High cholesterol, also called Hypercholesterolemia, is the presence of high levels of cholesterol in the blood. It is a form of hyperlipidemia (high levels of lipids in the blood), hyperlipoproteinemia (high levels of lipoproteins in the blood), and dyslipidemia (any abnormalities of lipid and lipoprotein levels in the blood). 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 type 2 diabetes and an underactive thyroid. Cholesterol is one of three major classes of lipids produced and used by all animal cells to form membranes. Plant cells manufacture phytosterols (similar to cholesterol) but in small quantities. Cholesterol is the precursor of the steroid hormones and bile acids. 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 HDL cholesterol levels are protective. Avoiding trans fats and replacing saturated fats in adult diets with polyunsaturated fats are recommended dietary measures to reduce total blood cholesterol and LDL in adults. In people with very high cholesterol (e.g., familial hypercholesterolemia), diet is often not sufficient to achieve the desired lowering of LDL, and lipid-lowering medications are usually required. If necessary, other treatments such as LDL apheresis or even surgery (for particularly severe subtypes of familial hypercholesterolemia) are performed. About 34 million adults in the United States have high blood cholesterol.
Signs and symptoms
Although hypercholesterolemia itself is asymptomatic, longstanding elevation of serum cholesterol can lead to atherosclerosis (build-up of fatty plaques in the arteries, so-called 'hardening of the arteries'). Over decades, elevated serum cholesterol contributes to the formation of atheromatous plaques in the arteries. This can lead to progressive narrowing of the involved arteries. Alternatively, smaller plaques may rupture and cause a clot to form and obstruct blood flow. A sudden blockage of a coronary artery may result in a heart attack. A blockage of an artery supplying the brain can cause a stroke. If the development of the stenosis or occlusion is gradual, the blood supply to the tissues and organs slowly diminishes until organ function becomes impaired. At this point 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, difficulty speaking, weakness or numbness or tingling, usually on one side of the body. Insufficient blood supply to the heart may cause 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.
Causes
Hypercholesterolemia is typically due to a combination of environmental and genetic factors. Environmental factors include weight, diet, and stress. Loneliness is also a risk factor.
Diet Diet affects blood cholesterol, but the size of this effect varies between individuals. A diet high in sugar or saturated fats increases total cholesterol and LDL. Trans fats have been shown to reduce levels of high-density lipoprotein while increasing levels of LDL. A 2016 review found tentative evidence that dietary cholesterol is associated with higher blood cholesterol. As of 2018 there appears to be a modest positive, dose-related relationship between cholesterol intake and LDL cholesterol.
Medical conditions and treatments A number of other conditions can also increase cholesterol levels including diabetes mellitus type 2, obesity, alcohol use, monoclonal gammopathy, dialysis therapy, nephrotic syndrome, hypothyroidism, Cushing's syndrome and anorexia nervosa. Several medications and classes of medications may interfere with lipid metabolism: thiazide diuretics, ciclosporin, glucocorticoids, beta blockers, retinoic acid, antipsychotics, certain anticonvulsants and medications for HIV as well as interferons.
Genetics Genetic contributions typically arise from the combined effects of multiple genes, known as "polygenic", although in certain cases, they may stem from a single gene defect, as seen in familial hypercholesterolemia. In familial hypercholesterolemia, mutations may be present in the APOB gene (autosomal dominant), the autosomal recessive LDLRAP1 gene, autosomal dominant familial hypercholesterolemia (HCHOLA3) variant of the PCSK9 gene, or the LDL receptor gene. Familial hypercholesterolemia affects about one in 250 individuals. The Lithuanian Jewish population may exhibit a genetic founder effect. One variation, G197del LDLR which is implicated in familial hypercholesterolemia, has been dated to the 14th century. The utility of these variations has been the subject of debate.
Diagnosis
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