Urine Cadmium and Risk of Cardiovascular Disease

尿镉与心血管疾病的风险

• 批准号: 9234827
• 负责人: Jaymie R Meliker
• 金额: $ 30.33万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-01 至 2020-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9234827
• 关键词: Acute myocardial infarction; Adult; Agreement; Animals; Atherosclerosis; Behavioral; Biological Markers; Blood Vessels; Cadmium; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Cholesterol; Clinical; Clinical Data; Cohort Studies; Cotinine; Creatinine; Data; Diabetes Mellitus; Dose; Environment; Environmental Exposure; Environmental Tobacco Smoke; Epidemiology; Event; Exposure to; Fertilizers; Food; Functional disorder; General Population; Half-Life; Health; Heart failure; Heavy Metals; Hypertension; Incidence; Incidence Study; Intake; Intervention; Kidney; Light; Link; Longitudinal Studies; Measures; Mediating; Mediation; Morbidity - disease rate; Myocardial Infarction; Osmolalities; Outcome; Participant; Peripheral arterial disease; Physical activity; Population; Population Study; Populations at Risk; Prevention; Prospective cohort; Recruitment Activity; Research; Research Design; Risk; Risk Factors; Role; Sample Size; Sampling; Shapes; Smoking; Source; Spottings; Stroke; Time; Tissues; Tobacco smoking; Trace metal; Uncertainty; Urine; Woman; base; cardiovascular disorder risk; cardiovascular risk factor; cigarette smoking; cohort; design; diet and cancer; disorder risk; endothelial dysfunction; environmental tobacco smoke exposure; epidemiology study; exposed human population; follow-up; hazard; hypercholesterolemia; innovation; inorganic phosphate; insight; men; mortality; never smoker; novel; population based; prospective; public health relevance; response; secondary analysis; urinary

Abstract Cardiovascular disease (CVD) is the major cause of morbidity and mortality in the US and globally. Despite established risk factors for CVD, many cases remain unexplained. Cadmium is a heavy metal that has been shown to damage vascular tissues, induce endothelial dysfunction and promote atherosclerosis in animal and mechanistic studies. Epidemiologic studies have linked cadmium to cardiovascular endpoints such as hypertension, peripheral arterial disease, and cardiovascular mortality. Establishing cadmium as a cardiovascular risk factor, however, has been limited by the lack of prospective incidence studies. In addition few studies have had sufficient statistical power to investigate the association among never smokers to alleviate serious concerns about potential confounding by tobacco smoking. The objective of this proposed study is to investigate the association between incident cardiovascular outcomes and cadmium exposure at levels that are relevant to the general population among never-smokers. Human exposure to cadmium occurs primarily via diverse food types and cigarette smoke. Following intake, cadmium is stored predominantly in the kidney, where it remains for decades (half-life: 10-30 years). A small portion of cadmium is slowly excreted in the urine, making urinary cadmium a well-established biomarker of long-term exposure. We will leverage existing samples and data from the 19,000+ never-smoking participants in the prospective population-based Danish Diet Cancer and Health Cohort which recruited participants 1993-1997 and collected urine at that time. We will include demographic, behavioral, and clinical data from up to 20 years of follow-up to prospectively evaluate the association between cadmium exposure and clinical cardiovascular events. Using a case-cohort study design we will select cases of stroke (N=549), acute myocardial infarction (N=641), and heart failure (N=761), and a comparison subcohort of 600 men and 600 women. Trace metals, creatinine, osmolality, and cotinine will be analyzed in baseline urine samples. As a secondary Aim, we will apply mediation analyses using a counterfactual framework based approach to estimate the extent to which cadmium’s influence on stroke, heart failure, and acute myocardial infarction might be mediated via hypertension, hypercholesterolemia, and diabetes. Results from the mediation analysis may help to identify additional targets for intervention as well as aid in understanding the role of cadmium in the pathophysiology of these CVD events. Our proposed research will be one of the first studies to quantify the association between cadmium and incidence of cardiovascular disease in a longitudinal study with a never-smoking cohort. Sources of cadmium in the environment are well known, including phosphate fertilizers; given widespread cadmium exposure, and that cadmium exposure via food can be lowered by regulating fertilizer, the identification of cadmium as a cardiovascular risk factor can have major implications for the prevention and control of cardiovascular disease.

抽象的 心血管疾病（CVD）是美国和全球发病率和死亡率的主要原因。 尽管已经确定了 CVD 的危险因素，但许多病例仍无法解释镉是一种重金属。 在动物和动物中显示会损伤血管组织，诱导内皮功能障碍并促进动脉粥样硬化 流行病学研究已将镉与心血管终点事件联系起来。 高血压、外周动脉疾病和心血管死亡率。 然而，由于缺乏前瞻性发病率研究，心血管危险因素受到限制。 很少有研究具有足够的统计能力来调查从不吸烟者与吸烟者之间的关系 对吸烟造成的潜在混淆的严重担忧 此项缓解措施的目标。 研究旨在调查心血管结局与镉暴露之间的关联 人类接触镉的水平与一般不吸烟者相关。 镉主要通过不同的食物类型和香烟烟雾摄入后储存在体内。 镉会在肾脏中保留数十年（半衰期：10-30 年）。 尿液中的镉，使尿镉成为长期暴露的成熟生物标志物。 来自 19,000 多名不吸烟参与者的现有样本和数据 丹麦饮食癌症与健康队列于 1993 年至 1997 年招募参与者并收集当时的尿液。 我们将包括长达 20 年的随访和前瞻性的人口统计、行为和临床数据 使用病例队列评估镉暴露与临床心血管事件之间的关联。 研究设计我们将选择中风（N=549）、急性心肌梗塞（N=641）和心力衰竭的病例 (N=761)，以及由 600 名男性和 600 名女性组成的比较小组。 将在基线尿液样本中分析可替宁 作为次要目标，我们将应用中介分析。 使用基于反事实框架的方法来估计镉对环境的影响程度 中风、心力衰竭和急性心肌梗塞可能是通过高血压介导的， 中介分析的结果可能有助于确定其他目标。 进行干预并帮助了解镉在这些 CVD 病理生理学中的作用 我们提出的研究将是量化镉和镉之间关系的首批研究之一。 一项针对从不吸烟人群的纵向研究中心血管疾病的发病率。 环境中的镉是众所周知的，包括磷肥；以及 可以通过调节肥料来降低通过食物摄入的镉，将镉确定为一种 心血管危险因素对心血管疾病的预防和控制具有重大影响。