Genetic Predisposition To Cardiovascular Disease Is Associated With Higher Risk Of Stroke In Persons With COVID-19

Background and Purpose: Stroke is a serious complication of COVID-19. However, the risk factors for this complication are poorly understood. We hypothesize that genetic predisposition to cardio- and cerebrovascular disease (CVD) leads to an increased risk of stroke in patients with COVID-19 infection. Methods: We evaluated data from a nested cohort study conducted within the UK Biobank focused on persons with documented COVID-19. Incident strokes (ischemic and hemorrhagic) were identified by combining inpatient data (including critical care and discharge diagnostic codes) and primary care data, the latter entered by providers within 30 days of a positive COVID-19 test. Genetic predisposition to CVD was evaluated through a polygenic risk score that integrated genomic information on 2,176 independent genetic risk variants for stroke, coronary artery disease and cardiometabolic risk factors. This score was divided into low (0-20 th percentile), intermediate (20 th -80 th percentile), and high (80 th -100 th percentile) genetic risk. Results: A total of 11,882 study participants (mean age 65.8, SD [8.6], female sex 6,306 [53.1%]) with documented COVID-19 infection were included in this study, including 99 (0.8%) persons that sustained a stroke during the infection. Compared to persons with low genetic predisposition to CVD, those with intermediate and high genetic risk had 35% (OR 1.35, 95%CI 1.14-1.55) and 2.4-fold (OR 2.38, 95% CI 1.71-3.05) higher risk of stroke (test for trend p=0.004). Sub-scoring analyses evaluating one polygenic risk score per CVD trait of interest indicated that genetic predisposition to hypertension (p=0.017) and smoking (p=0.03) were the most important genetic risk factors. Conclusions: Genetic predisposition to CVD is associated with a higher risk of stroke in persons with acute COVID-19 infection. Genetic risk factors for hypertension and smoking appear to mediate a significant portion of this association. Genetic information should be considered in the multiple ongoing efforts to create risk-stratification strategies to identify COVID-19 patients at high risk of stroke.