Phosphorus and Vitamin D Metabolism and Cardiovascular Outcomes: The MESA Study

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DESCRIPTION (provided by applicant): Evolving evidence suggests that phosphorous excess and vitamin D insufficiency contribute to cardiovascular disease (CVD) and premature death. Phosphorous excess directly transforms vascular smooth muscle tissue into osteoblast-like cells, which calcify the medial vessel wall. Vitamin D insufficiency activates the renin-angiotensin-aldosterone system, stimulates atherogenic cytokine expression, and directly promotes cardiomyocyte growth. Important gaps in existing knowledge constrain full understanding of mineral metabolism-CVD relationships in humans. First, current ascertainment of the phosphorous and vitamin D metabolic axes is crude, obscuring relationships with CVD outcomes and impeding translation to clinical application. Second, CVD pathways through which disturbed mineral metabolism may promote CVD are incompletely evaluated in humans. Third, phosphorous and vitamin D metabolism vary strongly by race/ethnicity, but knowledge of cardiovascular consequences of mineral metabolism disorders derive from populations with limited diversity. The overall goal of this proposal is to define relationships of phosphorous excess and vitamin D insufficiency with pathophysiologically relevant clinical and subclinical CVD outcomes in a community based, multi-ethnic population. We will characterize the phosphorous and vitamin D metabolic axes using multiple serum and urine biomarkers measured from previously collected baseline samples obtained from 6,736 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). MESA offers a unique opportunity to comprehensively evaluate novel CVD risk factors because of its multi-ethnic sampling strategy, exclusion of clinical CVD at baseline, state-of-the-art subclinical CVD measurements, and adjudicated cardiovascular events. We hypothesize that biomarkers of phosphorous excess (higher concentrations of serum phosphorous, serum fibroblast growth factor-23, and urine phosphorous) and vitamin D deficiency (lower 25- hydroxyvitamin D and higher parathyroid hormone concentrations) will be associated with incident cardiovascular events, incident hypertension, and incident chronic kidney disease. We further hypothesize that biomarkers of phosphorous excess and vitamin D deficiency will be associated with subclinical cardiovascular disease measurements that are directly relevant to mineral metabolism: coronary artery calcification, thoracic aorta calcification, arterial stiffness, and left ventricular mass.