Self‐Reported Smoking, Urine Cotinine, and Risk of Cardiovascular Disease: Findings From the PREVEND (Prevention of Renal and Vascular End‐Stage Disease) Prospective Cohort Study

Background We aimed to compare the associations of smoking exposure as assessed by self‐reports and urine cotinine with cardiovascular disease (CVD) risk and determine the potential utility of cotinine for CVD risk prediction. Methods and Results Smoking status by self‐reports and urine cotinine were assessed at baseline in 4737 participants (mean age, 53 years) of the PREVEND (Prevention of Renal and Vascular End‐Stage Disease) prospective study. Participants were classified as never, former, light current (≤10 cigarettes/day), and heavy current smokers (>10 cigarettes/day) according to self‐reports and analogous cutoffs for urine cotinine. During a median follow‐up of 8.5 years, 296 first CVD events were recorded. Compared with self‐reported never smokers, the hazard ratios (95% confidence interval) of CVD for former, light current, and heavy current smokers were 0.86 (0.64–1.17), 1.28 (0.83–1.97), and 1.80 (1.27–2.57) in multivariate analysis. Compared with urine cotinine–assessed never smokers, the corresponding hazard ratios of CVD for urine cotinine–assessed former, light current, and heavy current smokers were 1.70 (1.03–2.81), 1.62 (1.15–2.28), and 1.95 (1.39–2.73) respectively. The C‐index change on adding urine cotinine–assessed smoking status to a standard CVD risk prediction model (without self‐reported smoking status) was 0.0098 (0.0031–0.0164; P=0.004). The corresponding C‐index change for self‐reported smoking status was 0.0111 (0.0042–0.0179; P=0.002). Conclusions Smoking status as assessed by self‐reports and urine cotinine is associated with CVD risk; however, the nature of the association of urine cotinine with CVD is consistent with a dose‐response relationship. The ability of urine cotinine to improve CVD risk assessment is similar to that of self‐reported smoking status.