Abstract
To investigate the associations between tobacco smoking and mortality, focusing on all-cause, cardiovascular, and cancer mortality, with analyses stratified by sex. A total of 333 559 participants were included. Smoking status was categorized as current, past, or never. Cox proportional hazards regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality outcomes, adjusted for potential confounders. During a median follow-up of 11.8 years, 20 381 deaths occurred, including 4024 cardiovascular deaths. Current smokers had substantially increased risks of all-cause mortality (HR 2.37 [2.25-2.50] in males; HR 2.65 [2.47-2.84] in females), cardiovascular mortality (HR 2.58 [2.31-2.87] in males; HR 3.79 [3.17-4.54] in females), and cancer mortality (HR 2.47 [2.30-2.66] in males; HR 2.46 [2.25-2.69] in females) compared with never-smokers. Past smokers also exhibited elevated risks, and a clear dose-response relationship was observed with increasing smoking intensity and pack-years. Overall survival was higher in females, but the relative risks associated with smoking were largely comparable across sexes. Tobacco smoking is strongly associated with increased mortality risk, showing a clear dose-response relationship and long-term adverse effects even after cessation. The detrimental impact of smoking was broadly similar in males and females, with only minor differences. These findings reinforce the urgent need for universal prevention and cessation strategies to reduce the burden of smoking-related disease.