Marian Dejaeger1,2, Leen Antonio3,4, Roger Bouillon3,4, Hannes Moors1,2, Frederick C W Wu5, Terence W O'Neill6, Ilpo T Huhtaniemi7, Giulia Rastrelli8, Gianni Forti8, Mario Maggi8, Felipe F Casanueva9, Jolanta Slowikowska-Hilczer10, Margus Punab11,12, Evelien Gielen1,2, Jos Tournoy1,2, Dirk Vanderschueren3,4. 1. Department of Public Health and Primary Care, KU Leuven, 3000 Leuven, Belgium. 2. Department of Geriatrics, University Hospitals Leuven, 3000 Leuven, Belgium. 3. Department of Clinical and Experimental Medicine, KU Leuven, 3000 Leuven, Belgium. 4. Department of Endocrinology, University Hospitals Leuven, 3000 Leuven, Belgium. 5. Division of Endocrinology, Medicine and Health, University of Manchester, Manchester, UK. 6. Centre for Epidemiology Versus Arthritis, The University of Manchester & NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, M13 9PL Manchester, UK. 7. Department of Metabolism, Digestion and Reproduction, Imperial College London, Hammersmith Campus, London W12 ONN, UK. 8. Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50121 Florence, Italy. 9. Department of Medicine, Santiago de Compostela University, Complejo Hospitalario Universitario de Santiago (CHUS); CIBER de Fisiopatología Obesidad y Nutrición (CB06/03), Instituto Salud Carlos III, 15890 Santiago de Compostela, Spain. 10. Department of Andrology and Reproductive Endocrinology, Medical University of Łódź, 90 137 Lodz, Poland. 11. Andrology Centre, Tartu University Hospital, 50090 Tartu, Estonia. 12. Institute of Clinical Medicine, University of Tartu, 50090 Tartu, Estonia.
Abstract
CONTEXT: Low total 25-hydroxyvitamin D (25(OH)D) has been associated with mortality. Whether vitamin D in its free form or 1,25-dihydroxyvitamin D (1,25(OH)2D), provide any additional information is unclear. OBJECTIVE: To determine what level of 25(OH)D is predictive for mortality and if free 25(OH)D or 1,25(OH) 2 D concentrations have any added value. METHODS: This prospective cohort comprised 1915 community-dwelling men, aged 40 to 79 years. Intervention included determination of association of total and free 25(OH)D and 1,25(OH) 2 D concentrations with survival status. Vitamin D results were grouped into quintiles. For total 25(OH)D, specific cutoff values were also applied. Cox proportional hazard models were used adjusted for center, body mass index, smoking, alcohol, physical activity, season of blood sample, kidney function, and number of comorbidities. RESULTS: A total of 469 (23.5%) men died during a mean follow-up of 12.3 ± 3.4 years. Compared to those with normal vitamin D values (> 30 µg/L), men with a total 25(OH)D of less than 20 µg/L had an increased mortality (hazard ratio [HR] 2.03 [95% CI, 1.39-2.96]; P < .001). Likewise, men in the lowest 3 free 25(OH)D quintiles (< 4.43 ng/L) had a higher mortality risk compared to the highest quintile (HR 2.09 [95% CI, 1.34-3.25]; P < .01). Mortality risks were similar across all 1,25(OH)2D and vitamin D binding protein quintiles. CONCLUSION: Aging men with vitamin D deficiency have a 2-fold increased mortality risk. Determinations of either the free fractions of vitamin D or measurement of its active form offer no additional information on mortality risks.
CONTEXT: Low total 25-hydroxyvitamin D (25(OH)D) has been associated with mortality. Whether vitamin D in its free form or 1,25-dihydroxyvitamin D (1,25(OH)2D), provide any additional information is unclear. OBJECTIVE: To determine what level of 25(OH)D is predictive for mortality and if free 25(OH)D or 1,25(OH) 2 D concentrations have any added value. METHODS: This prospective cohort comprised 1915 community-dwelling men, aged 40 to 79 years. Intervention included determination of association of total and free 25(OH)D and 1,25(OH) 2 D concentrations with survival status. Vitamin D results were grouped into quintiles. For total 25(OH)D, specific cutoff values were also applied. Cox proportional hazard models were used adjusted for center, body mass index, smoking, alcohol, physical activity, season of blood sample, kidney function, and number of comorbidities. RESULTS: A total of 469 (23.5%) men died during a mean follow-up of 12.3 ± 3.4 years. Compared to those with normal vitamin D values (> 30 µg/L), men with a total 25(OH)D of less than 20 µg/L had an increased mortality (hazard ratio [HR] 2.03 [95% CI, 1.39-2.96]; P < .001). Likewise, men in the lowest 3 free 25(OH)D quintiles (< 4.43 ng/L) had a higher mortality risk compared to the highest quintile (HR 2.09 [95% CI, 1.34-3.25]; P < .01). Mortality risks were similar across all 1,25(OH)2D and vitamin D binding protein quintiles. CONCLUSION: Aging men with vitamin D deficiency have a 2-fold increased mortality risk. Determinations of either the free fractions of vitamin D or measurement of its active form offer no additional information on mortality risks.