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Circulation. 2019;139:e1082–e1143. DOI: 10.1161/CIR.0000000000000625 June 18/25, 2019 e1099 CLINICAL STATEMENTS AND GUIDELINES

5.	 According to a CTT analysis,S4.3-12 the higher the 10-year ASCVD risk, the greater is the benefit from increased LDL-C reduction. This is supported by the meta-analyses comparing highintensity versus -low-intensity statin therapyS4.3-12 and those comparing the benefit of statins and nonstatin therapeutic agents (ie, ezetimibe, bile sequestrants, PCSK9 antagonists) that upregulate LDL receptors.S4.3-27 Therefore, a risk discussion may be held on the benefits of achieving ≥50% LDL-C lowering in adults with diabetes mellitus who have ≥20% ASCVD risk. Addition of ezetimibe 10 mg/d to moderate-intensity statin therapy can achieve the same percent LDL-C lowering as that achieved with high-intensity statin therapy.S4.3-14 In this RCT, 27% of patients had diabetes mellitus.S4.3-28 Thus, ezetimibe added to a moderate-intensity statin can be considered if a high-intensity statin cannot be tolerated or does not lower LDL-C, as expected, by ≥50%. 6.	 Although the risk of ASCVD is high in adults >75 years of age with diabetes mellitusS4.3-5,S4.3-6,S4.3-8 who are not receiving statin therapy, particularly those with additional risk factors or risk modifiers, the benefit of initiating statin therapy in these individuals may be limited by their reduced life span or increased susceptibility to adverse effects of treatment. Among this group will also be individuals with recent or newly diagnosed diabetes mellitus for whom the impact of diabetes mellitus on ASCVD risk is not well known. It may therefore be reasonable to have a clinician–patient discussion in which the potential benefits and risks of initiating statin therapy in this age group are reviewed. 7.	 There is limited information on ASCVD rates among individuals 20 to 39 years of age with diabetes mellitus and no information on whether statin therapy is beneficial in these individuals. Available evidence indicates that although rates of ASCVD are low in those <30 years of age, they increase with timeS4.3-6,S4.3-17,S4.3-20,S4.3-23 and may reach intermediate-risk levels by 30 to 39 years of age, especially in individuals with longstanding type 2 diabetes mellitus,S4.3-17 who may have more advanced subclinical coronary atherosclerosis than do nondiabetic subjects,S4.3-21 and in those with type 1 diabetes mellitus of >20 years’ duration.S4.3-23 ASCVD rates will also be influenced by hypertension and diabetic microvascular complications that may be prevalent in these age groups.S4.3-18,S4.3-23 Thus, it may be reasonable to have a discussion about initiating moderateintensity statin therapy with patients who have had type 2 diabetes mellitus for at least 10 years or type 1 diabetes mellitus for at least 20 years and with patients with 1 or more major CVD risk factors or complications, such as diabetic retinopathy,S4.3-19 neuropathy,S4.3-16 nephropathy (eGFR <60 mL/min/1.73 m2 or albuminuria ≥30 mcg albumin/mg creatinine),S4.3-25 or an ABI of <0.9S4.3-22,S4.3-24 (Table 5).

4.4 Primary Prevention

Primary prevention of ASCVD over the life span requires attention to prevention or management of ASCVD risk factors beginning early in life (Figure 2). One major AS- CVD risk factor is elevated serum cholesterol, usually identified clinically as measured LDL-C. Screening can be performed with fasting or nonfasting measurement of lipids. In children, adolescents (10 to 19 years of age), and young adults (20 to 39 years of age), priority should be given to estimation of lifetime risk and promotion of lifestyle risk reduction. Drug therapy is needed only in selected patients with moderately high LDL-C levels (≥160 mg/dL [≥4.1 mmol/L]) or patients with very high LDL-C levels (190 mg/dL [4.9 mmol/L]). Three major higher-risk categories are patients with severe hypercholesterolemia (LDL-C levels ≥190 mg/dL [≥4.9 mmol/L]), adults with diabetes mellitus, and adults 40 to 75 years of age. Patients with severe hypercholesterolemia and adults 40 to 75 years of age with diabetes mellitus are candidates for immediate statin therapy without further risk assessment. Adults with diabetes mellitus should start with a moderate-intensity statin, and as they accrue multiple risk factors, a high-intensity statin may be indicated. In other adults 40 to 75 years of age, 10-year ASCVD risk should guide therapeutic considerations. The higher the estimated ASCVD risk, the more likely the patient is to benefit from evidence-based statin treatment. The risk discussion should also consider several “risk enhancers” that can be used to favor initiation or intensification of statin therapy. When risk is uncertain or if statin therapy is problematic, it can be helpful to measure CAC to refine risk assessment. A CAC score predicts ASCVD events in a graded fashion and is independent of other risk factors, such as age, sex, and ethnicity.S4.4-1 A CAC score equal to zero is useful for reclassifying patients to a lower-risk group, often allowing statin therapy to be withheld or postponed unless higher risk conditions are present. For patients >75 years of age, RCT evidence for statin therapy is not strong, so clinical assessment of risk status in a clinician–patient risk discussion is needed for deciding whether to continue or initiate statin treatment.S4.4-2–S4.4-21

4.4.1 Evaluation and Risk Assessment

4.4.1.1. Essential Process of Risk Assessment Children and adolescents should be tested for lipid disorders as described in Section 4.4.4.3. Risk assessment in young adults 20 to 39 years of age is discussed in

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