Abstract

Borne Y, Barregard L, Persson M, Hedblad B, Fagerberg B, Engstrom G: Cadmium exposure and incidence of heart failure and atrial fibrillation: a population-based prospective cohort study. BMJ Open 2015 June 15; 5(6): e007366. Background: Cadmium is an environmental toxin without a known biological function in humans. Tobacco smoke, dietary intake (e.g., legumes and grains), and occupational contact have previously been described as exposure sources. Although a number of adverse health outcomes are associated with cadmium exposure (renal injury, malignancy, and osteoporosis), there are only two prior studies discussing an association with heart failure (HF), with some theoretical data supporting the concept of cadmium-induced cardiotoxicity. No prior studies have evaluated the association between cadmium and atrial fibrillation (AF). Research Question: Are blood cadmium levels associated with the incidence of HF or AF? Methods: TheMalmoDiet and Cancer (MDC) study was a prospective cohort study based in Sweden from March 1991 through September 1996 with an overall participation rate of 41 %. The MDC cardiovascular cohort (MDC-CC) was a random sampling of the MDC taken from 1991 to 1994 and included 4952 individuals from which blood cadmium concentrations were obtained. Self-reported, independent variables included medication use, smoking habits, marital status, educational status, and history of diabetesmellitus.Waist circumference, blood pressure, high-density lipoprotein, low-density lipoprotein, creatinine, C-reactive protein, and blood and erythrocyte cadmium concentrations were all objectively measured. Histories of prior coronary events were retrieved from the Swedish Hospital Discharge Register. Subjects with preexistent HF orAFwere excluded. Ultimately, 4378 subjectswere included in the analysis after exclusion of those with absent measured biomarkers. Cases of incident HF and AF were ascertained from the Swedish Hospital Discharge Register. Cox proportional hazards ratios (HRs) were generated in an age-adjusted model and in a model adjusted for confounders including multiple cardiovascular risk factors. Results: New-onset HF was diagnosed in 143 subjects (53 % men), while new AF was diagnosed in 385 (52 % men). Blood cadmium concentrations (μg/L) were divided into quartiles for the purpose of analysis [median (range): Q1 0.12 (0.02–0.15); Q2 0.19 (0.15–0.24); Q3 0.31 (0.24– 0.49); Q4 0.98 (0.49–5.07)]. Age-adjusted HR for new-onset HF was 2.64 (CI 1.60–4.36) when comparing the first to the fourth quartiles and remained significant in the fully adjusted model (HR 1.95; CI 1.02–3.71); however, the test for trend across quartiles was neither significant (p=0.21) nor linear. Sensitivity analysis was performed separately for each gender and only found a significant association between cadmium and new-onset HF among men. Further analysis revealed a persistently significant difference in HF between the first and fourth blood cadmium quartiles when adjustment for tobacco was performed, which remained significant when assessing blood cadmium and erythrocyte cadmium concentrations. In the multivariant adjusted model, antihypertensive use, diabetes mellitus, waist circumference, CRP, and history of a coronary event were all associated with an increased HF risk. Similarly, age, waist circumference, lipid-lowering agent use, antihypertensive use, and low serum low-density lipoprotein were associated with incident AF. No association was identified between blood cadmium concentration quartiles and AF. Conclusion: The authors conclude that an elevated blood cadmium concentration is associated with an increased risk of HF but not AF, in this population. * Travis D Olives travis.olives@gmail.com

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