Mineral Metabolism and Cardiovascular Risk among Older Adults

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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.