Clinical meaning
Hyperlipidemia is the elevation of serum lipids (cholesterol and/or triglycerides) that accelerates atherosclerosis, the pathological process underlying cardiovascular disease. Lipoproteins transport lipids through the bloodstream: chylomicrons (transport dietary triglycerides from gut), VLDL (transport hepatic triglycerides), LDL (primary atherogenic particle — delivers cholesterol to peripheral tissues), and HDL (reverse cholesterol transport — removes cholesterol from peripheral tissues to the liver for excretion). Atherosclerosis begins with endothelial dysfunction from risk factors (HTN, smoking, diabetes, dyslipidemia). LDL particles penetrate the damaged endothelium and become oxidized. Oxidized LDL triggers inflammatory cascade: monocytes migrate into the intima, differentiate into macrophages, and engulf oxidized LDL via scavenger receptors (unregulated — no negative feedback), becoming lipid-laden foam cells. Foam cell accumulation forms the fatty streak (earliest lesion). Continued inflammation and smooth muscle cell migration form a fibrous cap over a necrotic lipid core (atherosclerotic plaque). Unstable plaques (thin fibrous cap, large lipid core, inflammatory cell infiltration) are prone to rupture, exposing thrombogenic contents to the bloodstream and triggering acute thrombosis → myocardial infarction or ischemic stroke. Statins reduce LDL by inhibiting HMG-CoA reductase (rate-limiting enzyme in hepatic cholesterol synthesis), upregulating hepatic LDL receptors, and providing pleiotropic anti-inflammatory and plaque-stabilizing effects. Familial hypercholesterolemia (FH) is an autosomal dominant LDL receptor mutation causing markedly elevated LDL (heterozygous: 190-400; homozygous: >400-1000) with premature ASCVD.