Since elevated C-reactive protein (CRP) concentrations are associated with an increased risk of ischemic heart disease (IHD) and ischemic cerebrovascular disease, this study sought to test whether these associations were causal in nature. Levels of high-sensitivity CRP (hs-CRP) and four CRP polymorphisms were assessed in three different cohorts. The risk of IHD and ischemic cerebrovascular disease increased by 1.6 and 1.3, respectively, in individuals with hs-CRP>3 mg/l compared to those with hs-CRP<1 mg/l. Although genotype combinations of CRP polymorphisms were associated with a theoretically 32% increased risk of IHD and 25% increased risk of ischemic cerebrovascular disease, the observed odds ratios were not significant. Results of this study indicated that genetic variants of CRP are associated with high CRP levels but are not associated with a greater risk of ischemic vascular disease. This finding suggests that the higher risk of ischemic vascular disease in the presence of elevated CRP levels observed in epidemiological studies may not be causal. High CRP levels are probably rather a marker of the presence of factors/markers increasing risk of ischemic vascular disease.
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