Cardiovascular risk stratification (ESC/EAS 2019, SCORE2/SCORE2-OP): 1) Very high risk - established ASCVD, DM with target organ damage, severe CKD (eGFR <30), familial hypercholesterolemia with ASCVD or another major risk factor, SCORE2 ≥7.5%; 2) High risk - DM ≥10 yr without TOD, severe HT, FH without other risks, SCORE2 5-<7.5%; 3) Moderate - DM <10 yr without other risks, SCORE2 2.5-<5%; 4) Low - SCORE2 <2.5%. LDL-C targets correspond to category. ApoB targets - very high <65, high <80, moderate <100 mg/dL.
Diagnostic workup: fasting (or non-fasting, 2018 AHA/ACC) lipid panel - TC, LDL-C (calculated by Friedewald if TG <400; direct LDL if TG higher), HDL-C, TG, non-HDL-C. Secondary causes screen - TSH (hypothyroidism), HbA1c, BUN/Cr/UA (CKD, nephrotic), liver enzymes, alcohol history, drugs (steroids, retinoids, antipsychotics). Lipid panel after 4-12 weeks of statin to assess response. Familial hypercholesterolemia - clinical (DLCN), genetic (LDLR, APOB, PCSK9). Lp(a) once in lifetime if ASCVD or family history. CAC score in moderate-risk for treatment decisions.
Treatment algorithm: Step 1) High-intensity statin (rosuvastatin 20-40 mg, atorvastatin 40-80 mg) - achieves 50% LDL-C reduction; moderate-intensity (rosuvastatin 5-10, atorvastatin 10-20, simvastatin 20-40, pravastatin 40-80, pitavastatin 1-4) - 30-50%; Step 2) If LDL-C target unmet, add ezetimibe 10 mg (additional 15-25%); Step 3) PCSK9 inhibitor (alirocumab 75-150 mg q2w, evolocumab 140 mg q2w, inclisiran 284 mg q6mo subcutaneous) - 50-60% reduction; Step 4) Bempedoic acid in statin intolerance (CLEAR Outcomes); Step 5) Lifestyle - Mediterranean diet, plant sterols, fiber, weight loss, exercise. Hypertriglyceridemia - omega-3 (icosapent ethyl, REDUCE-IT in high-risk), fenofibrate (especially TG >500 to prevent pancreatitis).