Yang Fangkun, Hu Teng, He Kewan, Ying Jiajun, Cui Hanbin
Department of Cardiology, Ningbo Hospital of Zhejiang University (Ningbo First Hospital), School of Medicine, Zhejiang University, Ningbo, China.
Department of Cardiology, Second Affiliated Hospital of Zhejiang University, School of Medicine, Zhejiang University, Hangzhou, China.
Front Immunol. 2022 Mar 15;13:861885. doi: 10.3389/fimmu.2022.861885. eCollection 2022.
Observational studies suggested that multiple sclerosis (MS) is associated with cardiovascular diseases (CVDs). However, the causal association has not been fully elucidated. Thus, we aim to assess the causality of the associations of MS with risk of CVDs.
A two-sample Mendelian randomization (MR) study was performed to explore the causality. Genetic instruments were identified for MS from a genome-wide association study (GWAS) involving 115,803 individuals. Summary-level data for CVDs were obtained from different GWAS meta-analysis studies. MR analysis was conducted mainly using the inverse-variance weighted (IVW) method. Sensitivity analyses were further performed to ensure the robustness of the results.
This MR study found suggestive evidence that genetic liability to MS was associated with an increased risk of coronary artery disease (CAD) [odds ratio (OR), 1.02; 95% confidence interval (CI), 1.00-1.04; = 0.03], myocardial infarction (MI) (OR, 1.03; 95% CI, 1.00-1.06; = 0.01), heart failure (HF) (OR, 1.02; 95% CI, 1.00-1.04; = 0.02), all-cause stroke (AS) (OR, 1.02; 95% CI, 1.00-1.05; = 0.02), and any ischemic stroke (AIS) (OR, 1.02; 95% CI, 1.00-1.05; = 0.04). The null-association was observed between MS and the other CVDs. Further analyses found little evidence of pleiotropy.
We provided suggestive genetic evidence for the causal associations of MS with increased risk of CAD, MI, HF, AS, and AIS, which highlighted the significance of active monitoring and prevention of cardiovascular risk to combat cardiovascular comorbidities in MS patients.
观察性研究表明，多发性硬化症（MS）与心血管疾病（CVD）相关。然而，因果关联尚未完全阐明。因此，我们旨在评估MS与CVD风险之间关联的因果关系。
进行了一项两样本孟德尔随机化（MR）研究以探究因果关系。从一项涉及115,803人的全基因组关联研究（GWAS）中确定了MS的遗传工具。CVD的汇总数据来自不同的GWAS荟萃分析研究。MR分析主要使用逆方差加权（IVW）方法进行。进一步进行敏感性分析以确保结果的稳健性。
这项MR研究发现了提示性证据，表明MS的遗传易感性与冠状动脉疾病（CAD）风险增加相关[比值比（OR），1.02；95%置信区间（CI），1.00 - 1.04；P = 0.03]、心肌梗死（MI）（OR，1.03；95%CI，1.00 - 1.06；P = 0.01）、心力衰竭（HF）（OR，1.02；95%CI，1.00 - 1.04；P = 0.02）、全因性卒中（AS）（OR，1.02；95%CI，1.00 - 1.05；P = 0.02）和任何缺血性卒中（AIS）（OR，1.02；95%CI，1.00 - 1.05；P = 0.04）。在MS与其他CVD之间观察到无关联。进一步分析发现几乎没有多效性的证据。
我们为MS与CAD、MI、HF、AS和AIS风险增加之间的因果关联提供了提示性遗传证据，这突出了积极监测和预防心血管风险以对抗MS患者心血管合并症的重要性。
