Hyperlipidemia is acknowledged to be a major risk factor for atherosclerosis. Most of the evidence specifically implicates hypercholesterolemia; hypertriglyceridemia plays a less significant role, but its effect may be greater in women than men. The major component of the total serum cholesterol that is associated with increased risk is low-density lipoprotein (LDL) cholesterol. In contrast , there is an inverse relationship between symptomatic atherosclerosis and high-density lipoprotein (HDL) level; thus, the higher the levels of HDL, the lower is the risk of ischemic heart disease. HDL is believed to mobilize cholesterol from developing and existing atheroma and transport it to the liver for excretion in the bile. Thus HDL participates in reverse transport of cholestrol, thereby earning its designation as the good cholesterol. There is thus great interest in dietary, pharmacologic, and behavioral methods of lowering serum LDL and raising serum HDL. Exercise and moderate consumption of ethanol both raise the HDL level whereas obesity and smoking lower it .



The various classes of blood lipids are transported as lipoproteins complexed to specific apoproteins. Apoproteins have many functions, among them activating or inhibiting particular enzymes, facilitating transmembrane transport of certain lipoproteins, and serving as ligands to high affinity cellular receptors that guide the lipoproteing to specific sites of catabolism.

Dyslipoproteinemias result either from genetic mutations that yield defective apolipoproteing or from some other underlying disorder, such as the nephrotic syndrome, alchoholism, hypothyroidsm, or diabetes mellitus. Four types of lipoprotein abnormalities are frequently found in the population ( and one or more are present in many myocardial infarction survivors): (1)increased LDL cholesterol levels, (2) decreased levels of an abnormal lipoprotein Lp

The major evidence implicating hypercholesterolemia in the genesis of atherosclerosis includes the following:

Genetic defects in lipoprotein metabolism causing hyperlipoproteinemia are associated with accelerated atherosclerosis. For example homozygous familia hypercholesterolemia often results in myocardial infarction before age 20 years. Familial hypercholesterolemia is caused by defects in the LDL receptor, leading to inadequate hepatic uptake of LDL and markedly in creasing circulating ldl. In another syndrome increased LDL levels are due to the presence of a genetically variant apoprotein E that fails to bind properly to the LDL receptor. This defect has been traced to a single amino acid substitution in the receptor binding site of the apo E molecule which reduces binding activity to 1 to 2% of normal. Mutations produciing defective apo B-100 cause similar binding , resulting in increased serum LDL. There is also evidence that genetic polymorphisms in apolipoproteins or other protein important to cholesterol metabolism contribut to atherosclerosis susceptibility and progression in the general population. Other genetic or acquired disorders that cause hypercholesterolemia lead to premature and severe atherosclerosis. The major lipids in atheromas are cholesterol and cholesterol esters derived from the plasma. Visit for

The major lipids in atheromas are cholesterol and cholesterol esters devided from the plasma. Many large-scale epidemiologic analyses have demonstrated a significant correlation between the severity of atherosclerosis as judged by the mortality rate from ischemic heart disease and the levels of total plasma cholesterol or LDL the lipoprotein moiety richest in cholesterol. No single level of plasma cholesterol identifies those at risk. The higher the level, the higher the risk, although the risk rises more steeply once a plateau level of approximately 200 mg/dl is exceeded. Atherosclerotic events are uncommon with with total serum cholesterol levels below 150 mg / dl. High cholesterol diets can produce atherosclerotic plaques in experimental animals, including nonhuman primates , that are nearly identical to those observed in human disease.

When levels of serum cholesterol are lowered by diet or drugs , the rate of progression of atherosclerotic disease is slowed, some atherosclerotic plaques regress and the risk of cardiovascular events is reduced. Cholesterol lowering increases overall survival and reduces risk of atherosclerosis related events in patients with established coronary heart disease with elevated or average cholesterol levels as well as in patients with hypercholesterlemia but without overt atherosclerosis related disease.

Transgenic mice difficient in apo E and with other genetic abnormalities of lipid metabolism develop atherosclerosis with cholesterol feeding. Such models also emphasize the combined effects of genes and environmental influences in atherogenesis.

High dietary intake of cholesterol and saturated fats, such as those present in egg yolk, animal, fats, and butter, raises the plasma cholesterol level. Conversely and a diet low in cholesterol and low in the ratio of saturated to polyunsaturated fats lowers plasma cholesterol levels. Paradoxically, persons in Greenland and japan have low rates of ischemic heart disease despite a high dietary fat consumption in the form of fish, possibly owing to the high content of omega-3 fatty acids abundant in fish oils. Such fatty acids have a number of potentially antiatherogenic effects, including lowering of plasma LDL increasing vasodilation, and reducing platelet aggregation.