CRP impact on mortality questioned
MedWire News: C-reactive protein (CRP) is a robust marker of all-cause mortality risk but may not itself directly affect mortality risk, shows an analysis of the Copenhagen City Heart Study.
"This does not appear to be a causal association for CRP per se but more likely reflects association of hidden, potentially fatal inflammatory disease with increased all-cause mortality," say Børge Nordestgaard (Copenhagen University Hospital, Denmark) and colleagues.
"Alternatively, it is possible that biomarkers of inflammation reflect a final common biochemical pathway of poor health status, (possibly triggered by cytokines) resulting in increased levels of CRP, which predispose to cardiovascular and non-cardiovascular mortality in old age."
A total of 10,388 White people participated in the study, 3124 of whom died during 16 years of follow-up.
The risk for death from any cause was 2.1-fold higher in people with baseline CRP levels exceeding 3 mg/l than in those with levels below 1 mg/l, after accounting for age, gender, and statin use.
The researchers genotyped all participants for four single nucleotide polymorphisms in the CRP gene that are known to affect levels of the protein. Accounting for CRP genotype, and further confounders, did not influence the mortality risk associated with raised CRP levels, they report in the European Heart Journal.
The association between high CRP levels and mortality was significant for cardiovascular death, cancer death, and death from other causes.
These associations were attenuated after accounting for levels of the acute phase reactant fibrinogen, however, although they remained significant.
"The claim for causality for the CRP molecule itself was further weakened because genetically elevated CRP levels did not associate with increased risk of all-cause mortality," says the team.
A doubling in CRP caused by genetic variations was associated with a nonsignificant 6% decrease in mortality risk, whereas a nongenetic doubling of CRP level was associated with a significant 25% increase in mortality risk.
In contrast, a genetically driven doubling in cholesterol levels was associated with a 6.3-fold increased mortality risk.
"If elevated CRP per se does not lead to increased risks, then a more likely interpretation of previous and present data is that inflammation per se may contribute towards increased risk of cardiovascular disease and all-cause mortality," says the team.
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By Eleanor McDermid