High Cholesterol (Dyslipidemia)

Cholesterol is not a single number. The clinically useful measures are LDL cholesterol, non-HDL cholesterol and apolipoprotein B, which counts the atherogenic particles directly and is increasingly preferred where available. Total cholesterol on its own is a poor guide because it lumps in HDL, and high HDL does not offset high LDL the way once assumed. The relationship between LDL and atherosclerotic cardiovascular disease is one of the more firmly established in medicine, supported by randomized trials, Mendelian randomization and dose-response consistency across drug classes. Lower is better, and lifetime exposure matters as much as the current reading. Targets are set by absolute risk rather than by a universal cut-off. Someone with established cardiovascular disease or diabetes is treated to a much lower LDL than a low-risk 35-year-old with the same reading. Lipoprotein(a), largely genetically determined, should be measured at least once because it modifies risk substantially and is invisible on a standard panel. Diet works, within limits. Replacing saturated with unsaturated fat, adding 5-10 g of soluble fibre daily, and including 2 g of plant sterols can together lower LDL by 10-15%. Weight loss and activity help. Statins lower LDL by 30-50% and reduce events, which is why they remain first-line for anyone at meaningful risk. Omega-3 is frequently misunderstood here. It lowers triglycerides in a dose-dependent way — 20-30% at 4 g daily — and has essentially no LDL-lowering effect. At high doses EPA may even raise LDL slightly. It is a triglyceride agent, not a cholesterol agent.

• •No symptoms in the overwhelming majority of cases
• •Xanthelasma — yellow deposits around the eyelids
• •Tendon xanthomas, suggesting familial hypercholesterolaemia
• •Corneal arcus before age 45
• •Symptoms appear only once atherosclerotic disease develops — angina, claudication, stroke

• •Diet high in saturated and trans fat
• •Excess body weight, particularly central adiposity
• •Physical inactivity
• •Familial hypercholesterolaemia
• •Type 2 diabetes and insulin resistance
• •Hypothyroidism
• •Chronic kidney disease
• •Excess alcohol, chiefly raising triglycerides
• •Certain medications including thiazides, corticosteroids and some antiretrovirals
• •Smoking, which lowers HDL and oxidises LDL

LDL particles carrying apolipoprotein B enter the arterial intima, become oxidised and are taken up by macrophages, forming foam cells and eventually plaque. The rate of entry is driven by particle number, which is why apoB is a better predictor than cholesterol mass. Hepatic LDL receptor activity governs clearance from the circulation — the mechanism statins exploit, and the mechanism disabled in familial hypercholesterolaemia.