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Smoking-induced risk of future cardiovascular disease is partly mediated by cadmium in tobacco: Malmo Diet and Cancer Cohort Study

Journal article
Authors Huiqi Li
Björn Fagerberg
Gerd Sällsten
Y. Borne
B. Hedblad
G. Engstrom
Lars Barregård
Eva M. Andersson
Published in Environmental Health
Volume 18
ISSN 1476-069X
Publication year 2019
Published at Institute of Medicine, Department of Public Health and Community Medicine, Section of Occupational and environmental medicine
Institute of Medicine, Department of Molecular and Clinical Medicine
Language en
Keywords Smoking, Cadmium, Cardiovascular diseases, Mediation analysis, Prospective cohort, atherosclerotic plaques, carotid plaques, exposure, stroke, blood, mechanisms, cessation, adults, lead, bias, Environmental Sciences & Ecology, Public, Environmental & Occupational, Health
Subject categories Public health science


BackgroundSmoking is a strong risk factor for cardiovascular disease (CVD) and causes exposure to cadmium, which is a pro-atherosclerotic metal. Cadmium exposure has also been shown to increase the risk of CVD, even after adjustment for smoking. Our hypothesis was that part of the risk of CVD in smokers may be mediated by cadmium exposure from tobacco smoke. We examined this hypothesis in a mediation analysis, trying to assess how much of the smoking-induced CVD risk could be explained via cadmium.MethodsWe used prospective data on CVD (incidence and mortality) in a Swedish population-based cohort of 4304 middle-aged men and women (the Malmo Diet and Cancer Study). Blood cadmium was analyzed in base-line samples from 1991, and clinical events were followed up for 16-19years based on registry data. Mediation analysis was conducted to evaluate the indirect effect (via cadmium) of smoking on CVD. Survival was analyzed by the accelerated failure time (AFT) model and the Aalen additive hazard model.ResultsThe mean blood cadmium level in the study population was 0.43g/L (median 0.24g/L) and increased with recent and current smoking. As expected, shorter survival time (AFT model) and higher incidence rate (Aalen model) were found in current smokers for all CVD outcomes and this effect seemed to be partly mediated by cadmium. For the sum of acute myocardial infarction, bypass grafts and percutaneous coronary intervention, and death in ischemic heart disease, about half of the increased risk of such events in current smokers was mediated via cadmium, with similar results for the AFT and Aalen models.ConclusionsCadmium plays an important role in smoking-induced CVDs. This provides evidence for mechanisms and is of importance for both individuals and policy makers.

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