C-reactive protein, fibrinogen, and cardiovascular disease prediction
Open accessAbstract
BACKGROUND: There is debate about the value of assessing levels of C-reactive protein (CRP) and other biomarkers of inflammation for the prediction of first cardiovascular events. METHODS: We analyzed data from 52 prospective studies that included 246,669 participants without a history of cardiovascular disease to investigate the value of adding CRP or fibrinogen levels to conventional risk factors for the prediction of cardiovascular risk. We calculated measures of discrimination and reclassification during follow-up and modeled the clinical implications of initiation of statin therapy after the assessment of CRP or fibrinogen. RESULTS: The addition of information on high-density lipoprotein cholesterol to a prognostic model for cardiovascular disease that included age, sex, smoking status, blood pressure, history of diabetes, and total cholesterol level increased the C-index, a measure of risk discrimination, by 0.0050. The further addition to this model of information on CRP or fibrinogen increased the C-index by 0.0039 and 0.0027, respectively (P<0.001), and yielded a net reclassification improvement of 1.52% and 0.83%, respectively, for the predicted 10-year risk categories of "low" (<10%), "intermediate" (10% to <20%), and "high" (≥20%) (P<0.02 for both comparisons). We estimated that among 100,000 adults 40 years of age or older, 15,025 persons would initially be classified as being at intermediate risk for a cardiovascular event if conventional risk factors alone were used to calculate risk. Assuming that statin therapy would be initiated in accordance with Adult Treatment Panel III guidelines (i.e., for persons with a predicted risk of ≥20% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), additional targeted assessment of CRP or fibrinogen levels in the 13,199 remaining participants at intermediate risk could help prevent approximately 30 additional cardiovascular events over the course of 10 years. CONCLUSIONS: In a study of people without known cardiovascular disease, we estimated that under current treatment guidelines, assessment of the CRP or fibrinogen level in people at intermediate risk for a cardiovascular event could help prevent one additional event over a period of 10 years for every 400 to 500 people screened. (Funded by the British Heart Foundation and others.).
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PAD is an independent risk factor for myocardial infarction and cardiovascular death.
“PAD is a common manifestation of atherosclerosis and such patients are at elevated risk of coronary events, with PAD representing an independent risk factor for MI and CV death [510,511].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [510]
PAD is a common manifestation of atherosclerosis.
“PAD is a common manifestation of atherosclerosis and such patients are at elevated risk of coronary events, with PAD representing an independent risk factor for MI and CV death [510,511].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [510]
Patients with PAD are at elevated risk of coronary events.
“PAD is a common manifestation of atherosclerosis and such patients are at elevated risk of coronary events, with PAD representing an independent risk factor for MI and CV death [510,511].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [510]
Studies conducted in Japan have reported that the TC/HDL-C ratio is significantly associated with coronary artery calcification, even after correction for the confounding factors.
“Studies conducted in Japan have reported that the TC/HDL-C ratio is significantly associated with coronary artery calcification, even after correction for the confounding factors277).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [277]
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- Authors
- The Emerging Risk Factors Collaboration
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- The Emerging Risk Factors Collaboration
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2012-10-04
- Volume
- 367
- Issue
- 14
- Pages
- 1310-1320
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC3714101
- OpenAlex
- W1520348292
- Cited by
- 1,150
- References
- 36
- Citations by year
- 2026: 40 · 2025: 66 · 2024: 61 · 2023: 61 · 2022: 68 · 2021: 93 · 2020: 79 · 2019: 78 · 2018: 87 · 2017: 103 · 2016: 81 · 2015: 103 · 2014: 127 · 2013: 95 · 2012: 8
- FWCI
- 108.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Socio-Environmental Systems Modeling (acceptedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion, other-oa)
- VU Research Portal (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion, other-oa)
- Bristol Research (University of Bristol) (submittedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- Funders
- British Heart Foundation (RG/08/013/25942, RG/08/014, PG/09/002/26056, RG/07/008/23674, RG/08/014/24067)
- National Heart, Lung, and Blood Institute (R01HL091099, K24HL084034, P01HL088117)
- Topics
- Health Sciences › Medicine › Surgery › 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, fibrinogen, cardiovascular disease prediction, inflammatory markers, cardiovascular risk reclassification, statin therapy, intermediate cardiovascular risk, 10-year cardiovascular risk prediction, HDL cholesterol, Adult Treatment Panel III guidelines, cardiovascular event prevention, risk discrimination, concordance index, net reclassification improvement, primary prevention of cardiovascular disease
- MeSH terms
- Adult, C-Reactive Protein, Cardiovascular Diseases, Female, Fibrinogen, Humans, Lipids, Male, Mass Screening, Middle Aged, Prognosis, Risk Factors, Cohort Studies, Biomarkers, Proportional Hazards Models, Practice Guidelines as Topic
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