Cecelja Marina, Lewis Cathryn M, Shah Ajay M, Chowienczyk Phil
Department of Clinical Pharmacology, King's College London British Heart Foundation Centre, School of Cardiovascular Medicine & Sciences, St Thomas' Hospital, London, UK.
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
JRSM Cardiovasc Dis. 2021 Nov 19;10:20480040211059374. doi: 10.1177/20480040211059374. eCollection 2021 Jan-Dec.
Susceptibility to and severity of COVID-19 is associated with risk factors for and presence of cardiovascular disease.
We performed a 2-sample Mendelian randomization to determine whether blood pressure (BP), body mass index (BMI), presence of type 2 diabetes (T2DM) and coronary artery disease (CAD) are causally related to presentation with severe COVID-19. Variant-exposure instrumental variable associations were determined from most recently published genome-wide association and meta-analysis studies (GWAS) with publicly available summary-level GWAS data. Variant-outcome associations were obtained from a recent GWAS meta-analysis of laboratory confirmed diagnosis of COVID-19 with severity determined according to need for hospitalization/death. We also examined reverse causality using exposure as diagnosis of severe COVID-19 causing cardiovascular disease.
We found no evidence for a causal association of cardiovascular risk factors/disease with severe COVID-19 (compared to population controls), nor evidence of reverse causality. Causal odds ratios (OR, by inverse variance weighted regression) for BP (OR for COVID-19 diagnosis 1.00 [95% confidence interval (CI): 0.99-1.01, P = 0.604] per genetically predicted increase in BP) and T2DM (OR for COVID-19 diagnosis to that of genetically predicted T2DM 1.02 [95% CI: 0.9-1.05, P = 0.927], in particular, were close to unity with relatively narrow confidence intervals.
The association between cardiovascular risk factors/disease with that of hospitalization with COVID-19 reported in observational studies could be due to residual confounding by socioeconomic factors and /or those that influence the indication for hospital admission.
新型冠状病毒肺炎(COVID-19)的易感性和严重程度与心血管疾病的危险因素及存在情况相关。
我们进行了一项两样本孟德尔随机化研究,以确定血压(BP)、体重指数(BMI)、2型糖尿病(T2DM)的存在情况和冠状动脉疾病(CAD)是否与重症COVID-19的表现存在因果关系。从最近发表的全基因组关联和荟萃分析研究(GWAS)以及公开可用的汇总水平GWAS数据中确定变异暴露工具变量关联。变异-结局关联来自最近一项关于实验室确诊COVID-19的GWAS荟萃分析,其严重程度根据住院需求/死亡情况确定。我们还通过将暴露作为重症COVID-19导致心血管疾病的诊断来检验反向因果关系。
我们没有发现心血管危险因素/疾病与重症COVID-19(与总体对照相比)存在因果关联的证据,也没有反向因果关系的证据。血压(每基因预测的血压升高,COVID-19诊断的比值比[OR]为1.00[95%置信区间(CI):0.99 - 1.01,P = 0.604])和T2DM(COVID-19诊断与基因预测的T2DM的OR为1.02[95%CI:0.9 - 1.05,P = 0.927])的因果比值比,特别是接近1,且置信区间相对较窄。
观察性研究中报道的心血管危险因素/疾病与COVID-19住院之间的关联可能是由于社会经济因素和/或那些影响住院指征的因素造成的残余混杂。