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Original Investigation
July 14, 2021

Assessment of Coronary Artery Calcium Scoring to Guide Statin Therapy Allocation According to Risk-Enhancing Factors: The Multi-Ethnic Study of Atherosclerosis

Author Affiliations
  • 1Pauley Heart Center, Division of Cardiology, Virginia Commonwealth University Medical Center, Richmond
  • 2Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Baltimore, Maryland
  • 3Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
  • 4National Institute for Prevention and Cardiovascular Health, School of Medicine, National University of Ireland Galway, Galway, Ireland
  • 5Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
  • 6Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, Texas
  • 7Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis
  • 8Departments of Medicine and Epidemiology, Columbia University, New York, New York
  • 9Department of Cardiology, Wake Forest Baptist Health, Winston-Salem, North Carolina
  • 10Division of Hematology, University of Vermont, Burlington
  • 11Division of Cardiovascular Prevention and Wellness, Department of Cardiovascular Medicine, Houston Methodist DeBakey Heart and Vascular Center, Houston, Texas
  • 12Center for Cardiovascular, Computational, and Precision Health, Department of Cardiovascular Medicine, Houston Methodist DeBakey Heart and Vascular Center, Houston, Texas
  • 13Division of Health Equity and Disparities Research, Center for Outcomes Research, Houston Methodist Hospital, Houston, Texas
JAMA Cardiol. Published online July 14, 2021. doi:10.1001/jamacardio.2021.2321
Key Points

Question  What is the association between risk-enhancing factors and incident atherosclerotic cardiovascular disease by coronary artery calcium burden among intermediate-risk individuals?

Findings  In this cross-sectional study of a multiethnic sample of 1688 adults with an intermediate risk of atherosclerotic cardiovascular disease, most risk-enhancing factors (individual and combined) had an absolute atherosclerotic cardiovascular disease incidence rate of less than 7.5 events per 1000 person-years in the absence of subclinical atherosclerosis (coronary artery calcium score of 0). The use of coronary artery calcium scoring was associated with significant improvements in the reclassification and discrimination of atherosclerotic cardiovascular events.

Meaning  The study’s findings suggested that, among individuals at intermediate risk with risk-enhancing factors, atherosclerotic cardiovascular event rates were generally lower than the recommended threshold to initiate statin therapy when the coronary artery calcium score was 0; for cases in which additional risk stratification is required or uncertainty exists regarding the utility of statin therapy, coronary artery calcium scoring may be used to further guide the clinician-patient risk discussion.

Abstract

Importance  The 2018 American Heart Association/American College of Cardiology 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 (≥7.5% 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 Measures  Incident 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 Relevance  In 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-enhancing factor assessment to more accurately classify individuals with an intermediate risk of ASCVD who might benefit from statin therapy.

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