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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, MD;
Stefan Pilz, MD;
Hubert Scharnagl, PhD;
Wilfried Renner, PhD;
Ursula Seelhorst, MA;
Britta Wellnitz, LLD;
Jürgen Kinkeldei, DEng;
Bernhard O. Boehm, MD;
Gisela Weihrauch, MSc;
Winfried Maerz, MD
Arch Intern Med. 2008;168(12):1340-1349.
Background 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.
Methods 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.
Results 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).
Conclusions 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.
Author Affiliations: Division of Endocrinology and Nuclear Medicine, Department of Internal Medicine (Dr Dobnig), and Clinical Institute of Medical and Chemical Laboratory Diagnostics (Drs Scharnagl, Renner, and Maerz and Ms Weihrauch), Medical University of Graz, Graz, Austria; and Department of Public Health, Social and Preventive Medicine, Mannheim Medical Faculty, University of Heidelberg, Heidelberg (Dr Pilz), LURIC Study Nonprofit LLC, Freiburg (Ms Seelhorst and Dr Wellnitz), Synlab Center of Laboratory Diagnostics Stuttgart, Leinfelden-Echterdingen (Dr Kinkeldei), Division of Endocrinology and Diabetes, Department of Internal Medicine, University of Ulm, Ulm (Dr Boehm), and Synlab Center of Laboratory Diagnostics Heidelberg, Eppelheim (Dr Maerz), Germany.
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