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 (TGs)
• System(s) affected: cardiovascular (CV)

Epidemiology

According to the CDC between 2017 and 2020, 10% of U.S. adults aged >20 years old have hypercholesterolemia, and 7% of U.S. children and adolescents between the ages of 6 and 19 years have hypercholesterolemia.

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 have a multifactorial etiology.
• Etiology of hypercholesterolemia
  • Primary: genetic causes (familial dyslipidemia)
  • Secondary: obesity, diet, excessive alcohol intake, hypothyroidism, diabetes mellitus (DM), inflammatory disease, 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; individuals with homozygous FH typically die before 20 years old.
  • Early lipid-lowering drug therapy has been shown to reduce ASCVD risk.
• Early lipid screening of first-degree relatives is recommended.

Risk Factors

Obesity, physical inactivity, family history, cigarette smoking, excessive alcohol use; the relationship between dietary saturated fat and hypercholesterolemia and coronary artery disease is complex.

General Prevention

Regular physical activity, weight control (see “Ongoing Care”), diet lower in saturated fats (grade 1B)

Commonly Associated Conditions

Hypertension, DM, obesity