Guideline on the Management of Blood Cholesterol recommends the use of risk-enhancing factor assessment and the selective use of coronary artery calcium (CAC) scoring to guide the allocation of statin therapy among individuals with an intermediate risk of atherosclerotic cardiovascular disease (ASCVD). OBJECTIVE To examine the association between risk-enhancing factors and incident ASCVD by CAC burden among those at intermediate risk of ASCVD. DESIGN, SETTING, AND PARTICIPANTS The Multi-Ethnic Study of Atherosclerosis is a multicenter population-based prospective cross-sectional study conducted in the US.Baseline data for the present study were collected between July 15, 2000, and July 14, 2002, and follow-up for incident ASCVD events was ascertained through August 20, 2015. Participants were aged 45 to 75 years with no clinical ASCVD or diabetes at baseline, were at intermediate risk of ASCVD (Ն7.5% to <20.0%), and had a low-density lipoprotein cholesterol level of 70 to 189 mg/dL. EXPOSURES Family history of premature ASCVD, premature menopause, metabolic syndrome, chronic kidney disease, lipid and inflammatory biomarkers, and low ankle-brachial index. MAIN OUTCOMES AND MEASURESIncident ASCVD over a median follow-up of 12.0 years. RESULTS A total of 1688 participants (mean [SD] age, 65 [6] years; 976 men [57.8%]). Of those, 648 individuals (38.4%) were White, 562 (33.3%) were Black, 305 (18.1%) were Hispanic, and 173 (10.2%) were Chinese American. A total of 722 participants (42.8%) had a CAC score of 0. Among those with 1 to 2 risk-enhancing factors vs those with 3 or more risk-enhancing factors, the prevalence of a CAC score of 0 was 45.7% vs 40.3%, respectively. Over a median follow-up of 12.0 years (interquartile range [IQR], 11.5-12.6 years), the unadjusted incidence rate of ASCVD among those with a CAC score of 0 was less than 7.5 events per 1000 person-years for all individual risk-enhancing factors (with the exception of ankle-brachial index, for which the incidence rate was 10.4 events per 1000 person-years [95% CI, 1.5-73.5]) and combinations of risk-enhancing factors, including participants with 3 or more risk-enhancing factors. Although the individual and composite addition of risk-enhancing factors to the traditional risk factors was associated with improvement in the area under the receiver operating curve, the use of CAC scoring was associated with the greatest improvement in the C statistic (0.633 vs 0.678) for ASCVD events. For incident ASCVD, the net reclassification improvement for CAC was 0.067. CONCLUSIONS AND RELEVANCEIn this cross-sectional study, among participants with CAC scores of 0, the presence of risk-enhancing factors was generally not associated with an overall ASCVD risk that was higher than the recommended treatment threshold for the initiation of statin therapy. The use of CAC scoring was associated with significant improvements in the reclassification and discrimination of incident ASCVD. The results of this study support the utility of CAC scoring as an adjunct to risk-enhan...

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When initiating statin therapy, attention to risk factors for statin intolerance is strongly recommended. Most patients will tolerate some degree of statin therapy; thus statin re-challenge is advisable. If alternative dosing regimens are not tolerated, non-statin medications are acceptable alternatives. To limit errors in the diagnosis of statin intolerance, improvements in clinician-patient communication about the side effects and benefits of statins should be attempted.

Background The prognostic value of coronary artery calcium (CAC) or carotid intima-media thickness (CIMT) among asymptomatic adults with a family history (FH) of premature coronary heart disease (CHD) is unclear. Methods and Results MESA enrolled 6814 adults without known atherosclerotic cardiovascular disease (ASCVD). Hard ASCVD events were ascertained over a median follow-up of 10.2 years. We estimated adjusted-hazard ratios (HRs) across CAC and CIMT categories using Cox regression, both between and within FH status groups. Improvement in discrimination with CAC or CIMT added to variables from the ASCVD pooled-cohort equation was also evaluated using receiver operator characteristic curve and likelihood ratio analysis. Of 6125 individuals (62 ± 10 years, 47% males) who reported information on FH, 1262 (21%) had a FH of premature CHD. Among these, 104 hard ASCVD events occurred. Crude incidence-rates (per 1,000 person years) for hard ASCVD were 4.4 for CAC=0 (N=574, 46% of the sample), 8.8 for CAC 1–99 (N=368), 14.9 for CAC 100–399 (N=178), and 20.8 for CAC ≥400 (N=142). Relative to CAC=0, adjusted hard ASCVD HRs for each CAC category among persons with a FH were; 1.64 (95% CI, 0.94–2.87), 2.45 (1.31–4.58), and 2.80 (1.44–5.43), respectively. However, there was no increased hazard for hard ASCVD in high versus low CIMT categories. In participants with a FH of premature CHD, CAC improved discrimination of hard ASCVD events (p<0.001). However, CIMT did not discriminate ASCVD (p=0.70). Conclusions Nearly half of individuals reporting FH have zero CAC and may receive less net benefit from aspirin or statin therapy. Among persons with a FH, CAC is a robust marker of absolute and relative risk of ASCVD, whereas CIMT is not.