Management of High LDL Cholesterol

Initial Assessment and Risk Stratification

The American College of Cardiology recommends obtaining fasting lipid profile on two separate occasions to confirm LDL-C >200 mg/dL, and rule out secondary causes such as hypothyroidism, nephrotic syndrome, obstructive liver disease, and certain medications 1
The American College of Cardiology suggests screening for familial hypercholesterolemia using clinical criteria, even without family history, as LDL-C >190 mg/dL warrants FH evaluation 1, 2
The American College of Cardiology recommends measuring baseline ALT, AST, creatine kinase, glucose, and creatinine before starting therapy, and evaluating for risk-enhancing factors such as metabolic syndrome, chronic inflammatory conditions, and elevated lipoprotein(a) 1, 3

The American College of Cardiology recommends initiating atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily as first-line therapy, with a target LDL-C reduction of at least 50% and an absolute LDL-C goal <100 mg/dL 1, 4
The American College of Cardiology suggests a fat-modified, heart-healthy diet with <10% of calories from saturated fat, regular physical exercise, weight management if overweight, and smoking cessation if applicable 1, 2

The American College of Cardiology recommends a primary goal of ≥50% reduction from baseline LDL-C, and a secondary goal of absolute LDL-C <100 mg/dL in absence of other major risk factors 1
The American College of Cardiology suggests reassessing fasting lipid profile 4-12 weeks after initiating statin therapy, and monitoring liver enzymes if risk factors for hepatotoxicity are present 1, 3

The American College of Cardiology recommends adding ezetimibe 10 mg daily if LDL-C remains >100 mg/dL or <50% reduction on maximally tolerated statin, with an additional 15-20% LDL-C reduction expected 1, 3, 5
The American College of Cardiology suggests considering PCSK9 inhibitors if ezetimibe is insufficient or not tolerated, with a reduction of LDL-C by 50-60% and proven cardiovascular outcomes benefit 5, 6

The American College of Cardiology recommends referring to a lipid specialist if baseline LDL-C ≥190 mg/dL and unable to achieve goals with statin plus ezetimibe, or if genetic FH is suspected despite negative family history 1, 2, 5
The American College of Cardiology suggests referring all patients with LDL-C >190 mg/dL to a registered dietitian for dietary counseling, with intensive lifestyle intervention critical for long-term success 1, 5