User:Editor-aay/Dyslipidemia

Screening
There is no clear consensus of when screening for dyslipidemia should be initiated. In general, those with a high risk of cardiovascular disease should be screened at a younger age with males between 25–30 years old and females between 30–35 years of age. Testing the general population under the age of 40 without symptoms is of unclear benefit. UpToDate suggests screening males at age 35 and females at age 45 in those without any risk of cardiovascular disease. All individuals regardless of age, should be screened if they have the risk factors listed below. Cardiovascular risk can be determined using the Framingham Risk Score (FRS) and should be reassessed every 5 years for patients who are 40 to 75 years of age.

== Risk Factors ==


 * Family history of dyslipidemia
 * Current cigarette smoking
 * Diabetes mellitus
 * Hypertension
 * Obesity (BMI>30kg/m2)
 * Atherosclerosis
 * Family history of premature coronary artery disease
 * HIV infection
 * Erectile dysfunction
 * Chronic kidney disease (eGFR < 60ml/min/1.73 m2)
 * Abdominal aneurysm
 * Chronic obstructive pulmonary disease
 * Clinical manifestations of hyperlipidemias (xanthelasmas, xanthomas, premature arcus cornealis)
 * Hypertensive disorders of pregnancy
 * Inflammatory bowel disease

Non-pharmacological Choices
An important non-pharmacological intervention in dyslipidemia is a diet aimed at reducing blood lipid levels and also weight loss if needed. These dietary changes should always be a part of treatment and the involvement of a dietician is recommended in the initial evaluation and also in follow-up as well. A 3-month trial of dietary changes is recommended in primary prevention before considering medication, but in secondary prevention and in individuals at high-risk, cholesterol-lowering medication is used in conjunction with diet modifications.

Recommended diets include the DASH diet, Mediterranean diet, Low-glycemic Index diet, Portfolio diet, and vegetarian diet. Patients should reduce their intake of saturated fats, dietary cholesterol, and alcohol, and increase their intake of total fibre ( > 30g/day), viscous soluble fibre ( > 10g/day), and omega-3 (EPA and DHA [2-4g/d] used to lower TG only). They should also increase the proportion of mono-and polyunsaturated fats that they intake.

Other lifestyle modifications include weight loss (5-10% of body weight loss) and reduction of abdominal obesity, 30-60 minutes per day of moderate-vigorous exercise, smoking cessation, stress management, and getting 6-8 hours of sleep at night.

Pharmacological Choices
Based on the Framingham Risk Scores, there are different thresholds that indicate whether treatment should be initiated. Individuals with a score of > 20% are considered to have a high cardiovascular risk, a score of 10-19% indicates an intermediate risk, and patients with a score less than 10% are at low risk. Statin therapy and non-pharmacological interventions are indicated in those with high cardiovascular risk. In those at intermediate risk or low risk, the use of statin therapy depends on individual patient factors such as age, cholesterol levels, and risk factors.

Statins are considered the first-line agents but other drugs can be substituted if the lipid targets are not achieved with statin therapy or if they are not tolerated.

HMG-CoA Reductase Inhibitors (Statins)
Statins competitively inhibit hydroxymethylglutaryl (HMG) CoA reductase which is used in the biosynthesis of cholesterol and they include atorvastatin, lovastatin, simvastatin, rosuvastatin, pravastatin, fluvastatin, and pitavastatin. These agents work to lower LDL-C levels and are also associated with a decrease in CVD mortality, CVD morbidity, and total deaths. They have a small effect on HDL-C levels as well.

Resins
Resins are bile acid sequesterants that work by preventing the intestinal re-uptake of bile acids, thus increasing their fecal loss. Resins include cholestyramine, colestipol, and colesevalem, and they all decrease LDL-C while increasing HDL-C levels slightly. The Lipid Research Council - Cardiovascular Primary Prevention Trial (LRC-CPPT) also showed that when these agents were used alone, they improved cardiovascular outcomes.

Fibrates
The cholesterol lowering effect of fibrates is due to their ability to activate a nuclear receptor called peroxisome proliferator activated receptor alpha. They include fenofibrate, gemfibrozil, and bezafibrate and work to decrease triglycerides, increase HDL-C, and also decrease LDL-C which is variable depending on which drug is used. The FIELD Study showed that fenofibrate reduced both coronary revascularization as well as nonfatal myocardial infarctions (but not in patients with DM2).

PCSK9 Inhibitors
PCSK9 inhibitors are monoclonal antibodies that target an important protein in the degradation of LDL called proprotein convertase substilisin/kexin type 9 (PCSK9). These agents reduce LDL-C, increase HDL-C, decrease triglycerides, and decrease lipoprotein(a). The FOURNIER and ODYSSEY trials showed that these agents also reduced the risk of cardiovascular events.

Cholesterol Absorption Inhibitors
Ezetimibe inhibits the intestinal absorption of cholesterol and can be used alone or with statins. Regarding cardiovascular events, patients with chronic kidney disease saw a reduction in vascular and major atherosclerotic events when on simvastatin and ezetimibe compared to placebo. This same combination was also shown to reduce death, major coronary events, and nonfatal stroke in patients after acute coronary syndromes.

Icosapent Ethyl
This agent is comprised of eicosapentaenoic acid (EPA), an omega-3 fatty acid from fish oil and works to lower the hepatic production of triglycerides. In the REDUCE-IT trial, patients on statin therapy and 4g daily of icosapent ethyl saw a reduction in major cardiovascular events.

Microsomal Triglyceride Transfer Protein Inhibitors
Lomitapide works to inhibit the microsomal triglyceride transfer protein (MTP) which results in a reduction of LDL plasma levels.