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Vitamin-D concentrations, cardiovascular risk and events - a review of epidemiological evidence

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Abstract

Vitamin D has long been established as an elemental factor of bone physiology. Beyond mineral metabolism, the expression of the vitamin D receptor has been identified throughout the cardiovascular (CV) system. Experimental studies showed beneficial effects of vitamin D on heart and vessels, but vitamin D intoxication in animals also led to hypercalcemia and vascular calcification. Our knowledge has been extended by epidemiological studies that showed that 25-hydroxyvitamin D (25(OH)D) levels are inversely associated with an increased CV risk itself, but also with established CV risk factors, such as arterial hypertension, endothelial dysfunction and atherosclerosis. Conversely, randomized controlled trials could not document significant and consistent effects of vitamin D supplementation on CV risk or events. Potential explanations may lie in differences in reference ranges or the possibility that low vitamin D in CV disease is only an epiphenomenon. In the latter case, the key question is why low 25(OH)D levels are such a strong predictor of health. While we wait for new data, the current conclusion is that vitamin D is a strong risk marker for CV risk factors and for CV diseases itself.

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Authors and Affiliations

  1. Swiss Cardiovascular Centre Bern, Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 8, 3010, Bern, Switzerland

    Martin Robert Grübler

  2. Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria

    Martin Robert Grübler, Stefan Pilz, Christian Trummer, Christian Müllner, Verena Schwetz & Marlene Pandis

  3. Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, and Rheumatology), Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany

    Winfried März

  4. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria

    Winfried März

  5. Synlab Academy, Synlab Services GmbH, and Augsburg, Mannheim, Germany

    Winfried März

  6. Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, Netherlands

    Stefan Pilz

  7. Mannheim Institute of Public Health, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany

    Tanja B. Grammer

  8. Department of Internal Medicine, Division of Cardiology, Medical University of Graz, Graz, Austria

    Nicolas Verheyen & Andreas Tomaschitz

  9. Bad Gleichenberg Clinic, Schweizereiweg 4, 8344, Bad Gleichenberg, Austria

    Andreas Tomaschitz

  10. I.O.S. Coleman, Naples, Italy

    Antonella Fiordelisi & Daniela Laudisio

  11. Department of Medicine, Surgery Odontoiatrics-Scuola Medica Salernitana, University of Salerno, Salerno, Italy

    Ersilia Cipolletta & Guido Iaccarino

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Conflict of interest

M.R.G. received partial travel support by Amgen Switzerland AG and Synlab Holding Deutschland Germany, GmbH. WM reports grants and personal fees from AMGEN, BASF, Sanofi, Siemens Diagnostics, Aegerion Pharmaceuticals, Astrazeneca, Danone Research, Numares, Pfizer, Hoffmann LaRoche: personal fees from MSD, Alexion; grants from Abbott Diagnostics, all outside the submitted work. W.M. is employed with synlab Holding Deutschland GmbH. Other authors report no potential conflicts of interest in regard to the present work.

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All studies cited in the current manuscript that were performed by the authors and include procedures performed involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. That includes that informed consent was obtained from all individual participants included in the studies cited hat where performed by any of the authors.

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Grübler, M.R., März, W., Pilz, S. et al. Vitamin-D concentrations, cardiovascular risk and events - a review of epidemiological evidence. Rev Endocr Metab Disord 18, 259–272 (2017). https://doi.org/10.1007/s11154-017-9417-0

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