Abstract: Objective To explore the causal relationship between physical exercise and ischemic stroke recurrence using a multiple imputation approach based on the potential outcomes framework. Methods We collected data from 636 patients who were diagnosed with first-ever ischemic stroke between July, 2010 and December, 2018 at West China Hospital, Sichuan University. All the patients had motor ability and were followed up at least for 1 year. According to the intensity of physical exercise, the patients were divided into low-level physical exercise (LPE) group (n=244) and moderate-to high-intensity exercise (MHPE) group (n=392). With both the result and the time of recurrence as the potential outcomes, a multiple imputation method was used to impute the missing values based on a predictive matrix. Based on the imputed datasets, a causal inference model was built to estimate the average causal effect of physical exercise on the risk of stroke recurrence. Results Among the enrolled patients, 148 experienced recurrent stroke with a median recurrence time of 24.0 months and a cumulative recurrence rate of 23.3% during follow-up. As there were no outliers and the marginal distributions of the potential outcomes were basically consistent, both the Strip plots and Kenel density plots indicated that the imputed values could have been plausible measurements if they had not been missing. The average causal effect (ACE) of physical exercise on stroke recurrence was 0.578 (95% CI: 0.186-0.970, P=0.012). Conclusion There is a causal relationship between physical exercise and the risk of ischemic stroke recurrence, indicating the value of moderate or high-level exercise after stroke in reducing the risk of stroke recurrence.

Key words: physical exercise; ischemic stroke; potential outcome; multiple imputation; causal inference