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)

Oxidative stress is a key element of the pathophysiology of heart failure (HF). As free thiols are readily oxidized by reactive oxygen and sulfur species, their circulating level may directly reflect the systemic redox status. This study addresses the role of serum free thiols in chronic HF, which is of particular interest as free thiols are amenable to therapeutic modulation and thus are a potential target for therapy.Free thiols were measured in serum of 101 previously characterized stable chronic HF patients (93% male, age 63.7 ± 10.0 y, left ventricular ejection fraction 34.6 ± 8.2%), adjusted for total serum protein, and subsequently analysed for associations with clinical and outcome parameters.The mean serum free thiol concentration was 3.6 ± 0.5 μM/g protein. Patients with aboveaverage levels were younger, had better renal function, lower levels of NT-proBNP and PTH, and higher levels of cholesterol. Furthermore, above-average levels were associated with favourable disease outcome, i.e. a decreased rehospitalisation rate and increased patient survival (HR 0.27 (95% CI 0.11-0.62), P=0.002) independent of associated clinical parameters, age and PTH. After adjustment for cholesterol or established prognostic factors in HF, eGFR and NT-proBNP the association was no longer significant, suggesting involvement of these variables in a common pathophysiological pathway.This exploratory study demonstrates favourable associations of serum free thiols with markers of HF severity and prognosis as well as disease outcome, which should be further investigated in larger prospective studies. Restoring redox status by therapeutic modulation of free thiols may be a promising strategy to improve disease outcome in CHF.

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“…The cohort has previously been described in more detail. (16,17) The study was conducted in accordance with the Declaration of Helsinki.…”

Section: Patient Populationmentioning

confidence: 99%

“…Measurements of plasma renin concentration (PRC), plasma renin activity (PRA), and aldosterone have been described before. (16) The estimated glomerular filtration rate (eGFR) was calculated using the 4-variable Modification of Diet in Renal Disease (MDRD) formula.…”

Section: 2baseline Characteristicsmentioning

confidence: 99%

Serum free thiols in chronic heart failure

Koning

Meijers

Pasch

et al. 2016

Pharmacological Research

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“…Although most interventional studies did not show a vitamin D effect on the RAAS, one open-level, randomized trial in patients with congestive heart failure, and thus high RAAS activity, reported on a significant reduction in plasma renin activity after vitamin D supplementation. 36 According to these data, we recommend further RCTs on vitamin D supplementation and the RAAS, which should at best be performed in populations with high RAAS activity and low 25(OH)D concentrations.With regard to heart diseases, the missing effect of vitamin D supplementation on QTc interval and N-terminal-pro-B-type natriuretic peptide is of relevance when considering that vitamin D deficiency has been previously associated with increased risk of sudden cardiac death and heart failure. In 5292 study participants of the RECORD (Randomized Evaluation of Calcium or Vitamin D) trial, the hazard ratio (95% CIs) for vitamin D supplementation compared with no vitamin D supplementation for cardiac failure was 0.75 (0.58-0.97), whereas the hazard ratio was 0.82 (0.58-1.15) in a meta-analysis, including 13 033 study participants.…”

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confidence: 99%

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confidence: 99%

Effects of Vitamin D on Blood Pressure and Cardiovascular Risk Factors

et al. 2015

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A part from skeletal diseases, vitamin D deficiency is considered a risk factor for cardiovascular events and mortality. [1][2][3][4][5][6] Nevertheless, it remains unclear whether low 25-hydroxyvitamin D (25[OH]D) concentrations are a significant causal risk factor or are simply related to adverse outcomes because of reverse causation and confounding factors, such as obesity, reduced mobility with low sunlight exposure, poor nutrition, or inflammation. [1][2][3][4][5][6] Because high blood pressure (BP) has emerged as the leading risk factor for the global disease burden, it is important to evaluate whether vitamin D has a beneficial effect on lowering BP to clarify the potential role of vitamin D for public health. 7 Large observational studies and meta-analyses have shown that low 25(OH)D concentrations are a significant risk marker for arterial hypertension. 8,9 Molecular effects of vitamin D receptor activation, such as suppression of the renin-angiotensin-aldosterone system (RAAS), nephroprotective actions, or improvements in endothelial/vascular function, suggest Abstract-Vitamin D deficiency is a risk factor for arterial hypertension, but randomized controlled trials showed mixed effects of vitamin D supplementation on blood pressure (BP). We aimed to evaluate whether vitamin D supplementation affects 24-hour systolic ambulatory BP monitoring values and cardiovascular risk factors. The Styrian Vitamin D Hypertension Trial is a single-center, double-blind, placebo-controlled study conducted from June 2011 to August 2014 at the endocrine outpatient clinic of the Medical University of Graz, Austria. We enrolled 200 study participants with arterial hypertension and 25-hydroxyvitamin D levels below 30 ng/mL. Study participants were randomized to receive either 2800 IU of vitamin D3 per day as oily drops (n=100) or placebo (n=100) for 8 weeks. Primary outcome measure was 24-hour systolic BP. Secondary outcome measures were 24-hour diastolic BP, N-terminal-pro-B-type natriuretic peptide, QTc interval, renin, aldosterone, 24-hour urinary albumin excretion, homeostasis model assessment-insulin resistance, triglycerides, highdensity lipoprotein cholesterol, and pulse wave velocity. Methods Study DesignThe Styrian Vitamin D Hypertension Trial was sponsored by the Medical University of Graz, Austria, and is a single-center, double-blind, placebo-controlled, parallel-group study conducted at the Medical University of Graz, Austria. The publication of this trial adheres to the Consolidated Standards of Reporting Trials (CONSORT) 2010 statement. 29 The trial was initially registered at http://www.clinicaltrialsregister.eu (EudraCT number, 2009-018125-70) and was additionally registered at clinicaltrials.gov (ClinicalTrials.gov Identifier NCT02136771). ParticipantsEligible study participants were adults aged ≥18 years with arterial hypertension and a 25(OH)D serum concentration below 30 ng/mL (multiply by 2.496 to convert ng/mL to nmol/L). Arterial hypertension was classified in patients with an office BP of systol...

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“…79 In the context of cardiovascular health, the pathophysiology suggested is that vitamin D deficiency up-regulates the renin-angiotensin-aldosterone system and predisposes to arterial hypertension, smooth muscle hypertrophy and chronic heart failure. 81 Two major studies associating low vitamin D level and cardiovascular diseases are well documented. The Whitehall study conducted a 13-year follow up of approximately 5409 older adults and reported that higher concentration of vitamin D was inversely and linearly correlated with both vascular and nonvascular disease mortality and that doubling of serum vitamin D concentration was associated with significant reduction in the mortality rates.…”

Section: Neuropsychiatric Conditionmentioning

confidence: 99%

Vitamin D for Depression with a Seasonal Pattern: an Effective Treatment Strategy

Sarkar¹

2017

IPMRJ

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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)

Cited by 107 publications

References 31 publications

Serum free thiols in chronic heart failure

Serum free thiols in chronic heart failure

Effects of Vitamin D on Blood Pressure and Cardiovascular Risk Factors

Vitamin D for Depression with a Seasonal Pattern: an Effective Treatment Strategy

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