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

Abstract

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.

Keywords: cardiovascular disease; cohort study; cotinine; risk factor; risk prediction; smoking.

Figure 1

Cumulative Kaplan‐Meier curves for cardiovascular disease during follow‐up according to smoking exposure categories as assessed by self‐reports and urine cotinine. CVD indicates cardiovascular disease.

Figure 2

Hazard ratios for incident cardiovascular disease, by baseline concentrations of urine cotinine using multivariate fractional polynomial models. A, Hazard ratios were adjusted for age and sex; B, adjustment in A plus history of diabetes mellitus, systolic blood pressure, total cholesterol, and high‐density lipoprotein cholesterol. A fractional polynomial was used to model the relationship between urine cotinine as a continuous risk factor and cardiovascular disease. The shaded regions denote the 95% confidence interval for the fractional polynomial model.

Figure 3

Hazard ratios for self‐reported smoking and cardiovascular disease risk by several participant‐level characteristics. Hazard ratios were adjusted for age, sex, history of diabetes mellitus, systolic blood pressure, total cholesterol, and high‐density lipoprotein cholesterol; CI indicates confidence interval (bars); CVD, cardiovascular disease; HDL, high‐density lipoprotein; HR, hazard ratio. *P value for interaction; cutoffs used for fasting glucose, body mass index, systolic blood pressure, total cholesterol, HDL cholesterol, estimated glomerular filtration rate (GFR), and C‐reactive protein are median values.

Figure 4

Hazard ratios for urine cotinine assessed smoking and cardiovascular disease risk by several participant level characteristics. Hazard ratios were adjusted for age, sex, history of diabetes mellitus, systolic blood pressure, total cholesterol, and high‐density lipoprotein‐cholesterol; CI indicates confidence interval (bars); CVD, cardiovascular disease; HDL, high‐density lipoprotein; HR, hazard ratio. *P value for interaction; cutoffs used for fasting glucose, body mass index, systolic blood pressure, total cholesterol, HDL cholesterol, estimated glomerular filtration rate (GFR), and C‐reactive protein are median values.