Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Canadian Cardiac Research Center, Department of Internal Medicine, Division of Cardiology, University of Saskatchewan, Saskatoon, SK S7N 5A2, Canada.
Int J Mol Sci. 2023 May 23;24(11):9129. doi: 10.3390/ijms24119129.
Elevated C-reactive protein (CRP) levels are an indicator of inflammation, a major risk factor for cardiovascular disease (CVD). However, this potential association in observational studies remains inconclusive. We performed a two-sample bidirectional Mendelian randomization (MR) study using publicly available GWAS summary statistics to evaluate the relationship between CRP and CVD. Instrumental variables (IVs) were carefully selected, and multiple approaches were used to make robust conclusions. Horizontal pleiotropy and heterogeneity were evaluated using the MR-Egger intercept and Cochran's Q-test. The strength of the IVs was determined using F-statistics. The causal effect of CRP on the risk of hypertensive heart disease (HHD) was statistically significant, but we did not observe a significant causal relationship between CRP and the risk of myocardial infarction, coronary artery disease, heart failure, or atherosclerosis. Our primary analyses, after performing outlier correction using MR-PRESSO and the Multivariable MR method, revealed that IVs that increased CRP levels also increased the HHD risk. However, after excluding outlier IVs identified using PhenoScanner, the initial MR results were altered, but the sensitivity analyses remained congruent with the results from the primary analyses. We found no evidence of reverse causation between CVD and CRP. Our findings warrant updated MR studies to confirm the role of CRP as a clinical biomarker for HHD.
C 反应蛋白（CRP）水平升高是炎症的一个指标，也是心血管疾病（CVD）的一个主要危险因素。然而，观察性研究中这种潜在的关联仍不确定。我们使用公开的 GWAS 汇总统计数据进行了两样本双向 Mendelian 随机化（MR）研究，以评估 CRP 与 CVD 之间的关系。我们仔细选择了工具变量（IVs），并使用多种方法得出了稳健的结论。使用 MR-Egger 截距和 Cochran's Q 检验评估水平遗传异质性。使用 F 统计量确定 IVs 的强度。CRP 对高血压性心脏病（HHD）风险的因果效应具有统计学意义，但我们没有观察到 CRP 与心肌梗死、冠心病、心力衰竭或动脉粥样硬化风险之间存在显著的因果关系。在使用 MR-PRESSO 和多变量 MR 方法进行异常值校正后进行的主要分析中，我们发现增加 CRP 水平的 IVs 也增加了 HHD 风险。然而，在排除使用 PhenoScanner 识别的异常 IVs 后，最初的 MR 结果发生了变化，但敏感性分析仍然与主要分析的结果一致。我们没有发现 CVD 和 CRP 之间存在反向因果关系的证据。我们的研究结果需要更新的 MR 研究来证实 CRP 作为 HHD 临床生物标志物的作用。
