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Nontraditional Risk Factors in Cardiovascular Disease Risk Assessment: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force
Open accessAbstract
Importance: Incorporating nontraditional risk factors may improve the performance of traditional multivariable risk assessment for cardiovascular disease (CVD). Objective: To systematically review evidence for the US Preventive Services Task Force on the benefits and harms of 3 nontraditional risk factors in cardiovascular risk assessment: the ankle-brachial index (ABI), high-sensitivity C-reactive protein (hsCRP) level, and coronary artery calcium (CAC) score. Data Sources: MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials for studies published through May 22, 2017. Surveillance continued through February 7, 2018. Study Selection: Studies of asymptomatic adults with no known cardiovascular disease. Data Extraction and Synthesis: Independent critical appraisal and data abstraction by 2 reviewers. Main Outcomes and Measures: Cardiovascular events, mortality, risk assessment performance measures (calibration, discrimination, or risk reclassification), and serious adverse events. Results: Forty-three studies (N = 267 244) were included. No adequately powered trials have evaluated the clinical effect of risk assessment with nontraditional risk factors on patient health outcomes. The addition of the ABI (10 studies), hsCRP level (25 studies), or CAC score (19 studies) can improve both discrimination and reclassification; the magnitude and consistency of improvement varies by nontraditional risk factor. For the ABI, improvements in performance were the greatest for women, in whom traditional risk assessment has poor discrimination (C statistic change of 0.112 and net reclassification index [NRI] of 0.096). Results were inconsistent for hsCRP level, with the largest analysis (n = 166 596) showing a minimal effect on risk prediction (C statistic change of 0.0039, NRI of 0.0152). The largest improvements in discrimination (C statistic change ranging from 0.018 to 0.144) and reclassification (NRI ranging from 0.084 to 0.35) were seen for CAC score, although CAC score may inappropriately reclassify individuals not having cardiovascular events into higher-risk categories, as determined by negative nonevent NRI. Evidence for the harms of nontraditional risk factor assessment was limited to computed tomography imaging for CAC scoring (8 studies) and showed that radiation exposure is low but may result in additional testing. Conclusions and Relevance: There are insufficient adequately powered clinical trials evaluating the incremental effect of the ABI, hsCRP level, or CAC score in risk assessment and initiation of preventive therapy. Furthermore, the clinical meaning of improvements in measures of calibration, discrimination, and reclassification risk prediction studies is uncertain.
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“A recent meta-analysis from the US Preventive Services Task Force summarized the available evidence on the value of non-traditional risk factors for risk prediction, and found that, although there are no randomized trials showing that the use of CAC reduces health outcomes, nevertheless it improves both discrimination and reclassification [19].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [19]
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- US Preventive Services Task Force, 2015, US Preventive Services Task Force Procedure Manual
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Mach, F., Baigent, C., Catapano, A. L., Koskinas, K. C., Casula, M., Badimon, L., Chapman, M. J., De Backer, G. G., Delgado, V., Ference, B. A., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz455 · Cited by 8,961
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Visseren, F. L. J., Mach, F., Smulders, Y. M., Carballo, D., Koskinas, K. C., Bäck, M., Benetos, A., Biffi, A., Boavida, J.-M., Capodanno, D., et al. (2021) · European Heart Journal · doi:10.1093/eurheartj/ehab484 · Cited by 6,485
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2024 ESC Guidelines for the management of peripheral arterial and aortic diseases
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2025 Focused Update of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias
Mach, F., Koskinas, K. C., Roeters van Lennep, J. E., Tokgözoğlu, L., Badimon, L., Baigent, C., Benn, M., Binder, C. J., Catapano, A. L., De Backer, G. G., et al. (2025) · European Heart Journal · doi:10.1093/eurheartj/ehaf190 · Cited by 688
Metadata
- Authors
- Lin, J. S., Evans, C. V., Johnson, E., Redmond, N., Coppola, E. L., & Smith, N.
- Affiliations
- Kaiser Permanente (US)
- Corresponding author
- Lin, Jennifer S.
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2018-07-17
- Volume
- 320
- Issue
- 3
- Pages
- 281
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC13564044
- OpenAlex
- W2852998865
- Cited by
- 216
- References
- 100
- Citations by year
- 2026: 19 · 2025: 28 · 2024: 24 · 2023: 30 · 2022: 27 · 2021: 38 · 2020: 30 · 2019: 14 · 2018: 6
- FWCI
- 3.99
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- public-domain
- Locations
- JAMA (publishedVersion, public-domain)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, public-domain)
- Funders
- U.S. Department of Health and Human Services
- Agency for Healthcare Research and Quality (HHSA 290-2015-00007-I)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Health Promotion and Cardiovascular Prevention
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiac Imaging and Diagnostics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- cardiovascular disease risk assessment, non-traditional risk factors, ankle-brachial index, high-sensitivity C-reactive protein, coronary artery calcium score, risk reclassification, risk discrimination, cardiovascular events, cardiovascular mortality, radiation exposure, women, asymptomatic adults, USPSTF recommendations, cardiovascular risk prediction models, computed tomography, net reclassification improvement
- MeSH terms
- Adult, C-Reactive Protein, Cardiovascular Diseases, Clinical Trials as Topic, Coronary Artery Disease, Humans, Risk Factors, Biomarkers, Risk Assessment, Ankle Brachial Index, Vascular Calcification
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