C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis

By S. Kaptoge, E. di Angelantonio, G. Lowe, M. Pepys, S. Thompson, R. Collins, John Danesh. The Lancet, 2010

2,380 citations recorded by the source corpus.

Summary 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 Loge 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 loge 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.

Subfields: Epidemiology, Oncology, Pulmonary and Respiratory Medicine

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In Epidemiology

1. Peter Libby
2. P. Ridker
3. G. Hansson
4. A. Lichtman
5. T. Thuren
6. A. Zalewski
7. Mitchell S. V. Elkind
8. G. Moneta

In Oncology

1. Peter Libby
2. A. Lichtman
3. G. Hansson
4. P. Ridker

In Pulmonary and Respiratory Medicine

1. C. Matthews
2. P. Ridker

Citations in the corpus

• Immune Effector Mechanisms Implicated in Atherosclerosis: From Mice to Humans (2013, background): “…more modest increases in CRP, measured with a high-sensitivity assay (denoted hsCRP), predict first and recurrent cardiovascular events in a way that adds prognostic information to conventional risk biomarkers (Emerging Risk Factors Collaboration, 2012; Kaptoge et al., 2010; Wennberg et al., 2012).”
• The role of vascular biomarkers for primary and secondary prevention. A position paper from the European Society of Cardiology Working Group on peripheral circulation: Endorsed by the Association for Research into Arterial Structure and Physiology (ARTERY) Society. (2015, background): “48) when adjusted for age, sex and conventional risk factors [191].”
• European Guidelines on Cardiovascular Disease Prevention in Clinical Practice (Version 2012) (2012, neutral): “This marker was used in individuals showing a moderate level of risk from clinical assessment of major CVD risk factors.(125,126) However, several weak points exist when including this novel biomarker for risk assessment:”
• From CRP to IL-6 to IL-1: Moving Upstream To Identify Novel Targets for Atheroprotection (2016, background): “76) for future cardiovascular mortality.(17) Importantly, the magnitude of effect for hsCRP was at least as large as that for total cholesterol, high-density lipoprotein cholesterol, and blood pressure (Figure 2).”
• Loneliness, social isolation, and behavioral and biological health indicators in older adults. (2011, background): “Similarly, elevated levels of CRP have been associated with coronary events (Kaptoge et al., 2010), although the causal significance of the association is debatable (Danesh & Pepys, 2009).”
• Global vascular guidelines on the management of chronic limb-threatening ischemia (2019, background): “vascular risk with a magnitude of effect at least as large as that of blood pressure or cholesterol.(305) Even after adjustment for age, sex, and traditional risk factors, pa-”
• Interleukin-1β inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). (2011, result): “In a comprehensive overview of N50 prospective cohort studies, the magnitude of risk associated with a 1 SD increase in hsCRP was found equal to or greater than that associated with a similar increase in risk due to hyperlipidemia or blood pressure.(7) Furthermore, in this overview as in earlier stu”