Fibrinogen, C-reactive protein and coronary heart disease: does Mendelian randomization suggest the associations are non-causal?

Abstract

Two recent reviews in QJM have evaluated the role of fibrinogen ¹ and C-reactive protein (CRP) ² as risk factors for cardiovascular disease. Both raised fibrinogen and CRP levels clearly predict future risk of cardiovascular events, and could be used to identify those patients who would get the greatest absolute benefit from intervention targeting blood pressure and cholesterol lowering, smoking cessation or exercise promotion. The reviews also raise the issue of a causal relationship between fibrinogen or CRP and cardiovascular disease, and discuss the roles of pharmacological or lifestyle changes as means of modifying fibrinogen or CRP levels. ^{1, 2} However, doubt is cast on the causal nature of either factor by evidence produced by studies using the ‘Mendelian randomization’ paradigm. ³ Here we briefly outline Mendelian randomization, and review what studies using this approach have to say regarding the potential causal roles of fibrinogen and CRP with respect to cardiovascular disease.