Reevaluation of risk factors for time to subsequent events after first stroke occurrence using a new weighted all-cause effect measure

Abstract

Background : Risk factors for stroke include atrial fibrillation, hypertension, diabetes mellitus, smoking, and high cholesterol. However, the role of these factors on subsequent cardiovascular events or death is less clear due to therapeutic measures. We therefore aim to get insights into the persistence of known risk factors on subsequent stroke or death one year after the first stroke and to illustrate how the new weighted all-cause hazard ratio can ease the interpretation of competing time-to-event endpoints with different clinical relevance. Methods : This study evaluates the one year follow-up of 470 first ever stroke cases identified in the area of Ludwigshafen, Germany, with 23 deaths and 34 subsequent stroke events. The recently introduced weighted all-cause hazard ratio was used which allows a weighting of the competing endpoints in a composite endpoint. We extended this approach to allow adjustment for covariates. The investigated risk factors were those listed above. Results : None of these risk factors, most probably being treated after the first stroke, remained to be associated with subsequent death or stroke [weighted hazard ratios (95% confidence interval) for diabetes mellitus, atrial fibrillation, high cholesterol, hypertension, and smoking are 0.4 (0.2, 0.9), 0.8 (0.4, 2.2), 1.3 (0.5, 2.5), 1.2 (0.3, 2.7), 1.6 (0.8, 3.6), respectively]. Cause-specific effects sometimes point into opposite directions. Conclusions : Using the new weighted hazard ratio, we can support that well established risk factors for the occurrence of an index stroke are no good predictors of further disease progress defined by death or recurrent stroke, e.g. in our study diabetic patients even showed a decreased risk for recurrent stroke. It has been demonstrated that the new weighted hazard ratio provides interpretation advantages over the common all-cause hazard ratio and can thus be used for a more adequate analysis of cardiovascular risk and disease progress. The results have to be confirmed within a larger study with more events.