Dataset Information

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

ABSTRACT: BACKGROUND:Smoking 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. METHODS:We used prospective data on CVD (incidence and mortality) in a Swedish population-based cohort of 4304 middle-aged men and women (the Malmö Diet and Cancer Study). Blood cadmium was analyzed in base-line samples from 1991, and clinical events were followed up for 16-19 years 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. RESULTS:The mean blood cadmium level in the study population was 0.43 μg/L (median 0.24 μg/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. CONCLUSIONS:Cadmium plays an important role in smoking-induced CVDs. This provides evidence for mechanisms and is of importance for both individuals and policy makers.

SUBMITTER: Li H

PROVIDER: S-EPMC6570857 | biostudies-other | 2019 Jun

REPOSITORIES: biostudies-other

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

Li Huiqi H Fagerberg Björn B Sallsten Gerd G Borné Yan Y Hedblad Bo B Engström Gunnar G Barregard Lars L Andersson Eva M EM

Environmental health : a global access science source 20190614 1

<h4>Background</h4>Smoking 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 ...[more]

PMID: 31200698

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Project description:Cadmium exposure may increase the risk of cardiovascular disease. The only published longitudinal study on cadmium and incident cardiovascular disease was performed in American Indians with relatively high cadmium exposure.Our aim was to examine the association between blood cadmium at baseline and incident cardiovascular events in a population-based study of Swedish men and women with cadmium levels similar to those of most European and U.S.A Swedish population-based cohort (n = 6,103, age 46-67 years) was recruited between 1991 and 1994. After we excluded those with missing data on smoking, 4,819 participants remained. Acute coronary events, other major cardiac events, stroke, and cardiovascular mortality were followed until 2010. Associations with blood cadmium (estimated from cadmium in erythrocytes) were analyzed using Cox proportional hazards regression including potential confounders and important cardiovascular risk factors.Hazard ratios for all cardiovascular end points were consistently increased for participants in the 4th blood cadmium quartile (median, 0.99 ?g/L). In models that also included sex, smoking, waist circumference, education, physical activity, alcohol intake, serum triglycerides, HbA1c, and C-reactive protein, the hazard ratios comparing the highest and lowest quartiles of exposure were 1.8 (95% CI: 1.2, 2.7) for acute coronary events, and 1.9 (1.3, 2.9) for stroke. Hazard ratios in never-smokers were consistent with these estimates.Blood cadmium in the highest quartile was associated with incident cardiovascular disease and mortality in our population-based samples of Swedish adults. The consistent results among never-smokers are important because smoking is a strong confounder. Our findings suggest that measures to reduce cadmium exposures are warranted, even in populations without unusual sources of exposure.Barregard L, Sallsten G, Fagerberg B, Borné Y, Persson M, Hedblad B, Engström G. 2016. Blood cadmium levels and incident cardiovascular events during follow-up in a population-based cohort of Swedish adults: the Malmö Diet and Cancer Study. Environ Health Perspect 124:594-600;?http://dx.doi.org/10.1289/ehp.1509735.

Project description:AIMS/HYPOTHESIS:Growth differentiation factor 15 (GDF-15) is an anti-inflammatory cytokine of the transforming growth factor-? superfamily. Circulating levels of GDF-15 are associated with hyperglycaemia among people with obesity or diabetes, but longitudinal evidence on the association between GDF-15 levels and diabetes risk is scarce. Our aim was to explore whether circulating levels of GDF-15 at baseline are positively associated with future diabetes incidence in a middle-aged urban population. METHODS:Between 1991 and 1994, baseline fasting plasma GDF-15 levels were measured in 4360 individuals without diabetes (mean age 57.4?±?5.96 years, 38.6% men) who were participants in the Malmö Diet and Cancer-Cardiovascular Cohort. After a follow-up of 19.0?±?5.16 years (mean?±?SD), Cox proportional hazards regression analysis was used for the study of the relationship between baseline GDF-15 and incident diabetes, with adjustment for established confounders. A sensitivity analysis included further adjustment for levels of C-reactive protein (CRP). RESULTS:During the follow-up period, 621 individuals developed diabetes. The multivariate-adjusted HR for diabetes incidence was 1.43 (95% CI 1.11, 1.83; p for trend = 0.007) for the fourth compared with the first quartile of GDF-15, and was 1.17 (95% CI 1.07, 1.28; p?<?0.001) per SD increase of GDF-15. If participants were grouped according to baseline fasting glucose, the association between GDF-15 and diabetes risk was only evident in the group without impaired fasting glucose (n?=?3973). The association tended to be less significant with increasing age: multivariate-adjusted HRs for diabetes per SD increase of GDF-15 were 1.24 (95% CI 1.08, 1.42), 1.19 (95% CI 1.00, 1.41) and 1.04 (95% CI 0.89, 1.23) for participants aged ?55, 56-60 (>55 and ?60) and >60 years, respectively. With adjustment for levels of CRP, the HR per SD increase of GDF-15 (1.21, 95% CI 1.09, 1.35) was significant (p?=?0.015), but the HR for the fourth compared with the first quartile of GDF-15 was not significant (HR 1.30; 95% CI 1.01, 1.67; p for trend = 0.061). CONCLUSIONS/INTERPRETATION:GDF-15 may be useful for identification of people with a risk of incident diabetes, especially if those people are ?60 years old.

Dataset Information

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

Publications

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

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