Updated: 12/21/2019

Hypercholersterolemia / Hyperlipidemia

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Snapshot
  • A 45-year-old woman presents to her primary care physician for a routine visit. She reports feeling very tired over the past few months. She also reports gaining weight over the past year due to physical inactivity and poor dieting habits. She has a 4 pack-year history of smoking. On physical exam, she is overweight but otherwise without any abnormal findings. Given her risk factors, her physician recommends a screening lipid panel as well as thyroid function tests.
Introduction
  • Clinical definition
    • elevated serum levels of cholesterol
      • parameters are total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL)
  • Epidemiology
    • risk factors
      • obesity
      • smoking
      • hypertension
      • family history
      • older age
  • Etiology
    • familial hypercholesterolemia
    • physical inactivity
    • metabolic syndrome
    • diabetes
    • chronic kidney disease
    • hypothyroidism
    • drugs
      • steroids
      • protease inhibitors
  • Pathogenesis
    • hypercholesterolemia results from excess cholesterol from the diet, bile, or intestines
    • triglycerides enter the plasma from the liver (as very low-density lipoproteins, VLDLs) or intestines (as chylomicrons)
      • VLDLs are converted into LDLs
      • cells with LDL receptor then receive cholesterol from LDLs
    • HDL carries extra cholesterol back to the liver to be metabolized
  • Associated conditions
    • diabetes
    • hypertension
    • hypertriglyceridemia
    • atherosclerosis
  • Prognosis
    • associated with ↑ risk of cardiovascular disease
Presentation
  • Symptoms
    • typically asymptomatic
  • Physical exam
    • metabolic syndrome
      • high blood pressure
    • in severe cases, may see
      • xanthomas
        • yellow nodules or plaques, especially on the Achilles tendon or fingers
      • xanthelasma
        • yellow papules and plaques eyelids
      • corneal arcus
        • white opaque ring at the border of the cornea
Studies
  • Labs
    • fasting lipid panel
      • total cholesterol
        • > 200 mg/dL is abnormal
      • LDL cholesterol
        • > 130 mg/dL is abnormal
      • HDL cholesterol
      • triglycerides
    • rule out secondary causes of hyperlipidemia
      • fasting blood glucose
      • hemoglobin A1c
      • thyroid stimulating hormone
      • alkaline phosphatase
      • urinalysis
        • to assess for proteinuria
  • Making the diagnosis
    • based on laboratory studies
Differential
  • Hypothyroidism
    • distinguishing factors
      • abnormal thyroid function tests
      • often presents with other symptoms of hypothyroidism, including weight gain, cold intolerance, and lethargy
Treatment
  • Management approach
    • screening
      • men at 40 years of age
      • women at 50 years of age
      • men and women 20 years of age with risk factors for coronary artery disease (CAD)
      • family history of familial hypercholesterolemia
    • target numbers
      • low-density lipoprotein < 100 mg/dL
        • < 70 mg/dL for those with diabetes
      • high-density lipoprotein  40 mg/dL
      • triglycerides <150 mg/dL
  • Conservative
    • dietary modification
      • indication
        • all patients
      • modalities
        • minimize saturated fats, trans fats, sugars, and red meats
    • increased physical activity
      • indication
        • all patients
  • Medical
    • statins
      • indications
        • hyperlipidemia
        • coronary artery disease
        • stroke
        • > 10% 10-year risk for coronary artery disease
        • lowers mortality
      • side effects
        • liver toxicity
    • ezetimibe
      • indication
        • adjuvant therapy to statins in patients with acute coronary syndrome
    • PCSK9 inhibitors
      • indications
        • hyperlipidemia even with statins at maximum dose
      • drugs
        • alirocumab
        • evolocumab
Complications
  • Heart disease

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