Mineral Metabolism and Cardiovascular Risk among Older Adults

描述(申请人提供)：矿物质代谢紊乱在老年人中非常普遍，并可能通过不同的机制对心血管(CV)健康造成不利影响。在实验模型中，维生素D抑制肾素-血管紧张素系统，降低炎症细胞因子，并防御甲状旁腺激素过剩。较高的甲状旁腺激素水平促进细胞内钙离子进入，高血压和心室肥厚。磷酸盐滞留，即使在实验室的高正常范围内，也会引发血管平滑肌钙化。将矿物质代谢紊乱与病理心血管疾病相联系的实验结果已被人类血清矿物质代谢标记物与心血管风险标记物相关的横断面研究所证实。然而，现有的研究有很大的局限性，阻碍了对人体矿物质代谢和心血管风险之间因果关系的推断。当前知识的基本差距支持对矿物质代谢紊乱和心血管疾病结果进行全面的流行病学评估，这是最合适的下一步科学步骤。我们建议将25-羟基维生素D(25-OH2)、甲状旁腺素、磷酸盐和钙的血清测量添加到先前从一项已建立的心血管健康研究收集的数据中，并评估这些标记物是否预测长期随访期间发生的心血管事件。拟议的分析旨在阐明单个矿物质标记物在老年人心血管健康方面的作用，并为未来针对这些标记物的试验铺平道路，以此作为改善心血管疾病结果的一种手段。

Description (provided by applicant): Disturbances in mineral metabolism are highly prevalent among older people and may adversely impact cardiovascular (CV) health through diverse mechanisms. In experimental models, vitamin D suppresses the renin-angiotensin system, lowers inflammatory cytokines and defends against parathyroid hormone excess. Higher parathyroid hormone levels promote intracellular calcium entry, hypertension and ventricular hypertrophy. Phosphate retention, even within the high-normal laboratory range, instigates vascular smooth muscle calcification. Experimental findings that connect mineral metabolism disturbances with pathologic CV findings have been corroborated by cross sectional studies in humans correlating serum markers of mineral metabolism with CV risk markers. However, existing studies have major limitations that hinder inference of causal relationships between mineral metabolism and CV risk in humans. Essential gaps in current knowledge support a comprehensive epidemiologic evaluation of mineral metabolism disturbances and CV outcomes as the most appropriate next scientific step. We propose to add serum measurements of 25-hydroxy vitamin D (25-OH2), PTH, phosphate, and calcium to previously collected data from an established cardiovascular health study, and to evaluate whether these markers predict incident CV events during long-term follow-up. Proposed analyses aim to clarify the roles of individual mineral markers with respect to CV health among older adults and to pave the way for future trials that target these markers as a means to improve CV outcomes.