Serum vitamin D, parathyroid hormone levels, and carotid atherosclerosis
Introduction
Vitamin D and parathyroid hormone (PTH) are widely recognized for their important roles in maintaining extracellular calcium and phosphorous homeostasis and in regulating bone formation and bone resorption. Vitamin D, largely obtained from cutaneous exposure to ultraviolet B radiation (290–315 nm) and to a lesser extent from dietary and supplemental sources, is metabolized by the liver to 25-hydroxyvitamin D [25(OH)D], the primary circulating storage form of vitamin D. 1,25-dihydroxyvitamin D [1,25(OH)2D], produced largely in the kidney following a second hydroxylation, is the tightly regulated activated molecule of vitamin D. PTH, on the other hand, is a peptide hormone secreted by the parathyroid gland in response to low circulating calcium and phosphorus concentrations. PTH stimulates the reabsorption of calcium in the kidney, the resorption of calcium from the skeleton, and enhances the renal production of 1,25(OH)2D.
Evidence from several lines of scientific inquiry suggests vitamin D and PTH may also play a role in the pathogenesis of cardiovascular disease. Hypovitaminosis D has been independently associated with increased rates of hypertension [1], diabetes [2], peripheral arterial disease [3], myocardial infarction [4], [5], and related mortality [6], [7]. Numerous studies have shown patients with hyperparathyroidism experience an excess risk of mortality from cardiovascular disease [8], [9]. High PTH levels have also been independently associated with higher rates of cardiovascular disease in the general population [10]. Vitamin D and PTH may influence cardiovascular risk through a shared association with atherosclerotic plaque formation and progression. However, both vitamin D and PTH have been inconsistently found to be associated with early signs of atherosclerosis, such as increased carotid intima-media wall thickness (IMT) determined with B-mode ultrasound [11], [12], [13]. Existing studies have been limited by small clinic-based samples and the failure to examine the combined influence of both vitamin D metabolites and PTH. Therefore, in the current study we aimed to determine the individual and combined associations of 25(OH)D, 1,25(OH)2D, and PTH levels with the extent of carotid artery IMT in a population-based cohort of community-dwelling older adults from the Rancho Bernardo Heart and Chronic Disease Study.
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Study population
The Rancho Bernardo Study has been described in detail elsewhere [14]. Briefly, between 1972 and 1974, 82% of all adults living in the southern California community of Rancho Bernardo were enrolled in a study of heart disease risk factors as part of the Lipid Research Clinics Prevalence Study. Nearly all were white and middle to upper-middle class, as assessed by Hollingshead's index [15]. Between 1997 and 1999, 89% of the local surviving community-dwelling members attended a clinic visit when
Results
The demographic, anthropometric, and clinical characteristics of the study population are presented in Table 1. On average, the 654 adults included in this analysis were aged 75.5 ± 8.5 (range 55–96) years, 64% were women, and the mean body mass index was 25.6 ± 4.1 kg/m2. Most reported a healthy lifestyle, with current smoking in only 4.2%, regular exercise in 74.6%, calcium supplement use in 46.1%, and vitamin D supplement use in 23.6%. Mean 25(OH)D, 1,25(OH)2D, and geometric mean (95% CI) PTH
Discussion
In this community-based cohort, we found a significant inverse stepwise association between serum 25(OH)D levels and internal carotid IMT, but no association with common carotid IMT. The association with internal carotid IMT was independent of age, sex, and multiple other potential confounding factors. There was no evidence of an association between 1,25(OH)2D, the activated metabolite of vitamin D, or PTH with either common carotid or internal carotid IMT. In only one of several subgroup
Acknowledgements
The Rancho Bernardo Study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (DK31801) and by the National Institute on Aging (AG07181). JPR was supported by a grant from the National Heart, Lung, and Blood Institute (T32 HL07024). None of the other authors have any personal or professional conflict of interest.
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