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C-Reactive Protein and Reclassification of Cardiovascular Risk in the Framingham Heart Study
Open accessAbstract
Background— The relationship of circulating levels of high-sensitivity C-reactive protein (CRP) with cardiovascular disease (CVD) risk, particularly with consideration of effects at intermediate levels of risk, has not been fully assessed. Methods and Results— Among 3006 offspring participants in the Framingham Heart Study free of CVD (mean age, 46 years at baseline), there were 129 hard coronary heart disease (CHD) events and 286 total CVD events during 12 years of follow-up. Cox regression, discrimination with area under the receiver operating characteristic curve, and net reclassification improvement were used to assess the role of CRP on vascular risk. In an age-adjusted model that included both sexes, the hazard ratios for new hard CHD and total CVD were significantly associated with higher CRP levels. Similar analyses according to increasing homocysteine level showed significant protective associations for hard CHD but not for total CVD. In multivariable analyses that included age, sex, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, diabetes mellitus, current smoking, hypertension treatment, and homocysteine, the log CRP level remained significantly related to development of hard CHD and total CVD and provided moderate improvement in the discrimination of events. The net reclassification improvement when CRP was added to traditional factors was 5.6% for total CVD ( P =0.014) and 11.8% for hard CHD ( P =0.009). Conclusions— Circulating levels of CRP help to estimate risk for initial cardiovascular events and may be used most effectively in persons at intermediate risk for vascular events, offering moderate improvement in reclassification of risk.
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“It should be stressed, however, that although many risk factors other than the few included in the available risk functions have been identified [such as C-reactive protein (CRP) and homocysteine levels], their contribution to absolute cardiovascular risk estimations of individual patients (in addition to traditional risk factors) is generally modest.66”
From European Guidelines on cardiovascular disease prevention in clinical practice (version 2012) (2012) · cites this paper as [66]
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“For example, a Although hsCRP may not causally contribute to atherosclerosis, as indicated by Mendelian randomisation studies, it is a useful marker for predicting inflammation and cardiovascular risks [27, 28].”
Zhang, Y., Schaefer, E. J., Ikezaki, H., Diffenderfer, M. R., Lloyd‐Jones, D. M., Hoogeveen, R. C., Ballantyne, C. M., DeFilippis, A. P., Guan, W., Tsai, M. Y., et al. (2026) · Journal of the American Heart Association · doi:10.1161/jaha.125.049726
Bečirović, E., Bećirović, M., Bećirović, A., Tursunović, A., Bajrić, A., Softić, A., Mujkic, A., Mujaković, E., Abdić, A., & Ferhatbegović, L. (2026) · Clinics and Practice · doi:10.3390/clinpract16080143
“Although CRP did not remain an independent predictor after multivariable adjustment, its inclusion improved the model’s overall discrimination and reclassification [18].”
Metadata
- Authors
- Wilson, P. W. F., Pencina, M., Jacques, P., Selhub, J., D'Agostino, R., & O'Donnell, C. J.
- Affiliations
- Boston University (US)
- From EPICORE (P.W.F.W.), Emory University School of Medicine, and the Atlanta VAMC Epidemiology and Genetics Section, Atlanta, Ga; National Heart, Lung, and Blood Institute (C.J.O.D.); National Heart, Lung and Blood Institute’s Framingham Heart Study (M.P., R.D.A., C.J.O.D.), Framingham Mass; Department of Mathematics (M.P., R.D.A.), Boston University, Boston, Mass; Tufts USDA Nutrition Center (P.J., J.S.), Boston, Mass.
- Venue
- Circulation: Cardiovascular Quality and Outcomes
- Published
- 2008-11
- Volume
- 1
- Issue
- 2
- Pages
- 92-97
- ISSN
- 1941-7705 (ISSN-L)
- 1941-7713
- PMC
- PMC3033831
- OpenAlex
- W2144684988
- Cited by
- 299
- References
- 38
- Citations by year
- 2026: 4 · 2025: 14 · 2024: 3 · 2023: 13 · 2022: 8 · 2021: 16 · 2020: 6 · 2019: 5 · 2018: 19 · 2017: 12 · 2016: 20 · 2015: 15 · 2014: 21 · 2013: 18 · 2012: 36
- FWCI
- 29.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation Cardiovascular Quality and Outcomes (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- School of Medicine, Boston University
- Centre International de Recherche sur le Cancer
- National Institutes of Health (n01hc25195-41-0-1)
- National Heart, Lung, and Blood Institute (R01HL073272, N01‐HC25195, N01-HC-025195)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Oncology › Inflammatory Biomarkers in Disease Prognosis
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Risk Factors
- Keywords
- C-reactive protein, cardiovascular risk reclassification, coronary artery disease, cardiovascular disease, intermediate cardiovascular risk, homocysteine, risk prediction, net reclassification improvement
- MeSH terms
- Adult, C-Reactive Protein, Coronary Disease, Female, Follow-Up Studies, Homocysteine, Humans, Male, Middle Aged, Prospective Studies, Risk Factors, Biomarkers, Prevalence, Risk Assessment
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.
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