Association of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone with mortality among middle-aged and older European men

David M Lee; Dirk Vanderschueren; Steven Boonen; Terence W O'Neill; Neil Pendleton; Stephen R Pye; Rathi Ravindrarajah; Evelien Gielen; Frank Claessens; György Bartfai; Felipe F Casanueva; Joseph D Finn; Gianni Forti; Aleksander Giwercman; Thang S Han; Ilpo T Huhtaniemi; Krzysztof Kula; Michael E J Lean; Margus Punab; Frederick C W Wu; European Male Ageing Study Group

doi:10.1093/ageing/aft206

Association of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone with mortality among middle-aged and older European men

Age Ageing. 2014 Jul;43(4):528-35. doi: 10.1093/ageing/aft206. Epub 2013 Dec 26.

Authors

David M Lee¹, Dirk Vanderschueren², Steven Boonen³, Terence W O'Neill⁴, Neil Pendleton⁵, Stephen R Pye⁴, Rathi Ravindrarajah⁶, Evelien Gielen³, Frank Claessens⁷, György Bartfai⁸, Felipe F Casanueva⁹, Joseph D Finn⁶, Gianni Forti¹⁰, Aleksander Giwercman¹¹, Thang S Han¹², Ilpo T Huhtaniemi¹³, Krzysztof Kula¹⁴, Michael E J Lean¹⁵, Margus Punab¹⁶, Frederick C W Wu⁶; European Male Ageing Study Group

Affiliations

¹ Cathie Marsh Centre for Census and Survey Research, School of Social Sciences, The University of Manchester, Manchester, UK.
² Andrology and Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium.
³ Geriatric Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
⁴ Arthritis Research UK Centre for Epidemiology, Institute of Inflammation and Repair, The University of Manchester, Manchester, UK.
⁵ Clinical & Cognitive Neurosciences, Institute of Brain, Behaviour and Mental Health, The University of Manchester, UK.
⁶ Andrology Research Unit, Centre for Endocrinology and Diabetes, Institute of Human Development, The University of Manchester, Manchester, UK.
⁷ Molecular Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium.
⁸ Department of Obstetrics, Gynecology and Andrology, Albert Szent-György Medical University, Szeged, Hungary.
⁹ Department of Medicine, Santiago de Compostela University, Complejo Hospitalario Universitario de Santiago, CIBER de Fisiopatología Obesidad y Nutricion, Instituto Salud Carlos III, Santiago de Compostela, Spain.
¹⁰ Endocrinology Unit, Department of Clinical Physiopathology, University of Florence, Florence, Italy.
¹¹ Reproductive Medicine Centre, Malmö University Hospital, University of Lund, Malmö, Sweden.
¹² Department of Endocrinology, Royal Free and University College Hospital Medical School, Royal Free Hospital, London, UK.
¹³ Department of Reproductive Biology, Imperial College London, London, UK.
¹⁴ Department of Andrology and Reproductive Endocrinology, Medical University of Łódź, Łódź, Poland.
¹⁵ Division of Developmental Medicine, Human Nutrition Section, University of Glasgow, Glasgow, UK.
¹⁶ Andrology Unit, United Laboratories of Tartu University Clinics, Tartu, Estonia.

PMID: 24375224
DOI: 10.1093/ageing/aft206

Abstract

Background: vitamin D deficiency has been associated with an increased risk of mortality, but whether this relationship is causal or linked to co-existent comorbidity and adverse life factors remains uncertain. Our objective was to determine whether endogenous 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D) and parathyroid hormone (PTH) levels predicted all-cause, cardiovascular and cancer mortality independently of health and lifestyle factors.

Setting: : prospective cohort analysis within the European Male Ageing Study.

Participants: : 2,816 community-dwelling men aged 40-79 years at baseline.

Methods: : Cox regression was used to examine the association of all-cause mortality with 25(OH)D, 1,25(OH)2D and PTH; cardiovascular and cancer mortality were modelled using competing-risks regression. Results were expressed as hazard ratios (HR) and 95% confidence intervals (CIs) for Cox models; sub-hazard ratios (SHR) and 95% CIs for competing-risks models.

Results: : a total of 187 men died during a median of 4.3 years of follow-up. Serum levels of 25(OH)D (per 1 SD decrease: HR = 1.45; 95% CI = 1.16, 1.81) and 1,25(OH)2D (per 1 SD decrease: HR = 1.20; 95% CI = 1.00, 1.44) were associated with an increased risk of all-cause mortality after adjusting for age, centre, smoking, self-reported morbidities, physical activity and functional performance. Only levels of 25(OH)D <25 nmol/l predicted cancer mortality (SHR = 3.33; 95% CI = 1.38, 8.04).

Conclusion: : lower 25(OH)D and 1,25(OH)2D levels independently predicted all-cause mortality in middle-aged and older European men. Associations with cancer mortality were only observed among men with very low levels of 25(OH)D. These associations were only partially explained by the range of adverse health and lifestyle factors measured here.

Keywords: 1,25-dihydroxyvitamin D; 25-hydroxyvitamin D; mortality; older people; parathyroid hormone; population based.

Publication types

Multicenter Study

MeSH terms

Adult
Aged
Aging / blood*
Biomarkers / blood
Cardiovascular Diseases / mortality*
Cohort Studies
Europe
Follow-Up Studies
Humans
Life Style
Male
Middle Aged
Neoplasms / mortality*
Parathyroid Hormone / blood*
Prospective Studies
Regression Analysis
Risk Factors
Surveys and Questionnaires
Survival Rate
Vitamin D / analogs & derivatives*
Vitamin D / blood

Substances

Biomarkers
Parathyroid Hormone
Vitamin D
1,25-dihydroxyvitamin D
25-hydroxyvitamin D