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. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL084443-01A2
Application #
7317846
Study Section
Special Emphasis Panel (ZRG1-HOP-Q (02))
Program Officer
Olson, Jean
Project Start
2007-09-01
Project End
2010-05-31
Budget Start
2007-09-01
Budget End
2008-05-31
Support Year
1
Fiscal Year
2007
Total Cost
$510,956
Indirect Cost
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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de Boer, Ian H; Levin, Gregory; Robinson-Cohen, Cassianne et al. (2012) Serum 25-hydroxyvitamin D concentration and risk for major clinical disease events in a community-based population of older adults: a cohort study. Ann Intern Med 156:627-34
Levin, Gregory P; Robinson-Cohen, Cassianne; de Boer, Ian H et al. (2012) Genetic variants and associations of 25-hydroxyvitamin D concentrations with major clinical outcomes. JAMA 308:1898-905
Shoben, Abigail B; Levin, Gregory; de Boer, Ian H et al. (2012) Variation in oral calcitriol response in patients with stages 3-4 CKD. Am J Kidney Dis 59:645-52
Robinson-Cohen, Cassianne; Katz, Ronit; Hoofnagle, Andrew N et al. (2011) Mineral metabolism markers and the long-term risk of hip fracture: the cardiovascular health study. J Clin Endocrinol Metab 96:2186-93
Linefsky, Jason P; O'Brien, Kevin D; Katz, Ronit et al. (2011) Association of serum phosphate levels with aortic valve sclerosis and annular calcification: the cardiovascular health study. J Am Coll Cardiol 58:291-7
de Boer, Ian H; Katz, Ronit; Chonchol, Michel et al. (2011) Serum 25-hydroxyvitamin D and change in estimated glomerular filtration rate. Clin J Am Soc Nephrol 6:2141-9

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