Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Schizophr Bull. 2022 Mar 1;48(2):463-473. doi: 10.1093/schbul/sbab132.
Individuals with schizophrenia have a reduced life-expectancy compared to the general population, largely due to an increased risk of cardiovascular disease (CVD). Clinical and epidemiological studies have been unable to unravel the nature of this relationship. We obtained summary-data of genome-wide-association studies of schizophrenia (N = 130 644), heart failure (N = 977 323), coronary artery disease (N = 332 477), systolic and diastolic blood pressure (N = 757 601), heart rate variability (N = 46 952), QT interval (N = 103 331), early repolarization and dilated cardiomyopathy ECG patterns (N = 63 700). We computed genetic correlations and conducted bi-directional Mendelian randomization (MR) to assess causality. With multivariable MR, we investigated whether causal effects were mediated by smoking, body mass index, physical activity, lipid levels, or type 2 diabetes. Genetic correlations between schizophrenia and CVD were close to zero (-0.02-0.04). There was evidence that liability to schizophrenia causally increases heart failure risk. This effect remained consistent with multivariable MR. There was also evidence that liability to schizophrenia increases early repolarization pattern, largely mediated by BMI and lipids. Finally, there was evidence that liability to schizophrenia increases heart rate variability, a direction of effect contrasting clinical studies. There was weak evidence that higher systolic blood pressure increases schizophrenia risk. Our finding that liability to schizophrenia increases heart failure is consistent with the notion that schizophrenia involves a systemic dysregulation of the body with detrimental effects on the heart. To decrease cardiovascular mortality among individuals with schizophrenia, priority should lie with optimal treatment in early stages of psychosis.
个体患有精神分裂症的预期寿命比一般人群短，主要是由于心血管疾病（CVD）的风险增加。临床和流行病学研究未能揭示这种关系的本质。我们获得了精神分裂症（N=130644）、心力衰竭（N=977323）、冠心病（N=332477）、收缩压和舒张压（N=757601）、心率变异性（N=46952）、QT 间期（N=103331）、早期复极和扩张型心肌病心电图模式（N=63700）的全基因组关联研究的汇总数据。我们计算了遗传相关性，并进行了双向孟德尔随机化（MR）以评估因果关系。通过多变量 MR，我们研究了因果效应是否通过吸烟、体重指数、体力活动、血脂水平或 2 型糖尿病来介导。精神分裂症和 CVD 之间的遗传相关性接近零（-0.02-0.04）。有证据表明，精神分裂症的易感性会导致心力衰竭风险增加。这种影响在多变量 MR 中仍然一致。也有证据表明，精神分裂症的易感性会增加早期复极模式，这主要是由 BMI 和脂质介导的。最后，有证据表明精神分裂症的易感性会增加心率变异性，这与临床研究的方向相反。有微弱的证据表明，较高的收缩压会增加精神分裂症的风险。我们发现精神分裂症的易感性会增加心力衰竭，这与精神分裂症涉及身体的系统性失调，对心脏产生不利影响的观点一致。为了降低精神分裂症患者的心血管死亡率，应优先在精神病早期进行最佳治疗。
