Hypercholesterolemia

Hypercholesterolemia is "a condition with abnormally high levels of cholesterol in the blood. It is defined as a cholesterol value exceeding the 95th percentile for the population." It should be differentiated from dyslipidemia, where the total cholesterol may not be abnormally high, but the ratios of lipid components are in an unhealthy reange.

Treatment
Antilipemic agents such as hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) and clofibric acid derivatives can help.

A meta-analysis estimated that after 5 to 7 years of treatment with statins, the relative risk reduction of coronary heart disease events is decreased by approximately 30%. More recently, a meta-analysis reported an almost identical relative risk reduction of 29.2% in low risk patients treated for 4.3 years. A relative risk reduction of 19% in coronary mortality was found in a meta-analysis of patients at all levels of risk.

It is not clear whether to treat to LDL targets. Studies are currently evaluating this.

Clinical practice guidelines
Various clinical practice guidelines have addressed the treatment of hypercholesterolemia.

Clinical practice guidelines by the National Institute for Health and Clinical Excellence in 2008 recommend treatment if the estimated 10 year risk of cardiovascular disease is at least 20%.

The American College of Physicians in 2004 addressed hypercholesterolemia in patients with diabetes. Their recommendations are:
 * Recommendation 1: Lipid-lowering therapy should be used for secondary prevention of cardiovascular mortality and morbidity for all patients (both men and women) with known coronary artery disease and type 2 diabetes.
 * Recommendation 2: Statins should be used for primary prevention against macrovascular complications in patients (both men and women) with type 2 diabetes and other cardiovascular risk factors.
 * Recommendation 3: Once lipid-lowering therapy is initiated, patients with type 2 diabetes mellitus should be taking at least moderate doses of a statin (the accompanying evidence report states "simvastatin, 40 mg/d; pravastatin, 40 mg/d; lovastatin, 40 mg/d; atorvastatin, 20 mg/d; or an equivalent dose of another statin").
 * Recommendation 4: For those patients with type 2 diabetes who are taking statins, routine monitoring of liver function tests or muscle enzymes is not recommended except in specific circumstances.

The National Cholesterol Education Program revised their 2001 guidelines in 2004 to include goal LDL values. ; however, their 2004 revisions have been criticized for use of nonrandomized, observational data. A decision analysis found that treating to targets is not efficient.

Primary prevention
Two meta-analyses found that overall mortality is insignificantly reduced.

A third meta-analysis reported that statins can significantly help in the primary prevention of coronary heart disease among patients at risk.

Treating based on risk factors is probably better than treating to a specific target LDL cholesterol.

Treating patients with normal cholesterol level may benefit patients if their high sensitivity c-reactive protein is elevated according to the Jupiter randomized controlled trial. However, in the Jupiter trial, only 16% of patients were taking aspirin.

It is not clear that combination therapy is better than high dose hydroxymethylglutaryl-coenzyme A reductase inhibitors.
 * Combination treatment

If treatment with a hydroxymethylglutaryl-coenzyme A reductase inhibitor does not achieve a desirable cholesterol, other drugs that have been studied include eicosapentaenoic acid which is a metabolite of fish oil. Ezetimibe, a cholesterol-absorption inhibitor, was not clearly beneficial in a study of diabetes mellitus type 2 and a study of mixed primary prevention and secondary prevention. Niacin has been studied with improvements in the LDL and HDL with uncertain effects on carotid intima-media thickness.

Secondary prevention
Clinical practice guidelines by the National Institute for Health and Clinical Excellence recommend a treatment goal of <4 mmol/l (154 mg/dl) for total cholesterol or a low density lipoprotein cholesterol concentration of <2 mmol/l (77 mg/dl). A systematic review summarized randomized controlled trials in secondary prevention.

If treatment with a hydroxymethylglutaryl-coenzyme A reductase inhibitor does not achieve a desirable cholesterol, other drugs that may be added for additional benefit include niacin  and fish oil. Ezetimibe, a cholesterol-absorption inhibitor, was not clearly beneficial in a study of diabetes mellitus type 2 and a study of mixed primary prevention and secondary prevention.
 * Combination treatment

Diabetic patients
Whether diabetes is an equivalent risk factor to having an existing myocardial infarction is debated.

Statin therapy prevents major vascular events in about 1 of every 24 patients with diabetes who use the treatment for 5 years if they are similar to the patients in the meta-analysis by Kearney et al (Number needed to treat is 24).

Treating to a goal of LDL-C < 70 mg/dl and systolic blood pressure to < 115 mm Hg may cause regression of carotid intima-media thickness in a randomized controlled trial.

Complementary and alternative medicine
Preliminary research suggests possible benefit from artichoke leaf.