Vitamin D deficiency is much more common in African Americans than whites. The prevalence of elevated parathyroid hormone (PTH), typically a consequence of depressed vitamin D levels and/or low calcium intake, is also high in African Americans. Obesity, which disproportionately affects African Americans (especially women), has also been linked to an excessive prevalence of vitamin D deficiency and elevated PTH. However, maintenance of serum calcium concentrations by chronic PTH elevations has known deleterious physiological effects within the vasculature and myocardium such as vasoconstriction, activation of fibroblasts, insulin resistance, dyslipidemia, fat deposition and down regulation of endothelial nitric oxide - all of which plausibly contribute to elevated blood pressure (BP)and vascular and pressure- sensitive target organ injury, weight gain, dyslipidemia, and glucose intolerance. We propose a study in ~ 65 healthy, normotensive African Americans enrolled in the NIH-funded ONOSS study to examine the following before and after a 6 week period of dietary sodium supplementation:
Aim #1 : determine blood pressure (BP)(cuff and ambulatory 24 hour), arterial stiffness (AS), peripheral vascular resistance(PVR) and nitric oxide (NO)production and their relation to circulating levels of 25-OH vitamin D (25-OH D) and PTH at baseline;
Aim #2 : determine the relationship of baseline 25-OH D and PTH levels with subsequent changes in BP, AS, and PVR after dietary salt loading;
Aim #3 :Determine the relationship of the change in NO metabolites and stimulated NO production in platelets to changes in BP, AS and PVR after dietary salt loading;
Aim #4 : Determine the association of baseline 25-OH D and PTH levels with baseline levels of circulating markers of oxidative stress (total isoprostanes, nuclear factor kappa beta) and free radicals (nitrotyrosine, dityrosine, chlorotyrosine), and in turn, link circulating markers of oxidative stress to changes in BP, AS, PVR, urinary NO metabolites, and platelet production of NO after dietary salt loading Relevance: Vitamin D deficiency and secondary increase in PTH are common, particularly amongst obese persons and African Americans. They both have vascular and physiological effects that lead to the excessive prevalence of elevated BP, vascular and pressure-related target-organ injury, endothelial dysfunction, and salt sensitivity in African Americans. It is important to understand the role of vitamin D deficiency and prolonged elevation of PTH to the abnormal physiology that likely contributes to common cardiovascular complication since vitamin D supplementation is affordable, relatively non-toxic, and is available in oral formulations. ? ? ? ?
| Valiña-Tóth, Anna Liza B; Lai, Zongshan; Yoo, Wonsuk et al. (2010) Relationship of vitamin D and parathyroid hormone with obesity and body composition in African Americans. Clin Endocrinol (Oxf) 72:595-603 |
