Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Nutrients. 2023 Jul 1;15(13):3013. doi: 10.3390/nu15133013.
To elucidate the bidirectional correlation of sarcopenia with coronary heart disease (CHD), as well as to investigate the mediating role of cardiometabolic factors and inflammatory biomarkers, a bidirectional two-sample, two-step Mendelian randomization (MR) study was conducted.
Summary statistics were obtained from genome-wide association studies (GWAS). In our bidirectional two-sample MR, genetic variants associated with sarcopenia-related traits and CHD were instrumented for the estimation of bidirectional correlations. Besides, genetic variants associated with thirteen cardiometabolic factors and six inflammatory biomarkers were selected for further mediation analyses. To confirm the consistency of the results, several sensitivity analyses were carried out.
Genetically predicted higher appendicular lean mass (OR = 0.835, 95% CI: 0.790-0.882), left hand grip strength (OR = 0.703, 95% CI: 0.569-0.869), right hand grip strength (OR = 0.685, 95% CI: 0.555-0.844), and walking pace (OR = 0.321, 95% CI: 0.191-0.539) reduced CHD risk, while genetic predisposition to CHD did not affect any of the sarcopenia-related traits. Seven mediators were identified for the effects of appendicular lean mass on CHD, including waist-to-hip ratio, hip circumference, systolic blood pressure, low-density lipoprotein cholesterol, total cholesterol, triglycerides, and fasting insulin. The mediation proportion ranged from 10.23% for triglycerides to 35.08% for hip circumference. Hip circumference was found to mediate the relationships between both left (mediation proportion: 24.61%) and right-hand grip strength (24.14%) and CHD, and the link between walking pace and CHD was partially mediated by waist-to-hip ratio (31.15%) and body mass index (26.66%).
Our results showed that higher appendicular lean mass, hand grip strength, and walking pace reduced CHD risk, but the causal relationship was not bidirectional. Several mediators were found to mediate the causal pathways between sarcopenia-related traits and CHD, and intervention of these factors may be helpful in terms of CHD prevention in sarcopenia patients.
通过双向两样本两步孟德尔随机化（MR）研究，阐明肌少症与冠心病（CHD）之间的双向相关性，并探讨心脏代谢因素和炎症生物标志物的中介作用。
从全基因组关联研究（GWAS）中获取汇总统计数据。在我们的双向两样本 MR 中，使用与肌少症相关特征和 CHD 相关的遗传变异作为工具，以估计双向相关性。此外，选择与 13 种心脏代谢因素和 6 种炎症生物标志物相关的遗传变异进行进一步的中介分析。为了确认结果的一致性，进行了几项敏感性分析。
遗传预测的较高四肢瘦体重（OR=0.835，95%CI：0.790-0.882）、左手握力（OR=0.703，95%CI：0.569-0.869）、右手握力（OR=0.685，95%CI：0.555-0.844）和步行速度（OR=0.321，95%CI：0.191-0.539）降低了 CHD 风险，而遗传易感性对 CHD 则没有影响任何肌少症相关特征。确定了 7 种中介物用于解释四肢瘦体重对 CHD 的影响，包括腰臀比、臀围、收缩压、低密度脂蛋白胆固醇、总胆固醇、甘油三酯和空腹胰岛素。中介比例范围从甘油三酯的 10.23%到臀围的 35.08%。发现臀围介导了左（中介比例：24.61%）和右手握力（24.14%）与 CHD 之间的关系，以及步行速度与 CHD 之间的关系部分由腰臀比（31.15%）和体重指数（26.66%）介导。
我们的研究结果表明，较高的四肢瘦体重、握力和步行速度降低了 CHD 风险，但因果关系不是双向的。发现一些中介物介导了肌少症相关特征与 CHD 之间的因果关系，干预这些因素可能有助于预防肌少症患者的 CHD。
