Age and sex-specific stroke epidemiology in COVID-19.

Abstract

Background: COVID-19 has emerged as an independent risk factor for stroke. We aimed to determine age and sex-specific stroke incidence and risk factors with COVID-19 in the US using a large electronic health record (EHR) that included both inpatients and outpatients.

Methods: A retrospective cohort study was conducted using individual-level data from Optum^® de-identified COVID-19 EHR. A total of 387,330 individuals aged ≥18 with laboratory-confirmed COVID-19 between March 1, 2020 and December 31, 2020 were included. The primary outcome was cumulative incidence of stroke after COVID-19 confirmation within 180 days of follow-up or until death. Kaplan-Meier cumulative incidence curves for acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), and a composite outcome of all strokes were stratified by sex and age, and the differences in curves were assessed using a log-rank test. The relative risk of stroke by demographics and risk factors was estimated using multivariable Cox-proportional hazards regressions and adjusted hazard ratios (aHRs).

Results: Of 387,330 COVID-19 patients, 2,752 patients (0.71%, 95% CI 0.68-0.74) developed stroke during the 180-day follow-up, AIS in 0.65% (95% CI 0.62-0.67), and ICH in 0.11% (95% CI 0.10-0.12). Of strokes among COVID-19 patients, 57% occurred within 3 days. Advanced age was associated with a substantially higher stroke risk, with aHR 6.92 (5.72-8.38) for ages 65-74, 9.42 (7.74-11.47) for ages 75-84, and 11.35 (9.20-14.00) for ages 85 and older compared to ages 18-44 years. Men had a 32% higher risk of stroke compared to women. African-American [aHR 1.78 (1.61-1.97)] and Hispanic patients [aHR 1.48 (1.30-1.69)] with COVID-19 had an increased risk of stroke compared to white patients.

Conclusion: This study has several important findings. AIS and ICH risk in patients with COVID-19 is highest in the first 3 days of COVID-19 positivity; this risk decreases with time. The incidence of stroke in patients with COVID-19 (both inpatient and outpatient) is 0.65% for AIS and 0.11% for ICH during the 180-day follow-up. Traditional stroke risk factors increase the risk of stroke in patients with COVID-19. Male sex is an independent risk factor for stroke in COVID-19 patients across all age groups. African-American and Hispanic patients have a higher risk of stroke from COVID-19.