Hypercholesterolemia

Hypercholesterolemia is a topic covered in the 5-Minute Clinical Consult.

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Basics

Description

  • Elevated cholesterol is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD).
  • Lipoprotein subtypes:
    • Low-density lipoproteins (LDL): atherogenic; primary target of therapy
    • High-density lipoproteins (HDL): atheroprotective
    • Triglycerides (TG)
  • System(s) affected: cardiovascular (CV)

Epidemiology

  • Nearly 37% of U.S. adults have LDL cholesterol levels above treatment thresholds (1).
  • Only 55% of U.S. adults who warrant cholesterol medication are currently taking it (1).
  • 7% of U.S. children and adolescents ages 6 to 19 years have high total cholesterol (1).

Prevalence
Disease incidence and prevalence increases with age.

Etiology and Pathophysiology

  • Pathophysiology
    • Deposition of cholesterol in vascular walls creates fatty streaks which become fibrous plaques.
    • Inflammation causes plaque instability, leading to plaque rupture.
  • Etiology
    • Primary: genetic causes (familial dyslipidemia)
    • Secondary: obesity, diet, excessive alcohol intake, hypothyroidism, diabetes, nephrotic syndrome, liver disease, chronic renal failure, medications (thiazide diuretics, carbamazepine, cyclosporine, progestins, anabolic steroids, corticosteroids, protease inhibitors)

Genetics
  • Familial hypercholesterolemia (FH)
    • Elevated LDL levels from birth
    • Prevalence is 1:500 in the United States.
    • Predisposition to atherosclerotic disease in early adulthood and high coronary heart disease risk at younger ages (40s and 50s)
    • Tendon xanthomas on Achilles and extensor tendons of the hands are common.
    • Early lipid-lowering drug therapy has been shown to reduce ASCVD risk.
  • Early cholesterol testing of first-degree relatives is recommended and beneficial.

Risk Factors

Obesity (BMI >30 kg/m2), physical inactivity, heredity, cigarette smoking, excessive alcohol use. Unclear relationship between diet rich in saturated fat and hypercholesterolemia. The relationship of diet to disease is very complex and is not explained by how much cholesterol is present in an individual’s diet. Eggs and whole fat dairy sources are likely not significant contributors to atherosclerosis.

General Prevention

  • Regular physical activity
  • Weight control (see “Ongoing Care”)

Commonly Associated Conditions

Hypertension (HTN), diabetes mellitus (DM), obesity

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