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Multicenter Study
. 2021 Oct 1;6(10):1161-1170.
doi: 10.1001/jamacardio.2021.2321.

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

Jaideep Patel  1   2 , Vincent A Pallazola  2 , Ramzi Dudum  2 , Philip Greenland  3 , John W McEvoy  2   4 , Roger S Blumenthal  2 , Salim S Virani  5   6 , Michael D Miedema  7 , Steven Shea  8 , Joseph Yeboah  9 , Antonio Abbate  1 , William G Hundley  1 , Amy B Karger  7 , Michael Y Tsai  7 , Vasanth Sathiyakumar  2 , Oluseye Ogunmoroti  2 , Mary Cushman  10 , Nazir Savji  2 , Kiang Liu  3 , Khurram Nasir  2   11   12   13 , Michael J Blaha  2 , Seth S Martin  2 , Mahmoud Al Rifai  2   6
Affiliations
Multicenter Study

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

Jaideep Patel et al. JAMA Cardiol. .

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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Conflict of interest statement

Conflict of Interest Disclosures: Dr Greenland reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Virani reported receiving grants from the US Department of Veterans Affairs, the World Heart Federation, and the Tahir and Jooma Family and serving as a member of the steering committee of the American College of Cardiology outside the submitted work. Dr Shea reported receiving grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Abbate reported receiving grants from Novartis, Olatec Therapeutics, and Serpin Pharma and personal fees from Janssen Pharmaceuticals, Merck & Co, Olatec Therapeutics, and Serpin Pharma outside the submitted work. Dr Liu reported receiving grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Nasir reported receiving research funding from the Katz Academy of Translational Research and serving as an advisory board member for Amgen, Esperion Therapeutics, and Novartis outside the submitted word. Dr Blaha reported receiving grants from the Aetna Foundation, the American Heart Association, the Amgen Foundation, the National Institutes of Health, and the US Food and Drug Administration and personal fees from 89Bio, Akcea Therapeutics, the Amgen Foundation, Bayer, Gilead Sciences, Novartis, Novo Nordisk, Regeneron Pharmaceuticals, Sanofi, Tricida, and Zogenix outside the submitted work. Dr Martin reported receiving grants from the National Institutes of Health during the conduct of the study and grants from the Aetna Foundation, the American Heart Association, the Cascade Screening for Awareness and Detection of Familial Hypercholesterolemia (CASCADE FH) Registry, the David and June Trone Family Foundation, and the National Institutes of Health; personal fees from 89bio, Akcea Therapeutics, Amgen, AstraZeneca, Esperion Therapeutics, Kaneka Corp, Novo Nordisk, Quest Diagnostics, Regeneron Pharmaceuticals, REGENXBIO, and Sanofi; having a patent pending for a system for the calculation of low-density lipoprotein cholesterol; and being a cofounder of and owning equity in Corrie Health outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Distribution of Coronary Artery Calcium Scores at Baseline by Risk-Enhancing Factor Group
Coronary artery calcium scores based on 2018 American Heart Association/American College of Cardiology Guideline on the Management of Blood Cholesterol. ABI indicates ankle-brachial index; Apo B100, apolipoprotein B100; CAC, coronary artery calcium; CKD, chronic kidney disease; FamHx, family of history of premature atherosclerotic cardiovascular disease; hsCRP, high-sensitivity C-reactive protein; Lp(a), lipoprotein a; MetS, metabolic syndrome; PM, premature menopause; and TG, triglycerides.
Figure 2.
Figure 2.. Unadjusted Incidence Rates of Individual Risk-Enhancing Factors
Incidence rates among individuals with an intermediate risk of ASCVD. The dashed line represents the reference line (7.5%) above which statin therapy is recommended. ABI indicates ankle-brachial index; Apo B100, apolipoprotein B100; CAC, coronary artery calcium; CKD, chronic kidney disease; FamHx, family of history of premature atherosclerotic cardiovascular disease; hsCRP, high-sensitivity C-reactive protein; Lp(a), lipoprotein a; MetS, metabolic syndrome; PM, premature menopause; and TG, triglycerides.
Figure 3.
Figure 3.. Unadjusted Incidence Rates for Risk-Enhancing Factors Across Coronary Artery Calcium Categories
A, Combined risk-enhancing factors with low ABI excluded. B, Individual risk-enhancing factors. The dashed line represents the reference line (7.5%) above which statin therapy is recommended. ABI indicates ankle-brachial index; Apo B100, apolipoprotein B100; CAC, coronary artery calcium; CKD, chronic kidney disease; FamHx, family of history of premature atherosclerotic cardiovascular disease; hsCRP, high-sensitivity C-reactive protein; Lp(a), lipoprotein a; MetS, metabolic syndrome; PM, premature menopause; RENF, risk-enhancing factors; and TG, triglycerides.
See this image and copyright information in PMC

Comment in

  • Hypertriglyceridemia in the MESA Study.
    Hansel B, Roussel R, Giral P. Hansel B, et al. JAMA Cardiol. 2022 Apr 1;7(4):462. doi: 10.1001/jamacardio.2021.5785. JAMA Cardiol. 2022. PMID: 35107580 No abstract available.
  • Hypertriglyceridemia in the MESA Study-Reply.
    Patel J, Blumenthal RS, Al Rifai M. Patel J, et al. JAMA Cardiol. 2022 Apr 1;7(4):462-463. doi: 10.1001/jamacardio.2021.5782. JAMA Cardiol. 2022. PMID: 35107581 No abstract available.

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