Prevents Stroke - WebMD, 1/7/03 - "Cozaar reduced the risk of stroke by about 25% compared with atenolol" FDA Advisors Recommend Losartan for Stroke Prevention - Medscape, 1/7/03 Averting Migraines With Few Side Effects - WebMD, 12/31/02 Valsartan Improves Augmentation Index In Essential Hypertension - Doctor's Guide, 12/23/02 BP Lowering May Halt Descent Into Dementia - Clinical Psychiatry News, 12/02 - "those in the candesartan arm had a mean 0.5-point decline in MMSE scores during follow-up, compared with a 6-point drop in those on a diuretic. The cognitive benefit was even more pronounced in patients over age 85" Irbesartan Improves Cardiac Repolarization In Hypertensive Left Ventricular Hypertrophy - Doctor's Guide, 11/26/02 Telmisartan Efficacy in Mild-Moderate Hypertension Confirmed - Doctor's Guide, 11/25/02 Valsartan Produces Sustained Aldosterone Decrease in Heart Failure Patients - Doctor's Guide, 11/18/02 Losartan Reduces Proteinuria in Non-Diabetic Patients with Nephropathy - Doctor's Guide, 11/7/02 Angiotensin Receptor Blocker Plus Angiotensin Converting Enzyme Inhibitor Enhances Angiotensin II Blocking Effect - Doctor's Guide, 11/4/02 Albumin Secretion, Blood Pressure Lowered by Angiotensin II Receptor Blocker Telmisartan - Doctor's Guide, 11/1/02 Incidence of Cardiac Events Similar Between Amlodipine And Irbesartan in Diabetic Patients with Overt Nephropathy - Doctor's Guide, 11/1/02 Angiotensin II Receptor Blockers Reduce Proteinuria In Lupus Nephritis - Doctor's Guide, 10/29/02 New Angiotensin II Blocker Counters Hypertension Effectively And Safely - Doctor's Guide, 10/22/02 Valsartan Improves Survival, Reduces Hospitalisations In Heart Failure Patients Not Taking Ace Inhibitors - Doctor's Guide, 10/16/02 Valsartan's Benefit in Heart Failure Confirmed - Doctor's Guide, 10/4/02 Candesarten Effectively Reduces Proteinuria in Patients with Chronic Glomerulonephritis - Doctor's Guide, 10/1/02 Losartan Superior in Isolated Systolic Hypertension with Left Ventricular Hypertrophy - Doctor's Guide, 9/25/02 Losartan Better Than Atenolol at Reducing Cardiovascular Risk - Medscape, 9/25/02 FDA Approves Avapro (Irbesartan) For The Treatment Of Diabetic Nephropathy (Kidney Disease) In Patients With High Blood Pressure And Type 2 Diabetes - Doctor's Guide, 9/18/02 Lisinopril But Not Losartan Boosts Myocardial Perfusion In Hypertensives With Left Ventricular Hypertrophy - Doctor's Guide, 9/18/02 LIFE Substudy Shows Losartan Superior to Atenolol at Reducing Stroke Risk - Doctor's Guide, 9/16/02 Losartan Superior To Atenolol In Reducing Left Ventricular Hypertrophy In Hypertensives - Doctor's Guide, 9/4/02 Losartan Reduces Incidence of End-Stage Renal Disease in Type 2 Diabetics, Also Lowers Cost Burden - Doctor's Guide, 9/4/02 New Data From Val-HeFT Shows Diovan (Valsartan) Is Highly Cost-Effective In Treating Heart Failure Patients Not Taking ACE Inhibitors - Doctor's Guide, 9/2/02 FDA Approves Blood Pressure Treatment Diovan(R) (valsartan) for Heart Failure - Doctor's Guide, 8/15/02 Lercanidipine and Losartan Effective, Well-Tolerated Monotherapies for Mild to Moderate Hypertension - Doctor's Guide, 8/13/02 Low Dose Valsartan Therapy May Reduce Urinary Albumin Excretion In Type 2 Diabetics With Nephropathy - Doctor's Guide, 7/31/02 Patient Compliance with Antihypertensive Therapy Appears Longer for Those Taking Angiotensin II Antagonists - Doctor's Guide, 7/18/02 - "The researchers found that the class of drug had a statistically significant effect on the patients' persistence of compliance. Angiotensin II antagonists had the highest rate of persistence followed by ACE inhibitors, calcium channel blockers, beta-blockers, and diuretics" Antiproteinuric Effect of Losartan Related to its Haemodynamic Effects - Doctor's Guide, 7/18/02 Cozaar (Losartan) Lowered Risk Of Total Mortality In Patients With Diabetes By 39% Versus Atenolol - Doctor's Guide, 6/27/02 - "treatment with losartan resulted in a 24 per cent reduction in the primary composite endpoint of cardiovascular death, stroke and heart attack compared to the beta-blocker atenolol (p=0.03). Blood pressure and pulse pressure reductions were similar with both therapies. In addition, losartan significantly reduced the risk of cardiovascular death by 37 per cent (p=0.03) and total mortality by 39 per cent ... A 39 per cent reduction in total mortality with losartan is an important observation given that the observed reduction is versus an established antihypertensive, atenolol ... It is widely accepted that elevated systolic blood pressure is an even stronger risk factor for cardiovascular events than diastolic blood pressure" Reducing Hypertension In The Elderly Leads To A Significant Reduction In The Incidence Of Stroke - Doctor's Guide, 6/27/02 Losartan Plus Hydrochlorothiazide Reduces Essential Hypertension - Doctor's Guide, 6/26/02 Severe Fibrosis Appears To Decrease Following Losartan Therapy - Doctor's Guide, 6/6/02 Results Published Demonstrate that Irbesartan Provides Greater Blood Pressure Reduction than Valsartan in Patients with Elevated Blood Pressure - Doctor's Guide, 5/24/02 Losartan Restores Normal Dilation Of The Left Main Coronary Artery After Cold Pressor Test - Doctor's Guide, 5/23/02 Irbesartan More Effective than Atenolol in Reducing Cardiac Electrical Instability - Doctor's Guide, 5/20/02 Impotent Patients on Valsartan Find Increased Interest in Sex; Use Sildenafil More Often - Doctor's Guide, 5/19/02 - "Because the use of sildenafil significantly increased with the use of valsartan, it suggests that angiotensin II antagonism induces an increase in sexual desire in impotent hypertensive men ... It could be related to the reactive stimulation of angiotensin cascade due to AT1 receptors blockade" VALUE trial Shows Lower Diastolic Blood Pressure After One Year in 90% of Patients - Doctor's Guide, 5/19/02 Olmesartan Medoxomil and Amlodipine Equally Effective for Mild to Moderate Hypertension - Doctor's Guide, 5/19/02 Eplerenone Appears Superior to Losartan in Salt-Sensitive Hypertensive Patients - Doctor's Guide, 5/19/02 Losartan Reduces Platelet Activity When Compared to Candesartan in Patients With Diabetes and Hypertension - Doctor's Guide, 5/17/02 Results of a New Study Show That Irbesartan May Provide Additional Benefits For High Risk Patients With High Blood Pressure - Doctor's Guide, 5/16/02 Telmisartan/Hydrochlorothiazide Combination Superior To Telmisartan Alone For Hypertension - Doctor's Guide, 5/13/02 FDA Grants Marketing Approval For Benicar (Olmesartan Medoxomil) For Treatment Of Hypertension - Doctor's Guide, 4/26/02 - "is a member of the rapidly growing angiotensin II receptor blocker (ARB) class ... Studies have shown that Benicar 20 mg once a day, the recommended starting dose, resulted in double-digit blood pressure reduction, lowering systolic blood pressure by an average of 15mm Hg* and diastolic blood pressure by an average of 12mm Hg. In these studies, patients receiving placebo had average reductions in systolic blood pressure of 5.6 mm Hg and in diastolic blood pressure of 6.2mm Hg." Losartan Reduces QT Dispersion In Patients With Mild To Moderate Hypertension - Doctor's Guide, 4/16/02 Combination ACE Inhibitors and Angiotensin II Blockers Decreases Proteinuria in Patients with Diabetic Nephropathy - Doctor's Guide, 4/11/02 Diabetic Hypertensives Benefit More From Losartan Than Atenolol - Doctor's Guide, 3/22/02 Drug for high blood pressure reduces diabetes risk - USA Today, 3/21/02 - "using the drug Cozaar to treat people with high blood pressure reduces their risk of developing diabetes by 25%" LIFE Study Finds Losartan More Effective than Atenolol in Hypertensive Patients - Doctor's Guide, 3/20/02 A Better Blood-Pressure Drug [Cozaar] - WebMD, 3/20/02 Morbidity Risk Reduced When Valsartan Administered In Hypertensive Heart Failure - Doctor's Guide, 3/19/02 Losartan/Quinapril Combination Therapy Suppresses Cardiac Sympathetic Activity - Doctor's Guide, 1/29/02 Eprosartan Reduces Blood Pressure Throughout 24 Hours - Doctor's Guide, 12/27/01 Support Qualified For Valsartan In Chronic Heart Failure - Doctor's Guide, 12/6/01 New Data Support Early Intervention With Atacand (Candesartan Cilexetil) In Acute Ischaemic Stroke - Doctor's Guide, 12/6/01 Stroke Patients Show Significant Risk Reduction When Given Atacand (Candesartan Cilexetil) - Doctor's Guide, 11/29/01 Diovan (Valsartan) Reduces Total Heart Failure Hospitalizations - Doctor's Guide, 11/13/01 Diovan (Valsartan) Significantly Reduces Marker of Heart Failure Severity - Doctor's Guide, 11/12/01 FDA Issues Approvable Letter For Diovan (Valsartan) For Treatment Of Heart Failure - Doctor's Guide, 10/25/01 Losartan Cuts Costs of Kidney Failure and Incidence of End-Stage Renal Disease in Diabetics - Doctor's Guide, 10/17/01 Avapro (Irbesartan) Effectively Stops Progression of Type 2 Diabetic Nephropathy - Doctor's Guide, 10/17/01 Long-term Irbesartan, Amlodipine Normalizes Resistance Artery Structure and Endothelial Function - Doctor's Guide, 9/25/01 Blood Pressure Drug May Help Kidneys - Intelihealth, 9/20/01 - "Doctors found that the medicines, called angiotensin II receptor blockers, forestall complete kidney failure by about two years in diabetics with advanced kidney disease. They predict the effects will be even more dramatic in those with less severe kidney damage, potentially protecting them from ever reaching end-stage disease ... If the data keep getting stronger, it will become a recommendation, because there is very little downside to these drugs ... Angiotensin blockers have fewer side effects than ACE inhibitors, which cause a cough in about 20 percent of users" Cozaar (Losartan) Slows Progression of Kidney Disease in Type 2 Diabetes - Doctor's Guide, 9/19/01 Irbesartan Protects Against Kidney Disease Progression in Hypertension, Type 2 Diabetes - Doctor's Guide, 9/4/01 Blood pressure drug reverses sexual dysfunction - Life Extension Magazine, 7/01 - "the active ingredient in Cozaar and Hyaar (losartan) can significantly improve sex lives of men who suffer from sexual dysfunction" Low-Dose Perindopril/Indapamide Combination More Effective Than Irbesartan Alone - Doctor's Guide, 6/21/01 Long-Term Compliance to Losartan Superior To Other Antihypertensives - Doctor's Guide, 6/20/01 Telmisartan Effective And Well-Tolerated In Long-Term Treatment Of Hypertension - Doctor's Guide, 6/20/01 Candesartan Shown Equivalent To Enalapril In Regressing Left Ventricular Hypertrophy - Doctor's Guide, 6/19/01 Irbesartan Delays Nephropathy In Diabetic Patients - Doctor's Guide, 6/17/01 Better Compliance Found With Once Daily Irbesartan Over Atenolol in Treatment of Pediatric Severe Hypertension - Doctor's Guide, 5/30/01 Cozaar (Losartan) Significantly Reduces Progression of Kidney Disease in Type 2 Diabetics - Doctor's Guide, 5/24/01 Diabetics Get Kidney Protection From ARBs, High Blood Pressure Drugs Reduce Need for Dialysis, Transplant - WebMD, 5/20/01 - "results from three landmark studies of almost 4,000 diabetic patients suggest that a specific class of blood pressure drugs called angiotensin receptor blockers, or ARBs, can protect kidneys and reduce the need for kidney dialysis or transplant" Irbesartan Slows Kidney Disease In Diabetics - Doctor's Guide, 5/20/01 Telmisartan With Hydrochlorithiazide Controls Hypertension - Doctor's Guide, 5/18/01 - "after eight weeks on the FDC, both SBP/DBP dropped by 7.4/3.5 mmHg, compared with the telmisartan 40 mg monotherapy" Diovan (Valsartan) Effective in Reducing Microalbuminuria - Doctor's Guide, 5/17/01 - "Diovan® (valsartan), is more effective in reducing microalbuminuria (p<0.001), an early sign of diabetic kidney disease, compared to the calcium channel blocker, amlodipine" Newest Hypertension Drug, Losartan, May Improve Sexual Function - Doctor's Guide, 5/1/01 Angiotensin II Antagonist Telmisartan Fights Stiffening Arteries In Hypertensive Diabetics - Doctor's Guide, 4/6/01 - "not only effectively lowered blood pressure compared with placebo, but also significantly decreased arterial stiffness" Angiotensin II Antagonist Plus Conventional Treatment Improves Blood Pressure Control, Kidney Function - Doctor's Guide, 4/6/01 - "Adding candesartan cilexetil to conventional therapy significantly reduced albuminuria by a mean of 25 percent, fractional albumin clearance by a mean of 35 percent, 24-hour systolic blood pressure by a mean of 10 mmHg, and GFR by a mean of 5 ml/minute/1.73 m2. The mean reduction in diastolic blood pressure (3 mmHg) was not statistically significant" Carvedilol Reduces But Valsartan May Increase Sexual Activity In Hypertensive Men - Doctor's Guide, 2/1/01 - "carvedilol induces a chronic reduction of sexual activity whereas valsartan, an angiotensin II antagonist, not only does not significantly reduce sexual activity but may even increase it." FDA Approves Micardis HCT (Telmisartan/Hydrochlorothiazide) For Hypertension - Doctor's Guide, 11/21/00 - "Micardis HCT 80/12.5 mg significantly reduced diastolic and systolic blood pressures by an average of 14.9 mmHg and 23.9 mmHg, respectively" Triple Therapy Including Angiotensin Blockers Shows Benefits In Heart Failure Treatment - Doctor's Guide, 11/21/01 - "This finding contradicts the long-held belief that the drugs should not be combined, and means it may be possible to use a form of "triple therapy" for some congestive heart failure patients" Valsartan Provides Significant Reduction In Combined Risk Of Death, Morbidity From Heart Failure - Doctor's Guide, 11/15/00 Atacand HCT (Candesartan Cilexetil-Hydrochlorothiazide), Anti-Hypertensive, Now Available In US - Doctor's Guide, 10/26/00 Angiotensin-converting Enzyme Inhibitors, Beta Blockers May Postpone Kidney Failure - Doctor's Guide, 10/13/00 FDA Approves Atacand HCT (Candesartan Cilexetil HCl) For Hypertension - Doctor's Guide, 9/6/00 Irbesartan Improves Quality Of Life In Hypertensives - Doctor's Guide, 8/24/00 - "although the use of antihypertensive drugs before inclusion of irbesartan appeared to make quality of life worse, the addition of irbesartan produced a positive impact on quality of life" Enalapril And Losartan Reverse Arterial Vessel Stiffening - Doctor's Guide, 8/24/00 Valsartan And Warfarin May Be Co-administered Safely - Doctor's Guide, 8/24/00 Candesartan/Lisonopril Combination Decreases Blood Pressure In Diabetics - Doctor's Guide, 8/23/00 - "The effect of combination therapy was much more than could be achieved by doubling the dose of each of the drugs separately" Olmesartan Decreases Plasma Angiotensin II Levels - Doctor's Guide, 8/22/00 - "Olmesartan was able to significantly decrease both the systolic and diastolic blood pressure in healthy adults to an average of 136/84 mm Hg [from 164/100 mm Hg]" Valsartan Effectively Lowers Blood Pressure in African Americans on High-Salt Diets - Doctor's Guide, 7/18/00 Atacand (Candesartan Cilexetil) Significantly More Effective Than Cozaar (Losartan) In Lowering Blood Pressure - Doctor's Guide, 7/11/00 - "the use of Atacand at the maximum once-daily dose of 32 mg reduced trough sitting diastolic blood pressure (DBP) by 10.9 mm Hg and trough sitting systolic blood pressure (SBP) by 13.3 compared to 8.7 mm Hg and 9.8 mm Hg for the once-daily maximum dose of 100 mg losartan. In the second CLAIM Study, Atacand 32 mg reduced DBP by 10.5 mm Hg and SBP by 13.4 mm Hg compared to 9.1 mm Hg and 10.1 mm HG for 100 mg losartan" Atacand(Candesartan) Effective Antihypertensive, More Tolerable Than Norvasc(Amlodipine) - Doctor's Guide, 5/19/00 - "The angiotensin II receptor blocker (ARB) Atacand® (candesartan cilexetil) demonstrated similar efficacy in lowering blood pressure with significantly less swelling in patients' feet and ankles compared to the most prescribed antihypertensive medication, the calcium channel blocker Norvasc® (amlodipine, Pfizer)" Diovan (Valsartan) Reduces Systolic Hypertension In The Elderly - Doctor's Guide, 3/3/00 Losartan Doesn’t Unseat Reigning Therapy For Heart Failure - Doctor's Guide, 11/11/99 - "The angiotensin II receptor blocker losartan (Cozaar) did not outperform gold-standard ACE inhibitor therapy in the treatment of heart failure in a large, randomized trial, following a smaller trial that suggested it might be more effective." Antihypertensive Teveten Tablets Now Available In The U.S. - Doctor's Guide, 10/18/99 Avalide Available In U.S. For High Blood Pressure Treatment - Doctor's Guide, 5/13/99 - "(irbesartan/hydrochlorothiazide tablets)" Micardis Available In U.S. For Hypertension - Doctor's Guide, 2/22/99 Atacand Available In U.S. For Hypertension - Doctor's Guide, 10/20/98 - "One of the advantages of a medication like Atacand is that the overall incidence of side effects is similar to placebo" FDA-Approved Diovan HCT Combines Two Hypertension Drug Classes - Doctor's Guide, 3/10/99 FDA Advisory Panel Recommends Approval of Verdia For Hypertension - Doctor's Guide, 1/28/98 New Drug [PrDiovan(tm) (valsartan) Puts The Brakes On Hypertension - Doctor's Guide, 12/2/97 Diovan Reduces Left Ventricular Hypertrophy - Doctor's Guide, 7/17/97 Diovan For First-Line Treatment of Hypertension Cleared by FDA - Doctor's Guide, 12/26/96 Related Searches:

Doctor's Guide search of angiotensin II receptor blocker Doctor's Guide (2) search of angiotensin II receptor blocker Doctor's Guide hypertension channel Intelihealth search of angiotensin Life Extension Foundation search Medline search of angiotensin II receptor blocker Medscape search of angiotensin II receptor blocker Nutrition Science News search WebMD search of angiotensin II receptor blocker 70604

Angiotensin II Blockers new research --->

Central ACE & ACE Inhibitors

 * Mass spectral fragmentation reactions of angiotensin-converting enzyme (ACE) inhibitors
 * Mass spectral fragmentation reactions of angiotensin-converting enzyme (ACE) inhibitors: n interesting dissociation process (rearrangement) unique to one of the compounds, lisinopril, has been investigated using isotopic labeling experiments and exact mass measurements. The general nature of the process has been probed through both the positive and negative ion analyses of fourteen related compounds exhibiting structural homolog

Wondering : ACE ARBS BP Statins : Interactions and complexities
<!--- Actions mediated by the renin-angiotensin system may be inhibited at various levels: renin itself may be inhibited, angiotensin-I (A-1) conversion to angiotensin-II (A-II), or binding of A-II at the A-II type 1 (A-II1) receptor. The angiotensin-converting enzyme (ACE) inhibitors and the A-II1 receptor antagonists are now clinically established. Because ACE is a relatively unspecific peptidase which catalyses the breakdown of A-I, bradykinin and neuropeptides like substance P and neurotensin, the effects of ACE inhibitors go far beyond the prevention of A-II production. On the other hand, in certain tissues like vascular and cardiac tissue, A-II is produced by other enzymes, for instance chymase, and ACE inhibitors do not consistently prevent A-II production. The action of A-II1 receptor antagonists may also not be confined to prevention of binding of A-II at the A-II1 receptor, as by rebound more A-II may bind at the A-II type 2 (A-II2) receptor and thus mediate until now not well defined effects. Thus, anti-ischemic actions of these drugs may be related to multiple mechanisms. Inhibition of A-II effects at the A-II1 receptor may prevent systemic and coronary vasoconstriction and growth effects of A-II on various cell types. In addition, A-II may potentiate, by pre- and postsynaptic mechanisms, activation of the sympathetic nervous system. Prevention of breakdown of bradykinin, substance P and neurotensin may result in direct vasodilation or release of nitrous oxide from the endothelium. Thus, growth-inhibiting effects may also be mediated. All these mechanisms seem to direct to a reduction of cardiac load by vasodilation and to a limitation of cardiovascular cell growth. While the systemic circulating renin-angiotensin system is probably responsible for control of cardiac load, local systems seem to control cell growth. Systemic effects seem to depend on activation of the renin-angiotensin system which has been shown in various ischemic syndromes. Activation of various components of the renin-angiotensin system has been demonstrated in myocardial ischemia, acute myocardial infarction and coronary occlusion and reperfusion models as well as in chronic left ventricular dysfunction post-myocardial infarction. While animal models of stress-induced myocardial ischemia have revealed predominantly positive results, clinical studies, which mostly were small and not well controlled, were equivocal. Large clinical trials with ACE inhibitors in acute myocardial infarction showed small benefits over placebo. Hypotension seems to be a critical side-effect in this situation. Experimental models show protective effects of both ACE inhibitors and A-II1 receptor antagonists in the situation of ischemia and reperfusion. New data on large clinical trials in patients at risk of cardiovascular events but normal left ventricular function demonstrate clear benefits of an ACE inhibitor. Large clinical trials in patients with chronic left ventricular dysfunction post-myocardial infarction show reduction of ischemic events.--->
 * Interactions and complexities
 * Angiotensin-converting enzyme in renal and cerebral tissue and implications for successful blood pressure management.
 * Plasma and tissue ACE Activity and ACE Inhibitors e.g. Quinapril tissue ACE -aorta
 * The renin-angiotensin system in the heart and vascular wall: new therapeutic aspects.1994 a deletion polymorphism in the gene encoding ACE is a risk factor in myocardial infarction (MI)
 * Anti-ischemic potential of drugs related to the renin-angiotensin system.
 * Anti-ischemic potential of drugs related to the renin-angiotensin system.
 * Anti-ischemic potential of drugs related to the renin-angiotensin system.
 * Bradykinin-mediated cardiovascular protective actions of ACE inhibitors. A new dimension in anti-ischaemic therapy?
 * Bradykinin-mediated cardiovascular protective actions of ACE inhibitors. A new dimension in anti-ischaemic therapy?
 * The sympathetic nervous system and ischaemic heart disease.
 * The sympathetic nervous system and ischaemic heart disease.


 * Effect of ACE inhibition on neurohormones.
 * Effect of ACE inhibition on neurohormones.


 * Effect of ACE inhibition on myocardial ischaemia.
 * Effect of ACE inhibition on myocardial ischaemia. ACE inhibition improves endothelial function, exerts anti-atherogenic and anti-proliferation activity and modulates sympathetic activity.
 * Vascular protective effects of angiotensin converting enzyme inhibitors and their relation to clinical events.
 * Vascular protective effects of angiotensin converting enzyme inhibitors and their relation to clinical events. ACE inhibitors augment endothelium-dependent relaxation to bradykinin, while those to acetylcholine remain unaffected, at least in the time frame of the published studies, i.e. 3-6 months. In patients with coronary artery disease, however, paradoxical vasoconstriction to acetylcholine is markedly reduced after 6 months of ACE inhibition. After myocardial infarction ACE inhibitors reduce the development of overt heart failure, the occurrence of reinfarction and cardiovascular death in hypertensive patients. These effects have also been demonstrated in a subgroup analysis of the SOLVD (Studies of Left Ventricular Dysfunction) trial. Thus, in summary, ACE inhibitors are an important class of drugs providing cardiovascular protection in patients with increased cardiovascular risk.

BBB Crossing Statins and effecton brain, RAAS ACE ARBS Dementia
<!--- wrong about Lipitor penetrating the BBB. Search on statins and cognative dysfunction : reported (wow 60 cases), the case reports distribute nothing like the market share of statins. Most of the reports involve Lipitor/atorvastatin and Zocor/simvastatin, and one out of 60 was Pravachol; yet the market share of Pravachol/pravastatin is much higher than that.
 * Lipophilic but not hydrophilic statins selectively induce cell death in gynecological cancers expressing high levels of HMGCoA reductase. apoptotic potential of two lipophilic statins (lovastatin and simvastatin) and one hydrophilic statin (pravastatin) was assessed in cancer cell lines (ovarian, endometrial, and cervical) and primary cultured cancerous and normal tissues.
 * Amyloid beta toxicity dependent upon endothelial cell state. ? statins may helpbesides conventional endothelial effect
 * Statins for the prevention of dementia

Statins have been looked at in a number of studies of cognative function, since there is epidemiological suggestion (not proof) that they might *prevent* Alzheimer's. Incidentally, this evidence is much better than a bunch of case reports, so the statistical evidence that statins lessen risk of cognative impairment is far more impressive than the opposite. Observational data suggest that statins deserve further investigation in chemoprevention and therapeutic clinical trials." He added that the use of nonstatin cholesterol-lowering agents was not associated with reduced risk of colorectal cancer, suggesting that the protective effect was due to the statins rather than to the reduction in cholesterol. Gruber also noted that statins inhibit RAS and RhoA, two proteins that are potentially carcinogenic. In vivo and cell culture experiments have demonstrated that treatment with statins reduces production of β-amyloid protein. Since neurons receive only small amounts of exogenous cholesterol, statins that efficiently cross the blood-brain barrier may reduce the amount of neuronal cholesterol below a critical level. Decreased neuronal cholesterol levels inhibit the β-amyloid-forming pathway, which in turn results in reduced capability of β-amyloid to act as a seed for neurofibrillary tangle formation. A widely accepted theory involves myelin. Cholesterol is essential in the formation of myelin. The more lipophilic statins are able to cross the blood-brain barrier and decrease the amount of CNS cholesterol below the critical value necessary for the formation of myelin. Inadequate myelin production results in demyelination of nerve fibers in the CNS, resulting in memory loss. Once the offending statin is removed from the patient's system, myelin stores are replenished and mental status returns to normal. In our two patients, as well as another patient who received simvastatin, mental status returned to normal within 1 month of discontinuing the statin.
 * Simvastatin Protects against Amyloid β and HIV-1 Tat-Induced Promoter Activities of Inflammatory Genes in Brain Endothelial Cells
 * Simvastatin Protects against Amyloid β and HIV-1 Tat-Induced Promoter Activities of Inflammatory Genes in Brain Endothelial Cells : ALL STATINS LIKELY TO DO THIS beneficially; those without ability to cross BBB without internal side effect such as demyelation orther adverse effects etc, that goes along with BBB Crossing.  Aβ(1-40) and HIV-1 Tat protein cross-amplified promoter activities of three different proinflammatory genes in HBMECs. Similar synergistic effects were observed in HBMECs exposed to Aβ in the presence of HIV-1-infected Jurkat cells. It is most interesting that simvastatin effectively attenuated these effects. The present results indicate that Aβ and HIV Tat may synergistically induce inflammatory reactions in brain endothelial cells. In addition, statins may provide a beneficial influence by reducing these effects at the BBB level.
 * Dementia Prevention. Cognitive Impairment Associated: Atorvastatin and Simvastatin: Discussion
 * Dementia Prevention. Cognitive Impairment Associated: Atorvastatin and Simvastatin: Two epidemiologic studies indicated a decreased prevalence of Alzheimer's disease associated with statin therapy. Dementia was defined as the loss of both cognitive and intellectual functions. Although most studies have referred to statins as possibly preventing dementia of the Alzheimer's type, it is often difficult to distinguish the difference between dementia and isolated cognitive impairment. Thus, the statins' effects are referred to as cognitive impairment; a decline in intellectual function may not always a part.

In addition to demyelination of nerves in the CNS, nerves in the peripheral nervous system may be affected. Patients may experience tingling sensations of the extremities and loss of the sense of touch secondary to peripheral nervous system demyelination. Our second patient experienced some peripheral adverse effects. Diagnosing a patient with statin-induced dementia is complicated since many patients at risk for this complication also fit the profile of other types of dementia. The most important risk factor in the assessment of statin-induced dementia is, of course, the presence and temporal association of a statin. Statins with the greatest lipophilicity -- simvastatin and atorvastatin -- more easily cross the blood-brain barrier, which may affect memory. In a previously published report identifying simvastatin-associated memory loss, simvastatin was discontinued and pravastatin begun. The patient did not experience memory loss while taking pravastatin, which is highly hydrophilic and less likely to cross the blood-brain barrier. According to the myelin theory, pravastatin would be much less likely to cause statin-induced dementia and might have been a more appropriate choice in our two patients.

Onset of statin-induced dementia appears to occur within 1 year of the start of treatment, with memory impairment progressively worsening. This gradual onset helps to distinguish statin-induced dementia with the dementia usually associated with acute onset, such as with a stroke. Other causes of gradual onset of dementia, such as Alzheimer's disease, depression, and hypothyroidism, must be considered. Statin-induced dementia may be distinguished by the complete reversal of symptoms that occurs after statin discontinuation. Both of our patients, as well as the one in the previously published report,[1] returned to their baseline mental status within 1 month of statin discontinuation.
 * Statins Show Promise in Protecting Against Alzheimer's
 * Statins Show Promise in Protecting Against Alzheimer's: There was no association for nonstatin cholesterol-lowering drugs. However, there was for statins. Compared with the nonuse of cholesterol-lowering drugs, statin use was associated with a 43 percent lower risk of Alzheimer's.

Notably, the link between statin use and a reduced risk of Alzheimer's was the same whether the statins were lipophilic (having an affinity for lipids and probably capable of easily crossing the blood-brain barrier into the brain) or hydrophilic (having an affinity for water and probably not so adept at crossing the barrier). Further, the protective effect was observed regardless of statin dosage or duration of use. An abstract of “Statins Are Associated With a Reduced Risk of Alzheimer Disease Regardless of Lipophilicity. The Rotterdam Study” is posted at http://jnnp.bmj.com/cgi/content/abstract/jnnp.2008.150433v1. Could They Actually Help Dementia? Irrespective of BBB Crossing ability, Statins cause improvement in endothelial function even at a relative lowest dose being used clinically; effect not necessary dependent short term on cholesterol lowering; latter effect helps long term to prevent or reverse arteriosclerosis, thereby improving circulation to brain.
 * Can Statin Medications Cause Memory Loss?
 * Can Statin Medications Cause Memory Loss? BBB Crossing ability varies; e.g. Simvastatin crosses more than Pravastatin and hence the former has more memory loss which is thought to be reversible.
 * Can Statin Medications Cause Memory Loss? BBB Crossing ability varies; e.g. Simvastatin crosses more than Pravastatin and hence the former has more memory loss which is thought to be reversible.


 * Simvastatin-Associated Memory Loss


 * Differential-Effects-of-Statins-and-Alendronate-on-Cholinesterases
 * Statins Show Promise in Protecting Against Alzheimer's! -statins might be able to protect against Alzheimer's earlier in the disease process in persons who do not yet have any cognitive impairment
 * Side Effects and Dangers of Statin Drugs
 * Which Statin Should I Take?
 * Statins Prevent You from Getting Dementia?-5-year follow-up, persons who had used statins were about half as likely as those who did not use statins to develop dementia. experts suggest that brain permeant (crossing blood-brain-barrier) statins (such as simvastatin) might be far more effective than statins that don't get into the brain (atorvastatin). People should take statins only for purposes they are originally indicated for, that is: for cholesterol-lowering.

BLOOD-BRAIN BARRIER DRUG TARGETING: THE FUTURE OF BRAIN DRUG DEVELOPMENT
BLOOD-BRAIN BARRIER DRUG TARGETING: THE FUTURE OF BRAIN DRUG DEVELOPMENT

BBB Crossing & non Crossing ARB(s) and effect on brain, RAAS & Dementia

 * Franz Volhard Lecture. Renin-angiotensin system: a dual tissue and hormonal system for cardiovascular control.


 * Franz Volhard Lecture. Renin-angiotensin system: a dual tissue and hormonal system for cardiovascular control


 * Clinical Profile of Eprosartan: A Different Angiotensin II Receptor Blocker-only that crosses BBB

BBB Crossing ACE Inhibitors, though Amyloid-Plaquogenic, reported Preventing Progress of Dementia: Conundum Redux

 * Omapatrilat could have some advantages over lisinopril in the treatment of patients with congestive heart failure.
 * Omapatrilat could have some advantages over lisinopril in the treatment of patients with congestive heart failure.
 * Most of the ACE inhibitors on the market today are non-selective towards the two active sites of ACE because their binding to the enzyme is based mostly on the strong interaction between the zinc atom in the enzyme and the strong chelating group on the inhibitor. The resolution of the 3D structure of germinal ACE, which has only one active site that corresponds with C-domain of the somatic ACE, offers a structural framework for structure-based design approach.  Although N- and C-domain have comparable rates in vitro of ACE hydrolyzing, it seems like that in vivo the C-domain is mainly responsible for regulating blood pressure. This indicates that C-domain selective inhibitors could have similar profile to that of a current non-selective inhibitors.  Angiotensin I is mainly hydrolyzed by the C-domain in vivo but bradykinin is hydrolyzed by both active sites.  Thus, by developing a C-domain selective inhibitor would permit some degradation of bradykinin by the N-domain and this degradation could be enough to prevent accumulation of excess bradykinin which has been observed during attacks of angioedema.  C-domain selective inhibition could possibly result in specialized control of blood pressure with less vasodilator-related adverse effects.  N-domain selective inhibitors on the other hand give the possibility of opening up novel therapeutic areas.  Apparently, the N-domain doesn’t have a big role in controlling blood pressure but it seems to be the principal metabolizing enzyme for AcSDKP, a natural haemoregulatory hormone.
 * In Vitro and In Vivo Inhibition of the 2 Active Sites of ACE by Omapatrilat, a Vasopeptidase Inhibitor
 * The vasopeptidase inhibitor omapatrilat inhibits both neutral endopeptidase and angiotensin-converting enzyme (ACE). The in vitro and in vivo inhibitory potency of omapatrilat and the specific ACE inhibitor fosinopril toward the 2 active sites of ACE (called N- and C-domains) was investigated with the use of 3 substrates: angiotensin I, which is equally cleaved by the 2 ACE domains; hippuryl-histidyl-leucine, specific synthetic substrate of the C-domain in high- salt conditions; and a newly synthesized specific substrate of the N-domain designed by acetylating the lysine residue of AcSDKP. In vitro, omapatrilat was 5 times more potent than fosinoprilat in inhibiting angiotensin I hydrolysis. Omapatrilat inhibited similarly both N- and C-domain hydrolysis, whereas fosinoprilat was slightly more specific for the N-domain. The in vivo selective inhibitory potency of single oral doses of 10 mg omapatrilat and 20 mg fosinopril were investigated in a double-blind, placebo-controlled, cross-over study in 9 mildly sodium-depleted normotensive subjects. In accordance with the in vitro results, fosinopril appeared to be more specific for the N-domain than the C-domain in vivo, since plasma and urine AcSDKP concentrations were significantly higher than those observed with omapatrilat. This study shows that it is possible to assess separately in vitro and in vivo the selectivity of ACE or ACE/neutral endopeptidase inhibitors. A differential selectivity may explain some peculiar properties observed with some ACE inhibitors.


 * Angiotensin converting enzyme domain structure and properties
 * Structure of angiotensin I-converting enzyme. The inhibitor complex does provide insights into the network of hydrogen-bonding and ionic interactions in the active site as well as the mechanism of ACE substrate hydrolysis. The three-dimensional structure of ACE now paves the way for the rational design of a new generation of domain-selective ACE inhibitors.
 * Abeta40 protects non-toxic Abeta42 monomer from aggregation.
 * The N-terminal active centre of human angiotensin-converting enzyme degrades Alzheimer amyloid beta-peptide.
 * ACE N & C domains in competition


 * Potency For C domain L > E > C Lisinopril, Enalprilat, Captopril
 * Potency For N domain C > E > L


 * Aß42-40 converting inhibition is solely in N domain where Captopril is the strongest N: C>E>L
 * ACE Inhibiting activity is solely in C domain where.........Lisionopril is the strongest C: L>E>C

Aβ42-to-Aβ40-converting activity is solely found in the N-domain of ACE and the angiotensin-converting activity is found predominantly in the C-domain of ACE. The N-linked glycosylation is essential for both Aβ42-to-Aβ40- and angiotensin-converting activities and that unglycosylated ACE rapidly degraded. The domain-specific converting activity of ACE suggests that ACE inhibitors could be designed to specifically target the angiotensin-converting C-domain, without inhibiting the Aβ42-to-Aβ40-converting activity of ACE or increasing neurotoxic Aβ42.
 * ACE angiotensin-converting enzyme
 * Aβ amyloid β-protein
 * F-ACE full-domain ACE
 * N-ACE N-terminal domain ACE
 * C-ACE C-terminal domain ACE
 * ACE N & C domains in competition
 * While ACE inhibitors as a class do not appear to be independently associated with dementia risk or cognitive decline in older hypertensive adults, there may be within-class differences in regard to these outcomes. These results should be confirmed with a randomized clinical trial of a centrally active ACE inhibitor in the prevention of cognitive decline and dementia... no washout
 * Aß42–40 conversion 120 links
 * Angiotensin-Converting Enzyme Converts Amyloid ß-Protein 1–42 (Aß1–42) to Aß1–40, and Its Inhibition Enhances Brain Aß Deposition
 * Aß42–40 conversion 120 links
 * Angiotensin-Converting Enzyme Converts Amyloid ß-Protein 1–42 (Aß1–42) to Aß1–40, and Its Inhibition Enhances Brain Aß Deposition


 * The upregulation of ACE activity can be a novel therapeutic strategy for AD.


 * ACE inhibitors could be designed to specifically target the angiotensin-converting C-domain, without inhibiting the Aβ42-to-Aβ40-converting activity of ACE or increasing neurotoxic Aβ42

''' Centrally Active ACE Inhibitors May Help Prevent Dementia -coming soon -! can? non central ACE & possibly other Non ACE antihypertensives, be more preventive? Why recent study finds otherwise? FACTORS IN CONSTRUCT. ACE Degrades/converts Amyloid Aβ42 ( fibrillogenic, plaque forming ! ) to favorable Aβ40 more soluble possibly 'removable' amyloid & Central acting (BBB crossing) ACE Inhibitors thus likely to increase dementia; anti-inflammatory effects of ACE Inhibitors likely to decrease dementia, Acute effect of ACE on Ach likely to increase short term acuity confusing the picture for evaluation ''' The following Construct development in progress and involve all these and more points in hypothesis development.
 * Centrally acting ACE Inhibitors have acute Ach effects helping in mental acuity short term during which measurement may be biased and the long term effect of amyloid Aβ42 accumulation may be masked in testing; favorable anti-inflammatory effect not withstanding, long term more  Aβ42 is deposited or not converted to more soluble, disposable or removable Aβ40. Vascular Aβ42  vs  Aβ40 to be considered and could be important along with the favorable anti-inflammatory effect.
 * Acute, Chronic and Chronic with short term non use ( washed off ) use of ACE considering short term acuity enhancing effects of Ach.
 * Acute, Chronic and Chronic with short term non use ( washed off ) use of ACE considering short term acuity enhancing effects of Ach.
 * Acute, Chronic and Chronic with short term non use ( washed off ) use of ACE considering short term acuity enhancing effects of Ach.
 * Acute, Chronic and Chronic with short term non use ( washed off ) use of ACE considering short term acuity enhancing effects of Ach.

ALL above to be considered in both below: along with congruency of the two studies with each other and restrospective congruency with prior knowledge base of studies and general understanding of the science.
 * Difference between Aβ42 ? more in nerves and ? Aβ40  more in vessel
 * Aβ42 vs  Aβ40
 * Pleomorphism and genetics of ACE
 * RAAS -Systemic vs Local and interactions and cross influence
 * ACE Inhibitors: BBB crossing vs Non crossing
 * Non-BBB crossing ACE negative effect studies ie if increased dementia, then..
 * Other enzyme systems besides ACE


 * Currently reported study in Archives of Intl Med July 09-BBB crossing ACE reduce Dementia needs explanation.... Standby
 * Current AII AT1 Inhibitors -Sartan--retrospective VA study expl and corroboration standby......

Results From the Cardiovascular Health Study: While ACE inhibitors as a class do not appear to be independently associated with dementia risk or cognitive decline in older hypertensive adults, there may be within-class differences in regard to these outcomes. These results should be confirmed with a randomized clinical trial of a centrally active ACE inhibitor in the prevention of cognitive decline and dementia.]
 * 2013 find needs to be processed: [http://archinte.jamanetwork.com/article.aspx?articleid=415176 Angiotensin-Converting Enzyme Inhibitors and Cognitive Decline in Older Adults With Hypertension

<!---

Genetics
Autosomal-dominant mutations in APP cause hereditary early-onset Alzheimer's disease, likely as a result of altered proteolytic processing. Increases in either total Aβ levels or the relative concentration of both Aβ40 and Aβ42 (where the former is more concentrated in cerebrovascular plaques and the latter in neuritic plaques) have been implicated in the pathogenesis of both familial and sporadic Alzheimer's disease. Due to its more hydrophobic nature, the Aβ42 is the most amyloidogenic form of the peptide. However the central sequence KLVFFAE is known to form amyloid on its own, and probably forms the core of the fibril.

The "amyloid hypothesis", that the plaques are responsible for the pathology of Alzheimer's disease, is accepted by the majority of researchers but is by no means conclusively established. Intra-cellular deposits of tau protein are also seen in the disease, and may also be implicated. The oligomers that form on the amyloid pathway, rather than the mature fibrils, may be the cytotoxic species.

http://cme.medscape.com/viewarticle/706868?src=cmemp

From Medscape Medical News CME Centrally Active ACE Inhibitors May Help Prevent Dementia CME News Author: Janis Kelly

August 3, 2009 — New observational data from the Cardiovascular Health Study show that centrally active angiotensin-converting enzyme (ACE) inhibitors reduce cognitive decline by 65% per year of exposure, an effect that is likely due to their ability to cross the blood-brain barrier.

"If confirmed in a randomized clinical trial, our findings would add another potential therapeutic option" for prevention of cognitive decline and related diseases, lead author Kaycee M. Sink, MD, from Wake Forest University School of Medicine, in Winston-Salem, North Carolina, told Medscape Neurology.

The study is published in the July 13 issue of Archives of Internal Medicine.

Class of ACE Inhibitor Important

Dr. Sink and colleagues used data from the Cardiovascular Health Study to determine whether cumulative exposure to ACE inhibitors was associated with a lower risk for incident dementia, cognitive decline, or incident disability in instrumental activities of daily living (IADLs), compared with treatment with other antihypertensive agents in 1054 patients with treated hypertension and no congestive heart failure.

The study included 414 subjects who had taken ACE inhibitors and 640 who had taken other antihypertensive medications. The researchers found no association between exposure to all ACE inhibitors and risk for dementia, difference in cognitive-function scores, or odds of disability in IADLs.

However, analysis according to type of ACE inhibitor showed a different effect. The results showed centrally active ACE inhibitors were associated with 65% less decline in cognitive-function scores per year of exposure.

The data also reveal that non–centrally active ACE inhibitors were associated with a greater risk for incident dementia and greater odds of disability in IADLs compared with other antihypertensive medications.

Centrally active ACE inhibitors included captopril (Capoten, Bristol-Myers Squibb), fosinopril (Monopril, Bristol-Myers Squibb), lisinopril, perindopril, ramipril (Altace, King Pharmaceuticals), and trandolapril (Mavik, Abbott Laboratories). Non–centrally active ACE inhibitors included benazepril (Lotensin, Novartis Pharmaceuticals), enalapril (Vasotec, Merck), moexipril (Univasc, Schwarz Pharma), and quinapril (Accupril, Pfizer).

The study did not include enough people taking angiotensin receptor blockers to extend the analysis to those drugs, said Dr. Sink.

Reduced Incidence Likely Not Due to Antihypertensive Effect

"Our most important findings in this observational study were that centrally acting ACE inhibitors were associated with a 65% reduction in cognitive decline per year of taking the centrally active ACE inhibitors," said Dr. Sink.

"In addition, compared with participants with high blood pressure who took other types of blood-pressure–lowering medications, non–centrally active ACE inhibitors did not have this effect and might be associated with a greater risk for incremental dementia, and that cumulative (or chronic) exposure to ACE inhibitors may be needed to achieve the protective effect," Dr. Sink said.

The researchers suspect that this difference is due primarily not to the antihypertensive effects of centrally acting ACE inhibitors but to their effect on the brain's intrinsic renin-angiotensin system, which is involved in memory and cognition.

Stimulation of the renin-angiotensin system also mediates activation of inflammatory cytokines that have been implicated in degenerative dementias, explained Dr. Sink.

The researchers also suspect that the slight increase in dementia risk associated with the non–centrally acting ACE inhibitors in this comparison was probably a sign that they are "simply less helpful in the prevention of dementia and IADL disability than other antihypertension drug classes combined."

Due to the huge public-health implications of finding an intervention that could more than halve dementia risk in the elderly population, confirmation of these observational findings in a randomized clinical trial is needed.

"Randomizing older adults with hypertension to a centrally active ACE inhibitor vs a non–centrally active ACE inhibitor would test the hypothesis that centrally active ACE inhibitors have protective benefits on cognition beyond the effects of blood-pressure control," said Dr. Sink.

Should Patients Switch Medications?

Whether clinicians should switch their hypertensive patients to a centrally acting ACE inhibitor must be decided on a case-by-case basis, said Dr. Sink.

"Because there are often multiple reasons for a particular choice of antihypertensive drug in any particular patient, the decision about switching blood-pressure medications should be discussed between patient and provider.

"However, if the patient does not have a contraindication for an ACE inhibitor, then switching to a centrally active ACE inhibitor is a reasonable choice. In addition, for those already on ACE inhibitors, our study results would support the use of a centrally active ACE inhibitor over a non–centrally active one," Dr. Sink said.

Asked by Medscape Neurology to comment on the findings, Ihab Hajjar, MD, from the Institute for Aging Research and assistant professor of medicine at Harvard Medical School, in Boston, Massachusetts, said that this study adds to the support for clinical trials.

"This is the right time to study ACE inhibition on cognitive function. However, it is important to select the appropriate drug [agents that cross the blood-brain barrier] and the appropriate population [hypertensives and other high-risk groups]," Dr. Hajjar said in an interview.

However, he emphasized that lowering blood pressure is the most important goal for managing high-risk elderly patients and that the choice of drug is secondary.

"Drugs that inhibit the renin angiotensin system seem to have a preferential effect on cognition compared with other antihypertensives. As a third issue, antihypertensives that cross the blood-brain barrier may also have an even superior effect to other non–blood-brain-barrier-penetrating drugs. This is true not only for those without cognitive impairment but also for those with dementia and Alzheimer's disease," Dr. Hajjar said.

Study investigator David C. Goff Jr, MD, PhD, from Wake Forest University, has a research grant from Merck. The study was supported in part by the National Heart, Lung, and Blood Institute; the National Institute of Neurological Disorders and Stroke; and the National Institute on Aging.

Arch Intern Med. 2009;169:1195-1202. Abstract

Clinical Context

Hypertension is an important risk factor for the development of dementia. An association has been noted between use of antihypertensive agents and a reduced risk for dementia, but mixed results have been reported on the protective effect of blood pressure reduction on cognitive decline and dementia. The brain is known to possess an intrinsic renin-angiotensin system, and centrally acting ACE inhibitors may be involved in the protective effect on dementia.

This is a prospective multicenter, population-based cohort study of cardiovascular risk factors in community-dwelling older adults to examine the association between ACE inhibitors as a class and centrally and non–centrally acting ACE inhibitors on the risk for dementia and cognitive decline in older people in the United States.

Study Highlights

Included in analysis were 1054 participants from among 5888 participants of the Cardiovascular Health Study, selected for absence of dementia at baseline and hypertension treated with medications. Excluded were those with congestive heart failure and prevalent dementia at baseline. At baseline, all participants received magnetic resonance imaging, physical examination, cognitive and functional assessments, and laboratory tests. The predictor was ACE inhibitor use, and ACE inhibitors were further classified into centrally acting and non–centrally acting. Centrally acting ACE inhibitors were captopril, fosinopril, perindopril, ramipril, and trandolapril. Non–centrally acting ACE inhibitors were benazepril, enalapril, moexipril, and quinapril. The study start was when participants received magnetic resonance imaging, and study end was defined as date of dementia diagnosis, last evaluation, or time of loss to follow-up. Primary outcome was all-cause dementia consisting mainly of Alzheimer's disease and vascular dementia. Secondary outcomes were cognitive decline measured by the Modified Mini-Mental State Examination (3MSE) and IADLs. IADLs were assessed in 6 areas: shopping, meal preparation, money management, telephone use, and light and heavy housework. The 3MSE used an 100-point scale with higher scores indicating better cognitive performance. Average age at baseline was 75 years, 64% were women, and 76% were white. 54% reported no alcohol use, 11% to 22% had type 2 diabetes, and 18% had a history of coronary artery disease. Of 414 participants exposed to ACE inhibitors, 224 took only centrally acting and 138 only non–centrally acting, with the remaining taking both. Those using centrally acting ACE inhibitors had a higher baseline 3MSE score (93.2 vs 01.7 points). At median follow-up of 6 years, mean exposure to all ACE inhibitors was 3.24 years with mean exposure to centrally acting ACE inhibitors of 3.06 years and non–centrally acting ACE inhibitors of 2.70 years. 38% of ACE inhibitor users were continuous users with no difference in duration of use between the centrally and non–centrally acting groups. There were 158 cases of incident dementia, with 11 among those never exposed to ACE inhibitors and 47 among those exposed to all ACE inhibitors. Relative risk (RR) for dementia in ACE inhibitor users vs other antihypertensive drug users was 1.01. When analyzed by centrally vs non–centrally acting ACE inhibitors, centrally acting agents reduced the RR for dementia by 20% per year of exposure, for a hazard ratio (HR) of 1.73 for 3 years. HR for dementia for non–centrally acting ACE inhibitors vs other antihypertensives was 1.20. There was no significant difference in decline in 3MSE scores between ACE inhibitor users and non-ACE inhibitor users. When analyzed by centrally and non–centrally acting ACE inhibitors vs other antihypertensives, centrally acting agents were associated with 65% less decline per year of exposure. For IADL disability, ACE inhibitors as a class had higher risk for disability vs other antihypertensives. When non–centrally acting ACE inhibitors were examined, there was a 56% greater risk for IADL disability at 3 years vs non-ACE inhibitor drugs. HR for non–centrally acting ACE inhibitors on impaired IADL vs other antihypertensives was 1.16. Centrally acting ACE inhibitors did not show a negative impact on IADLs. The authors concluded that all outcomes favored centrally acting ACE inhibitors and that protective effects of ACE inhibitors on dementia and cognitive decline were restricted to centrally acting ACE inhibitors.

Clinical Implications

ACE inhibitors as a class vs other antihypertensive agents are not associated with protection against dementia, cognitive decline, or disability in IADLs. Centrally acting ACE inhibitors are associated with a reduced risk for dementia, cognitive decline, and disability in IADLs vs non–centrally acting ACE inhibitors and other antihypertensive agents.

Alzheimer's-beta amyloid, tau protein,-- Drug Rember, Methylene Blue
Alzheimer's researchers are divided on whether the disease is caused by 'beta amyloid' (a peptide found in Alzheimer brains) or by 'tau protein' (normally used for cellular scaffolding, but can aggregate out of control and destroy neurons). Today in Chicago a new drug has been announced that stops tau aggregation and appears to have halted Alzheimer's-related decline in 300 clinical trial patients. The drug is known as 'rember.

Angiotensin Receptor Blockers lower progression of Alzheimer's Disease- ! explanation coming and Construct intergration in progress
SHORT Explanation for this: mech related to above ACE AND ACE Inhibitors and BP dynamcs. Standby for full expl......
 * Amelioration of cerebrovascular dysfunction with an angiotensin receptor blocker could be a novel therapeutic strategy for the early stage of Alzheimer disease.

http://www.physorg.com/print136426165.html Angiotensin receptor blockers are lower incidence, progression of Alzheimer's disease July 28th, 2008 in Medicine & Health / Diseases Researchers at Boston University School of Medicine (BUSM) have, for the first time, found that angiotensin receptor blockers (ARBs)—a particular class of anti-hypertensive medicines—are associated with a striking decrease in the occurrence and progression of dementia. Data from this study will be presented this weekend (July 27) at the 2008 International Conference on Alzheimer's disease in Chicago. Using data from the Decision Support System Database of the U.S. Department of Health System Veterans Affairs (with information on more than 5 million people), researchers looked at records from patients using ARBs, and compared them with subjects who had a similar health status, but were taking different medications. They found patients taking ARBs had about a 35-40 percent lower chance of getting Alzheimer's disease or dementia. The researchers also examined patients who were already suffering from Alzheimer's disease or dementia, and found those subjects had up to a 45 percent lower chance of developing delirium, being admitted to nursing homes or dying. Patients who appeared to benefit particularly well from use of ARBs were those who had experienced strokes before or during the course of their illness. According to the researchers these results suggest that ARBs might protect against developing Alzheimer's disease and dementia. "For those who already have dementia, use of ARBs might delay deterioration of brain function and help keep patients out of nursing homes," said lead presenter Benjamin Wolozin, MD, PhD, a professor of pharmacology at BUSM. "The study is particularly interesting because we compared the effects of ARBs to other medications used for treating blood pressure or cardiovascular disease. This suggests that ARBs are more effective than other blood pressure and cardiovascular medications for preventing Alzheimer's disease or dementia," he added. Although the researchers are unsure why ARBs might be so beneficial, they believe one possibility suggested by prior studies on animal models is that ARBs help prevent nerve cell injury from blood vessel damage or help promote nerve cell recovery after blood vessel damage. Damage to blood vessels is thought to reduce brain capacity and promote dementia, so reducing this damage might prevent the occurrence or progression of dementia. Source: Boston University

ACE-I vs angiotensin II receptor antagonists vs Vasopeptidase inhibitor (VPI)

 * Comparison of vasopeptidase inhibitor omapatrilat and angiotensin receptor blocker candesartan on extracellular matrix, myeloperoxidase, cytokines, and ventricular remodeling during healing after reperfused myocardial infarction

Insulin: Heart Function & Inflammation
<!--- ANTI-INFLAMMATORY AND CARDIOPROTECTIVE EFFECTS OF INSULIN Prof. Paresh Dandona Following the discovery of insulin in 1921 by Banting and Best, it has been used to control hyperglycemia and to treat diabetes mellitus. It is also suppresses free fatty acid concentration and ketogenesis and promotes lipogenesis and the storage of fat in adipose tissue and protein synthesis in the skeletal muscle. These observations have insulin the status of the ‘ultimate anabolic hormone’. However, the association of fasting hyperinsulinemia with increased incidence of cardiovascular events in four prospective epidemiological studies, insulin was labeled as an atherogenic hormone. However, this statistical association does not establish a causal relationship. Our recent work has shown that insulin exerts a rapid and potent ROS suppressive and anti-inflammatory effect as reflected in the suppression of ROS generation, p47phox expression, intranuclear NFkB binding and plasma ICAM-1, MCP-1, tissue factor, PAI-1, MMP-9 and VEGF. In addition, there was a suppression of plasma concentrations of chemokines, MCP-1 and RANTES and the expression of their respective receptors, CCR-2 and CCR-5. Thus, insulin could be anti-atherogenic since atherosclerosis is a chronic inflammation of the arterial wall. Consistent with these observations, it has now been shown that the administration of insulin exerts an anti-atherogenic effect in experimental animals and the deletion of the insulin receptor systemically and in the endothelial cell results in accelerated atherogenesis. It has also been shown to prevent restenosis after balloon induced injury in an artery. It has also been shown to reduce the size of an infarct if infused in patients with ST elevation acute myocardial infarction along with the suppression of inflammatory indices, CRP, SAA, PAI-1 and p47phox. It was recently shown that such an infusion in patients with AMI reduced tissue inflammation in the peri-infarct tissue and to suppress Caspase-3, the major mediator of apoptosis. In addition, the infusion of insulin reduces the size of the infarct and to improve myocardial function. Consistent with this, it has also been shown to reduce the rate of re-infarction and congestive cardiac failure. Clearly, the stage is set for a large multicenter trial to test the hypothesis that the infusion of insulin is cardio-protective in patients with AMI and that its use will improve the clinical outcomes of AMI. In patients undergoing coronary artery bypass surgery, insulin has been shown to reduce plasma CRP and SAA concentrations and to reduce the incidence of post-surgical atrial fibrillation. In patients undergoing surgery for peripheral vascular disease, insulin infusion reduces the risk for post surgical myocardial infarction and stroke. Insulin has also been shown to reduce the size of an experimental ischemic infarct in the brain of experimental animals. Most recently, it has been shown to suppress amyloid precursor protein involved in the pathogenesis of Alzheimer’s disease and IL-4 which is a key cytokine involved in the pathogenesis of asthma. The scope of the anti-inflammatory action of insulin is likely to expand over the next decade. Work is currently being undertaken to create analogs of insulin which will have a potent anti-inflammatory effect with a minimal glucose lowering effect so that insulin can be safely used as an anti-inflammatory drug without the potential risk of hypoglycemia. Insulin as an Anti-Inflammatory and Antiatherogenic Modulator:Paresh Dandona, MD, PhD*,*, Ajay Chaudhuri, MD*, Husam Ghanim, PhD* and Priya Mohanty, MD Kaleida Health, Buffalo, New York --->
 * Insulin as an Anti-Inflammatory and Antiatherogenic

Unicode In typesetting technical literature β.Unicode number for β is U+03B2, and with &beta; or &#946; the β is coded in HTML.
In typesetting technical literature, it is a commonly made mistake to use the German letter ß as a replacement for the β. The two letters resemble each other superficially, but they are unrelated. This substitution looks extremely unprofessional to the eyes of German or Greek readers. The Unicode number for β is U+03B2, and with &beta; or &#946; the β is coded in HTML. The internal version, ϐ, is encoded as U+03D0 in Unicode or &#976; in HTML. S