In patients with LDL-C levels 190 mg/dL ( 4.9 mmol/L), advancing age is associated with pro- gressively increasing ASCVD risk,S4.2-4 and age- related risk would likely apply to those with heterozygous FH because of their higher lifetime exposure to increased LDL-C concentration.S4.2-18 A long-term prospective cohort registry study of CLINICAL STATEMENTS AND GUIDELINES 2404 patients with heterozygous FH (molecularly defined) taking contemporary statin with or with- out ezetimibe treatment regimens identified age >30 years, male sex, history of ASCVD, high blood pressure, increased waist circumference, active smoking, Lp(a) 50 mg/dL, and LDL-C levels 100 mg/dL ( 2.6 mmol/L) as independent predictors of incident ASCVD over a 5.5-year follow-up Because other medical interventions that lower LDL-C levels via increased expression of LDL receptors reduce ASCVD risk,S4.2-9 the use of PCSK9 inhibitors in selected maximally treated patients with heterozygous FH with persistently elevated LDL-C levels may be considered after a clinician patient discussion of the net benefits versus the cost of such therapy. 5. Regardless of whether a patient with LDL-C lev- els 190 mg/dL ( 4.9 mmol/L) is found to have a genetic mutation associated with FH, those with very high LDL-C values are most likely to achieve the greatest benefit from evidence-based LDL-C lowering therapy. Consequently, patients who have a baseline LDL-C level 220 mg/dL ( 5.7 mmol/L) and an on-treatment LDL-C level 130 mg/dL ( 3.4 mmol/L) despite maximally tolerated statin and ezetimibe therapy may be considered for treatment with a PCSK9 inhibitor after a clini- cian patient discussion of the net benefits versus the costs of such therapy. 6. 