Comparison of novel risk markers for improvement in cardiovascular risk assessment in intermediate-risk individuals
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CONTEXT: Risk markers including coronary artery calcium, carotid intima-media thickness, ankle-brachial index, brachial flow-mediated dilation, high-sensitivity C-reactive protein (CRP), and family history of coronary heart disease (CHD) have been reported to improve on the Framingham Risk Score (FRS) for prediction of CHD, but there are no direct comparisons of these markers for risk prediction in a single cohort. OBJECTIVE: We compared improvement in prediction of incident CHD/cardiovascular disease (CVD) of these 6 risk markers within intermediate-risk participants (FRS >5%-<20%) in the Multi-Ethnic Study of Atherosclerosis (MESA). DESIGN, SETTING, AND PARTICIPANTS: Of 6814 MESA participants from 6 US field centers, 1330 were intermediate risk, without diabetes mellitus, and had complete data on all 6 markers. Recruitment spanned July 2000 to September 2002, with follow-up through May 2011. Probability-weighted Cox proportional hazard models were used to estimate hazard ratios (HRs). Area under the receiver operator characteristic curve (AUC) and net reclassification improvement were used to compare incremental contributions of each marker when added to the FRS, plus race/ethnicity. MAIN OUTCOME MEASURES: Incident CHD defined as myocardial infarction, angina followed by revascularization, resuscitated cardiac arrest, or CHD death. Incident CVD additionally included stroke or CVD death. RESULTS: After 7.6-year median follow-up (IQR, 7.3-7.8), 94 CHD and 123 CVD events occurred. Coronary artery calcium, ankle-brachial index, high-sensitivity CRP, and family history were independently associated with incident CHD in multivariable analyses (HR, 2.60 [95% CI, 1.94-3.50]; HR, 0.79 [95% CI, 0.66-0.95]; HR, 1.28 [95% CI, 1.00-1.64]; and HR, 2.18 [95% CI, 1.38-3.42], respectively). Carotid intima-media thickness and brachial flow-mediated dilation were not associated with incident CHD in multivariable analyses (HR, 1.17 [95% CI, 0.95-1.45] and HR, 0.95 [95% CI, 0.78-1.14]). Although addition of the markers individually to the FRS plus race/ethnicity improved AUC, coronary artery calcium afforded the highest increment (0.623 vs 0.784), while brachial flow-mediated dilation had the least (0.623 vs 0.639). For incident CHD, the net reclassification improvement with coronary artery calcium was 0.659, brachial flow-mediated dilation was 0.024, ankle-brachial index was 0.036, carotid intima-media thickness was 0.102, family history was 0.160 and high-sensitivity CRP was 0.079. Similar results were obtained for incident CVD. CONCLUSIONS: Coronary artery calcium, ankle-brachial index, high-sensitivity CRP, and family history were independent predictors of incident CHD/CVD in intermediate-risk individuals. Coronary artery calcium provided superior discrimination and risk reclassification compared with other risk markers.
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Carotid intima-media thickness measurement is inferior to coronary artery calcium score and carotid plaque detection.
“while the measurement of the carotid intima-media thickness is inferior to CAC score and carotid plaque detection [16,24,25].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [16]
In studies comparing markers, coronary artery calcium had the best reclassification ability.
“In studies comparing these markers, CAC had the best reclassification ability [14-16].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [16]
Total CV risk will be higher than indicated in SCORE charts in asymptomatic persons with abnormal markers of subclinical atherosclerotic vascular damage detected by CAC, ABI, pulse wave velocity, or carotid ultrasonography.
“Total CV risk will also be higher than indicated in the SCORE charts in asymptomatic persons with abnormal markers of subclinical atherosclerotic vascular damage detected by coronary artery calcium (CAC), ankle-brachial index (ABI), pulse wave velocity or carotid ultrasonography.”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [59]
In studies comparing these markers, CAC had the best reclassification ability.
“In studies comparing these markers, CAC had the best reclassification ability. 58-60”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [59]
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Self-citationMeasurement and Application of Incidentally Detected Coronary Calcium
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Dekker, M., Waissi, F., Bank, I. E. M., Lessmann, N., Išgum, I., Velthuis, B. K., Scholtens, A. M., Leenders, G. E., Pasterkamp, G., de Kleijn, D. P. V., et al. (2020) · IJC Heart & Vasculature · doi:10.1016/j.ijcha.2019.100434 · Cited by 20 · see citing works
Predicted Risk, Preclinical Heart Failure Measures, and Incident Heart Failure
Grant, J. K., Zhang, S., Khan, S. S., Ozkan, B., Blumer, V., Nambi, V., Echouffo-Tcheugui, J. B., Pandey, A., Blumenthal, R. S., Ballantyne, C. M., et al. (2025) · JACC: Heart Failure · doi:10.1016/j.jchf.2025.102659 · Cited by 8 · see citing works
- Authors
- Yeboah, J., McClelland, R. L., Polonsky, T. S., Burke, G. L., Sibley, C. T., O’Leary, D., Carr, J. J., Goff, D. C., Greenland, P., & Herrington, D. M.
- Affiliations
- Wake Forest University Health Sciences (US)
- University of Washington (US)
- University of Chicago (US)
- Wake Forest University (US)
- National Institutes of Health (US)
- Tufts University (US)
- Colorado School of Public Health (US)
- Northwestern University (US)
- Corresponding author
- Yeboah, Joseph
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2012-08-22
- Volume
- 308
- Issue
- 8
- Pages
- 788
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC4141475
- OpenAlex
- W2165187589
- Cited by
- 1,122
- References
- 27
- Citations by year
- 2026: 34 · 2025: 37 · 2024: 48 · 2023: 67 · 2022: 63 · 2021: 104 · 2020: 94 · 2019: 72 · 2018: 84 · 2017: 89 · 2016: 113 · 2015: 97 · 2014: 104 · 2013: 99 · 2012: 15
- FWCI
- 64.84
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (n01hc95164-17-0-1, n01hc95165-34-0-1, n01hc95161-24-0-1, n01hc95166-21-0-1, n01hc95162-31-0-1, n01hc95160-18-0-1, n01hc095167-000, n01hc95163-22-0-1, n01hc95159-40-0-1)
- National Heart, Lung, and Blood Institute (N01 HC-95159, N01-HC-95160, N01-HC-095165, N01 HC95167, (N01-HC-95163, N01 HC-95161, N01 HC95165, N01HC95164, N01-HC-095159, N01 HC095167, N01‐HC‐95166, N01 HC-95162, R01HL098445)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiac Imaging and Diagnostics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Health Promotion and Cardiovascular Prevention
- Keywords
- cardiovascular risk prediction, coronary artery calcium, carotid intima-media thickness, ankle-brachial index, flow-mediated dilation, high-sensitivity C-reactive protein, family history of coronary heart disease, Framingham risk score, coronary artery disease, cardiovascular disease, Multi-Ethnic Study of Atherosclerosis, net reclassification improvement, risk indicators, myocardial infarction
- MeSH terms
- Aged, C-Reactive Protein, Calcium, Cardiovascular Diseases, Coronary Vessels, Female, Humans, Male, Middle Aged, Predictive Value of Tests, Sensitivity and Specificity, United States, Cohort Studies, Biomarkers, Risk Assessment, Ankle Brachial Index, Carotid Intima-Media Thickness
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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