Association Between C-Reactive Protein Genotype, Circulating Levels, and Aortic Pulse Wave Velocity

Circulating C-reactive protein (CRP) level is associated with cardiovascular disease. Whether this relationship is causal has been subject of debate, especially as a potential therapeutic target. Previous studies have demonstrated an association between circulating CRP levels and arterial pulse wave velocity, an accepted measure of arterial stiffness. We investigated the association between circulating CRP levels, CRP genotype, and aortic pulse wave velocity by examining data on 790 healthy male participants of the Caerphilly study. Circulating CRP levels were associated with aortic pulse wave velocity after adjustment for cardiovascular risk factors and other potential confounders (P=0.001). Three single nucleotide polymorphisms in the CRP gene (rs1130864, rs1800947, and rs1205) were associated with differences in circulating CRP levels (ratio of geometric means: 1.12, 95% CI 1.03 to 1.21, P=0.005; 0.76, 95% CI 0.66 to 0.87, P<0.001; 0.88, 95% CI 0.81 to 0.95, P=0.001, respectively). However, there was no relationship between any of the genotypes and aortic pulse wave velocity (regression coefficient for C:G/G:G versus C:C genotypes for single nucleotide polymorphism rs1800947 beta=0.005; 95% CI, -0.57 to 0.58; P=0.99). These results suggest that although circulating CRP levels are associated with aortic pulse wave velocity, CRP does not have a causal role in the development of arterial stiffness. CRP may simply act as a marker of vascular damage (ie, reverse causality), or the association reflects residual confounding. Further studies are needed to confirm these findings, particularly in view of the central role CRP has played in cardiovascular disease so far.