Vitamin D supplementation of 4000 IU daily and cardiac function in patients with advanced heart failure: The EVITA trial
Introduction
Heart failure (HF) continues to be a medical problem in aging societies with globally almost 23 million people being affected [1]. The illness usually results in cardiac dilatation and decreasing left ventricular ejection fraction (LVEF) [2]. Pharmacologic treatment aims to prevent progressive cardiac hypertrophy and LVEF decline [3], but 5% of patients develop end-stage HF that is refractory to effective medical treatment [4]. Ventricular assist device implants and heart transplantation are the last treatment options for these patients.
Vitamin D may be critical for the heart because vitamin D receptor knockout mice yield elevated production of renin and angiotensin II, hypertension, and cardiac hypertrophy [[5], [6], [7]]. In patients with HF, low circulating 25‑hydroxyvitamin D (25OH) levels (i.e. <75 nmol/L) are prevalent [[8], [9], [10], [11]] and some observational studies indicate an inverse association between circulating 25OHD levels and HF [12,13].
With respect to randomized controlled trials (RCTs), a recent meta-analysis [14] indicated that in patients with HF, vitamin D supplementation may suppress biochemical markers of inflammation. Moreover, based on four studies (303 patients) lasting 12 weeks to 9 months and using vitamin D doses equivalent to 1000 IU to 7143 IU daily, this meta-analysis reported a non-significant increase in LVEF by vitamin D supplementation (weighted mean difference: +4.1% [95%CI: −0.91% to +9.12%], P = 0.11). A more recent RCT in 163 patients with HF and mean circulating 25OHD levels of 37 nmol/L [15] reported a significant improvement in LVEF (difference in mean change: +6.07% [95%CI: +3.20% to +8.94%], P < 0.001) and also in left ventricular (LV) remodelling by daily vitamin D supplementation with 4000 IU for one year.
Since a beneficial vitamin D effect on LVEF would have important consequences regarding prevention and treatment of HF, we aimed to investigate in a post-hoc analysis of the EVITA (effect of vitamin D on mortality in heart failure) trial [16] whether these reported beneficial effects on cardiac function can be confirmed in patients with advanced HF refractory to optimal medical therapy. Further, we expanded the existing knowledge by investigating the effects of vitamin D supplementation on left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) in this population.
Section snippets
Study design and participants
EVITA was a single-center, randomized, placebo-controlled, clinical trial, performed at the Clinic for Thoracic and Cardiovascular Surgery of the Heart- and Diabetes Center North Rhine Westphalia, Bad Oeynhausen, Germany. Study design and main study results have already been published elsewhere [[16], [17], [18], [19], [20]]. Briefly, 400 patients of HF with reduced LVEF participated in the trial. Eligible patients were aged ≥18 to 79 years, had New York Heart Association functional class
Results
Of the 400 study participants, 113 patients dropped out, 75 patients died, and additional 35 patients were lost-to follow-up. At baseline, 12 and 36 months post-randomization LV echocardiographic data were available in 400, 311, and 242 patients for the intention-to-treat analysis, respectively (Fig. 1). Baseline characteristics of the study cohort are presented in Table 1. The vast majority of patients had moderately or severely abnormal LVEF, LVEDD, and LVESD values. Moreover, in both groups
Discussion
The present investigation indicates that a daily vitamin D3 supplement of 4000 IU for three years does not significantly influence LV echocardiography data in a cohort of patients with advanced HF, neither 12 months nor 36 months post-randomization. However, our data also indicate that vitamin D probably improves LV function in patients aged ≥50 years.
In our study, the mean difference in LVEF change between study groups at 12 and 36 months was within the 95% confidence interval of the
Conflict of interest
The authors report no relationships that could be construed as a conflict of interest.
Acknowledgement
We thank Birgit Drawe and Bärbel Kammel, Institute for Laboratory and Transfusion Medicine, Heart- and Diabetes Center NRW, Ruhr-University of Bochum, Bad Oeynhausen, Germany for their excellent technical assistance.
Funding
The study was sponsored by the Heart and Diabetes Center North Rhine-Westphalia, Ruhr-University of Bochum, Germany. The Friede Springer Stiftung (Berlin, Germany) and Merck KGaA (Darmstadt, Germany) provided funding for the study. Merck also provided the study medication. The funding sources were not involved in the study design, collection, analysis, or interpretation of data, or in preparation or submission of the manuscript for publication.
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2022, Geriatric NursingCitation Excerpt :Classically, adequate serum levels of 25(OH)D are associated with calcium homeostasis and bone metabolism.2 More recently, there has been an increasing interest in extra-skeletal functions of vitamin D, especially those capable of interfering in the functionality and quality of life of older adults, such as the ability to attenuate the low-grade chronic inflammatory state in those with sarcopenia;4 and to improve depression scores,5 left ventricular function,6 muscle mass and lower limb function.7 Moreover, other studies have also examined the role of vitamin D in reducing the risk of respiratory tract infections,8 its association with metabolic syndrome, and mobility performance among older adults.9,10
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This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.