Mineral Metabolism and Cardiovascular Risk among Older Adults

描述（由申请人提供）：矿物质代谢紊乱在老年人中非常普遍，并可能通过多种机制对心血管（CV）健康产生不利影响。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，防御甲状旁腺激素过量。高甲状旁腺激素水平促进细胞内钙进入，高血压和心室肥厚。磷酸盐潴留，即使在高正常实验室范围内，也会促使血管平滑肌钙化。将矿物质代谢紊乱与病理性CV结果联系起来的实验发现，已被将血清矿物质代谢标志物与CV危险标志物相关联的人类横断面研究所证实。然而，现有的研究存在很大的局限性，阻碍了对人类矿物质代谢与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CV结果进行全面的流行病学评估，作为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）、甲状旁腺激素（PTH）、磷酸盐和钙的血清测量值添加到先前已建立的心血管健康研究中，并评估这些标志物是否能在长期随访中预测心血管事件的发生。拟议的分析旨在澄清个体矿物质标志物在老年人心血管健康方面的作用，并为未来的试验铺平道路，以这些标志物为目标，作为改善心血管结果的手段。

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.