Urinary cadmium and risk of incident heart failure and acute myocardial infarction among never-smokers in the Danish Diet, Cancer, and Health Cohort

Abstract

Background: Epidemiologic studies suggest cadmium exposure is associated with hypertension, peripheral arterial disease, and risk of cardiovascular mortality. However, these associations may be confounded by tobacco smoking, a dominant source of cadmium exposure. To clarify cardiovascular risk of cadmium exposure independent of smoking, we investigated the association of urinary cadmium with risk of incident heart failure and acute myocardial infarction (AMI) in a case-cohort study of never-smokers.Methods: Between 1993-1997, 19,394 never-smoking participants (ages 50-64 years) were enrolled in The Danish Diet, Cancer, and Health cohort. From the full cohort, we identified incident heart failure (n=958) and AMI (n=809) cases occurring between baseline and 2015 using the Danish National Patient Registry. We randomly selected a sub-cohort of 600 males and 600 females for comparison. We quantified cadmium and creatinine concentrations in urine samples collected at baseline. Using an unweighted case-cohort approach, we estimated adjusted hazard ratios for heart failure and AMI in separate Cox proportional hazards models with age as the time scale, and stratified by sex.Results: Overall, participants had relatively low concentrations of urinary cadmium as expected for never smokers (median= 0.20; 25th, 75th= 0.13, 0.32 g cadmium/g creatinine). In adjusted models, higher urinary cadmium concentrations were associated with a higher risk for heart failure (HR=1.11 per interquartile range difference; 95% CI= 1.02-1.21). Furthermore, sex modified this association (Pheterogeneity=0.012). Higher urinary cadmium concentrations were associated with higher risk for heart failure among males (HR= 1.48; 95% CI= 1.18, 1.85), but not among females (HR= 1.06; 95%CI= 0.97, 1.17). Higher urinary cadmium concentrations were not associated with a higher risk of AMI (HR=1.02; 95% CI= 0.93, 1.12).Conclusion: Among never-smokers, urinary cadmium may be associated with higher risk for heart failure, especially among males. We did not observe an association between urinary cadmium and risk of AMI.