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      Associations of Serum 25-Hydroxyvitamin D, Parathyroid Hormone and Calcium with Cardiovascular Risk Factors: Analysis of 3 NHANES Cycles (2001–2006)

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      Journal: PLoS ONE
      Publisher: Public Library of Science

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          Abstract

          Background

          Increasing evidence suggests a role for mineral metabolism in cardiovascular disease risk. 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH), and calcium may be directly associated with cardiovascular risk factors or mediated by each other.

          Methodology/Principal Findings

          We combined data for adult participants in three cycles of the National Health and Nutrition Examination Survey (2001–2, 2003–4, 2005–6), a representative sample of the civilian, non-institutionalized US population (N = 3,958). Using this data we examined joint associations of 25(OH)D, PTH and calcium with a range of cardiovascular risk factors. 25(OH)D was inversely associated with fasting insulin (mean difference in insulin per 1 standard deviation 25(OH)D: −0.053 (95%CI: −0.091, −0.015)), glucose (−0.046 95%CI: −0.081, −0.012) and systolic blood pressure (SBP) (−0.032 95%CI: −0.062, −0.001), and positively associated with high density lipoprotein cholesterol HDL-c (0.088 95%CI: 0.044, 0.148), after adjustment for ethnicity, smoking, socio-economic status and waist circumference. PTH was positively associated with diastolic blood pressure (0.110, 95%CI: 0.055, 0.164) in confounder adjusted models, but was not associated with other cardiovascular risk factors. Albumin adjusted calcium was associated with triglycerides (0.102 95%CI: 0.063, 0.141), postload glucose (0.078, 95%CI: 0.025, 0.130), fasting insulin (0.074, 95%CI: 0.044, 0.104), HbA1c (0.070, 95%CI: 0.036, 0.105), SBP (0.064, 95%CI: 0.028, 0.100), fasting glucose (0.055, 95%CI: 0.018, 0.092) and low density lipoprotein cholesterol (0.052, 95%CI: 0.014, 0.091). With mutual adjustment for each other, these associations remained essentially unchanged.

          Conclusions/Significance

          Lower levels of 25(OH)D and higher levels of calcium and PTH appear to be associated with different cardiovascular risk factors and may therefore affect cardiovascular disease risk through different mechanisms.

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          Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality.

          Harald Dobnig, Stefan Pilz, Hubert Scharnagl … (2008)
          In cross-sectional studies, low serum levels of 25-hydroxyvitamin D are associated with higher prevalence of cardiovascular risk factors and disease. This study aimed to determine whether endogenous 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels are related to all-cause and cardiovascular mortality. Prospective cohort study of 3258 consecutive male and female patients (mean [SD] age, 62 [10] years) scheduled for coronary angiography at a single tertiary center. We formed quartiles according to 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels within each month of blood drawings. The main outcome measures were all-cause and cardiovascular deaths. During a median follow-up period of 7.7 years, 737 patients (22.6%) died, including 463 deaths from cardiovascular causes. Multivariate-adjusted hazard ratios (HRs) for patients in the lower two 25-hydroxyvitamin D quartiles (median, 7.6 and 13.3 ng/mL [to convert 25-hydroxyvitamin D levels to nanomoles per liter, multiply by 2.496]) were higher for all-cause mortality (HR, 2.08; 95% confidence interval [CI], 1.60-2.70; and HR, 1.53; 95% CI, 1.17-2.01; respectively) and for cardiovascular mortality (HR, 2.22; 95% CI, 1.57-3.13; and HR, 1.82; 95% CI, 1.29-2.58; respectively) compared with patients in the highest 25-hydroxyvitamin D quartile (median, 28.4 ng/mL). Similar results were obtained for patients in the lowest 1,25-dihydroxyvitamin D quartile. These effects were independent of coronary artery disease, physical activity level, Charlson Comorbidity Index, variables of mineral metabolism, and New York Heart Association functional class. Low 25-hydroxyvitamin D levels were significantly correlated with variables of inflammation (C-reactive protein and interleukin 6 levels), oxidative burden (serum phospholipid and glutathione levels), and cell adhesion (vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 levels). Low 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels are independently associated with all-cause and cardiovascular mortality. A causal relationship has yet to be proved by intervention trials using vitamin D.
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            25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study.

            Edward L. Giovannucci, Yan Liu, Bruce W. Hollis … (2008)
            Vitamin D deficiency may be involved in the development of atherosclerosis and coronary heart disease in humans. We assessed prospectively whether plasma 25-hydroxyvitamin D (25[OH]D) concentrations are associated with risk of coronary heart disease. A nested case-control study was conducted in 18,225 men in the Health Professionals Follow-up Study; the men were aged 40 to 75 years and were free of diagnosed cardiovascular disease at blood collection. The blood samples were returned between April 1, 1993, and November 30, 1999; 99% were received between April 1, 1993, and November 30, 1995. During 10 years of follow-up, 454 men developed nonfatal myocardial infarction or fatal coronary heart disease. Using risk set sampling, controls (n = 900) were selected in a 2:1 ratio and matched for age, date of blood collection, and smoking status. After adjustment for matched variables, men deficient in 25(OH)D ( or=30 ng/mL) (relative risk [RR], 2.42; 95% confidence interval [CI], 1.53-3.84; P < .001 for trend). After additional adjustment for family history of myocardial infarction, body mass index, alcohol consumption, physical activity, history of diabetes mellitus and hypertension, ethnicity, region, marine omega-3 intake, low- and high-density lipoprotein cholesterol levels, and triglyceride levels, this relationship remained significant (RR, 2.09; 95% CI, 1.24-3.54; P = .02 for trend). Even men with intermediate 25(OH)D levels were at elevated risk relative to those with sufficient 25(OH)D levels (22.6-29.9 ng/mL: RR, 1.60 [95% CI, 1.10-2.32]; and 15.0-22.5 ng/mL: RR, 1.43 [95% CI, 0.96-2.13], respectively). Low levels of 25(OH)D are associated with higher risk of myocardial infarction in a graded manner, even after controlling for factors known to be associated with coronary artery disease.
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              Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: data from the Third National Health and Nutrition Examination Survey.

              David Martins, Myles Wolf, Deyu Pan … (2007)
              Results of several epidemiologic and clinical studies have suggested that there is an excess risk of hypertension and diabetes mellitus in persons with suboptimal intake of vitamin D. We examined the association between serum levels of 25-hydroxyvitamin D (25[OH]D) and select cardiovascular disease risk factors in US adults. A secondary analysis was performed with data from the Third National Health and Nutrition Examination Survey, a national probability survey conducted by the National Center for Health Statistics between January 1, 1988, and December 31, 1994, with oversampling of persons 60 years and older, non-Hispanic black individuals, and Mexican American individuals. There were 7186 male and 7902 female adults 20 years and older with available data in the Third National Health and Nutrition Examination Survey. The mean 25(OH)D level in the overall sample was 30 ng/mL (75 nmol/L). The 25(OH)D levels were lower in women, elderly persons (>or=60 years), racial/ethnic minorities, and participants with obesity, hypertension, and diabetes mellitus. The adjusted prevalence of hypertension (odds ratio [OR], 1.30), diabetes mellitus (OR, 1.98), obesity (OR, 2.29), and high serum triglyceride levels (OR, 1.47) was significantly higher in the first than in the fourth quartile of serum 25(OH)D levels (P<.001 for all). Serum 25(OH)D levels are associated with important cardiovascular disease risk factors in US adults. Prospective studies to assess a direct benefit of cholecalciferol (vitamin D) supplementation on cardiovascular disease risk factors are warranted.
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                Author and article information

                Contributors
                : Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, USA )
                ISSN (Electronic): 1932-6203
                Publication date Collection: 2010
                Publication date (Electronic): 9 November 2010
                Volume: 5
                Issue: 11
                Electronic Location Identifier: e13882
                Affiliations
                [1]Department of Social Medicine, Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, United Kingdom
                Maastricht University, Netherlands
                Author notes

                Conceived and designed the experiments: AF DL. Analyzed the data: AF. Wrote the paper: AF DW DL.

                Article
                Publisher ID: 10-PONE-RA-19697R2
                DOI: 10.1371/journal.pone.0013882
                PMC ID: 2976699
                PubMed ID: 21085485
                SO-VID: f7a8f440-69c9-4151-9874-56ef9597d6f6
                Copyright © Fraser et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                Date received : 10 June 2010
                Date accepted : 14 October 2010
                Page count
                Pages: 6
                Categories
                Subject: Research Article
                Subject: Cardiovascular Disorders
                Subject: Diabetes and Endocrinology
                Subject: Public Health and Epidemiology/Epidemiology

                ScienceOpen disciplines: Uncategorized
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                ScienceOpen disciplines: Uncategorized

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