CRP is a strong and consistent marker for CV disease and other non-vascular diseases, like cancer and lung disease, but does not appear to be a cause of disease, according to a new meta-analysis in the Lancet. The new study is the largest effort yet to to sort out the controversial role of CRP. The study, by John Danesh and colleagues in the Emerging Risk Factors Collaboration (ERFC), combined information from 54 studies including 160,000 people in 18 countries. “The relevance of CRP to such a range of disorders is unclear,” the authors write. “Associations with ischaemic vascular disease depend considerably on conventional risk factors and other markers of inflammation.”
An accompanying comment by S Matthijs Boekholdt and John Kastelein noted that “even if CRP might not be involved in the causal pathway of atherogenesis and plaque rupture, it may still be a valuable tool in cardiovascular medicine…. it might be useful to identify individuals at cardiovascular risk and to quantify the efficacy of our interventions.”
Paul Ridker provided the following comment to CardioBrief:
This elegant meta-analysis confirms two important points for the clinical community. First, the year-to-year variation in CRP is fully comparable to that of blood pressure and cholesterol. Second, after correcting for traditional coronary risk factors, the adjusted hazard ratio for CRP (1.37) is if anything larger than that for non-HDLC (1.28) and systolic blood pressure (1.35). Thus, these data provide clear evidence that CRP independently predicts risk of heart attack, stroke, and mortality at least as well as already accepted markers commonly used for risk prediction. These data, along with results from the JUPITER trial, provide support for the 2009 recommendations from the Canadian Cardiovascular Society that “intermediate risk” individuals should have CRP evaluated and that they should consider statin therapy if elevated levels of CRP are found.
James de Lemos told CardioBrief that, “on the one hand it is a tour de force of collaborative work. On the other hand, however, it really just confirms what so many previous studies have shown, namely that CRP is a generally consistent, albeit modest, predictor of future events, but is not likely causally involved.”
Here is the press release from the Lancet:
C-REACTIVE PROTEIN LEVELS CORRELATE WITH FUTURE RISK OF HEART ATTACK, STROKE AND CANCERS, BUT CAUSALITY SEEMS UNLIKELY
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 Firstwww.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.”
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