Calcium-phosphorus metabolism and the risk of cardiovascular disease

钙磷代谢与心血管疾病风险

• 批准号: 7651515
• 负责人: ERIC N TAYLOR
• 金额: $ 52.34万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-15 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7651515
• 关键词: 25-hydroxyvitamin D; Address; Advanced Glycosylation End Products; Archives; Arterial Fatty Streak; Atherosclerosis; Blood Pressure; Calcium; Cardiovascular Diseases; Cessation of life; Chronic; Chronic Kidney Failure; Cohort Studies; Coronary heart disease; Creatinine; Data; Development; Endothelin A Receptor; Endothelium; Equilibrium; Estrogens; Follow-Up Studies; Functional disorder; Future; Goals; Health Professional; Homeostasis; Hormones; Hyperparathyroidism; Hypertension; Individual; Inflammation; Infusion procedures; Intake; Interleukin-6; Intestines; Kidney; Ligands; Measures; Mediating; Myocardial Infarction; Nested Case-Control Study; Nuclear; Nurses' Health Study; Organ; Parathyroid Hormone Receptor; Parathyroid Hormone Receptors; Parathyroid Hormones; Phosphorus; Plasma; Play; Population; Postmenopause; Premenopause; Prevention; Prospective Studies; Renin; Reporting; Research; Resistance; Risk; Risk Factors; Role; Rupture; Sample Size; Skeleton; Stimulus; TNFSF11 gene; Update; Variant; Vascular Smooth Muscle; Vascular calcification; Woman; bone; bone turnover; cardiovascular disorder risk; cytokine; heart disease risk; high risk; human PTH protein; hypertensive heart disease; insight; men; novel; phosphorus metabolism; prospective; public health relevance; receptor

DESCRIPTION (provided by applicant): The goal of this application is to answer clinically and scientifically important questions about the role of calcium-phosphorus homeostasis in the development of cardiovascular disease. First, we will determine the associations between parathyroid hormone (PTH) and the development of coronary heart disease (CHD) and hypertension. By direct or indirect actions on bone, kidney, and intestine, PTH plays a central role in calcium and phosphorus balance. However, the PTH receptor also is expressed in vascular smooth muscle and the endothelium, and PTH increases the endothelial expression of factors implicated in endothelial dysfunction and atherosclerosis, such as endothelin-1, the receptor of advanced glycation end products, and IL-6. Second, we will clarify the independent associations between plasma levels of 25-hydroxyvitamin D (25[OH]D), calcium, phosphorus, PTH, creatinine and incident CHD. Previous prospective studies of calcium-phosphorus metabolism and CHD risk did not simultaneously measure these interrelated factors. Finally, we aim to resolve existing controversies about supplemental calcium use, phosphorus intake and the risk of incident CHD. We plan to conduct prospective nested case-control studies of the independent associations between plasma levels of intact PTH, 25(OH)D, calcium, and phosphorus and the risk of CHD and hypertension in the Health Professionals Follow-up Study (HPFS; N=51,529 men) and the Nurses' Health Study (NHS; N=121,700 women). We also plan to conduct prospective cohort studies examining the relations between supplemental calcium use, phosphorus intake, and incident CHD. Because previous data suggest an association between PTH and hypertension in men but not pre-menopausal women, we will determine whether the impact of PTH on the risk of hypertension in post-menopausal women varies by use of post-menopausal hormones. This application represents the first large-scale prospective effort to examine the impact of PTH on CHD risk in individuals without primary hyperparathyroidism or chronic kidney disease. The unique strengths of this application include 1) updated, detailed exposure information accumulated prospectively over long periods, 2) archived plasma, and 3) large sample sizes providing high statistical power. PUBLIC HEALTH RELEVANCE: We expect our studies of calcium and phosphorus metabolism to provide new insights into the development of cardiovascular disease and to identify several novel and modifiable coronary heart disease risk factors. Our findings may stimulate future research that eventually allows factors regulating calcium- phosphorus balance to serve as targets for the prevention of coronary heart disease and hypertension.

描述（由申请人提供）：本申请的目的是在临床和科学上回答有关钙 - 磷稳态在心血管疾病发展中的作用的重要问题。首先，我们将确定甲状旁腺激素（PTH）与冠状动脉疾病（CHD）和高血压的发展之间的关联。通过对骨，肾脏和肠道的直接或间接作用，PTH在钙和磷平衡中起着核心作用。然而，PTH受体也在血管平滑肌和内皮中表达，PTH增加了与内皮功能障碍和动脉粥样硬化有关的因子的内皮表达，例如内皮蛋白1，例如晚期糖化终终产物的受体和IL-6。其次，我们将阐明25-羟基维生素D（25 [OH] D）的血浆水平之间的独立关联，钙，磷，PTH，PTH，肌酐和入射CHD。先前对钙代谢和冠心病风险的前瞻性研究并未同时衡量这些相互关联的因素。最后，我们旨在解决有关补充钙使用，磷摄入量和出现CHD风险的现有争议。我们计划对完整PTH的血浆水平，25（OH）D，钙和磷之间的独立关联进行前瞻性病例对照研究，以及在卫生专业人员随访研究（HPFS; n = 51,529名男性）和护士健康研究（NHS; NHS; NHS; n = 121,700妇女）中的CHD和高血压风险。我们还计划进行前瞻性队列研究，研究补充钙的使用，磷摄入量和入射CHD之间的关系。由于先前的数据表明男性的PTH与高血压之间的关联，但没有绝经前妇女，我们将确定PTH对绝经后妇女高血压风险的影响是否因使用后绝经后激素而变化。该应用是第一个大规模的前瞻性努力，以检查PTH对没有原发性甲状旁腺功能亢进症或慢性肾脏疾病的个体的CHD风险的影响。本应用程序的独特优势包括1）长时间前瞻性地累积的更新，详细的暴露信息，2）存档的等离子体和3）大型样本量提供高统计功率。 公共卫生相关性：我们希望我们对钙和磷代谢的研究可以为心血管疾病的发展提供新的见解，并确定几种新颖而可修改的冠心病危险因素。我们的发现可能会刺激未来的研究，最终允许调节钙 - 磷平衡的因素作为预防冠心病和高血压的靶标。