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September 10, 2019 Circulation. 2019;140:e596–e646. DOI: 10.1161/CIR.0000000000000678 e604

CLINICAL STATEMENTS AND GUIDELINES Arnett et al 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease

captured in current risk scoring models. Patients with familial hypercholesterolemia are at significant risk of having an early ASCVD event, and the use of risk calculators is not applicable to these patients. In contrast, other studies have found overestimation of risk with the PCE, particularly among those with higher socioeconomic position and those with continual access to care and preventive services, which could lead to overtreatment of individuals less likely to receive net benefit from preventive pharmacotherapies over the next decade.S2.2-15,S2.2-39–S2.2-47 The PCE may be suboptimally calibrated in more modern populations as compared with the older cohorts from which they were derived.S2.2-68 Therefore, among adults at borderline (5% to <7.5%) and intermediate (≥7.5% to <20%) risk, one may consider additional individual risk-enhancing clinical factors (Table 3) that can be used to revise the 10-year ASCVD risk estimate.S2.2-4 These factors may include having a family history of premature ASCVD,S2.2-5 chronic inflammatory disease [rheumatoid arthritis,S2.2-6 lupus,S2.2-7 or HIV infectionS2.2-12], South Asian ancestry,S2.2-13 a history of preeclampsiaS2.2-8 or preterm delivery,S2.2-9 early menopause,S2.2-10 erectile dysfunction,S2.2-11 chronic kidney disease (CKD), metabolic syndrome, persistently elevated inflammatory markers,S2.2-14 or elevated lipid biomarkers.S2.2-4 After these clinically available risk-enhancing factors have been considered, if there is still uncertainty about the reliability of the risk estimate for individuals in the borderline- or intermediate-risk categories, further testing to document subclinical coronary atherosclerosis is reasonable to more accurately reclassify the risk estimate upward or downward.S2.2-17–S2.2-19,S2.2-69

4 For individuals with intermediate predicted risk

(≥7.5% to <20%) by the PCE or for select adults with borderline (5% to <7.5%) predicted risk, coronary artery calcium measurement can be a useful tool in refining risk assessment for preventive interventions (eg, statin therapy).S2.2-4 In these groups, coronary artery calcium measurement can reclassify risk upward (particularly if coronary artery calcium score is ≥100 Agatston units (AU) or ≥75th age/sex/race percentile) or downward (if coronary artery calcium is zero) in a significant proportion of individuals.S2.2-15 The extent of reclassification is sufficient to provide confidence that borderline- or intermediate-risk patients with elevated coronary artery calcium will have event rates that clearly exceed benefit thresholds (ie, ≥7.5% in 10 years) and those with coronary artery calcium scores of zero will have event rates <7.5%, which can help guide shared decisionmaking about statinsS2.2-15,S2.2-16,S2.2-21 or potentially even aspirin.S2.2-70 In observational data, the presence and severity of coronary artery calcium have

Table 3.  Risk-Enhancing Factors for Clinician–Patient Risk Discussion

Risk-Enhancing Factors Family history of premature ASCVD (males, age <55 y; females, age <65 y) Primary hypercholesterolemia (LDL-C, 160–189 mg/dL [4.1–4.8 mmol/L]; non–HDL-C 190–219 mg/dL [4.9–5.6 mmol/L])* Metabolic syndrome (increased waist circumference [by ethnically appropriate cutpoints], elevated triglycerides [>150 mg/dL, nonfasting], elevated blood

pressure, elevated glucose, and low HDL-C [<40 mg/dL in men; <50 mg/dL in women] are factors; a tally of 3 makes the diagnosis) Chronic kidney disease (eGFR 15–59 mL/min/1.73 m2 with or without albuminuria; not treated with dialysis or kidney transplantation) Chronic inflammatory conditions, such as psoriasis, RA, lupus, or HIV/AIDS History of premature menopause (before age 40 y) and history of pregnancy-associated conditions that increase later ASCVD risk, such as preeclampsia High-risk race/ethnicity (eg, South Asian ancestry) Lipids/biomarkers: associated with increased ASCVD risk Persistently elevated* primary hypertriglyceridemia (≥175 mg/dL, nonfasting) If measured: Elevated high-sensitivity C-reactive protein (≥2.0 mg/L) Elevated Lp(a): A relative indication for its measurement is family history of premature ASCVD. An Lp(a) ≥50 mg/dL or ≥125 nmol/L constitutes a risk-

enhancing factor, especially at higher levels of Lp(a). Elevated apoB (≥130 mg/dL): A relative indication for its measurement would be triglyceride ≥200 mg/dL. A level ≥130 mg/dL corresponds to an LDL-C

>160 mg/dL and constitutes a risk-enhancing factor ABI (<0.9) *Optimally, 3 determinations. ABI indicates ankle-brachial index; AIDS, acquired immunodeficiency syndrome; apoB, apolipoprotein B; ASCVD, atherosclerotic cardiovascular disease; eGFR, estimated glomerular filtration rate; HDL-C, high-density lipoprotein cholesterol; HIV, human immunodeficiency virus; LDL-C, low-density lipoprotein cholesterol; Lp(a), lipoprotein (a); and RA, rheumatoid arthritis.

Reproduced with permission from Grundy et al.S2.2-4 Copyright © 2018, American Heart Association, Inc., and American College of Cardiology Foundation.

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