Dyslipidemia - classification, etiology, pathogenesis, and clinical manifestations.
Dyslipidemia refers to abnormal levels of lipids in the blood, including cholesterol, triglycerides (TG), and lipoproteins.
Classification
- 1 According to lipid abnormality
- 2 According to cause
Etiology
Primary dyslipidemia (genetic)
- Familial hypercholesterolemia: LDL receptor mutations → high LDL- C.
- Familial combined hyperlipidemia: increased production of VLDL and LDL.
- Familial hypertriglyceridemia: overproduction of VLDL.
- Apolipoprotein defects (e.g., ApoA- I deficiency → low HDL).
Secondary dyslipidemia
- Dietary factors: high saturated fats, trans fats, excess carbohydrates, alcohol.
- Obesity and metabolic syndrome: insulin resistance → increased VLDL production.
- Diabetes mellitus: increased TG and small dense LDL.
- Hypothyroidism: decreased LDL clearance → high cholesterol.
- Nephrotic syndrome: increased hepatic lipoprotein synthesis → high cholesterol and TG.
- Chronic kidney disease.
- Certain medications: steroids, beta-blockers, oral estrogens.
Pathogenesis
Lipoprotein metabolism imbalance
- Overproduction or impaired clearance of VLDL and LDL.
- Reduced HDL levels → decreased reverse cholesterol transport.
- Accumulation of lipids in plasma → deposition in arterial walls.
Atherosclerosis development
- LDL particles enter arterial wall → oxidized LDL taken up by macrophages → foam cells → fatty streaks → atheromatous plaques.
- Leads to narrowing of arteries, plaque rupture, and thrombosis.
Clinical manifestations
Often asymptomatic
- Dyslipidemia is typically silent for years.
Physical signs (severe or genetic forms)
- Xanthomas:
- Tendon xanthomas (Achilles tendon, extensor tendons).
- Tuberous xanthomas (elbows, knees).
- Xanthelasma:
- Cholesterol- rich deposits on eyelids.
- Corneal arcus:
- Grayish-white ring at the edge of cornea (especially in young patients with familial hypercholesterolemia).
Long- term complications
- Atherosclerotic cardiovascular disease:
- Coronary artery disease → angina, myocardial infarction.
- Cerebrovascular disease → stroke.
- Peripheral artery disease → claudication.
- Pancreatitis (in severe hypertriglyceridemia, >1000 mg/ dL).