Also Known As: Hypercholesterolemia, High cholesterol, Hyperlipidemia
Hypercholesterolemia is the presence of high levels of cholesterol in the blood. It is a form of "hyperlipidemia" (elevated levels of lipids in the blood) and "hyperlipoproteinemia" (elevated levels of lipoproteins in the blood).
Cholesterol is a sterol, a sort of fat; see the diagrammatic structure at the right. It is one of three major classes of lipids which all animal cells utilize to construct their membranes and is thus manufactured by all animal cells. Plant cells do not manufacture cholesterol. It is also the precursor of the steroid hormones, bile acids and vitamin D.
Since cholesterol is insoluble in water, it is transported in the blood plasma within protein particles (lipoproteins). Lipoproteins are classified by their density (very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), low density lipoprotein (LDL) and high density lipoprotein (HDL). All the lipoproteins carry cholesterol, but elevated levels of the lipoproteins other than HDL (termed non-HDL cholesterol), particularly LDL-cholesterol are associated with an increased risk of atherosclerosis and coronary heart disease. In contrast higher levels of HDL cholesterol are protective. Elevated levels of non-HDL cholesterol and LDL in the blood may be a consequence of diet, obesity, inherited (genetic) diseases (such as LDL receptor mutations in familial hypercholesterolemia), or the presence of other diseases such as diabetes and an underactive thyroid.
Reducing dietary fat is recommended to reduce total blood cholesterol and LDL in adults. In people with very high cholesterol (e.g. familial hypercholesterolemia) diet is often insufficient to achieve the desired lowering of LDL and medications which reduce cholesterol production or absorption are usually required. If necessary other treatments, including LDL apheresis or even surgery (for particularly severe subtypes of familial hypercholesterolemia) are performed..
Although hypercholesterolemia itself is asymptomatic, longstanding elevation of serum cholesterol can lead to atherosclerosis. Over a period of decades, chronically elevated serum cholesterol contributes to formation of atheromatous plaques in the arteries. This can lead to progressive stenosis (narrowing) or even complete occlusion (blockage) of the involved arteries. Alternatively smaller plaques may rupture and cause a clot to form and obstruct blood flow. A sudden occlusion of a coronary artery results in a myocardial infarction or heart attack. An occlusion of an artery supplying the brain can cause a stroke. If the development of the stenosis or occlusion is gradual blood supply to the tissues and organs slowly diminishes until organ function becomes impaired. At this point that tissue ischemia (restriction in blood supply) may manifest as specific symptoms. For example, temporary ischemia of the brain (commonly referred to as a transient ischemic attack) may manifest as temporary loss of vision, dizziness and impairment of balance, aphasia (difficulty speaking), paresis (weakness) and paresthesia (numbness or tingling), usually on one side of the body. Insufficient blood supply to the heart may manifest as chest pain, and ischemia of the eye may manifest as transient visual loss in one eye. Insufficient blood supply to the legs may manifest as calf pain when walking, while in the intestines it may present as abdominal pain after eating a meal. Some types of hypercholesterolemia lead to specific physical findings. For example, familial hypercholesterolemia (Type IIa hyperlipoproteinemia) may be associated with xanthelasma palpebrarum (yellowish patches underneath the skin around the eyelids), arcus senilis (white or gray discoloration of the peripheral cornea), and xanthomata (deposition of yellowish cholesterol-rich material) of the tendons, especially of the fingers. Type III hyperlipidemia may be associated with xanthomata of the palms, knees and elbows.
Hypercholesterolemia is typically due to a combination of environmental and genetic factors. Environmental factors include: obesity and dietary choices. Genetic contributions are usually due to the additive effects of multiple genes however occasionally may be due to a single gene defect such as in the case of familial hypercholesterolaemia. A number of secondary causes exist including: diabetes mellitus type 2, obesity, alcohol, monoclonal gammopathy, dialysis, nephrotic syndrome, obstructive jaundice, hypothyroidism, Cushing’s syndrome, anorexia nervosa, medications (thiazide diuretics, ciclosporin, glucocorticoids, beta blockers, retinoic acid).
Diet has an important effect on blood cholesterol but the size of this effect varies substantially between individuals. Approximately 50% of non-esterified cholesterol is absorbed in the intestine, but inter-individual variations in the efficiency of uptake, and the effect of other dietary components such as plant sterols and fiber content affect absorption. Moreover, when dietary cholesterol intake goes down, production (principally by the liver.) typically increases, though not always with complete compensation, so that reductions in blood cholesterol can be modest. Reductions in fat intake, particularly saturated fats, also reduce blood cholesterol. Recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia in 2011 were that people with familial hypercholesterolemia should follow the The National Cholesterol Education Program (NCEP) Third Adult Treatment Panel (ATP III) Therapeutic Lifestyle Changes (TLC) diet and restrict intakes of total fat to 25 - 35% of energy intake; that saturated fatty acids should make up less than 7% of energy intake, and that cholesterol intake should be less than 200 mg per day. There is also evidence that inclusion of 2 g per day of plant stanol or sterol esters and 10 to 20 g per day of soluble fiber decrease dietary cholesterol absorption. Dietary changes can typically achieve reductions of 10 to 15% in blood cholesterol.
Maintaining a healthy body weight through increased physical activity and appropriate caloric intake is also important. Overweight or obese individuals can lower blood cholesterol by losing weight - on average a kilogram of weight loss can reduce LDL cholesterol by 0.8 mg/dL.
Genetic abnormalities are in some cases completely responsible for hypercholesterolemia, such as in familial hypercholesterolemia where there is one or more genetic mutations in, for example, the LDL receptor.
Even when there is no single responsible mutation to explain hypercholesterolemia, genetic predisposition still plays a major role, potentially adding to lifestyle factors and multiplying the risk of late complications. Multiple genes are involved, and hypercholesterolemia where there is probably a genetic predisposition is called polygenic hypercholesterolemia. The involved genes have yet to be discovered.