C-reactive protein levels correlate with future risk of heart attack, stroke and cancers, but causality seems unlikely

December 21, 2009

There has been intense interest among researchers during the past decade about whether blood concentrations of C-reactive protein (CRP)--a sensitive indicator of tissue injury inflammation produced by the liver--is a causal factor in heart disease. Earlier studies had suggested that this protein might be as important in the causation of heart attack as are blood cholesterol levels.

In the most powerful and comprehensive study so far of associations of blood levels of CRP with major diseases (in an Article published Online First www.thelancet.com), Professor John Danesh at the University of Cambridge, UK, and 269 other scientists in the Emerging Risk Factors Collaboration (ERFC) combined information from 54 long-term medical surveys comprising over 160,000 people in 18 countries.

The researchers show that CRP concentration is associated with future risk of a wide range of common diseases, including: heart attack, stroke, deaths from various cancers, chronic lung disease, injuries, and other conditions. Most of the associations between CRP levels and heart disease were explained, however, by risk factors already known to cause heart disease (eg, smoking, blood pressure, obesity, cholesterol levels). This finding reduces the likelihood that CRP is a cause of heart disease.

The authors say: "Although our results support the idea that some process related to persistent inflammation is associated with vascular disease and other chronic disorders, most of the association with ischaemic vascular disease depends on conventional risk factors and fibrinogen concentration."

The authors conclude that further large studies are needed to assess other markers of inflammation, as well as their genetic and lifestyle determinants. They say: "Further work is also needed to assess whether evidence of low-grade inflammation mainly indicates external triggers (eg, socioeconomic position or infection), insulin resistance, hereditary predisposition, or some combination of such factors."

In an accompanying Comment, Dr S Matthijs Boekholdt and Professor John J P Kastelein, Academic Medical Center, Amsterdam, Netherlands, say: "One of the prominent topics in this debate is CRP's role in guiding decision-making for the primary prevention of cardiovascular disease. Current guidelines advise the use of established risk factors to quantify an individual's cardiovascular risk. These guidelines recommend that people at high risk should be treated, whereas for people at intermediate risk additional information should be obtained to guide decision-making. CRP measurement might be valuable in the fine-tuning of the choice of treatment in this specific subgroup... The wealth of data collected by ERFC will be an excellent source for future analyses to more accurately define the role of CRP in clinical decision-making."
Professor John Danesh, Emerging Risk Factors Collaboration, University of Cambridge, UK. T) +44 (0) 1223 741302 E) jd292@medschl.cam.ac.uk/erfc@phpc.cam.ac.uk

Dr S Matthijs Boekholdt, Academic Medical Center, Amsterdam, Netherlands. T) +31 20 566 6612 E) S.M.Boekholdt@amc.uva.nl

For full Article and Comment, see: http://press.thelancet.com/crp.pdf


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