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ESC Heart Fail. 2019 Feb 19. doi: 10.1002/ehf2.12413. [Epub ahead of print]

Vitamin D deficiency in patients with diastolic dysfunction or heart failure with preserved ejection fraction.

Author information

Department of Cardiology, University of Göttingen, Göttingen, Germany.
Department of Psychosomatic Medicine and Psychotherapy, University of Göttingen, Göttingen, Germany.
Clinical Trial Center, University of Leipzig, Leipzig, Germany.
Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria.
Department of Cardiology, Medical University of Graz, Graz, Austria.
Specialist Clinic of Rehabilitation Bad Gleichenberg, Bad Gleichenberg, Austria.
Department of Internal Medicine and Cardiology, Charité University Medicine, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany.
DZHK partner site Berlin, Berlin, Germany.
Department of Internal Medicine I, Comprehensive Heart Failure Center Würzburg, University Hospital Würzburg, Würzburg, Germany.
DZHK partner site Göttingen, Göttingen, Germany.
Department of Internal Medicine and Cardiology, German Heart Center Berlin, Berlin, Germany.
Berlin Institute of Health (BIH), Berlin, Germany.
Clinic and Policlinic for Cardiology, University Hospital Leipzig, Leipzig, Germany.



Vitamin D deficiency is prevalent in heart failure (HF), but its relevance in early stages of heart failure with preserved ejection fraction (HFpEF) is unknown. We tested the association of 25-hydroxyvitamin D [25(OH)D] serum levels with mortality, hospitalizations, cardiovascular risk factors, and echocardiographic parameters in patients with asymptomatic diastolic dysfunction (DD) or newly diagnosed HFpEF.


We measured 25(OH)D serum levels in outpatients with risk factors for DD or history of HF derived from the DIAST-CHF study. Participants were comprehensively phenotyped including physical examination, echocardiography, and 6 min walk test and were followed up to 5 years. Quality of life was evaluated by the Short Form 36 (SF-36) questionnaire. We included 787 patients with available 25(OH)D levels. Median 25(OH)D levels were 13.1 ng/mL, mean E/e' medial was 13.2, and mean left ventricular ejection fraction was 59.1%. Only 9% (n = 73) showed a left ventricular ejection fraction <50%. Fifteen per cent (n = 119) of the recruited participants had symptomatic HFpEF. At baseline, participants with 25(OH)D levels in the lowest tertile (≤10.9 ng/L; n = 263) were older, more often symptomatic (oedema and fatigue, all P ≤ 0.002) and had worse cardiac [higher N-terminal pro-brain natriuretic peptide (NT-proBNP) and left atrial volume index, both P ≤ 0.023], renal (lower glomerular filtration rate, P = 0.012), metabolic (higher uric acid levels, P < 0.001), and functional (reduced exercise capacity, 6 min walk distance, and SF-36 physical functioning score, all P < 0.001) parameters. Increased NT-proBNP, uric acid, and left atrial volume index and decreased SF-36 physical functioning scores were independently associated with lower 25(OH)D levels. There was a higher risk for lower 25(OH)D levels in association with HF, DD, and atrial fibrillation (all P ≤ 0.004), which remained significant after adjusting for age. Lower 25(OH)D levels (per 10 ng/mL decrease) tended to be associated with higher 5 year mortality, P = 0.05, hazard ratio (HR) 1.55 [1.00; 2.42]. Furthermore, lower 25(OH)D levels (per 10 ng/mL decrease) were related to an increased rate of cardiovascular hospitalizations, P = 0.023, HR = 1.74 [1.08; 2.80], and remained significant after adjusting for age, P = 0.046, HR = 1.63 [1.01; 2.64], baseline NT-proBNP, P = 0.048, HR = 1.62 [1.01; 2.61], and other selected baseline characteristics and co-morbidities, P = 0.043, HR = 3.60 [1.04; 12.43].


Lower 25(OH)D levels were associated with reduced functional capacity in patients with DD or HFpEF and were significantly predictive for an increased rate of cardiovascular hospitalizations, also after adjusting for age, NT-proBNP, and selected baseline characteristics and co-morbidities.


Diastolic dysfunction; HFpEF; Heart failure; NT-proBNP; Vitamin D


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