Hypercholesterolemia

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Basics

Description

  • Elevated cholesterol is considered a significant risk factor for atherosclerotic cardiovascular disease (ASCVD), although the relationship is not simple.
  • Lipoprotein subtypes:
    • Low-density lipoproteins (LDL): atherogenic; primary target of therapy
    • High-density lipoproteins (HDL): atheroprotective
    • Triglycerides (TG)
  • System(s) affected: cardiovascular (CV)

Epidemiology

  • 28% of U.S. adults >20 years old have total cholesterol levels >200 mg/dL.
  • 7% of U.S. children and adolescents between the ages of 6 and 19 years have high total cholesterol.

Prevalence
Disease incidence and prevalence increases with age.

Etiology and Pathophysiology

  • Pathophysiology
    • Deposition of cholesterol in vascular walls creates fatty streaks that become fibrous plaques.
    • Inflammation causes plaque instability, leading to plaque rupture.
    • Atherosclerosis, inflammation, and vascular reactivity are complex processes not explained by cholesterol alone.
  • Etiology of hypercholesterolemia
    • Primary: genetic causes (familial dyslipidemia)
    • Secondary: obesity, diet, excessive alcohol intake, hypothyroidism, diabetes, inflammatory disease (systemic lupus erythematosus, juvenile rheumatoid arthritis), liver disease, nephrotic syndrome, chronic renal failure, medications (thiazide diuretics, carbamazepine, cyclosporine, progestins, anabolic steroids, corticosteroids, protease inhibitors, antipsychotics, isotretinoin)

Genetics
  • Familial hypercholesterolemia (FH)
    • Elevated LDL levels from birth
    • Prevalence is 1:300 worldwide for heterozygous FH.
    • Predisposition to atherosclerotic disease in early adulthood and high coronary heart disease risk at younger ages (early middle ages for heterozygous carriers). Individuals with homozygous FH typically die before 20 years old.
    • 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

(For dyslipidemia) obesity (body mass index [BMI] >30 kg/m2), physical inactivity, heredity, cigarette smoking, excessive alcohol use. The relationship between dietary saturated fat and hypercholesterolemia and coronary artery disease is complex. Similarly, dietary cholesterol intake is only one factor potentially contributing to dyslipidemia.

General Prevention

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

Commonly Associated Conditions

Hypertension, diabetes mellitus (DM), obesity

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Basics

Description

  • Elevated cholesterol is considered a significant risk factor for atherosclerotic cardiovascular disease (ASCVD), although the relationship is not simple.
  • Lipoprotein subtypes:
    • Low-density lipoproteins (LDL): atherogenic; primary target of therapy
    • High-density lipoproteins (HDL): atheroprotective
    • Triglycerides (TG)
  • System(s) affected: cardiovascular (CV)

Epidemiology

  • 28% of U.S. adults >20 years old have total cholesterol levels >200 mg/dL.
  • 7% of U.S. children and adolescents between the ages of 6 and 19 years have high total cholesterol.

Prevalence
Disease incidence and prevalence increases with age.

Etiology and Pathophysiology

  • Pathophysiology
    • Deposition of cholesterol in vascular walls creates fatty streaks that become fibrous plaques.
    • Inflammation causes plaque instability, leading to plaque rupture.
    • Atherosclerosis, inflammation, and vascular reactivity are complex processes not explained by cholesterol alone.
  • Etiology of hypercholesterolemia
    • Primary: genetic causes (familial dyslipidemia)
    • Secondary: obesity, diet, excessive alcohol intake, hypothyroidism, diabetes, inflammatory disease (systemic lupus erythematosus, juvenile rheumatoid arthritis), liver disease, nephrotic syndrome, chronic renal failure, medications (thiazide diuretics, carbamazepine, cyclosporine, progestins, anabolic steroids, corticosteroids, protease inhibitors, antipsychotics, isotretinoin)

Genetics
  • Familial hypercholesterolemia (FH)
    • Elevated LDL levels from birth
    • Prevalence is 1:300 worldwide for heterozygous FH.
    • Predisposition to atherosclerotic disease in early adulthood and high coronary heart disease risk at younger ages (early middle ages for heterozygous carriers). Individuals with homozygous FH typically die before 20 years old.
    • 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

(For dyslipidemia) obesity (body mass index [BMI] >30 kg/m2), physical inactivity, heredity, cigarette smoking, excessive alcohol use. The relationship between dietary saturated fat and hypercholesterolemia and coronary artery disease is complex. Similarly, dietary cholesterol intake is only one factor potentially contributing to dyslipidemia.

General Prevention

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

Commonly Associated Conditions

Hypertension, diabetes mellitus (DM), obesity

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