Meta-analyses of prospective observational studies have demonstrated a positive association between circulating CRP and CHD risk.[35]–[37] However, it remains unclear whether this association is causal or explained by confounding factors or reverse causality, or even underestimated as a result of attenuation by errors.[7], [38] The best method to establish causality for this association would be by randomization to an intervention that altered CRP levels but did not affect any other cardiovascular risk factors. This evidence concerns the gene CRP and coronary artery disorder.