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Snapshot
  •  A 44-year-old obese Caucasian gentleman presents to his primary care physician for a routine check-up after having some blood work done. He is found to have a total cholesterol level of 430 mg/dL. He complains of calf pain while walking to the grocery store, which only seem to resolve with rest. He states that he has a follow up appointment with his cardiologist because of some "plugged up vessels". Additionally, you notice that he has well demarcated yellow deposits around his eyes. 
Introduction
  • Excess cholesterol/lipids in the blood
    • cholesterol is transported in the blood by lipoproteins
      • VLDL - very low density lipoprotein
      • IDL - intermediate density lipoprotein
      • LDL - low density lipoprotein
      • HDL - high density lipoprotein
  • Causes
    • environmental
      • obesity and dietary choices
      • diabetes mellitus type 2
      • nephrotic syndrome
      • hypothyroid
      • medications
        • thiazides, beta-blockers, glucocorticoids
      • alcohol
      • exogenous testosterone
    • genetics
      • commonly multigenic in nature
      • can have single gene defect - familial hypercholesterolemia
        • autosomal dominant
        • characterized by very high LDL and early cardiovascular disease
        • heterozygotes 1:500
          • cholesterol approximately 300 mg/dL
        • homozygotes (very rare)
          • cholesterol approximately 700+ mg/dL
        • mutations
          • LDLR gene
          • protein encoded for LDL receptor protein
  • Associated conditions
    • atherosclerosis
    • coronary artery disease
Presentation
  • Signs and symptoms
    • atheromas 
      • plaques in blood vessel walls
    • xanthomas
      • accumulation of lipid-laden histiocytes in the skin
      • xanthelasma - on the eyelids
      • tendinous xanthoma - on tendons, especially Achilles
    • corneal arcus 
      • lipid deposit in cornea
    • tissue ischemia (secondary to arterial occlusion)
      • TIA 
      • MI
      • claudication
      • mesenteric ischemia
Evaluation
  • Labs
    • NIH classifies total cholesterol of
      • < 200 mg/dL as desirable
      • 200-239 mg/dL as borderline high
      • > 240 as high 
    • HDL level results of
      • > 60 mg/dL as desirable
      • 40-59 mg/dL as acceptable
      • < 40 mg/dL as low and increasing risk of heart disease
    • LDL level results of 
      • < 100 mg/dL as optimal
      • 100-129 as near optimal
      • 130-159 as borderline high
      • > 160 as high
  • Secondary imaging may be necessary for work up of disease sequelae 
Treatment
  • Conservative
    • lifestyle modifications
      • indications
        • mildly elevated cholesterol
      • modalities
        • smoking cessation
        • decrease EtOH intake
        • increase physical activity
        • maintain healthy weight
      • outcomes
        • dietary modifications can alter cholesterol levels by 15%
  • Pharmacologic
    • statins (HMG-CoA reductase inhibitors)
      • indications
        • moderately elevated cholesterol
        • when lifestyle modifications have failed
      • first-line treatment
        • choose high intensity statin if the patient has the following risk factors
          • clinical atherosclerotic cardiovascular disease (ASCDV)
          • LDL-C > 190
          • diabetes between 45-70 years old
          • > 7.5% risk of ASCVD in next 10 years
        • otherwise choose medium intensity statin
      • outcomes
        • can reduce total cholesterol by ~50% in most people
      • side effects
        • elevated liver enzymes
        • myopathy / myositis / myalgia / rhabdomyolysis
        • diabetes
        • drug-drug interactions
    • fibrates
      • indications
        • accessory to statins in hypercholesterolemia
        • not used in monotherapy
      • side effects
        • mild stomach pain
        • myopathy
        • gallstones 
          • increase cholesterol content of bile
        • AKI
    • nicotinic acid (niacin; vitamin B3)
      • indications
        • helps to increase HDL
        • can also decrease LDL, VLDL, TGs
      • side effects
        • skin flushing
          • treat with aspirin
        • GI symptoms such as dyspepsia
        • hepatic toxicity
        • hyperglycemia
        • hyperuricemia
    • cholestyramine
      • indications
        • hypercholesterolemia
        • it is a bile acid sequestrant 
      • side effects
        • constipation - most frequent
        • gallstones
        • increased plasma TGs
        • drug-drug interactions
Prognosis and Prevention
  • Prognosis varies depending on severity 
  • Screening
    • 2 rounds of universal screening for children
      • 9 - 11 years old - before puberty
      • 17 - 21 years old - after puberty
  • Prevention
    • USPSTF recommends routine screening
      • men > 35 years old
      • women > 45 years old
    • USPSTF recommends screening if there are other risk factors (coronary heart disease)
      • men 20-35
      • women 20-45
 

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