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