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. SUMMARY 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 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 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 Prognosis associated with ↑ risk of cardiovascular disease