Welcome to InCirculation.net
InCirculation.net is a professional cardiovascular resource intended for a global audience of specialists, generalists, researchers, and other healthcare professionals
Cardiovascular news provides daily news updates to help you stay informed.
CRP lowering for CHD questioned
1 July 2009
MedWire News: A study has found that several genetic variants affecting C-reactive protein (CRP) levels do not affect coronary heart disease (CHD) risk, calling into question the value of therapies aimed at reducing levels of this inflammation biomarker.
Researchers say their Mendelian randomization study of more than 28,000 CHD cases and 100,000 control individuals argues against a causal role for CRP in atherosclerosis.
“Moreover, this study suggests that development of therapeutic strategies targeting specific reductions in plasma levels of CRP are unlikely to be fruitful,” they report in the Journal of the American Medical Association.
Paul Elliot (Imperial College, London, UK) and colleagues firstly conducted a genome-wide association study to identify genetic variants associated with CRP levels. This incorporated 17,967 individuals from several studies and was followed by a replication study in 13,615 individuals.
The team then carried out a Mendelian randomization study of the most closely associated SNP they found in the CRP locus, rs7553007, together with published data on other SNPs rs1130864 and rs1205 involving a total of 28,112 cases and 100,823 controls to investigate the relationship between CRP variants and CHD.
The variants were associated with approximately 20% lower CRP levels, which in a meta-analysis of 35 studies suggested corresponded to a significant 6% reduction in CHD risk.
However, in the Mendelian randomization experiment, SNP rs7553007 was not associated with a significant reduction in CHD, and neither were the other SNPs.
The authors say: “The lack of association with CHD of genetic variants in the CRP locus suggests that the observational data linking CRP levels and CHD may be confounded by association with other CHD risk factors, or reflect a secondary inflammatory response associated with atherosclerosis (reverse causation), rather than indicate a causal relationship.”
