Impact of seasonal variation and ambient temperature on cardiovascular events in anticoagulated patients with atrial fibrillation

Abstract Background Cold weather has been associated with an increased risk of cardiovascular events, particularly ischemic stroke, in patients with atrial fibrillation (AF). However, the widespread adoption of oral anticoagulation (OAC) therapy over decades may have influenced such variations. Furthermore, data on other adverse events such as heart failure (HF), bleeding is limited. Purpose To investigate the impact of seasonality and temperature fluctuations on cardiovascular adverse events in anticoagulated patients with AF. Methods This study was a sub-analysis of two multicenter cohort studies, SAKURA-AF registry and RAFFINE registry, which prospectively enrolled patients with AF in Japan and captured cardiovascular events. The registries were combined with the data of ambient temperatures corresponding to each institutional location. We examined dates of adverse events including HF hospitalization, stroke, major bleeding, and all cause of death. The study period was categorized into four seasonal groups based on calendar months to confirm the seasonality of events, and additionally, temperature fluctuations within each time window were analyzed as time-dependent covariates. The Fine and Gray model was employed to analyze events with competing risks. Results A total of 6,635 anticoagulated patients were included in the analysis (72±9 year-old, 71.3% male, CHA2DS2-VA score: 3 Interquartile range: 2 - 4). During a median follow-up period of 39 Interquartile range: 33-47 months, 418 HF hospitalizations, 270 ischemic strokes, 298 major bleeding events and 529 deaths occurred in this study cohort. Compared with summer (June to August), the incidence of HF (adjusted odds ratio aOR: 1.93, 95% confidence interval 95%CI: 1.43-2.61, p0.001) and mortality (aOR: 1.75, 95%CI: 1.32-2.31, p0.001) were significantly higher during winter season (December to February), whereas no clear trend was found in the seasonal variations for stroke events (aOR: 1.18, 95%CI: 0.82-1.70, p=0.38) and major bleeding events (aOR: 0.87, 95%CI: 0.60-1.24, p=0.43). On temperature-based analysis, lower one-week moving mean temperature was associated with both HF (adjusted hazard ratio aHR: 0.92, 95%CI: 0.87-0.98, p=0.004, per one degree Celsius) and mortality (aHR: 0.93, 95%CI: 0.89-0.98, p=0.009), whereas it had no association with stroke (aHR: 0.98, 95%CI: 0.92-1.06, p=0.63) or major bleeding (aHR: 1.00, 95%CI: 0.93-1.08, p=0.97). Conclusions Among anticoagulated patients with AF, winter surge of cardiovascular events was pronounced in HF hospitalization, but not in stroke or bleeding. The seasonality was influenced by recent exposure to cold temperatures. Despite contemporary management, the exacerbation of HF during cold weather remains a critical issue requiring further attention.Hazard ratio for heart failure Hazard ratio for stroke