Archief Roodbont

Link between CRP and vascular risk ‘may not be causal’

4 November 2008

MedWire News: Genetically determined elevations in C-reactive protein (CRP) are not associated with the risk for ischemic vascular disease, suggesting that the association between CRP levels and vascular risk is not causal.

The conclusion, by a Danish team, comes from a retrospective analysis of data from four independent cohort studies: The Copenhagen City Heart Study, the Copenhagen General Population Study, the Copenhagen Ischemic Heart Disease Study, and the Copenhagen Carotid Stroke Study.

Participants in each study were genotyped for four single-nucleotide polymorphisms (rs3091244, rs1130864, rs1205, and rs3093077) in the gene encoding CRP.

As expected, the CRP genotypes were significantly associated with plasma CRP levels; the most common genotype combinations resulted in a difference of up to 64% in CRP levels between the lowest and highest levels.

Using statistical modeling, and assuming a causal relationship between CRP and vascular disease, the researchers predicted that a 64% increment in plasma CRP levels due to CRP genotype would increase ischemic heart disease risk by up to 32% and ischemic cerebrovascular disease risk by up to 25%.

However, a pooled analysis of actual trial data indicated that the odds ratios for heart and cerebrovascular disease were not significantly affected by CRP genotype.

“In conclusion, we show that genetic variants that are associated with lifelong increases in plasma CRP levels are not associated with an increased risk of ischemic heart disease or ischemic cerebrovascular disease,” write Jeppe Zacho (University of Copenhagen) and co-authors in the New England Journal of Medicine.

“This finding suggests that the increase in the risk of ischemic vascular disease associated with higher plasma CRP levels observed in epidemiologic studies may not be causal, but rather that increased CRP levels are simply a marker for atherosclerosis and ischemic vascular disease.”

N Engl J Med 2008; 359: 1897–1908