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BASICS

Description

  • Elevated cholesterol is a major risk factor for atherosclerotic cardiovascular disease (ASCVD).
  • Lipoproteins:
  • LDL: atherogenic; primary treatment target.
  • HDL: atheroprotective.
  • Triglycerides (TGs).

Epidemiology

  • CDC (2017–2020): 10% of U.S. adults >20 years have hypercholesterolemia.
  • 7% of U.S. children/adolescents (6–19 years) affected.
  • Prevalence increases with age.

ETIOLOGY AND PATHOPHYSIOLOGY

  • Cholesterol deposits in vascular walls cause fatty streaks → fibrous plaques.
  • Plaque rupture from inflammation leads to ASCVD.
  • Multifactorial causes include genetics, obesity, diet, alcohol, hypothyroidism, DM, liver and kidney disease, medications (e.g., thiazides, steroids).

Genetics

  • Familial hypercholesterolemia (FH):
  • Elevated LDL from birth.
  • Prevalence: 1:300 heterozygous globally.
  • Early onset ASCVD risk; homozygous cases fatal before 20 years.
  • Early lipid-lowering therapy reduces risk.
  • Screen first-degree relatives early.

RISK FACTORS

  • Obesity, inactivity, family history, smoking, excessive alcohol.
  • Complex link between saturated fat intake and coronary artery disease.

GENERAL PREVENTION

  • Regular physical activity.
  • Weight control.
  • Diet lower in saturated fats (grade 1B evidence).

COMMONLY ASSOCIATED CONDITIONS

  • Hypertension, diabetes mellitus, obesity.

DIAGNOSIS

Screening Recommendations

  • USPSTF: lipid screening (total cholesterol, HDL-C) for men and women ≥40 years [A].
  • ADA: yearly dyslipidemia screening in diabetes.
  • Pediatric (NHLBI): universal lipid screening ages 9–11 and 17–21 endorsed by AAP.

History

  • Assess for secondary causes and ASCVD risk factors.

Physical Exam

  • Look for xanthomas; calculate BMI.

Diagnostic Tests

  • Lipid panel (nonfasting preferred).
  • LDL usually calculated; fasting needed if TG >440 mg/dL.
  • Genetic evaluation if LDL >190 mg/dL or TG >500 mg/dL.
  • AHA recommends GLP1-RA for ASCVD risk reduction regardless of DM status.

TREATMENT

Guidelines Overview

  • ACC/AHA guidelines target LDL levels with statins, especially for secondary prevention.
  • Four statin benefit groups:
  • LDL ≥190 mg/dL: high-intensity statin.
  • Diabetes aged 40–75 with LDL ≥70 mg/dL: moderate-intensity statin.
  • ASCVD risk ≥5-7.5%: moderate-intensity statin.
  • ASCVD risk ≥7.5-20%: moderate-intensity statin with 30–49% LDL reduction goal.
  • ASCVD risk ≥20%: high-intensity statin aiming >50% LDL reduction.
  • Secondary prevention:
  • Age ≤75: high-intensity statin; add ezetimibe if LDL ≥70 mg/dL post-max statin.
  • Age >75: moderate or high intensity as tolerated.

USPSTF 2022 Recommendations

  • Adults 40–75 with ≥10% 10-year CVD risk: low/moderate intensity statin (grade B).
  • Adults 40–75 with 7.5–10% risk: low/moderate statin (grade C).
  • Insufficient evidence for statins in adults >75 without CVD.

Hypertriglyceridemia

  • TG >500 mg/dL: focus on lowering TG to prevent pancreatitis.
  • Statins first line unless TG remains >500.
  • Fibrates used cautiously with statins.

MEDICATIONS

First-Line

  • Statins (HMG-CoA reductase inhibitors):
  • High intensity (LDL ↓ >50%): atorvastatin 40–80 mg, rosuvastatin 20–40 mg.
  • Moderate intensity (LDL ↓30–49%): atorvastatin 10–20 mg, rosuvastatin 5–10 mg, simvastatin, pravastatin, others.
  • Low intensity (LDL ↓ <30%): simvastatin 10 mg, pravastatin 10–20 mg, others.
  • Contraindications: pregnancy, lactation, active liver disease.
  • Adverse effects: myalgia, ALT elevation, slight increase in diabetes risk.
  • Avoid simvastatin 80 mg/day; dose restrictions with interacting drugs.
  • Avoid grapefruit juice.

Second-Line

  • Ezetimibe: monotherapy or combined with statin; modest LDL reduction.
  • Fibrates: best for TG lowering; no clear mortality benefit.
  • Niacin: raises HDL, no proven outcome benefit.
  • PCSK9 inhibitors (alirocumab, evolocumab): reduce CV events, costly.
  • Icosapent ethyl: adjunct for hypertriglyceridemia and CV risk.
  • Bempedoic acid: alternative if PCSK9 inhibitors cost-prohibitive.
  • Inclisiran: longer-acting LDL-lowering injection.

Additional

  • Antithrombotic therapy for diabetes with CVD risk factors.

COMPLEMENTARY & ALTERNATIVE MEDICINE

  • Omega-3 fatty acids (fish oil, flaxseed, nuts): reduce TG and LDL, raise HDL.
  • Overall cardiovascular benefit remains uncertain.

ONGOING CARE

  • Encourage moderate exercise (150 minutes/week).
  • No routine liver function monitoring if baseline ALT normal.
  • Diet: Mediterranean or plant-based diet reduces CV risk.

PATIENT EDUCATION

  • Use resources such as:
  • AHA Mediterranean Diet Guide: https://www.heart.org/en/healthy-living/healthy-eating/eat-smart/nutrition-basics/mediterranean-diet
  • American College of Lifestyle Medicine: https://lifestylemedicine.org/project/patient-resources/

PROGNOSIS

  • Risk of myocardial infarction, peripheral artery disease, stroke.
  • Statins reduce coronary heart disease incidence and mortality.

REFERENCES

  1. Mangione CM, Barry MJ, Nickolson WK, et al; US Preventive Services Task Force. Statin use for the primary prevention of cardiovascular disease in adults: USPSTF recommendation statement. JAMA. 2022;328(8):746-753.
  2. Berger JH, Chen F, Faerber JA, et al. Adherence with lipid screening guidelines in standard- and high-risk children and adolescents. Am Heart J. 2021;232:39-46.
  3. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC cholesterol guideline executive summary. J Am Coll Cardiol. 2019;73(24):3168-3209.

Clinical Pearls

  • Initiate statins for primary prevention based on individual ASCVD risk and preferences.
  • Lifestyle modification including Mediterranean diet and exercise is foundational.
  • Familial hypercholesterolemia requires early detection and aggressive treatment.
  • Avoid high-dose simvastatin due to myopathy risk.
  • Monitor adherence and side effects, adjust therapy as needed.