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

BackgroundWe 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 ResultsSmoking 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).ConclusionsSmoking 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.

Smoking and cardiovascular diseases – is there more paradox than expected?

“…Urine cotinine concentration has been reported to be a stronger predictor of cardiovascular risk than self -reporting of smoking cessation. 47 In most large randomized trials that assessed the clinical efficacy of clopidogrel, smoking was assessed only at baseline, and the proportion of patients who stopped smoking while on clopidogrel treatment was unknown. 48,49 An increase in platelet reactivity in this patient group might influence clinical outcomes and smoking cessation was also related to an increased frequency of HPR.…”

Angiotensin II Type I Receptor Antagonism Attenuates Nicotine-Induced Cardiac Remodeling, Dysfunction, and Aggravation of Myocardial Ischemia-Reperfusion Injury in Rats

“…Prolonged exposure to nicotine via cigarette smoking, chewable tobacco, as well as nicotine inhalation devices is associated with an increased risk of cardiovascular diseases (McEvoy et al, 2015;Kim et al, 2017;Kunutsor et al, 2018). In animal models, prolonged administration of nicotine not only promotes vascular endothelial dysfunction associated with hypertension, but also directly impacts the cardiac structure and function, promoting oxidative stress, inflammation, fibrosis, and cardiomyocyte apoptosis (Joukar et al, 2012;Zainalabidin et al, 2014;Ramalingam et al, 2016;Si et al, 2017a;Li et al, 2018).…”

The mediating role of inflammation in the association between cigarette smoking and intima-media thickness: the Guangzhou biobank cohort study

“…Cigarette smoking causes the development and progression of atherosclerosis [1,2], but the underlying mechanisms have yet to be confirmed [3,4]. There are several potential mechanisms that could be relevant, i.e., inducing endothelial dysfunction, modifying lipid profile, and increasing inflammatory response and thrombosis [5,6].…”

“…Thickening of carotid intima-media thickness (IMT) is a surrogate marker of early atherosclerosis and predicts the development of cardiovascular disease (CVD), independent of traditional CVD risk factors [7,8]. While there was general agreement with the 4 adverse effects of cigarette smoking and high inflammation on carotid IMT [1,2,9,10], whether and to what extent inflammation mediates the smoking-atherosclerosis association remains unclear.…”

“…As much evidence, including our previous papers from the Guangzhou Biobank Cohort Study (GBCS) [18,19], has shown the detrimental effects of smoking on carotid IMT [1,2], knowledge on the underlying mechanisms will be helpful for intervention strategies against smoking-induced atherosclerosis. We took advantage of the well-established GBCS using causal mediation analysis [20,21] to investigate the mediating effects of several common inflammatory markers on the association between cigarette smoking and carotid IMT.…”