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Martin R. Grübler
Department of Internal Medicine, Division of Endocrinology and Diabetology, Endocrinology Lab Platform, Medical University of Graz, 8036 Graz, Austria

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Journal article
Published: 30 November 2020 in Journal of Clinical Medicine
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Nitric oxide (NO) synthesis markers, comprising L-homoarginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), are significantly associated with cardiovascular events and mortality. Being involved in NO pathways, they may be of high importance regulating vascular tone and arterial hypertension, but data on this topic are sparse and controversial. In this study, we evaluated whether these NO synthesis markers are associated with blood pressure values and pulse wave velocity (PWV). This analysis was based on the data of the Styrian Vitamin D Hypertension Trial, which included adults with arterial hypertension. We analyzed correlations of NO synthesis markers with 24 h ambulatory blood pressure values and PWV (primary outcomes), as well as with anthropometric and laboratory data. A total of 509 patients were included in the present analysis. The mean age was 61.2 ± 10.5 years, mean PWV was 8.6 ± 2.4 m/s, mean 24 h systolic blood pressure was 127.5 ± 13.8 mmHg and mean 24 h diastolic blood pressure was 76.4 ± 9.5 mmHg. In bivariate analyses, there was a significant positive correlation between homoarginine and 24 h diastolic blood pressure (r = 0.1; p = 0.02), which was revealed to be no longer significant after adjustment for age, gender and glomerular filtration rate (GFR) in multivariate regression analysis. No other significant correlations of any NO synthesis markers with blood pressure or PWV were observed. In line with previous studies, there were inverse associations between homoarginine and age and between ADMA or SDMA and GFR (p < 0.05 for all). This study did not reveal a significant association between homoarginine, ADMA or SDMA and blood pressure or PWV in hypertensive adults. These results suggested that the associations of these parameters with adverse outcome may not be mediated by hypertension and/or endothelial dysfunction.

ACS Style

Oliver Malle; Christian Trummer; Verena Theiler-Schwetz; Andreas Meinitzer; Martin H. Keppel; Martin R. Grübler; Andreas Tomaschitz; Jakob Voelkl; Winfried März; Stefan Pilz. NO Synthesis Markers are Not Significantly Associated with Blood Pressure and Endothelial Dysfunction in Patients with Arterial Hypertension: A Cross-Sectional Study. Journal of Clinical Medicine 2020, 9, 3895 .

AMA Style

Oliver Malle, Christian Trummer, Verena Theiler-Schwetz, Andreas Meinitzer, Martin H. Keppel, Martin R. Grübler, Andreas Tomaschitz, Jakob Voelkl, Winfried März, Stefan Pilz. NO Synthesis Markers are Not Significantly Associated with Blood Pressure and Endothelial Dysfunction in Patients with Arterial Hypertension: A Cross-Sectional Study. Journal of Clinical Medicine. 2020; 9 (12):3895.

Chicago/Turabian Style

Oliver Malle; Christian Trummer; Verena Theiler-Schwetz; Andreas Meinitzer; Martin H. Keppel; Martin R. Grübler; Andreas Tomaschitz; Jakob Voelkl; Winfried März; Stefan Pilz. 2020. "NO Synthesis Markers are Not Significantly Associated with Blood Pressure and Endothelial Dysfunction in Patients with Arterial Hypertension: A Cross-Sectional Study." Journal of Clinical Medicine 9, no. 12: 3895.

Journal article
Published: 20 October 2020 in Annals of Internal Medicine
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ACS Style

Stefan Pilz; Martin R. Grübler; Verena Theiler-Schwetz; Oliver Malle; Christian Trummer. The Unrecognized Prevalence of Primary Aldosteronism. Annals of Internal Medicine 2020, 173, 681 -682.

AMA Style

Stefan Pilz, Martin R. Grübler, Verena Theiler-Schwetz, Oliver Malle, Christian Trummer. The Unrecognized Prevalence of Primary Aldosteronism. Annals of Internal Medicine. 2020; 173 (8):681-682.

Chicago/Turabian Style

Stefan Pilz; Martin R. Grübler; Verena Theiler-Schwetz; Oliver Malle; Christian Trummer. 2020. "The Unrecognized Prevalence of Primary Aldosteronism." Annals of Internal Medicine 173, no. 8: 681-682.

Journal article
Published: 01 July 2020 in The American Journal of Cardiology
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Recent experimental studies have suggested that galectin-3 has an interaction with aldosterone, and modifies its adverse effects. We therefore aimed to elucidate whether the relationship between plasma aldosterone concentrations (PACs) and long-term fatal cardiovascular (CV) events would depend on plasma galectin-3 levels. A total of 2,457 patients (median age: 63.5 [interquartile range (IQR) = 56.3 to 70.6] years, 30.1% women) from the LUdwigshafen RIsk and Cardiovascular Health study, with a median follow-up of 9.9 (IQR = 8.5 to 10.7) years, were included. We tested the interaction between aldosterone and galectin-3 for CV-mortality using a multivariate Cox proportional hazard model, reporting hazard ratios (HRs) with 95% confidence intervals (95%CIs). Adjustments for multiple CV risk factors as well as medication use were included. Mean PAC was 79.0 (IQR = 48.0 to 124.0) pg/ml and there were 558 (16.8%) CV deaths. There was a significant interaction between PAC and galectin-3 (p = 0.021). When stratifying patients by the median galectin-3, there was a significant association between aldosterone and CV-mortality for those above (HR per 1 standard deviation = 1.14; 95%CI [1.01 to 1.30], p = 0.023), but not below the cut-off value (HR per 1 standard deviation = 1.00; 95%CI [0.87 to 1.15], p = 0.185). In conclusion, the current study demonstrates for the first time a modifying effect of galectin-3 on the association between aldosterone and CV-mortality risk in humans. These findings indicate that galectin-3 is an intermediate between aldosterone and adverse outcomes.

ACS Style

Martin Robert Grübler; Graciela Delgado; Marcus Kleber; Bríain Ó. Hartaigh; Rudolf Allert de Boer; Nicolas Verheyen; Martin Keppel; Johannes Schmid; George Cm Siontis; Lorenz Räber; Burkert Pieske; Stefan Pilz; Andreas Tomaschitz; Winfried März. Effect of Galectin 3 on Aldosterone-Associated Risk of Cardiovascular Mortality in Patients Undergoing Coronary Angiography. The American Journal of Cardiology 2020, 127, 9 -15.

AMA Style

Martin Robert Grübler, Graciela Delgado, Marcus Kleber, Bríain Ó. Hartaigh, Rudolf Allert de Boer, Nicolas Verheyen, Martin Keppel, Johannes Schmid, George Cm Siontis, Lorenz Räber, Burkert Pieske, Stefan Pilz, Andreas Tomaschitz, Winfried März. Effect of Galectin 3 on Aldosterone-Associated Risk of Cardiovascular Mortality in Patients Undergoing Coronary Angiography. The American Journal of Cardiology. 2020; 127 ():9-15.

Chicago/Turabian Style

Martin Robert Grübler; Graciela Delgado; Marcus Kleber; Bríain Ó. Hartaigh; Rudolf Allert de Boer; Nicolas Verheyen; Martin Keppel; Johannes Schmid; George Cm Siontis; Lorenz Räber; Burkert Pieske; Stefan Pilz; Andreas Tomaschitz; Winfried März. 2020. "Effect of Galectin 3 on Aldosterone-Associated Risk of Cardiovascular Mortality in Patients Undergoing Coronary Angiography." The American Journal of Cardiology 127, no. : 9-15.

Journal article
Published: 19 February 2020 in Journal of Clinical Medicine
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The 25-Hydroxyvitamin D (25[OH)D) serum concentration depends on vitamin D intake, endogenous vitamin D production and genetic factors. The latter have been demonstrated in large genome-wide association studies indicating that single nucleotide polymorphisms (SNPs) in genes related to the vitamin D metabolism are as important for serum 25(OH)D levels as the influence of season. The mechanism on how these SNPs influence serum 25(OH)D levels are still unclear. The aim of the present study was to investigate the genetic effects of ten selected SNPs related to vitamin D metabolism on 25-hydroxyvitamin D increase (∆25(OH)D) after vitamin D supplementation in three randomized controlled trials. Genotypes of SNPs related to vitamin D metabolism were determined in 411 participants with 25(OH)D concentrations < 75 nmol/l receiving 20,000 IU cholecalciferol per week for 8 or 12 weeks after study inclusion. For the vitamin D receptor (VDR) rs10783219 polymorphism, the minor A-allele was associated with lower ∆25(OH)D values in the entire study population (p = 0.022), which was not consistent in all three cohorts when analysed separately. VDR rs10783219 might therefore be a genetic modulator of increasing 25-hydroxyvitamin D concentrations. Considering the wide-spread use of vitamin D supplementation, future large and well-designed randomized controlled trials (RCTs) should investigate the clinical impact of this polymorphism.

ACS Style

Olivia Trummer; Natascha Schweighofer; Christoph W. Haudum; Christian Trummer; Stefan Pilz; Verena Theiler-Schwetz; Martin H. Keppel; Martin Grübler; Thomas R. Pieber; Wilfried Renner; Barbara Obermayer-Pietsch; Elisabeth Lerchbaum. Genetic Components of 25-Hydroxyvitamin D Increase in Three Randomized Controlled Trials. Journal of Clinical Medicine 2020, 9, 570 .

AMA Style

Olivia Trummer, Natascha Schweighofer, Christoph W. Haudum, Christian Trummer, Stefan Pilz, Verena Theiler-Schwetz, Martin H. Keppel, Martin Grübler, Thomas R. Pieber, Wilfried Renner, Barbara Obermayer-Pietsch, Elisabeth Lerchbaum. Genetic Components of 25-Hydroxyvitamin D Increase in Three Randomized Controlled Trials. Journal of Clinical Medicine. 2020; 9 (2):570.

Chicago/Turabian Style

Olivia Trummer; Natascha Schweighofer; Christoph W. Haudum; Christian Trummer; Stefan Pilz; Verena Theiler-Schwetz; Martin H. Keppel; Martin Grübler; Thomas R. Pieber; Wilfried Renner; Barbara Obermayer-Pietsch; Elisabeth Lerchbaum. 2020. "Genetic Components of 25-Hydroxyvitamin D Increase in Three Randomized Controlled Trials." Journal of Clinical Medicine 9, no. 2: 570.

Randomized controlled trial
Published: 21 October 2019 in Nutrients
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25-hydroxyvitamin D (25(OH)D) is commonly measured to assess vitamin D status. Other vitamin D metabolites such as 24,25-dihydroxyvitamin D (24,25(OH)2D) provide additional insights into vitamin D status or metabolism. Earlier studies suggested that the vitamin D metabolite ratio (VMR), calculated as 24,25(OH)2D/25(OH)D, could predict the 25(OH)D increase after vitamin D supplementation. However, the evidence for this additional value is inconclusive. Therefore, our aim was to assess whether the increase in 25(OH)D after supplementation was predicted by the VMR better than baseline 25(OH)D. Plasma samples of 106 individuals (25(OH)D < 75 nmol/L) with hypertension who completed the Styrian Vitamin D Hypertension Trial (NC.T.02136771) were analyzed. Participants received vitamin D (2800 IU daily) or placebo for 8 weeks. The treatment effect (ANCOVA) for 25(OH)D3, 24,25(OH)2D3 and the VMR was 32 nmol/L, 3.3 nmol/L and 0.015 (all p < 0.001), respectively. Baseline 25(OH)D3 and 24,25(OH)2D3 predicted the change in 25(OH)D3 with comparable strength and magnitude. Correlation and regression analysis showed that the VMR did not predict the change in 25(OH)D3. Therefore, our data do not support routine measurement of 24,25(OH)2D3 in order to individually optimize the dosage of vitamin D supplementation. Our data also suggest that activity of 24-hydroxylase increases after vitamin D supplementation.

ACS Style

Vito Francic; Stan R. Ursem; Niek F. Dirks; Martin H. Keppel; Verena Theiler-Schwetz; Christian Trummer; Marlene Pandis; Valentin Borzan; Martin R. Grübler; Nicolas D. Verheyen; Winfried März; Andreas Tomaschitz; Stefan Pilz; Annemieke C. Heijboer; Barbara Obermayer-Pietsch. The Effect of Vitamin D Supplementation on its Metabolism and the Vitamin D Metabolite Ratio. Nutrients 2019, 11, 2539 .

AMA Style

Vito Francic, Stan R. Ursem, Niek F. Dirks, Martin H. Keppel, Verena Theiler-Schwetz, Christian Trummer, Marlene Pandis, Valentin Borzan, Martin R. Grübler, Nicolas D. Verheyen, Winfried März, Andreas Tomaschitz, Stefan Pilz, Annemieke C. Heijboer, Barbara Obermayer-Pietsch. The Effect of Vitamin D Supplementation on its Metabolism and the Vitamin D Metabolite Ratio. Nutrients. 2019; 11 (10):2539.

Chicago/Turabian Style

Vito Francic; Stan R. Ursem; Niek F. Dirks; Martin H. Keppel; Verena Theiler-Schwetz; Christian Trummer; Marlene Pandis; Valentin Borzan; Martin R. Grübler; Nicolas D. Verheyen; Winfried März; Andreas Tomaschitz; Stefan Pilz; Annemieke C. Heijboer; Barbara Obermayer-Pietsch. 2019. "The Effect of Vitamin D Supplementation on its Metabolism and the Vitamin D Metabolite Ratio." Nutrients 11, no. 10: 2539.

Journal article
Published: 02 January 2019 in Nutrients
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The aim of this study was to determine if increased mortality associated with low levels of serum 25-hydroxyvitamin D (25(OH)D) reflects a causal relationship by using a Mendelian randomisation (MR) approach with genetic variants in the vitamin D synthesis pathway. Individual participant data from three European cohorts were harmonized with standardization of 25(OH)D according to the Vitamin D Standardization Program. Most relevant single nucleotide polymorphisms of the genes CYP2R1 (rs12794714, rs10741657) and DHCR7/NADSYN1 (rs12785878, rs11234027), were combined in two allelic scores. Cox proportional hazards regression models were used with the ratio estimator and the delta method for calculating the hazards ratio (HR) and standard error of genetically determined 25(OH)D effect on all-cause mortality. We included 10,501 participants (50.1% females, 67.1±10.1 years) of whom 4003 died during a median follow-up of 10.4 years. The observed adjusted HR for all-cause mortality per decrease in 25(OH)D by 20 nmol/L was 1.20 (95% CI: 1.15–1.25). The HR per 20 nmol/L decrease in genetically determined 25(OH)D was 1.32 (95% CI: 0.80–2.24) and 1.35 (95% CI of 0.81 to 2.37) based on the two scores. In conclusion, the results of this MR study in a combined sample from three European cohort studies provide further support for a causal relationship between vitamin D deficiency and increased all-cause mortality. However, as the current study, even with ~10,000 participants, was underpowered for the study of the effect of the allele score on mortality, larger studies on genetics and mortality are needed to improve the precision.

ACS Style

Thor Aspelund; Martin R. Grübler; Albert V. Smith; Elias F. Gudmundsson; Martin Keppel; Mary Frances Cotch; Tamara B. Harris; Rolf Jorde; Guri Grimnes; Ragnar Martin Joakimsen; Henrik Schirmer; Tom Wilsgaard; Ellisiv B. Mathiesen; Inger Njølstad; Maja-Lisa Løchen; Winfried März; Marcus E. Kleber; Andreas Tomaschitz; Diana Grove-Laugesen; Lars Rejnmark; Karin M. A. Swart; Ingeborg A. Brouwer; Paul Lips; Natasja M. Van Schoor; Christopher T. Sempos; Ramón A. Durazo-Arvizu; Zuzana Škrabáková; Kirsten G. Dowling; Kevin D. Cashman; Mairead Kiely; Stefan Pilz; Vilmundur Gudnason; Gudny Eiriksdottir. Effect of Genetically Low 25-Hydroxyvitamin D on Mortality Risk: Mendelian Randomization Analysis in 3 Large European Cohorts. Nutrients 2019, 11, 74 .

AMA Style

Thor Aspelund, Martin R. Grübler, Albert V. Smith, Elias F. Gudmundsson, Martin Keppel, Mary Frances Cotch, Tamara B. Harris, Rolf Jorde, Guri Grimnes, Ragnar Martin Joakimsen, Henrik Schirmer, Tom Wilsgaard, Ellisiv B. Mathiesen, Inger Njølstad, Maja-Lisa Løchen, Winfried März, Marcus E. Kleber, Andreas Tomaschitz, Diana Grove-Laugesen, Lars Rejnmark, Karin M. A. Swart, Ingeborg A. Brouwer, Paul Lips, Natasja M. Van Schoor, Christopher T. Sempos, Ramón A. Durazo-Arvizu, Zuzana Škrabáková, Kirsten G. Dowling, Kevin D. Cashman, Mairead Kiely, Stefan Pilz, Vilmundur Gudnason, Gudny Eiriksdottir. Effect of Genetically Low 25-Hydroxyvitamin D on Mortality Risk: Mendelian Randomization Analysis in 3 Large European Cohorts. Nutrients. 2019; 11 (1):74.

Chicago/Turabian Style

Thor Aspelund; Martin R. Grübler; Albert V. Smith; Elias F. Gudmundsson; Martin Keppel; Mary Frances Cotch; Tamara B. Harris; Rolf Jorde; Guri Grimnes; Ragnar Martin Joakimsen; Henrik Schirmer; Tom Wilsgaard; Ellisiv B. Mathiesen; Inger Njølstad; Maja-Lisa Løchen; Winfried März; Marcus E. Kleber; Andreas Tomaschitz; Diana Grove-Laugesen; Lars Rejnmark; Karin M. A. Swart; Ingeborg A. Brouwer; Paul Lips; Natasja M. Van Schoor; Christopher T. Sempos; Ramón A. Durazo-Arvizu; Zuzana Škrabáková; Kirsten G. Dowling; Kevin D. Cashman; Mairead Kiely; Stefan Pilz; Vilmundur Gudnason; Gudny Eiriksdottir. 2019. "Effect of Genetically Low 25-Hydroxyvitamin D on Mortality Risk: Mendelian Randomization Analysis in 3 Large European Cohorts." Nutrients 11, no. 1: 74.

Review
Published: 01 June 2018 in The American Journal of Clinical Nutrition
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BackgroundEvidence from randomized controlled trials (RCTs) for the causal role of vitamin D on noncommunicable disease outcomes is inconclusive.ObjectiveThe aim of this study was to investigate whether there are beneficial or harmful effects of cholecalciferol (vitamin D3) supplementation according to subgroups of remeasured serum 25-hydroxyvitamin D [25(OH)D] on cardiovascular and glucometabolic surrogate markers with the use of individual participant data (IPD) meta-analysis of RCTs.DesignTwelve RCTs (16 wk to 1 y of follow-up) were included. For standardization, 25(OH)D concentrations for all participants (n = 2994) at baseline and postintervention were re-measured in bio-banked serum samples with the use of a certified liquid chromatography–tandem mass spectrometry method traceable to a reference measurement procedure. IPD meta-analyses were performed according to subgroups of remeasured 25(OH)D. Main outcomes were blood pressure and glycated hemoglobin (HbA1c). Secondary outcomes were LDL, HDL, and total cholesterol and triglycerides; parathyroid hormone (PTH); fasting glucose, insulin, and C-peptide; and 2-h glucose. In secondary analyses, other potential effect modifiers were studied.ResultsRemeasurement of 25(OH)D resulted in a lower mean 25(OH)D concentration in 10 of 12 RCTs. Vitamin D supplementation had no effect on the main outcomes of blood pressure and HbA1c. Supplementation resulted in 10–20% lower PTH concentrations, irrespective of the 25(OH)D subgroups. The subgroup analyses according to achieved 25(OH)D concentrations showed a significant decrease in LDL-cholesterol concentrations after vitamin D supplementation in 25(OH)D subgroups with <75, <100, and <125 nmol of −0.10 mmol/L (95% CI: −0.20, −0.00 mmol/L), −0.10 mmol/L (95% CI: −0.18, −0.02 mmol/L), and −0.07 mmol/L (95% CI: −0.14, −0.00 mmol/L), respectively. Patient features that modified the treatment effect could not be identified.ConclusionsFor the main outcomes of blood pressure and HbA1c, the data support no benefit for vitamin D supplementation. For the secondary outcomes, in addition to its effect on PTH, we observed indications for a beneficial effect of vitamin D supplementation only on LDL cholesterol, which warrants further investigation. This trial was registered at www.clinicaltrials.gov as NCT02551835.

ACS Style

Karin Ma Swart; Paul Lips; Ingeborg Brouwer; Rolf Jorde; Martijn W Heymans; Guri Grimnes; Martin R Grübler; Martin Gaksch; Andreas Tomaschitz; Stefan Pilz; Gudny Eiriksdottir; Vilmundur Gudnason; Louise Wamberg; Lars Rejnmark; Christopher T Sempos; Ramón A Durazo-Arvizu; Kirsten G Dowling; George Hull; Zuzana Škrabáková; Mairead Kiely; Kevin D Cashman; Natasja M Van Schoor. Effects of vitamin D supplementation on markers for cardiovascular disease and type 2 diabetes: an individual participant data meta-analysis of randomized controlled trials. The American Journal of Clinical Nutrition 2018, 107, 1043 -1053.

AMA Style

Karin Ma Swart, Paul Lips, Ingeborg Brouwer, Rolf Jorde, Martijn W Heymans, Guri Grimnes, Martin R Grübler, Martin Gaksch, Andreas Tomaschitz, Stefan Pilz, Gudny Eiriksdottir, Vilmundur Gudnason, Louise Wamberg, Lars Rejnmark, Christopher T Sempos, Ramón A Durazo-Arvizu, Kirsten G Dowling, George Hull, Zuzana Škrabáková, Mairead Kiely, Kevin D Cashman, Natasja M Van Schoor. Effects of vitamin D supplementation on markers for cardiovascular disease and type 2 diabetes: an individual participant data meta-analysis of randomized controlled trials. The American Journal of Clinical Nutrition. 2018; 107 (6):1043-1053.

Chicago/Turabian Style

Karin Ma Swart; Paul Lips; Ingeborg Brouwer; Rolf Jorde; Martijn W Heymans; Guri Grimnes; Martin R Grübler; Martin Gaksch; Andreas Tomaschitz; Stefan Pilz; Gudny Eiriksdottir; Vilmundur Gudnason; Louise Wamberg; Lars Rejnmark; Christopher T Sempos; Ramón A Durazo-Arvizu; Kirsten G Dowling; George Hull; Zuzana Škrabáková; Mairead Kiely; Kevin D Cashman; Natasja M Van Schoor. 2018. "Effects of vitamin D supplementation on markers for cardiovascular disease and type 2 diabetes: an individual participant data meta-analysis of randomized controlled trials." The American Journal of Clinical Nutrition 107, no. 6: 1043-1053.

Randomized controlled trial
Published: 01 December 2017 in Bone
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Mineralocorticoid receptor (MR) antagonism may affect bone turnover via direct and indirect pathways involving parathyroid hormone, but randomized controlled trials are lacking. In a pre-specified analysis of the "Eplerenone in primary hyperparathyroidism" placebo-controlled, randomized trial (ISRCTN 33941607), effects of eight weeks MR-blockade with eplerenone on bone turnover markers in 97 patients with primary hyperparathyroidism were tested. Mean age was 67.5±9.5years, and 76 (78.4%) were females. In analysis of covariance with adjustment for baseline values, eplerenone had no significant effect on isoform 5b of the tartrate-resistant acid phosphatase (TRAP), beta-crosslaps, N-terminal propeptide of procollagen type 1 (P1NP), osteocalcin and bone-specific alkaline phosphatase. There was no significant cross-sectional correlation between plasma aldosterone concentration or the aldosterone-to-renin ratio and markers of bone turnover in multivariate linear regression models at baseline. These data provide first evidence from a randomized and placebo-controlled trial that short-term MR antagonism may not affect bone turnover, at least in patients with primary hyperparathyroidism.

ACS Style

Nicolas Verheyen; Martin R. Grübler; Andreas Meinitzer; Christian Trummer; Verena Schwetz; Karin Amrein; Hans P. Dimai; Winfried März; Cristiana Catena; Dirk Von Lewinski; Jakob Voelkl; Ioana Alesutan; Astrid Fahrleitner-Pammer; Helmut Brussee; Stefan Pilz; Andreas Tomaschitz. Effect of eplerenone on markers of bone turnover in patients with primary hyperparathyroidism – The randomized, placebo-controlled EPATH trial. Bone 2017, 105, 212 -217.

AMA Style

Nicolas Verheyen, Martin R. Grübler, Andreas Meinitzer, Christian Trummer, Verena Schwetz, Karin Amrein, Hans P. Dimai, Winfried März, Cristiana Catena, Dirk Von Lewinski, Jakob Voelkl, Ioana Alesutan, Astrid Fahrleitner-Pammer, Helmut Brussee, Stefan Pilz, Andreas Tomaschitz. Effect of eplerenone on markers of bone turnover in patients with primary hyperparathyroidism – The randomized, placebo-controlled EPATH trial. Bone. 2017; 105 ():212-217.

Chicago/Turabian Style

Nicolas Verheyen; Martin R. Grübler; Andreas Meinitzer; Christian Trummer; Verena Schwetz; Karin Amrein; Hans P. Dimai; Winfried März; Cristiana Catena; Dirk Von Lewinski; Jakob Voelkl; Ioana Alesutan; Astrid Fahrleitner-Pammer; Helmut Brussee; Stefan Pilz; Andreas Tomaschitz. 2017. "Effect of eplerenone on markers of bone turnover in patients with primary hyperparathyroidism – The randomized, placebo-controlled EPATH trial." Bone 105, no. : 212-217.

Journal article
Published: 20 August 2017 in The Journal of Clinical Hypertension
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Patients with primary hyperparathyroidism are at increased risk for high blood pressure, vascular stiffening, and left ventricular hypertrophy, but previous studies have failed to demonstrate the direct associations with circulating parathyroid hormone (PTH) levels. The authors investigated cross-sectional relationships between PTH and 24-hour pulse wave velocity, nocturnal systolic blood pressure, and left ventricular mass index in patients with primary hyperparathyroidism who were treatment-naive with cinacalcet, renin-angiotensin-aldosterone-system inhibitors, and thiazide or loop diuretics. In 76 patients, mean±SD of pulse wave velocity, nocturnal systolic blood pressure, and left ventricular mass index values were 9.3±1.8 m/s, 116.6±17.0 mm Hg, and 92.8±23.0 g/m². In multivariate linear regression analyses with adjustment for potentially confounding parameters, PTH was independently associated with nocturnal systolic blood pressure (adjusted ß coefficient=.284, P=.040), mean 24-hour pulse wave velocity (ß=.199, P=.001), and left ventricular mass index (ß=.252, P=.025). PTH may promote vascular and cardiac remodeling in primary hyperparathyroidism. Interventional trials are needed to test the antihypertensive and cardioprotective effects of PTH-inhibitory treatment strategies.

ACS Style

Julia Wetzel; Stefan Pilz; Martin R. Grübler; Astrid Fahrleitner-Pammer; Hans P. Dimai; Dirk Von Lewinski; Ewald Kolesnik; Sabine Perl; Christian Trummer; Verena Schwetz; Andreas Meinitzer; Evgeny Belyavskiy; Jakob Völkl; Cristiana Catena; Vincent Brandenburg; Winfried März; Burkert Pieske; Helmut Brussee; Andreas Tomaschitz; Nicolas D. Verheyen. Plasma parathyroid hormone and cardiovascular disease in treatment-naive patients with primary hyperparathyroidism: The EPATH trial. The Journal of Clinical Hypertension 2017, 19, 1173 -1180.

AMA Style

Julia Wetzel, Stefan Pilz, Martin R. Grübler, Astrid Fahrleitner-Pammer, Hans P. Dimai, Dirk Von Lewinski, Ewald Kolesnik, Sabine Perl, Christian Trummer, Verena Schwetz, Andreas Meinitzer, Evgeny Belyavskiy, Jakob Völkl, Cristiana Catena, Vincent Brandenburg, Winfried März, Burkert Pieske, Helmut Brussee, Andreas Tomaschitz, Nicolas D. Verheyen. Plasma parathyroid hormone and cardiovascular disease in treatment-naive patients with primary hyperparathyroidism: The EPATH trial. The Journal of Clinical Hypertension. 2017; 19 (11):1173-1180.

Chicago/Turabian Style

Julia Wetzel; Stefan Pilz; Martin R. Grübler; Astrid Fahrleitner-Pammer; Hans P. Dimai; Dirk Von Lewinski; Ewald Kolesnik; Sabine Perl; Christian Trummer; Verena Schwetz; Andreas Meinitzer; Evgeny Belyavskiy; Jakob Völkl; Cristiana Catena; Vincent Brandenburg; Winfried März; Burkert Pieske; Helmut Brussee; Andreas Tomaschitz; Nicolas D. Verheyen. 2017. "Plasma parathyroid hormone and cardiovascular disease in treatment-naive patients with primary hyperparathyroidism: The EPATH trial." The Journal of Clinical Hypertension 19, no. 11: 1173-1180.

Randomized controlled trial
Published: 17 June 2017 in Nutrients
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Increasing evidence suggests a possible interaction between vitamin D and insulin-like growth factor-1 (IGF-1). We aimed to investigate effects of vitamin D supplementation on IGF-1 (primary outcome) and calcitriol (1,25(OH)2D) concentrations (secondary outcome). This is a post-hoc analysis of the Styrian Vitamin D Hypertension Trial—a single-center, double-blind, randomized, placebo-controlled trial (RCT) conducted from 2011 to 2014 at the Medical University of Graz, Austria. Two-hundred subjects with arterial hypertension and 25(OH)D concentrations <30 ng/mL were randomized to either receive 2800 IU of vitamin D daily or placebo for eight weeks. A total of 175 participants (mean ± standard deviation age, 60 ± 11 years; 49% women) with available IGF-1 concentrations were included in the present analysis. At baseline, IGF-1 concentrations were significantly correlated with 1,25(OH)2D (r = 0.21; p = 0.005) but not with 25(OH)D (r = −0.008; p = 0.91). In the RCT, vitamin D had no significant effect on IGF-1 (mean treatment effect 3.1; 95% confidence interval −5.6 to 11.9 ng/mL; p = 0.48), but it increased 1,25(OH)2D concentrations (mean treatment effect 9.2; 95% confidence interval 4.4 to 13.9 pg/mL; p ≤ 0.001). In this RCT, in hypertensive patients with low 25(OH)D concentrations, there was no significant effect of vitamin D supplementation on IGF-1 concentrations. However, we observed a cross-sectional correlation between 1,25(OH)2D and IGF-1 and an increase of 1,25(OH)2D after vitamin D supplementation.

ACS Style

Christian Trummer; Verena Schwetz; Marlene Pandis; Martin R. Grübler; Nicolas Verheyen; Martin Gaksch; Armin Zittermann; Winfried März; Felix Aberer; Angelika Lang; Claudia Friedl; Andreas Tomaschitz; Barbara Obermayer-Pietsch; Thomas R. Pieber; Stefan Pilz; Gerlies Treiber. Effects of Vitamin D Supplementation on IGF-1 and Calcitriol: A Randomized-Controlled Trial. Nutrients 2017, 9, 623 .

AMA Style

Christian Trummer, Verena Schwetz, Marlene Pandis, Martin R. Grübler, Nicolas Verheyen, Martin Gaksch, Armin Zittermann, Winfried März, Felix Aberer, Angelika Lang, Claudia Friedl, Andreas Tomaschitz, Barbara Obermayer-Pietsch, Thomas R. Pieber, Stefan Pilz, Gerlies Treiber. Effects of Vitamin D Supplementation on IGF-1 and Calcitriol: A Randomized-Controlled Trial. Nutrients. 2017; 9 (6):623.

Chicago/Turabian Style

Christian Trummer; Verena Schwetz; Marlene Pandis; Martin R. Grübler; Nicolas Verheyen; Martin Gaksch; Armin Zittermann; Winfried März; Felix Aberer; Angelika Lang; Claudia Friedl; Andreas Tomaschitz; Barbara Obermayer-Pietsch; Thomas R. Pieber; Stefan Pilz; Gerlies Treiber. 2017. "Effects of Vitamin D Supplementation on IGF-1 and Calcitriol: A Randomized-Controlled Trial." Nutrients 9, no. 6: 623.

Randomized controlled trial
Published: 27 April 2017 in Nutrients
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Bone turnover markers (BTMs) are used to evaluate bone health together with bone mineral density and fracture assessment. Vitamin D supplementation is widely used to prevent and treat musculoskeletal diseases but existing data on vitamin D effects on markers of bone resorption and formation are inconsistent. We therefore examined the effects of vitamin D supplementation on bone-specific alkaline phosphatase (bALP), osteocalcin (OC), C-terminal telopeptide (CTX), and procollagen type 1 N-terminal propeptide (P1NP). This is a post-hoc analysis of the Styrian Vitamin D Hypertension Trial, a single-center, double-blind, randomized, placebo-controlled trial (RCT) performed at the Medical University of Graz, Austria (2011–2014). Two hundred individuals with arterial hypertension and 25-hydroxyvitamin D (25[OH]D) levels <75 nmol/L were randomized to 2800 IU of vitamin D daily or placebo for eight weeks. One hundred ninety-seven participants (60.2 ± 11.1 years; 47% women) were included in this analysis. Vitamin D had no significant effect on bALP (mean treatment effect (MTE) 0.013, 95% CI −0.029 to 0.056 µg/L; p = 0.533), CTX (MTE 0.024, 95% CI −0.163 to 0.210 ng/mL, p = 0.802), OC (MTE 0.020, 95% CI −0.062 to 0.103 ng/mL, p = 0.626), or P1NP (MTE −0.021, 95% CI −0.099 to 0.057 ng/mL, p = 0.597). Analyzing patients with 25(OH)D levels <50 nmol/L separately (n = 74) left results largely unchanged. In hypertensive patients with low 25(OH)D levels, we observed no significant effect of vitamin D supplementation for eight weeks on BTMs.

ACS Style

Verena Schwetz; Christian Trummer; Marlene Pandis; Martin R. Grübler; Nicolas Verheyen; Martin Gaksch; Armin Zittermann; Winfried März; Felix Aberer; Angelika Lang; Gerlies Treiber; Claudia Friedl; Barbara Obermayer-Pietsch; Thomas R. Pieber; Andreas Tomaschitz; Stefan Pilz. Effects of Vitamin D Supplementation on Bone Turnover Markers: A Randomized Controlled Trial. Nutrients 2017, 9, 432 .

AMA Style

Verena Schwetz, Christian Trummer, Marlene Pandis, Martin R. Grübler, Nicolas Verheyen, Martin Gaksch, Armin Zittermann, Winfried März, Felix Aberer, Angelika Lang, Gerlies Treiber, Claudia Friedl, Barbara Obermayer-Pietsch, Thomas R. Pieber, Andreas Tomaschitz, Stefan Pilz. Effects of Vitamin D Supplementation on Bone Turnover Markers: A Randomized Controlled Trial. Nutrients. 2017; 9 (5):432.

Chicago/Turabian Style

Verena Schwetz; Christian Trummer; Marlene Pandis; Martin R. Grübler; Nicolas Verheyen; Martin Gaksch; Armin Zittermann; Winfried März; Felix Aberer; Angelika Lang; Gerlies Treiber; Claudia Friedl; Barbara Obermayer-Pietsch; Thomas R. Pieber; Andreas Tomaschitz; Stefan Pilz. 2017. "Effects of Vitamin D Supplementation on Bone Turnover Markers: A Randomized Controlled Trial." Nutrients 9, no. 5: 432.

Review
Published: 27 April 2017 in Reviews in Endocrine and Metabolic Disorders
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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.

ACS Style

Martin Robert Grübler; Winfried März; Stefan Pilz; Tanja B. Grammer; Christian Trummer; Christian Müllner; Verena Schwetz; Marlene Pandis; Nicolas Verheyen; Andreas Tomaschitz; Antonella Fiordelisi; Daniela Laudisio; Ersilia Cipolletta; Guido Iaccarino. Vitamin-D concentrations, cardiovascular risk and events - a review of epidemiological evidence. Reviews in Endocrine and Metabolic Disorders 2017, 18, 259 -272.

AMA Style

Martin Robert Grübler, Winfried März, Stefan Pilz, Tanja B. Grammer, Christian Trummer, Christian Müllner, Verena Schwetz, Marlene Pandis, Nicolas Verheyen, Andreas Tomaschitz, Antonella Fiordelisi, Daniela Laudisio, Ersilia Cipolletta, Guido Iaccarino. Vitamin-D concentrations, cardiovascular risk and events - a review of epidemiological evidence. Reviews in Endocrine and Metabolic Disorders. 2017; 18 (2):259-272.

Chicago/Turabian Style

Martin Robert Grübler; Winfried März; Stefan Pilz; Tanja B. Grammer; Christian Trummer; Christian Müllner; Verena Schwetz; Marlene Pandis; Nicolas Verheyen; Andreas Tomaschitz; Antonella Fiordelisi; Daniela Laudisio; Ersilia Cipolletta; Guido Iaccarino. 2017. "Vitamin-D concentrations, cardiovascular risk and events - a review of epidemiological evidence." Reviews in Endocrine and Metabolic Disorders 18, no. 2: 259-272.

Randomized controlled trial
Published: 01 January 2017 in Clinical Chemistry and Laboratory Medicine (CCLM)
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Background:Primary hyperparathyroidism (pHPT) is associated with low-grade inflammation, left ventricular hypertrophy and increased cardiovascular mortality, but the association between inflammatory markers and parameters of adverse cardiac remodeling is unknown. We investigated the relationship between C-reactive protein (CRP), the essential amino acid tryptophan and its pro-inflammatory derivatives kynurenine and quinolinic acid (QUIN) with echocardiographic parameters.Methods:Cross-sectional baseline data from the “Eplerenone in Primary Hyperparathyroidism” trial were analyzed. Patients with any acute illness were excluded. We assessed associations between CRP, serum levels of tryptophan, kynurenine and QUIN and left ventricular mass index (LVMI), left atrial volume index (LAVI) and E/e′.Results:Among 136 subjects with pHPT (79% females), 100 (73%) had arterial hypertension and the prevalence of left ventricular hypertrophy was 52%. Multivariate linear regression analyses with LVMI, LAVI and E/e′ as respective dependent variables, and C-reactive protein and tryptophan, kynurenine and QUIN as respective independent variables were performed. Analyses were adjusted for age, sex, blood pressure, parathyroid hormone, calcium and other cardiovascular risk factors. LVMI was independently associated with CRP (adjusted β-coefficient=0.193, p=0.030) and QUIN (β=0.270, p=0.007), but not kynurenine. LAVI was related with CRP (β=0.315, p[Correction added after online publication (22 April 2017: The sentence “Among 136 subjects with pHPT (79% females), 100 (73%) had left ventricular hypertrophy.” was corrected to “Among 136 subjects with pHPT (79% females), 100 (73%) had arterial hypertension and the prevalence of left ventricular hypertrophy was 52%.”]Conclusions:Cardiac remodeling is common in pHPT and is associated with low-grade inflammation and activation of the tryptophan-kynurenine pathway. The potential role of kynurenine and QUIN as cardiovascular risk factors may be further investigated in future studies.

ACS Style

Nicolas Verheyen; Andreas Meinitzer; Martin Robert Grübler; Klemens Ablasser; Ewald Kolesnik; Astrid Fahrleitner-Pammer; Evgeny Belyavskiy; Christian Trummer; Verena Schwetz; Elisabeth Pieske-Kraigher; Jakob Voelkl; Ioana Alesutan; Cristiana Catena; Leonardo Alberto Sechi; Helmut Brussee; Dirk Von Lewinski; Winfried März; Burkert Pieske; Stefan Pilz; Andreas Tomaschitz. Low-grade inflammation and tryptophan-kynurenine pathway activation are associated with adverse cardiac remodeling in primary hyperparathyroidism: the EPATH trial. Clinical Chemistry and Laboratory Medicine (CCLM) 2017, 55, 1034 -1042.

AMA Style

Nicolas Verheyen, Andreas Meinitzer, Martin Robert Grübler, Klemens Ablasser, Ewald Kolesnik, Astrid Fahrleitner-Pammer, Evgeny Belyavskiy, Christian Trummer, Verena Schwetz, Elisabeth Pieske-Kraigher, Jakob Voelkl, Ioana Alesutan, Cristiana Catena, Leonardo Alberto Sechi, Helmut Brussee, Dirk Von Lewinski, Winfried März, Burkert Pieske, Stefan Pilz, Andreas Tomaschitz. Low-grade inflammation and tryptophan-kynurenine pathway activation are associated with adverse cardiac remodeling in primary hyperparathyroidism: the EPATH trial. Clinical Chemistry and Laboratory Medicine (CCLM). 2017; 55 (7):1034-1042.

Chicago/Turabian Style

Nicolas Verheyen; Andreas Meinitzer; Martin Robert Grübler; Klemens Ablasser; Ewald Kolesnik; Astrid Fahrleitner-Pammer; Evgeny Belyavskiy; Christian Trummer; Verena Schwetz; Elisabeth Pieske-Kraigher; Jakob Voelkl; Ioana Alesutan; Cristiana Catena; Leonardo Alberto Sechi; Helmut Brussee; Dirk Von Lewinski; Winfried März; Burkert Pieske; Stefan Pilz; Andreas Tomaschitz. 2017. "Low-grade inflammation and tryptophan-kynurenine pathway activation are associated with adverse cardiac remodeling in primary hyperparathyroidism: the EPATH trial." Clinical Chemistry and Laboratory Medicine (CCLM) 55, no. 7: 1034-1042.

Randomized controlled trial
Published: 24 December 2016 in The Journal of Steroid Biochemistry and Molecular Biology
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Accumulating evidence has proposed a correlation between vitamin D (25(OH)D) insufficiency and cardiovascular (CV) disease. Vitamin D associated effects on endothelial function have been suggested to be a possible culprit. The present study investigated the association of vitamin D3 treatment on markers of endothelial dysfunction in patients with arterial hypertension. The Styrian Vitamin D Hypertension Trial is a double-blind, placebo-controlled, single-centre study conducted at the Medical University of Graz, Austria. A total of 200 study participants with arterial hypertension and 25(OH)D levels below 30 ng/mL were enrolled. The study participants were randomized to receive 2800 IU of vitamin D3 per day as oily drops (n = 100) or placebo (n = 100) for a duration of eight weeks. The present study uses an analysis of covariance (ANCOVA) to investigate the effect of vitamin D3 treatment on symmetric (SDMA) and asymmetric dimethylarginine (ADMA). A total of 187 participants (mean [SD] age 60.0 [11.3] years; 47% women; 25(OH)D 21.2 [5.6] ng/mL; mean systolic blood pressure of 131.4 [8.9] mmHg on a median of 2 antihypertensive drugs) completed the trial. Mean treatment effect was −0.004 (95%CI [−0.03 to 0.04]; P = 0.819) on ADMA and 0.001 (95%CI [−0.05 to 0.05]; P = 0.850) on SDMA. In the subgroup analysis patients with a 25(OH)D concentration <20 ng/mL had a significant increase in their log l-arginine/ADMA ratio (mean treatment effect 18.4 95%CI [1.84–34.9]μmol/L/μmol/L; P = 0.030). ClinicalTrials.gov Identifier: NCT02136771 EudraCT number: 2009-018125-70 Vitamin D3 supplementation in hypertensive patients with low 25-hydroxyvitamin D has no significant effect on ADMA and SDMA.

ACS Style

M.R. Grübler; M. Gaksch; K. Kienreich; N.D. Verheyen; Johannes Schmid; C. Müllner; G. Richtig; H. Scharnagl; C. Trummer; V. Schwetz; A. Meinitzer; B. Pieske; W. März; A. Tomaschitz; Stefan Pilz. Effects of Vitamin D3 on asymmetric- and symmetric dimethylarginine in arterial hypertension. The Journal of Steroid Biochemistry and Molecular Biology 2016, 175, 157 -163.

AMA Style

M.R. Grübler, M. Gaksch, K. Kienreich, N.D. Verheyen, Johannes Schmid, C. Müllner, G. Richtig, H. Scharnagl, C. Trummer, V. Schwetz, A. Meinitzer, B. Pieske, W. März, A. Tomaschitz, Stefan Pilz. Effects of Vitamin D3 on asymmetric- and symmetric dimethylarginine in arterial hypertension. The Journal of Steroid Biochemistry and Molecular Biology. 2016; 175 ():157-163.

Chicago/Turabian Style

M.R. Grübler; M. Gaksch; K. Kienreich; N.D. Verheyen; Johannes Schmid; C. Müllner; G. Richtig; H. Scharnagl; C. Trummer; V. Schwetz; A. Meinitzer; B. Pieske; W. März; A. Tomaschitz; Stefan Pilz. 2016. "Effects of Vitamin D3 on asymmetric- and symmetric dimethylarginine in arterial hypertension." The Journal of Steroid Biochemistry and Molecular Biology 175, no. : 157-163.

Review
Published: 19 October 2016 in International Journal of Environmental Research and Public Health
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Aside from its well-known effects on bone and mineral metabolism, vitamin D may also play an important role in extra-skeletal processes like immunologic diseases, cancer, or cardiovascular diseases. Even though meta-analyses showed that vitamin D supplementation reduces fractures, falls, and overall mortality, its potential benefits did not find universal acclaim. Several health care authorities published Recommended Dietary Allowances (RDAs) for vitamin D, most of them ranging from 600 to 800 international units (IU) per day, corresponding to a serum level of 25-hydroxyvitamin D of at least 20 ng/mL (50 nmol/L). However, studies conducted in the general population revealed a much lower overall intake of vitamin D than the proposed RDAs. Thus, strategies to increase the vitamin D intake in the general population, e.g., food fortification or vitamin D supplementation, are needed to match the existing evidence and recommendations. Therefore, several currently ongoing projects aim to investigate the effect of vitamin D supplementation in the general population and try to establish food-based solutions to improve vitamin D status.

ACS Style

Christian Trummer; Marlene Pandis; Nicolas Verheyen; Martin R. Grübler; Martin Gaksch; Barbara Obermayer-Pietsch; Andreas Tomaschitz; Thomas R. Pieber; Stefan Pilz; Verena Schwetz. Beneficial Effects of UV-Radiation: Vitamin D and beyond. International Journal of Environmental Research and Public Health 2016, 13, 1028 .

AMA Style

Christian Trummer, Marlene Pandis, Nicolas Verheyen, Martin R. Grübler, Martin Gaksch, Barbara Obermayer-Pietsch, Andreas Tomaschitz, Thomas R. Pieber, Stefan Pilz, Verena Schwetz. Beneficial Effects of UV-Radiation: Vitamin D and beyond. International Journal of Environmental Research and Public Health. 2016; 13 (10):1028.

Chicago/Turabian Style

Christian Trummer; Marlene Pandis; Nicolas Verheyen; Martin R. Grübler; Martin Gaksch; Barbara Obermayer-Pietsch; Andreas Tomaschitz; Thomas R. Pieber; Stefan Pilz; Verena Schwetz. 2016. "Beneficial Effects of UV-Radiation: Vitamin D and beyond." International Journal of Environmental Research and Public Health 13, no. 10: 1028.

Article
Published: 01 September 2016 in Journal of Hypertension
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The high prevalence of arterial hypertension in primary hyperparathyroidism (pHPT) is largely unexplained. Apart from parathyroid hormone (PTH), the mineral hormones fibroblast growth factor (FGF)-23 and aldosterone-to-renin ratio (ARR) are upregulated in pHPT. We aimed to determine whether nocturnal blood pressure (BP) is related with PTH, FGF-23 or ARR in a relatively large sample of pHPT patients. Cross-sectional data of the single-center “Eplerenone in Primary Hyperparathyroidism” trial were used. All patients with a biochemical diagnosis of pHPT who had both available 24-h ambulatory BP monitoring and valid laboratory data were included. Full data were available in 136 patients (mean age 67 ± 10 years, 78% women). Median PTH was 99 (interquartile range: 82–124) pg/ml and mean calcium was 2.63 ± 0.15 mmol/l. ARR, but not PTH or FGF-23, was significantly and directly related with nocturnal SBP (Pearson's r = 0.241, P Conclusion: ARR, but not FGF-23 or PTH, was independently and directly related with nocturnal BP parameters in patients with pHPT, and this relationship was dependent on pHPT disease severity. Inappropriately, elevated aldosterone may partially explain the high prevalence of arterial hypertension in pHPT.

ACS Style

Nicolas Verheyen; Astrid Fahrleitner-Pammer; Burkert Pieske; Andreas Meinitzer; Evgeny Belyavskiy; Julia Wetzel; Martin Gaksch; Martin R. Grübler; Cristiana Catena; Leonardo A. Sechi; Adriana J. Van Ballegooijen; Vincent M. Brandenburg; Hubert Scharnagl; Sabine Perl; Helmut Brussee; Winfried März; Stefan Pilz; Andreas Tomaschitz. Parathyroid hormone, aldosterone-to-renin ratio and fibroblast growth factor-23 as determinants of nocturnal blood pressure in primary hyperparathyroidism. Journal of Hypertension 2016, 34, 1778 -1786.

AMA Style

Nicolas Verheyen, Astrid Fahrleitner-Pammer, Burkert Pieske, Andreas Meinitzer, Evgeny Belyavskiy, Julia Wetzel, Martin Gaksch, Martin R. Grübler, Cristiana Catena, Leonardo A. Sechi, Adriana J. Van Ballegooijen, Vincent M. Brandenburg, Hubert Scharnagl, Sabine Perl, Helmut Brussee, Winfried März, Stefan Pilz, Andreas Tomaschitz. Parathyroid hormone, aldosterone-to-renin ratio and fibroblast growth factor-23 as determinants of nocturnal blood pressure in primary hyperparathyroidism. Journal of Hypertension. 2016; 34 (9):1778-1786.

Chicago/Turabian Style

Nicolas Verheyen; Astrid Fahrleitner-Pammer; Burkert Pieske; Andreas Meinitzer; Evgeny Belyavskiy; Julia Wetzel; Martin Gaksch; Martin R. Grübler; Cristiana Catena; Leonardo A. Sechi; Adriana J. Van Ballegooijen; Vincent M. Brandenburg; Hubert Scharnagl; Sabine Perl; Helmut Brussee; Winfried März; Stefan Pilz; Andreas Tomaschitz. 2016. "Parathyroid hormone, aldosterone-to-renin ratio and fibroblast growth factor-23 as determinants of nocturnal blood pressure in primary hyperparathyroidism." Journal of Hypertension 34, no. 9: 1778-1786.

Randomized controlled trial
Published: 28 July 2016 in Diabetes, Obesity and Metabolism
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BACKGROUNDExperimental data have indicated that vitamin D insufficiency has an important influence on glucose metabolism. The majority of epidemiological studies have demonstrated an association between low vitamin D and insulin resistance and/or type 2 diabetes mellitus. Nevertheless evidence from randomized controlled trials remains inconclusive.OBJECTIVETo investigate the efficacy of vitamin D supplementation on glycaemic control.DESIGNThe Styrian Vitamin D Hypertension Trial is a single-centre, double-blind, placebo-controlled study conducted between 2011 and 2014 at the Medical University of Graz, Austria. We enrolled 200 persons with arterial hypertension and 25-hydroxyvitamin D (25(OH)D) concentrations below 30 ng/mL. Study participants were randomized to receive either 2800 IU of vitamin D or placebo per day for 8 weeks. The present investigation is a post-hoc analysis that incorporated analysis of covariance (ANCOVA) approach while adjusting for baseline differences.RESULTSA total of 185 participants (mean±SD age, 60.1 ± 11.3 years; 47% women; mean 25-hydroxyvitamin D, 21.2 ± 5.6 ng/mL, mean HbA1c 44.8 ± 11.8 mmol/mol and mean BMI 30.4 ± 5.4 kg/m2) completed the trial. ANCOVA revealed a mean treatment effect (95% confidence interval) on HbA1c of -3.52 mmol/mol (95%CI -6.7 to -0.34; P = 0.045). There was no difference in fasting glucose -4.7 mg/dL (95%CI -16.3 to 6.9; P = 0.426).CONCLUSIONSVitamin D supplementation in obese hypertensive patients with low 25-hydroxyvitamin D reduces HbA1c. This finding warrants further investigations on potential vitamin D effects on glucose homeostasis.

ACS Style

Martin R. Grübler; Martin Gaksch; Katharina Kienreich; Nicolas Verheyen; Johannes Schmid; Bríain Ó Hartaigh; Georg Richtig; Hubert Scharnagl; Andreas Meinitzer; Astrid Fahrleitner‐Pammer; Winfried März; Andreas Tomaschitz; Stefan Pilz. Effects of vitamin D supplementation on glycated haemoglobin and fasting glucose levels in hypertensive patients: a randomized controlled trial. Diabetes, Obesity and Metabolism 2016, 18, 1006 -1012.

AMA Style

Martin R. Grübler, Martin Gaksch, Katharina Kienreich, Nicolas Verheyen, Johannes Schmid, Bríain Ó Hartaigh, Georg Richtig, Hubert Scharnagl, Andreas Meinitzer, Astrid Fahrleitner‐Pammer, Winfried März, Andreas Tomaschitz, Stefan Pilz. Effects of vitamin D supplementation on glycated haemoglobin and fasting glucose levels in hypertensive patients: a randomized controlled trial. Diabetes, Obesity and Metabolism. 2016; 18 (10):1006-1012.

Chicago/Turabian Style

Martin R. Grübler; Martin Gaksch; Katharina Kienreich; Nicolas Verheyen; Johannes Schmid; Bríain Ó Hartaigh; Georg Richtig; Hubert Scharnagl; Andreas Meinitzer; Astrid Fahrleitner‐Pammer; Winfried März; Andreas Tomaschitz; Stefan Pilz. 2016. "Effects of vitamin D supplementation on glycated haemoglobin and fasting glucose levels in hypertensive patients: a randomized controlled trial." Diabetes, Obesity and Metabolism 18, no. 10: 1006-1012.

Review article
Published: 18 July 2016 in Archives of Toxicology
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The objective was to provide the current state of the art regarding the role of vitamin D in chronic diseases (osteoporosis, cancer, cardiovascular diseases, dementia, autism, type 1 and type 2 diabetes mellitus, male and female fertility). The document was drawn up by panelists that provided their contribution according to their own scientific expertise. Each scientific expert supplied a first draft manuscript on a specific aspect of the document’s topic that was subjected to voting by all experts as “yes” (agreement with the content and/or wording) or “no” (disagreement). The adopted rule was that statements supported by ≥75 % of votes would be immediately accepted, while those with <25 % would be rejected outright. Others would be subjected to further discussion and subsequent voting, where ≥67 % support or, in an eventual third round, a majority of ≥50 % would be needed. This document finds that the current evidence support a role for vitamin D in bone health but not in other health conditions. However, subjects with vitamin D deficiency have been found to be at high risk of developing chronic diseases. Therefore, although at the present time there is not sufficient evidence to recommend vitamin D supplementation as treatment of chronic diseases, the treatment of vitamin D deficiency should be desiderable in order to reduce the risk of developing chronic diseases.

ACS Style

Giovanna Muscogiuri; Barbara Altieri; Cedric Annweiler; Giancarlo Balercia; H. B. Pal; Barbara J. Boucher; John J. Cannell; Carlo Foresta; Martin R. Grübler; Kalliopi Kotsa; Luca Mascitelli; Winfried März; Francesco Orio; Stefan Pilz; Giacomo Tirabassi; Annamaria Colao. Vitamin D and chronic diseases: the current state of the art. Archives of Toxicology 2016, 91, 97 -107.

AMA Style

Giovanna Muscogiuri, Barbara Altieri, Cedric Annweiler, Giancarlo Balercia, H. B. Pal, Barbara J. Boucher, John J. Cannell, Carlo Foresta, Martin R. Grübler, Kalliopi Kotsa, Luca Mascitelli, Winfried März, Francesco Orio, Stefan Pilz, Giacomo Tirabassi, Annamaria Colao. Vitamin D and chronic diseases: the current state of the art. Archives of Toxicology. 2016; 91 (1):97-107.

Chicago/Turabian Style

Giovanna Muscogiuri; Barbara Altieri; Cedric Annweiler; Giancarlo Balercia; H. B. Pal; Barbara J. Boucher; John J. Cannell; Carlo Foresta; Martin R. Grübler; Kalliopi Kotsa; Luca Mascitelli; Winfried März; Francesco Orio; Stefan Pilz; Giacomo Tirabassi; Annamaria Colao. 2016. "Vitamin D and chronic diseases: the current state of the art." Archives of Toxicology 91, no. 1: 97-107.

Randomized controlled trial
Published: 01 July 2016 in Journal of Hypertension
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Accumulating evidence points toward mutual interaction between parathyroid hormone (PTH) and aldosterone as potential mechanism for increasing cardiovascular risk in primary hyperparathyroidism (pHPT).The Eplerenone (EPATH) on parathyroid hormone levels in patients with primary hyperparathyroidism trial is a single-center, randomized, double-blind, parallel-group, placebo-controlled trial. The primary aim is to evaluate the effects of the mineralocorticoid receptor antagonist eplerenone on plasma intact PTH (iPTH) concentration in patients with pHPT. Secondary end points comprised surrogate parameters of cardiovascular health [24-h ambulatory SBP and DBP and echocardiographic parameters related to systolic/diastolic function as well as to cardiac dimensions].We enrolled 110 study participants with pHPT, 25-hydroxyvitamin D at least 20 ng/ml and estimated glomerular filtration rate more than 50 ml/min per 1.73 m. Patients were 1 : 1 randomly assigned to receive either 25 mg eplerenone once daily (up-titration after 4 weeks to 50 mg/day) or matching placebo for a treatment period of 8 weeks.The study was completed by 97 participants [mean (SD) age: 67.5 ± 9.5 years; 78.4% women). The mean treatment effect (95% confidence interval) for iPTH was 1.0 (0.9-1.1; P = 0.777) pg/ml. Mean 24-h ambulatory SBP and DBP decreased significantly [mean change (95% confidence interval) -6.3 (-9.4 to -3.3) and -3.7 (-5.7 to -1.7) mmHg, respectively; P < 0.001]. No differences were seen in any further secondary outcomes or frequency of adverse events.In pHPT, treatment with eplerenone compared with placebo had no effect on circulating iPTH levels. Eplerenone treatment was well tolerated and safe and followed by significant decrease of ambulatory blood pressure.

ACS Style

Andreas Tomaschitz; Nicolas Verheyen; Andreas Meinitzer; Burkert Pieske; Evgeny Belyavskiy; Helmut Brussee; Josef Haas; Winfried März; Elisabeth Pieske-Kraigher; Sarah Verheyen; Lisa Ofner-Ziegenfuss; Bríain Ó. Hartaigh; Verena Schwetz; Felix Aberer; Martin R. Grübler; Florian Lang; Ioana Alesutan; Jakob Voelkl; Martin Gaksch; Jörg H. Horina; Hans-Peter Dimai; Jutta Rus-Machan; Claudia Stiegler; Eberhard Ritz; Astrid Fahrleitner-Pammer; Stefan Pilz. Effect of eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism. Journal of Hypertension 2016, 34, 1347 -1356.

AMA Style

Andreas Tomaschitz, Nicolas Verheyen, Andreas Meinitzer, Burkert Pieske, Evgeny Belyavskiy, Helmut Brussee, Josef Haas, Winfried März, Elisabeth Pieske-Kraigher, Sarah Verheyen, Lisa Ofner-Ziegenfuss, Bríain Ó. Hartaigh, Verena Schwetz, Felix Aberer, Martin R. Grübler, Florian Lang, Ioana Alesutan, Jakob Voelkl, Martin Gaksch, Jörg H. Horina, Hans-Peter Dimai, Jutta Rus-Machan, Claudia Stiegler, Eberhard Ritz, Astrid Fahrleitner-Pammer, Stefan Pilz. Effect of eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism. Journal of Hypertension. 2016; 34 (7):1347-1356.

Chicago/Turabian Style

Andreas Tomaschitz; Nicolas Verheyen; Andreas Meinitzer; Burkert Pieske; Evgeny Belyavskiy; Helmut Brussee; Josef Haas; Winfried März; Elisabeth Pieske-Kraigher; Sarah Verheyen; Lisa Ofner-Ziegenfuss; Bríain Ó. Hartaigh; Verena Schwetz; Felix Aberer; Martin R. Grübler; Florian Lang; Ioana Alesutan; Jakob Voelkl; Martin Gaksch; Jörg H. Horina; Hans-Peter Dimai; Jutta Rus-Machan; Claudia Stiegler; Eberhard Ritz; Astrid Fahrleitner-Pammer; Stefan Pilz. 2016. "Effect of eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism." Journal of Hypertension 34, no. 7: 1347-1356.

Comparative study
Published: 23 June 2016 in Chemistry and Biology of Pteridines and Folates
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High concentrations of renin and aldosterone are risk factors for cardiovascular diseases (CVD) which are the leading cause of morbidity and mortality worldwide. Enhanced activation of the renin-angiotensin-aldosterone system (RAAS) by cigarette smoking has been reported. The aim of our study was to analyze the effect of cigarette smoking on parameters of the RAAS in active smokers (AS) and life-time non-smokers (NS) of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study as well as the utility of RAAS parameter for risk prediction. We determined the concentration of aldosterone, renin, angiotensin-I and angiotensin-II in participants of the LURIC study. Smoking status was assessed by a questionnaire and the measurement of plasma cotinine concentration. Parameters were log transformed before entering analyses, where appropriate. We used a multivariate Cox regression analysis to assess the effect of parameters on mortality. From the 3316 LURIC participants 777 were AS and 1178 NS. Within a median observation period of 10 years 221 (28.4 %) AS and 302 (25.6 %) NS died. After adjustment for age, gender, and the use of anti-hypertensive medication, only angiotensin-I was significantly different in AS compared to NS with an estimated marginal mean (95 % CI) of 1607 (1541-1673) ng/L and 1719 (1667-1772) ng/L, respectively. For both NS and AS renin and angiotensin-II were directly associated with mortality in the multivariate Cox regression analysis. Angiotensin-I was only associated with increased risk for mortality in NS (HR (95 % CI) of 0.69 (0.53-0.89)). We conclude that increased renin and angiotensin-II are independent predictors of mortality in AS and NS, while angiotensin-I was associated with reduced risk of death in NS only.

ACS Style

Graciela E. Delgado; Rüdiger Siekmeier; Bernhard K. Krämer; Martin R. Grübler; Andreas Tomaschitz; Winfried März; Marcus E. Kleber. The Renin-Angiotensin-Aldosterone System in Smokers and Non-Smokers of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study. Chemistry and Biology of Pteridines and Folates 2016, 935, 75 -82.

AMA Style

Graciela E. Delgado, Rüdiger Siekmeier, Bernhard K. Krämer, Martin R. Grübler, Andreas Tomaschitz, Winfried März, Marcus E. Kleber. The Renin-Angiotensin-Aldosterone System in Smokers and Non-Smokers of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study. Chemistry and Biology of Pteridines and Folates. 2016; 935 ():75-82.

Chicago/Turabian Style

Graciela E. Delgado; Rüdiger Siekmeier; Bernhard K. Krämer; Martin R. Grübler; Andreas Tomaschitz; Winfried März; Marcus E. Kleber. 2016. "The Renin-Angiotensin-Aldosterone System in Smokers and Non-Smokers of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study." Chemistry and Biology of Pteridines and Folates 935, no. : 75-82.