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

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 53; no. 2; pp. 150 - 157
• Main Authors: Schumacher, Wiebke, Cockcroft, John, Timpson, Nicholas J., McEniery, Carmel M., Gallacher, John, Rumley, Ann, Lowe, Gordon, Smith, George Davey, Wilkinson, Ian B., Ben-Shlomo, Yoav
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 01.02.2009; Lippincott Williams & Wilkins
• Subjects: Aorta - physiology; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Biomarkers - blood; Blood and lymphatic vessels; Blood Flow Velocity - genetics; Blood Flow Velocity - physiology; C-Reactive Protein - genetics; C-Reactive Protein - metabolism; Cardiology. Vascular system; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - metabolism; Cardiovascular Diseases - physiopathology; Cohort Studies; Development. Metamorphosis. Moult. Ageing; Elasticity - physiology; Fundamental and applied biological sciences. Psychology; Genotype; Humans; Male; Medical sciences; Middle Aged; Polymorphism, Single Nucleotide - genetics; Prognosis; Prospective Studies; Regional Blood Flow - genetics; Regional Blood Flow - physiology; Risk Factors; Vascular Resistance - genetics; Vascular Resistance - physiology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vascular disease; Hypertension; risk factors; C-reactive protein; Vascular resistance; Atherosclerosis; Risk factor; Aorta; Genotype; Cardiovascular disease; C reactive protein
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.108.117622

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 means1.12, 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 β=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.