Association Between C-Reactive Protein Genotype, Circulating Levels, and Aortic Pulse Wave Velocity
Association Between C-Reactive Protein Genotype, Circulating Levels, and Aortic Pulse Wave Velocity
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DOI：
10.1161/hypertensionaha.108.117622
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发表时间：
2009-02-01
期刊：
影响因子：
8.3
通讯作者：
Ben-Shlomo, Yoav
中科院分区：
文献类型：
--
作者：
Schumacher, Wiebke;Cockcroft, John;Ben-Shlomo, Yoav
循环C反应蛋白（CRP）水平与心血管疾病有关。这种关系是否是因果关系一直是争论的主题，特别是作为一个潜在的治疗靶点。以前的研究已经证明了循环CRP水平和动脉脉搏波速度之间的关联，动脉僵硬度的公认测量。我们通过对790名Caerphilly研究的健康男性参与者的数据进行分析，研究了循环CRP水平、CRP基因型和主动脉脉搏波速度之间的关系。校正心血管危险因素和其他潜在混杂因素后，循环CRP水平与主动脉脉搏波速度相关（P = 0.001）。C反应蛋白基因的三个单核苷酸多态性（rs 1130864、rs 1800947和rs 1205）与循环CRP水平的差异相关（几何平均值比值：1.12，95% CI 1.03 - 1.21，P = 0.005; 0.76，95% CI 0.66 - 0.87，P < 0.001; 0.88，95% CI 0.81 - 0.95，P = 0.001）。然而，任何基因型与主动脉脉搏波速度之间均无相关性（单核苷酸多态性rs 1800947 β的C：G/G：G与C：C基因型的回归系数= 0.005; 95%CI，-0.57至0.58; P = 0.99）。这些结果表明，尽管循环CRP水平与主动脉脉搏波速度相关，但CRP在动脉僵硬度的发展中没有因果关系。CRP可能只是作为血管损伤的标志物（即，反向因果关系），或相关性反映了残余混杂。需要进一步的研究来证实这些发现，特别是考虑到CRP在心血管疾病中发挥的核心作用。（高血压。2009; 53：150-157。）
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. (Hypertension. 2009; 53: 150-157.)