PDF(Pubmed)
Abstract：
Studies have shown that some inflammatory markers can predict the risk of cardiovascular disease (CVD) and affect the structure and function of the heart. However, a causal relationship between inflammatory markers and the cardiac structure and function has not yet been established. Thus, we conducted a 2-sample Mendelian randomization (MR) study to explore the potential causal relationship between inflammatory markers and prognostically-related left ventricular (LV) parameters. Instrumental variables (IVs) for C-reactive protein (CRP), interleukin-6 (IL-6), and myeloperoxidase (MPO) levels were selected from the databases of large genome-wide association studies (GWAS). Summary statistics for LV parameters, including LV mass, ejection fraction, end-diastolic and systolic volumes, and the ratio of LV mass to end-diastolic volume, were obtained from cardiovascular magnetic resonance studies of the UK Biobank (n = 16923). The inverse-variance weighted (IVW) method was the primary analytical method used, and was complemented with the MR-Egger, weighted median, simple mode, weighted mode, and MR pleiotropy residual sum and outlier (MR-PRESSO) methods. Sensitivity analysis was performed to evaluate the robustness of the results. CRP was significantly associated with the LV mass in the IVW method (β = -0.13 g [95% confidence interval [CI], 0.78 g-1.00 g], P = .046). A higher standard deviation of genetically-predicted CRP levels was associated with a 0.13 ± 0.06 g lower LV mass. No causal relationships of IL-6 and MPO with LV parameters were found. No evidence of heterogeneity and pleiotropy was detected. Sensitivity analyses confirmed the robustness of the results. Two-sample MR analysis revealed a causal association between increased CRP level and decreased LV mass, whereas IL-6 and MPO levels did not influence the LV parameters. However, further research is required to validate our findings.
摘要：
研究表明，一些炎症标志物可以预测心血管疾病（CVD）的风险，并影响心脏的结构和功能。然而,炎症标志物与心脏结构和功能之间的因果关系尚未确定.因此，我们进行了2个样本孟德尔随机化(MR)研究,以探讨炎症标志物与预后相关左心室(LV)参数之间的潜在因果关系.C反应蛋白（CRP）的仪器变量（IVs），白细胞介素-6（IL-6），和髓过氧化物酶（MPO）水平从大型全基因组关联研究（GWAS）的数据库中选择。低压参数汇总统计，包括左心室质量，射血分数,舒张末期和收缩容积,和左心室质量与舒张末期容积的比率，来自英国生物库的心血管磁共振研究（n=16923）。逆方差加权(IVW)方法是使用的主要分析方法，并补充了MR-Egger，加权中位数，简单模式，加权模式，和MR多效性残差和离群值(MR-PRESSO)方法。进行敏感性分析以评估结果的稳健性。在IVW方法中，CRP与LV质量显着相关（β=-0.13g[95％置信区间[CI]，0.78g-1.00g]，P=.046）。遗传预测的CRP水平的较高标准偏差与低LV质量的0.13±0.06g相关。未发现IL-6和MPO与LV参数的因果关系。未检测到异质性和多效性的证据。敏感性分析证实了结果的稳健性。双样本MR分析显示CRP水平升高和LV质量降低之间存在因果关系，而IL-6和MPO水平不影响LV参数。然而,我们需要进一步的研究来验证我们的发现.
