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

  • 29% of U.S. adults > 20 years old have total cholesterol levels greater than 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 1:500 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 (body mass index [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.

General Prevention

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

Commonly Associated Conditions

Hypertension (HTN), 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

  • 29% of U.S. adults > 20 years old have total cholesterol levels greater than 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 1:500 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 (body mass index [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.

General Prevention

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

Commonly Associated Conditions

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

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