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C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant
1, Stephen Kaptoge, Emanuele Di Angelantonio
1Emerging Risk Factors Collaboration Coordinating Centre, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge CB1 8RN, UK.
Insights
C-reactive protein (CRP) concentration is linked to increased risks of vascular and non-vascular diseases. These associations are influenced by conventional risk factors and inflammatory markers.
Area of Science:
- Cardiovascular Epidemiology
- Inflammation Biomarkers
Background:
- Assessing C-reactive protein (CRP) concentration's role in major disease risk requires large-scale, long-term prospective studies.
- This study investigated the associations between CRP levels and various vascular and non-vascular health outcomes.
Purpose of the Study:
- To meta-analyze individual participant data from 54 prospective studies.
- To assess the relationship between C-reactive protein (CRP) concentration and the risk of major vascular and non-vascular diseases.
Main Methods:
- Meta-analysis of individual records from 160,309 participants without prior vascular disease.
- Included 1.31 million person-years of follow-up and 27,769 disease outcomes.
- Within-study regression analyses were adjusted for within-person variation in risk factors.
Main Results:
- Log(e) CRP concentration showed a near log-linear association with the risk of ischemic vascular disease and non-vascular mortality.
- Elevated CRP levels were associated with increased risk ratios for coronary heart disease, ischemic stroke, vascular mortality, and non-vascular mortality.
- Adjusting for conventional risk factors and fibrinogen attenuated these risk ratios, indicating their influence.
Conclusions:
- CRP concentration demonstrates continuous associations with the risk of coronary heart disease, ischemic stroke, vascular mortality, and mortality from certain cancers and lung disease.
- The broad relevance of CRP across diverse disorders remains to be fully elucidated.
- Associations between CRP and ischemic vascular disease are significantly moderated by conventional risk factors and other inflammatory markers.
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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