C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis
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Background Associations of C-reactive protein (CRP) concentration with risk of major diseases can best be assessed by long-term prospective follow-up of large numbers of people. We assessed the associations of CRP concentration with risk of vascular and non-vascular outcomes under different circumstances.Methods We meta-analysed individual records of 160 309 people without a history of vascular disease (ie, 1.31 million person-years at risk, 27 769 fatal or non-fatal disease outcomes) from 54 long-term prospective studies. Within-study regression analyses were adjusted for within-person variation in risk factor levels.Results Log(e) CRP concentration was linearly associated with several conventional risk factors and inflammatory markers, and nearly log-linearly with the risk of ischaemic vascular disease and non-vascular mortality. Risk ratios (RRs) for coronary heart disease per 1-SD higher log(e) CRP concentration (three-fold higher) were 1.63 (95% CI 1.51-1.76) when initially adjusted for age and sex only, and 1.37 (1.27-1.48) when adjusted further for conventional risk factors; 1.44 (1.32-1.57) and 1.27 (1.15-1.40) for ischaemic stroke; 1.71 (1.53-1.91) and 1.55 (1.37-1.76) for vascular mortality; and 1.55 (1.41-1.69) and 1.54 (1.40-1.68) for non-vascular mortality. RRs were largely unchanged after exclusion of smokers or initial follow-up. After further adjustment for fibrinogen, the corresponding RRs were 1.23 (1.07-1.42) for coronary heart disease; 1.32 (1.18-1.49) for ischaemic stroke; 1.34 (1.18-1.52) for vascular mortality; and 1.34 (1.20-1.50) for non-vascular mortality.Interpretation CRP concentration has continuous associations with the risk of coronary heart disease, ischaemic stroke, vascular mortality, and death from several cancers and lung disease that are each of broadly similar size. The relevance of CRP to such a range of disorders is unclear. Associations with ischaemic vascular disease depend considerably on conventional risk factors and other markers of inflammation.Funding British Heart Foundation, UK Medical Research Council, BUPA Foundation, and GlaxoSmithKline.
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High levels of hsCRP, YKL-40, and ICAM-1 are associated with an increased risk of MACE.
“High levels of hsCRP, YKL‐40, and ICAM‐1 are associated with an increased risk of MACE.”
From The dual glucose‐dependent insulinotropic polypeptide and glucagon‐like peptide‐1 receptor agonist tirzepatide improves cardiovascular risk biomarkers in patients with type 2 diabetes: A p <scp>ost hoc</scp> analysis (2022) · cites this paper as [14]
The Results report that higher CRP was associated with greater risks of coronary heart disease and ischaemic stroke; the Methods note that most studies used high-sensitivity CRP assays. The paper does not establish the claimed associations for YKL-40 or ICAM-1, and it reports those vascular outcomes separately rather than as a MACE composite. (LLM, conf=0.90)
Experimental — accuracy not yet measuredPharmacological treatments that reduce hsCRP, including statins and anti-IL-1β antibody, are associated with improved cardiovascular outcomes.
“Pharmacological treatments that reduce hsCRP, including statins and anti‐IL‐1β antibody, are associated with improved cardiovascular outcomes. 13 , 14 , 15 , 16 , 17”
From The dual glucose‐dependent insulinotropic polypeptide and glucagon‐like peptide‐1 receptor agonist tirzepatide improves cardiovascular risk biomarkers in patients with type 2 diabetes: A p <scp>ost hoc</scp> analysis (2022) · cites this paper as [14]
The Discussion reports that statins reduce CRP and that rosuvastatin reduced first-ever vascular disease in a specified group. It does not report improved cardiovascular outcomes with anti-IL-1β antibody treatment; instead, it says anti-inflammatory drugs had not yet been adequately studied as prophylactic interventions. It also cautions that statin results cannot establish whether lowering CRP caused the benefit. (LLM, conf=0.87)
Experimental — accuracy not yet measuredIn epidemiological studies in humans, inflammatory biomarkers are positively associated with atherosclerotic cardiovascular disease.
“In epidemiological studies in humans, these inflammatory biomarkers are positively associated with atherosclerotic cardiovascular disease.”
High-sensitivity CRP has shown consistency across large prospective studies as a risk factor integrating multiple metabolic and low-grade inflammatory factors underlying unstable atherosclerotic plaques, with magnitude matching classical major risk factors.
“High-sensitivity CRP has shown consistency across large prospective studies as a risk factor integrating multiple metabolic and lowgrade inflammatory factors underlying the development of unstable atherosclerotic plaques, with a magnitude of effect matching that of classical major risk factors.”
From European Guidelines on cardiovascular disease prevention in clinical practice (version 2012) (2012) · cites this paper as [126]
Elevated levels of CRP are associated with increased risk for chronic diseases, including cardiovascular disease, cancers, and depression.
“In particular, elevated levels of CRP are associated with increased risk for chronic diseases, including cardiovascular disease, cancers, and depression.36,37”
From Social Media Use and Its Link to Physical Health Indicators (2022) · cites this paper as [36]
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- Authors
- ‡
- Corresponding author
- ‡
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 375
- Issue
- 9709
- Pages
- 132-140
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- PMC
- PMC3162187
- OpenAlex
- W1812416290
- Cited by
- 2,546
- References
- 54
- Citations by year
- 2026: 152 · 2025: 157 · 2024: 171 · 2023: 147 · 2022: 118 · 2021: 172 · 2020: 156 · 2019: 140 · 2018: 141 · 2017: 138 · 2016: 159 · 2015: 150 · 2014: 161 · 2013: 155 · 2012: 170
- FWCI
- 22.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- The Lancet (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion)
- OPUS (Augsburg University) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- British Heart Foundation
- Bupa Foundation
- GlaxoSmithKline
- Medical Research Council
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Oncology › Inflammatory Biomarkers in Disease Prognosis
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- C-reactive protein, coronary artery disease, ischemic stroke, vascular death, inflammation, fibrinogen, cardiovascular risk factors, cancer mortality, prospective cohort, within-person variability, inflammatory markers, cardiovascular risk prediction, risk thresholds
- MeSH terms
- Alcohol Drinking, Blood Pressure, C-Reactive Protein, Cholesterol, Coronary Disease, Diabetes Mellitus, Female, Fibrinogen, Humans, Leukocyte Count, Lung Diseases, Male, Middle Aged, Motor Activity, Neoplasms, Regression Analysis, Risk Factors, Serum Albumin, Sex Factors, Smoking, Triglycerides, Biomarkers, Interleukin-6, Body Mass Index, Databases, Factual, Risk Assessment, Stroke
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