High cholesterol

Lore & Background

Cholesterol is one of three major classes of lipids produced and used by all animal cells to form membranes. It is the precursor of steroid hormones and bile acids. Since cholesterol is insoluble in water, it is transported in blood plasma within lipoproteins, classified by density: VLDL, IDL, LDL, and HDL. Elevated levels of non-HDL cholesterol, particularly LDL, are associated with increased risk of atherosclerosis and coronary heart disease, while higher HDL levels are protective. Hypercholesterolemia itself is asymptomatic, but longstanding elevation can lead to atherosclerosis—the buildup of fatty plaques in arteries. Over decades, this can cause progressive narrowing or sudden rupture of plaques, leading to heart attack or stroke. Specific physical findings may include xanthelasma palpebrarum, arcus senilis, and xanthomata, especially in familial hypercholesterolemia. Causes are typically a combination of environmental and genetic factors. Diet high in sugar or saturated fats increases total cholesterol and LDL; trans fats reduce HDL while increasing LDL.

Reader's Guide

High cholesterol is a major modifiable risk factor for cardiovascular disease, the leading cause of death worldwide. Its significance lies in the well-established link between elevated LDL or non-HDL cholesterol and the development of atherosclerosis, which can lead to heart attacks, strokes, and peripheral artery disease. The condition is common—affecting about 34 million US adults—and often requires lifelong management. Dietary measures, such as avoiding trans fats and replacing saturated fats with polyunsaturated fats, are recommended for adults. However, in people with very high cholesterol, such as those with familial hypercholesterolemia, diet alone is often insufficient, and lipid-lowering medications are usually required. In severe cases, treatments like LDL apheresis or surgery may be performed. Diagnosis relies on blood lipid measurements, with different thresholds used in the US (mg/dL) versus the UK and Europe (mmol/L). There is no absolute cutoff between normal and abnormal; values must be considered alongside other risk factors. Genetic screening is advised when familial hypercholesterolemia is suspected. The legacy of research on high cholesterol has shaped public health guidelines, dietary recommendations, and pharmaceutical development, though debates persist over the relative predictive value of LDL versus non-HDL cholesterol and the role of dietary cholesterol.

Did You Know?

• About 34 million adults in the United States have high blood cholesterol.
• Higher HDL cholesterol levels are protective against atherosclerosis and coronary heart disease.
• The Lithuanian Jewish population may exhibit a genetic founder effect for a familial hypercholesterolemia mutation dated to the 14th century.