[en] [en] OBJECTIVES: The role of vitamin D deficiency in cardiovascular disease (CVD) is controversial. Inherent biological and analytical limitations compromise the specificity of widely used 25-hydroxyvitamin D [25(OH)D] cut-offs. Simultaneous determination of 25(OH)D and 24,25-dihydroxyvitamin D [24,25(OH)2D] permits a functional assessment of vitamin D metabolism. The present study compared the associations of functional vitamin D deficiency and low vitamin D reservoirs with CVD mortality and CVD burden.
METHODS: 25(OH)D, 24,25(OH)2D, the degree of coronary obstruction on angiography, high-sensitive cardiac troponin T (hs-cTnT), N-terminal brain natriuretic peptide (NT-proBNP), and 10-year CVD mortality were obtained from 2,456 participants of the LURIC (Ludwigshafen Risk and Cardiovascular Health) study.
RESULTS: Neither low 25(OH)D concentrations nor functional vitamin D deficiency were associated with the number of atherosclerotic coronary arteries or the degree of coronary obstruction. Over a median follow-up of 9.9 years, 454 participants died (23.6 %) due to CVD. CVD mortality was doubled in individuals with 25(OH)D concentrations below the widely used cut-off for deficiency of <50 nmol/L [20 ng/mL] (21.6 vs. 11.5 %). In individuals with and without functional vitamin D deficiency, CVD mortality was 25.0 and 16.7 %, respectively. NT-proBNP and heart failure prevalence were also higher in vitamin D deficient individuals.
CONCLUSIONS: Vitamin D deficient individuals have markedly higher CVD mortality, but only marginally higher hs-cTnT concentrations. A higher prevalence of heart failure and higher NT-proBNP concentrations suggest a link between vitamin D deficiency and cardiac function. The traditional and metabolic assessment of vitamin D status showed comparable associations for the different parameters of cardiac health.
Disciplines :
Laboratory medicine & medical technology
Author, co-author :
Herrmann, Markus ; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
Keppel, Martin H ; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
Zelzer, Sieglinde; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
Alonso, Nerea; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
Cavalier, Etienne ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Kleber, Marcus ; Department of Internal Medicine 5 (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany ; Synlab Human Genetics Laboratory, Synlab AG, Mannheim, Germany
Enko, Dietmar ; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
Scharnagl, Hubert; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
Pilz, Stefan ; Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
März, Winfried; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria ; Synlab Human Genetics Laboratory, Synlab AG, Mannheim, Germany ; Synlab Academy, Synlab Holding Germany GmbH, Mannheim, Germany
Language :
English
Title :
The role of functional vitamin D deficiency and low vitamin D reservoirs in relation to cardiovascular health and mortality.
Giuliani S, Barbieri V, Di Pierro AM, Rossi F, Widmann T, Lucchiari M, LC-MS/MS based 25(OH)D status in a large Southern European outpatient cohort: gender-and age-specific differences Eur J Nutr 2019 58 2511 20 https://doi.org/10.1007/s00394-018-1803-1
Jolin Howland BK, Calcium and phosphorus in the serum in relation rickets AMA J Dis Child 1921 22 15
Simmonds N, Becker J, Shipley P, Studies on experimental rickets: Xxi. An experimental demonstration of the existence of a vitamin which promotes calcium deposition JBC 1922 53 293 312 https://doi.org/10.1016/s0021-9258(18)85783-0
Alonso N, Zelzer S, Eibinger G, Herrmann M, Vitamin D metabolites: analytical challenges and clinical relevance Calcif Tissue Int 2023 112 158 77 https://doi.org/10.1007/s00223-022-00961-5
Priemel M, von Domarus C, Klatte TO, Kessler S, Schlie J, Meier S, Bone mineralization defects and vitamin D deficiency: histomorphometric analysis of iliac crest bone biopsies and circulating 25-hydroxyvitamin D in 675 patients J Bone Miner Res 2010 25 305 12 https://doi.org/10.1359/jbmr.090728
Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G, Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects Physiol Rev 2016 96 365 408 https://doi.org/10.1152/physrev.00014.2015
Muscogiuri G, Tirabassi G, Bizzaro G, Orio F, Paschou SA, Vryonidou A, Vitamin D and thyroid disease: to D or not to D? Eur J Clin Nutr 2015 69 291 6 https://doi.org/10.1038/ejcn.2014.265
Cosentino N, Campodonico J, Milazzo V, De Metrio M, Brambilla M, Camera M, Vitamin D and cardiovascular disease: current evidence and future perspectives Nutrients 2021 13 https://doi.org/10.3390/nu13103603
Janjusevic M, Gagno G, Fluca AL, Padoan L, Beltrami AP, Sinagra G, The peculiar role of vitamin D in the pathophysiology of cardiovascular and neurodegenerative diseases Life Sci 2022 289 120193 https://doi.org/10.1016/j.lfs.2021.120193
Amrein K, Scherkl M, Hoffmann M, Neuwersch-Sommeregger S, Köstenberger M, Tmava Berisha A, Vitamin D deficiency 2.0: an update on the current status worldwide Eur J Clin Nutr 2020 74 1498 513 https://doi.org/10.1038/s41430-020-0558-y
Altieri B, Cavalier E, Bhattoa HP, Pérez-López FR, López-Baena MT, Pérez-Roncero GR, Vitamin D testing: advantages and limits of the current assays Eur J Clin Nutr 2020 74 231 47 https://doi.org/10.1038/s41430-019-0553-3
Zittermann A, Pilz S, Vitamin D and cardiovascular disease: an update Anticancer Res 2019 39 4627 35 https://doi.org/10.21873/anticanres.13643
Herrmann M, Zelzer S, Cavalier E, Kleber M, Drexler-Helmberg C, Schlenke P, Functional assessment of vitamin D status by a novel metabolic approach: the low vitamin D profile concept Clin Chem 2023 69 1307 16 https://doi.org/10.1093/clinchem/hvad151
Gholami F, Moradi G, Zareei B, Rasouli MA, Nikkhoo B, Roshani D, The association between circulating 25-hydroxyvitamin D and cardiovascular diseases: a meta-analysis of prospective cohort studies BMC Cardiovasc Disord 2019 19 248 https://doi.org/10.1186/s12872-019-1236-7
Zhang P, Guo D, Xu B, Huang C, Yang S, Wang W, Association of serum 25-hydroxyvitamin D with cardiovascular outcomes and all-cause mortality in individuals with prediabetes and diabetes: results from the UK Biobank prospective cohort study Diabetes Care 2022 45 1219 29 https://doi.org/10.2337/dc21-2193
Mason RS, Rybchyn MS, Abboud M, Brennan-Speranza TC, Fraser DR, The role of skeletal muscle in maintaining vitamin D status in winter Curr Dev Nutr 2019 3 nzz087 https://doi.org/10.1093/cdn/nzz087
Scragg R, Stewart AW, Waayer D, Lawes CMM, Toop L, Sluyter J, Effect of monthly high-dose vitamin D supplementation on cardiovascular disease in the vitamin D assessment study: a randomized clinical trial JAMA Cardiol 2017 2 608 16 https://doi.org/10.1001/jamacardio.2017.0175
Bouillon R, LeBoff MS, Neale RE, Health effects of vitamin D supplementation: lessons learned from randomized controlled trials and mendelian randomization studies J Bone Miner Res 2023 38 1391 403 https://doi.org/10.1002/jbmr.4888
Winkelmann BR, März W, Boehm BO, Zotz R, Hager J, Hellstern P, Rationale and design of the LURIC study - a resource for functional genomics, pharmacogenomics and long-term prognosis of cardiovascular disease Pharmacogenomics 2001 2 S1 73 https://doi.org/10.1517/14622416.2.1.s1
Gaksch M, Jorde R, Grimnes G, Joakimsen R, Schirmer H, Wilsgaard T, Vitamin D and mortality: individual participant data meta-analysis of standardized 25-hydroxyvitamin D in 26916 individuals from a European consortium PLoS One 2017 12 e0170791 https://doi.org/10.1371/journal.pone.0170791
Zelzer S, Meinitzer A, Enko D, Simstich S, Le Goff C, Cavalier E, Simultaneous determination of 24,25-and 25,26-dihydroxyvitamin D3 in serum samples with liquid-chromatography mass spectrometry-a useful tool for the assessment of vitamin D metabolism J Chromatogr, B: Anal Technol Biomed Life Sci 2020 1158 122394 https://doi.org/10.1016/j.jchromb.2020.122394
Zelzer S, Le Goff C, Peeters S, Calaprice C, Meinitzer A, Enko D, Comparison of two LC-MS/MS methods for the quantification of 24,25-dihydroxyvitamin D3 in patients and external quality assurance samples Clin Chem Lab Med 2022 60 74 81 https://doi.org/10.1515/cclm-2021-0792
Carter GD, Ahmed F, Berry J, Cavalier E, Durazo-Arvizu R, Gunter E, External quality assessment of 24,25-dihydroxyvitamin D J Steroid Biochem Mol Biol 2019 187 130 3 https://doi.org/10.1016/j.jsbmb.2018.11.010
Binkley N, Sempos CT, VDSP) VDSP. Standardizing vitamin D assays: the way forward J Bone Miner Res 2014 29 1709 14 https://doi.org/10.1002/jbmr.2252
Zelzer S, Hofer E, Meinitzer A, Fritz-Petrin E, Simstich S, Goessler W, Association of vitamin D metabolites with cognitive function and brain atrophy in elderly individuals-the Austrian stroke prevention study Aging 2021 13 9455 67 https://doi.org/10.18632/aging.202930
Friesinger GC, Page EE, Ross RS, Prognostic significance of coronary arteriography Trans Assoc Am Phys 1970 83 78 92
Gensini GG, A more meaningful scoring system for determining the severity of coronary heart disease Am J Cardiol 1983 51 606 https://doi.org/10.1016/s0002-9149(83)80105-2
Rampidis GP, Benetos G, Benz DC, Giannopoulos AA, Buechel RR, A guide for Gensini Score calculation Atherosclerosis 2019 287 181 3 https://doi.org/10.1016/j.atherosclerosis.2019.05.012
Koller L, Kleber ME, Brandenburg VM, Goliasch G, Richter B, Sulzgruber P, Fibroblast growth factor 23 is an independent and specific predictor of mortality in patients with heart failure and reduced ejection fraction Circ Heart Fail 2015 8 1059 67 https://doi.org/10.1161/circheartfailure.115.002341
ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, 2. Classification and diagnosis of diabetes: Standards of care in diabetes-2023 Diabetes Care 2023 46 1715 https://doi.org/10.2337/dc23-s002
deFilippi CR, de Lemos JA, Christenson RH, Gottdiener JS, Kop WJ, Zhan M, Association of serial measures of cardiac troponin T using a sensitive assay with incident heart failure and cardiovascular mortality in older adults JAMA 2010 304 2494 502 https://doi.org/10.1001/jama.2010.1708
Saunders JT, Nambi V, de Lemos JA, Chambless LE, Virani SS, Boerwinkle E, Cardiac troponin T measured by a highly sensitive assay predicts coronary heart disease, heart failure, and mortality in the atherosclerosis risk in communities study Circulation 2011 123 1367 76 https://doi.org/10.1161/circulationaha.110.005264
Michos ED, Selvin E, Misialek JR, McEvoy JW, Ndumele CE, Folsom AR, 25-Hydroxyvitamin D levels and markers of subclinical myocardial damage and wall stress: the atherosclerosis risk in Communities study J Am Heart Assoc 2016 5 https://doi.org/10.1161/jaha.116.003575
van Ballegooijen AJ, Visser M, Kestenbaum B, Siscovick DS, de Boer IH, Gottdiener JS, Relation of vitamin D and parathyroid hormone to cardiac biomarkers and to left ventricular mass (from the cardiovascular health study) Am J Cardiol 2013 111 418 24 https://doi.org/10.1016/j.amjcard.2012.10.021
Liew JY, Sasha SR, Ngu PJ, Warren JL, Wark J, Dart AM, Circulating vitamin D levels are associated with the presence and severity of coronary artery disease but not peripheral arterial disease in patients undergoing coronary angiography Nutr Metabol Cardiovasc Dis 2015 25 274 9 https://doi.org/10.1016/j.numecd.2014.12.005
Teng Z, Wei M, Correlation between serum 25-hydroxyvitamin D level and coronary heart disease Am J Transl Res 2021 13 8379 84
Oz F, Cizgici AY, Oflaz H, Elitok A, Karaayvaz EB, Mercanoglu F, Impact of vitamin D insufficiency on the epicardial coronary flow velocity and endothelial function Coron Artery Dis 2013 24 392 7 https://doi.org/10.1097/mca.0b013e328362b2c8
Nolte K, Herrmann-Lingen C, Platschek L, Holzendorf V, Pilz S, Tomaschitz A, Vitamin D deficiency in patients with diastolic dysfunction or heart failure with preserved ejection fraction ESC Heart Fail 2019 6 262 70 https://doi.org/10.1002/ehf2.12413
Fall T, Shiue I, Bergeaf Geijerstam P, Sundstrom J, Arnlov J, Larsson A, Relations of circulating vitamin D concentrations with left ventricular geometry and function Eur J Heart Fail 2012 14 985 91 https://doi.org/10.1093/eurjhf/hfs091
Pandit A, Mookadam F, Boddu S, Aryal Pandit A, Tandar A, Chaliki H, Vitamin D levels and left ventricular diastolic function Open Heart 2014 1 e000011 https://doi.org/10.1136/openhrt-2013-000011
Chandra A, Picard MH, Huang S, Gupta DK, Agusala K, Buring JE, Impact of vitamin D3 versus placebo on cardiac structure and function: a randomized clinical trial J Am Heart Assoc 2022 11 e025008 https://doi.org/10.1161/jaha.121.025008
Gnudi L, Fountoulakis N, Panagiotou A, Corcillo A, Maltese G, Rife MF, Effect of active vitamin-D on left ventricular mass index: results of a randomized controlled trial in type 2 diabetes and chronic kidney disease Am Heart J 2023 261 1 9 https://doi.org/10.1016/j.ahj.2023.03.003
Schroten NF, Ruifrok WP, Kleijn L, Dokter MM, Silljé HH, Lambers Heerspink HJ, Short-term vitamin D3 supplementation lowers plasma renin activity in patients with stable chronic heart failure: an open-label, blinded end point, randomized prospective trial (VitD-CHF trial) Am Heart J 2013 166 357 64.e2 https://doi.org/10.1016/j.ahj.2013.05.009
Philouze C, Martin JC, Riva C, Marziou A, Defoort C, Couturier C, Vitamin D Cardiovasc Drugs Ther 2022 36 245 56 https://doi.org/10.1007/s10557-021-07143-9
Panizo S, Barrio-Vázquez S, Naves-Díaz M, Carrillo-López N, Rodríguez I, Fernández-Vázquez A, Vitamin D receptor activation, left ventricular hypertrophy and myocardial fibrosis Nephrol Dial Transplant 2013 28 2735 44 https://doi.org/10.1093/ndt/gft268
Jiang WL, Gu HB, Zhang YF, Xia QQ, Qi J, Chen JC, Vitamin D supplementation in the treatment of chronic heart failure: a meta-analysis of randomized controlled trials Clin Cardiol 2016 39 56 61 https://doi.org/10.1002/clc.22473
Busa V, Dardeir A, Marudhai S, Patel M, Valaiyaduppu SS, Ghani MR, Role of vitamin D supplementation in heart failure patients with vitamin D deficiency and its effects on clinical outcomes: a literature review Cureus 2020 12 e10840 https://doi.org/10.7759/cureus.10840
Thomas GN, O Hartaigh B, Bosch JA, Pilz S, Loerbroks A, Kleber ME, Vitamin D levels predict all-cause and cardiovascular disease mortality in subjects with the metabolic syndrome: the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study Diabetes Care 2012 35 1158 64 https://doi.org/10.2337/dc11-1714
