Publications by authors named "Nicolas Verheyen"

72 Publications

Advanced isolated light chain amyloid cardiomyopathy with negative immunofixation and normal free light chain ratio.

ESC Heart Fail 2021 May 7. Epub 2021 May 7.

Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, Graz, A-8036, Austria.

Amyloid light chain (AL) cardiomyopathy is the most malignant specific cardiomyopathy. According to international recommendations, it should be ruled out non-invasively using the serum free light chain (FLC) ratio and immunofixation electrophoresis in both serum and urine. Here, we report on a 69-year-old female patient with new-onset heart failure with mid-range ejection fraction. Cardiac imaging was highly suggestive of cardiac amyloidosis. Amyloid scintigraphy showed faint myocardial tracer uptake according to Perugini Score 1, but immunofixation was negative and the FLC ratio was normal, despite a slight increase in lambda FLCs. Endomyocardial biopsy revealed advanced myocardial lambda immunoglobulin light chain deposition. Clinically relevant extracardiac amyloid organ infiltration could not be detected. Conclusively, non-invasive testing can in rare cases fail to exclude isolated AL amyloid cardiomyopathy. We suggest that even slight increases in serum lambda or kappa FLCs should be considered abnormal in suspected cardiac amyloidosis if non-invasive testing delivers discrepant results.
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http://dx.doi.org/10.1002/ehf2.13381DOI Listing
May 2021

Associations of Serum Cortisol with Cardiovascular Risk and Mortality in Patients Referred to Coronary Angiography.

J Endocr Soc 2021 May 10;5(5):bvab017. Epub 2021 Feb 10.

Department of Internal Medicine, Division of Nephrology, Medical University of Graz, 8036 Graz, Austria.

Context: Serum cortisol may be associated with cardiovascular risk factors and mortality in patients undergoing coronary angiography, but previous data on this topic are limited and controversial.

Objective: We evaluated whether morning serum cortisol is associated with cardiovascular risk factors, lymphocyte subtypes, and mortality.

Methods: This is a prospective cohort study performed at a tertiary care centre in south-west Germany between 1997 and 2000. We included 3052 study participants who underwent coronary angiography. The primary outcome measures were cardiovascular risk factors, lymphocyte subtypes, and all-cause and cardiovascular mortality.

Results: Serum cortisol was associated with an adverse cardiovascular risk profile, but there was no significant association with coronary artery disease or acute coronary syndrome. In a subsample of 2107 participants, serum cortisol was positively associated with certain lymphocyte subsets, including CD16+CD56+ (natural killer) cells ( < 0.001). Comparing the fourth versus the first serum cortisol quartile, the crude Cox proportional hazard ratios (with 95% CIs) were 1.22 (1.00-1.47) for all-cause and 1.32 (1.04-1.67) for cardiovascular mortality, respectively. After adjustments for various cardiovascular risk factors, these associations were attenuated to 0.93 (0.76-1.14) for all-cause, and 0.97 (0.76-1.25) for cardiovascular mortality, respectively.

Conclusions: Despite significant associations with classic cardiovascular risk factors and natural killer cells, serum cortisol was not a significant and independent predictor of mortality in patients referred to coronary angiography. These findings might reflect that adverse cardiovascular effects of cortisol could be counterbalanced by some cardiovascular protective actions.
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http://dx.doi.org/10.1210/jendso/bvab017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041336PMC
May 2021

Prevalence and prognostic factors for aortic dilatation in giant cell arteritis - a longitudinal study.

Semin Arthritis Rheum 2020 Nov 21. Epub 2020 Nov 21.

Division of Angiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.

Objectives: Predictive data for the development of aortic dilatation (AD) in giant-cell arteritis (GCA) are controversial. The aim was to investigate by computed tomography (CT) the prevalence of AD in a consecutive cohort of GCA patients and controls, and to identify possible predictors for AD.

Methods: GCA patients and controls were identified by electronic search and underwent aortic contrast enhanced CT defining AD by aortic diameter adjusted to age, gender and body surface area. Pulse-wave velocity, intima-media thickness (IMT) and laboratory studies including lymphocyte subsets were conducted identifying potential factors associated with AD. Clinical and laboratory parameters at disease onset, occurrence of aortic rupture/dissection before and up to five years after study visit were retrieved by chart review.

Results: 144 GCA patients and 115 controls were included. GCA patients developed more frequently AD of the ascending and thoracic descending aorta compared to controls (OR 2.60, p = 0.016; OR 3.65, p = 0.005, respectively). Factors associated with AD development of thoracic descending aorta, but not of the ascending aorta, were higher percentages of circulating CD3+CD4+ cells, higher CD4/CD8 ratio, presence of polymyalgia rheumatica and increased carotid IMT at disease onset (OR range 1.10-3.11, all with p < 0.05). During follow-up, no GCA patient required surgical aortic repair or suffered aortic rupture/dissection.

Conclusions: Thoracic but not abdominal ADs occur more commonly in GCA patients, however, the subsequent risk for aortic repair, rupture or dissection is low. Changes of T-cell subsets, presence of polymyalgia rheumatica and increased carotid IMT at disease onset are associated with AD development.
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http://dx.doi.org/10.1016/j.semarthrit.2020.11.003DOI Listing
November 2020

Diagnosis and treatment of cardiac amyloidosis: an interdisciplinary consensus statement.

Wien Klin Wochenschr 2020 Dec 3;132(23-24):742-761. Epub 2020 Dec 3.

Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria.

The prevalence and significance of cardiac amyloidosis have been considerably underestimated in the past; however, the number of patients diagnosed with cardiac amyloidosis has increased significantly recently due to growing awareness of the disease, improved diagnostic capabilities and demographic trends. Specific therapies that improve patient prognosis have become available for certain types of cardiac amyloidosis. Thus, the earliest possible referral of patients with suspicion of cardiac amyloidosis to an experienced center is crucial to ensure rapid diagnosis, early initiation of treatment, and structured patient care. This requires intensive collaboration across several disciplines, and between resident physicians and specialized centers. The aim of this consensus statement is to provide guidance for the rapid and efficient diagnosis and treatment of light-chain amyloidosis and transthyretin amyloidosis, which are the most common forms of cardiac amyloidosis.
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http://dx.doi.org/10.1007/s00508-020-01781-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732807PMC
December 2020

Indications and Outcome in Patients Undergoing Left Atrial Appendage Closure-The Austrian LAAC Registry.

J Clin Med 2020 Oct 13;9(10). Epub 2020 Oct 13.

Department of Cardiology, Medical University of Graz, 8036 Graz, Austria.

Background: Complete real-world data on the indications and outcomes of left atrial appendage closure (LAAC) outside of clinical trials are rare. In this study, we stratified patients undergoing LAAC by indication groups.

Methods: This analysis of the national multicentre Austrian LAAC Registry comprised all patients that underwent LAAC up until 2018 at the currently active centres in Austria. The baseline characteristics, procedural details and outcomes between the following indication groups were compared: bleeding as an indication for LAAC ("bleeding" group) vs. thromboembolism despite oral anticoagulation (OAC; "thromboembolism" group) vs. an intolerance to OAC for reasons other than the above ("other" group).

Results: The analysis included 186 patients, with 59.7% in the "bleeding" group, 8.1% in the "thromboembolism" group and 32.2% in the "other" group. The CHADS score was the highest in the "thromboembolism" group and the HAS-BLED score was the highest in the "bleeding" group. The procedural outcomes were similar between groups (implantation success, 97.3%), with major complications occurring in 7.0% of patients. One-year survival free from stroke, bleeding or LAAC-associated hospitalisation was 83.9%, 90.0% and 81.4% in the "bleeding", "thromboembolism" and "other" groups, respectively ( = 0.891).

Conclusions: In routine clinical practice, LAAC was used in a heterogeneous patient population with atrial fibrillation (AF) and contraindication, inefficacy or intolerance to OAC. The long-term outcome was favourable in all groups.
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http://dx.doi.org/10.3390/jcm9103274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600032PMC
October 2020

Associations of Thyroid Hormones and Resting Heart Rate in Patients Referred to Coronary Angiography.

Horm Metab Res 2020 Dec 4;52(12):850-855. Epub 2020 Sep 4.

Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.

Resting heart rate (RHR) is associated with increased risk of cardiovascular morbidity and mortality. Thyroid hormones exert several effects on the cardiovascular system, but the relation between thyroid function and RHR remains to be further established. We evaluated whether measures of thyroid hormone status are associated with RHR in patients referred to coronary angiography. Thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxin (FT4), and RHR were determined in 2795 participants of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study. Median (25th to 75th percentile) serum concentrations were 1.25 (0.76-1.92) mU/l for TSH, 4.8 (4.2-5.3) pmol/l for FT3 and 17.1 (15.4-19.0) pmol/l for FT4, and mean (±standard deviation) RHR was 68.8 (±11.7) beats/min. Comparing the highest versus the lowest quartile, RHR (beats/min) was significantly higher in the fourth FT4 quartile [3.48, 95% confidence interval (CI): 2.23-4.73; p <0.001] and in the fourth FT3 quartile (2.30, 95% CI: 1.06-3.55; p <0.001), but there was no significant difference for TSH quartiles. In multiple linear regression analyses adjusting for various potential confounders, FT3 and FT4 were significant predictors of RHR (p <0.001 for both). In subgroups restricted to TSH, FT3, and FT4 values within the reference range, both FT3 and FT4 remained significant predictors of RHR (p <0.001 for all). In conclusion, in patients referred to coronary angiography, FT3 and FT4 but not TSH were positively associated with RHR. The relationship between free thyroid hormones and RHR warrants further investigations regarding its diagnostic and therapeutic implications.
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http://dx.doi.org/10.1055/a-1232-7292DOI Listing
December 2020

Hereditary ATTR Amyloidosis in Austria: Prevalence and Epidemiological Hot Spots.

J Clin Med 2020 Jul 14;9(7). Epub 2020 Jul 14.

Department of Neurology, Medical University of Innsbruck, 6020 Innsbruck, Austria.

Background: Hereditary transthyretin amyloidosis (hATTR) is an autosomal dominantly inherited disorder caused by an accumulation of amyloid fibrils in tissues due to mutations in the transthyretin () gene. The prevalence of hATTR is still unclear and likely underestimated in many countries. In order to apply new therapies in a targeted manner, early diagnosis and knowledge of phenotype-genotype correlations are mandatory. This study aimed to assess the prevalence and phenotypic spectrum of hATTR in Austria.

Methods: Within the period of 2014-2019, patients with ATTR-associated cardiomyopathy and/or unexplained progressive polyneuropathies were screened for mutations in the gene.

Results: We identified 43 cases from 22 families carrying 10 different missense mutations and confirmed two mutational hot spots at c.323A>G (p.His108Arg) and c.337G>C (p.Val113Leu). Two further patients with late onset ATTR carried variants of unknown significance. The majority of patients initially presented with heart failure symptoms that were subsequently accompanied by progressive polyneuropathy in most cases. A total of 55% had a history of carpal tunnel syndrome before the onset of other organ manifestations.

Conclusions: Our study underlined the relevance of hATTR in the pathogenesis of amyloid-driven cardiomyopathy and axonal polyneuropathy and indicated considerable genetic heterogeneity of this disease in the Austrian population. The estimated prevalence of hATTR in Austria based on this study is 1:200,000 but a potentially higher number of unknown cases must be taken into account. With respect to new therapeutic approaches, we strongly propose genetic testing of the gene in an extended cohort of patients with unexplained heart failure and progressive polyneuropathy.
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http://dx.doi.org/10.3390/jcm9072234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408866PMC
July 2020

Stork leg sign in acute pericarditis.

Pol Arch Intern Med 2020 08 3;130(7-8):683-684. Epub 2020 Jun 3.

Division of Angiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

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http://dx.doi.org/10.20452/pamw.15412DOI Listing
August 2020

Effect of Galectin 3 on Aldosterone-Associated Risk of Cardiovascular Mortality in Patients Undergoing Coronary Angiography.

Am J Cardiol 2020 07 22;127:9-15. Epub 2020 Apr 22.

Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, and Rheumatology), Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany; Cinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria; Synlab Academy, Synlab Services GmbH, Mannheim and Augsburg, Germany.

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.
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http://dx.doi.org/10.1016/j.amjcard.2020.04.017DOI Listing
July 2020

Circulating uromodulin inhibits vascular calcification by interfering with pro-inflammatory cytokine signalling.

Cardiovasc Res 2021 Feb;117(3):930-941

Institute for Physiology and Pathophysiology, Johannes Kepler University Linz, Altenberger Strasse 69, 4040 Linz, Austria.

Aims: Uromodulin is produced exclusively in the kidney and secreted into both urine and blood. Serum levels of uromodulin are correlated with kidney function and reduced in chronic kidney disease (CKD) patients, but physiological functions of serum uromodulin are still elusive. This study investigated the role of uromodulin in medial vascular calcification, a key factor associated with cardiovascular events and mortality in CKD patients.

Methods And Results : Experiments were performed in primary human (HAoSMCs) and mouse (MOVAS) aortic smooth muscle cells, cholecalciferol overload and subtotal nephrectomy mouse models and serum from CKD patients. In three independent cohorts of CKD patients, serum uromodulin concentrations were inversely correlated with serum calcification propensity. Uromodulin supplementation reduced phosphate-induced osteo-/chondrogenic transdifferentiation and calcification of HAoSMCs. In human serum, pro-inflammatory cytokines tumour necrosis factor α (TNFα) and interleukin-1β (IL-1β) co-immunoprecipitated with uromodulin. Uromodulin inhibited TNFα and IL-1β-induced osteo-/chondrogenic signalling and activation of the transcription factor nuclear factor kappa-light-chain-enhancer of activated β cells (NF-kB) as well as phosphate-induced NF-kB-dependent transcriptional activity in HAoSMCs. In vivo, adeno-associated virus (AAV)-mediated overexpression of uromodulin ameliorated vascular calcification in mice with cholecalciferol overload. Conversely, cholecalciferol overload-induced vascular calcification was aggravated in uromodulin-deficient mice. In contrast, uromodulin overexpression failed to reduce vascular calcification during renal failure in mice. Carbamylated uromodulin was detected in serum of CKD patients and uromodulin carbamylation inhibited its anti-calcific properties in vitro.

Conclusions : Uromodulin counteracts vascular osteo-/chondrogenic transdifferentiation and calcification, at least in part, through interference with cytokine-dependent pro-calcific signalling. In CKD, reduction and carbamylation of uromodulin may contribute to vascular pathology.
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http://dx.doi.org/10.1093/cvr/cvaa081DOI Listing
February 2021

Are soluble ST2 levels influenced by vitamin D and/or the seasons?

Endocr Connect 2019 06 1;8(6):691-700. Epub 2019 Jun 1.

Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

Objective: Cardiovascular disease manifestation and several associated surrogate markers, such as vitamin D, have shown substantial seasonal variation. A promising cardiovascular biomarker, soluble ST2 (sST2), has not been investigated in this regard – we therefore determined if systemic levels of sST2 are affected by seasonality and/or vitamin D in order to investigate their clinical interrelation and usability.

Design: sST2 levels were measured in two cohorts involving hypertensive patients at cardiovascular risk, the Styrian Vitamin D Hypertension Trial (study A; RCT design, 8 weeks 2800 IU cholecalciferol daily) and the Ludwigshafen Risk and Cardiovascular Health Study (LURIC; study B; cross-sectional design).

Methods: The effects of a vitamin D intervention on sST2 levels were determined in study A using ANCOVA, while seasonality of sST2 levels was determined in study B using ANOVA.

Results: The concentrations of sST2 remained unchanged by a vitamin D intervention in study A, with a mean treatment effect (95% confidence interval) of 0.1 (−0.6 to 0.8) ng/mL; P = 0.761), despite a rise in 25(OH)D (11.3 (9.2–13.5) ng/mL; P < 0.001) compared to placebo. In study B, seasonal variations were present in 25(OH)D levels in men and women with or without heart failure (P < 0.001 for all subgroups), while sST2 levels remained unaffected by the seasons in all subgroups.

Conclusions: Our study provides the first evidence that systemic sST2 levels are not interrelated with vitamin D levels or influenced by the seasons in subjects at cardiovascular risk.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6528407PMC
June 2019

Impact of EMpagliflozin on cardiac function and biomarkers of heart failure in patients with acute MYocardial infarction-The EMMY trial.

Am Heart J 2020 03 12;221:39-47. Epub 2019 Dec 12.

Medical University of Graz, Department of Internal Medicine, Division of Endocrinology and Diabetology, Graz, Austria.

Background: Sodium glucose cotransporter 2 (SGLT2) inhibitors are established antidiabetic drugs with proven cardiovascular benefit. Although growing evidence suggests beneficial effects on myocardial remodeling, fluid balance and cardiac function, the impact of empagliflozin initiated early after acute myocardial infarction (AMI) has not been investigated yet. Therefore, the impact of EMpagliflozin on cardiac function and biomarkers of heart failure in patients with acute MYocardial infarction (EMMY) trial was designed to investigate the efficacy and safety of empagliflozin in diabetic and non-diabetic patients after severe AMI.

Methods: Within a multicenter, randomized, double-blind, placebo-controlled, phase 3b trial we will enroll patients with AMI and characteristics suggestive of severe myocardial necrosis are randomized in a 1:1 ratio to empagliflozin (10 mg once daily) or matching placebo. The primary endpoint is the impact of empagliflozin on changes in NT-proBNP within 6 months after AMI. Secondary endpoints include changes in echocardiographic parameters, levels of ketone body concentrations, HbA1c levels and body weight, respectively. Hospitalization rate due to heart failure or other causes, the duration of hospital stay and all-cause mortality will be assessed as exploratory secondary endpoints.

Discussion: The EMMY trial will test empagliflozin in patients with AMI regardless of their diabetic status. The EMMY trial may therefore underpin the concept of SGLT2 inhibition to improve cardiac remodeling, pre-and afterload reduction and cardiac metabolism regardless of its antidiabetic effects. Results will provide the rationale for the conduct of a cardiovascular outcome trial to test the effect of empagliflozin in patients with AMI.
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http://dx.doi.org/10.1016/j.ahj.2019.12.004DOI Listing
March 2020

The Effect of Vitamin D Supplementation on its Metabolism and the Vitamin D Metabolite Ratio.

Nutrients 2019 Oct 21;11(10). Epub 2019 Oct 21.

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

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)D) provide additional insights into vitamin D status or metabolism. Earlier studies suggested that the vitamin D metabolite ratio (VMR), calculated as 24,25(OH)D/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)D, 24,25(OH)D and the VMR was 32 nmol/L, 3.3 nmol/L and 0.015 (all < 0.001), respectively. Baseline 25(OH)D and 24,25(OH)D predicted the change in 25(OH)D with comparable strength and magnitude. Correlation and regression analysis showed that the VMR did not predict the change in 25(OH)D. Therefore, our data do not support routine measurement of 24,25(OH)D 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.
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http://dx.doi.org/10.3390/nu11102539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836132PMC
October 2019

Diagnostic Accuracy of the Aldosterone-to-Active Renin Ratio for Detecting Primary Aldosteronism.

J Endocr Soc 2019 Sep 19;3(9):1748-1758. Epub 2019 Jul 19.

Bad Gleichenberg Clinic, Bad Gleichenberg, Austria.

Context: The aldosterone-to-active renin ratio (AARR) is the recommended screening test for primary aldosteronism (PA), but prospective study data on its sensitivity and specificity are sparse.

Objective: To investigate the diagnostic accuracy of the AARR for detecting PA.

Design: Prospective diagnostic accuracy study.

Setting: This study was conducted from February 2009 to August 2015 at the outpatient clinic of the Department of Endocrinology and Diabetology of the Medical University of Graz, Austria.

Participants: Four hundred patients with arterial hypertension who were referred to a tertiary care center for screening for endocrine hypertension.

Intervention: Participants had a determination of the AARR (index test) and a second AARR determination followed by a saline infusion test (SIT) after 2 to 6 weeks. PA was diagnosed in individuals with any AARR ≥3.7 ng/dL/µU/mL [including a plasma aldosterone concentration (PAC) of ≥9 ng/dL] who had a PAC ≥10 ng/dL after the SIT. We did not substantially alter antihypertensive drug intake.

Main Outcome Measures: Primary outcome was the receiver-operating characteristic (ROC) curve of the AARR in diagnosing PA.

Results: A total of 382 participants were eligible for analyses; PA was diagnosed in 18 (4.7%) patients. The area under the ROC curve of the AARR in detecting PA was 0.973 (95% CI, 0.956 to 0.990). Sensitivity and specificity for a positive AARR in diagnosing PA were 100% (95% CI, 81.5% to 100.0%) and 89.6% (95% CI, 86.0% to 92.5%), respectively.

Conclusions: The AARR has good diagnostic accuracy for detecting PA.
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http://dx.doi.org/10.1210/js.2019-00145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735732PMC
September 2019

Alternate Day Fasting Improves Physiological and Molecular Markers of Aging in Healthy, Non-obese Humans.

Cell Metab 2019 09 27;30(3):462-476.e6. Epub 2019 Aug 27.

Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Austria; Center for Biomarker Research in Medicine (CBmed), Graz, Austria; HEALTH Institute for Biomedicine and Health Sciences, JOANNEUM RESEARCH Forschungsgesellschaft mbH, Neue Stiftingtalstraße 2, Graz, Austria.

Caloric restriction and intermittent fasting are known to prolong life- and healthspan in model organisms, while their effects on humans are less well studied. In a randomized controlled trial study (ClinicalTrials.gov identifier: NCT02673515), we show that 4 weeks of strict alternate day fasting (ADF) improved markers of general health in healthy, middle-aged humans while causing a 37% calorie reduction on average. No adverse effects occurred even after >6 months. ADF improved cardiovascular markers, reduced fat mass (particularly the trunk fat), improving the fat-to-lean ratio, and increased β-hydroxybutyrate, even on non-fasting days. On fasting days, the pro-aging amino-acid methionine, among others, was periodically depleted, while polyunsaturated fatty acids were elevated. We found reduced levels sICAM-1 (an age-associated inflammatory marker), low-density lipoprotein, and the metabolic regulator triiodothyronine after long-term ADF. These results shed light on the physiological impact of ADF and supports its safety. ADF could eventually become a clinically relevant intervention.
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http://dx.doi.org/10.1016/j.cmet.2019.07.016DOI Listing
September 2019

The effect of vitamin D supplementation on plasma non-oxidised PTH in a randomised clinical trial.

Endocr Connect 2019 May;8(5):518-527

Department of Clinical Chemistry, Amsterdam Gastroenterology & Metabolism, Amsterdam UMC, Vrije Universiteit Amsterdam, Endocrine Laboratory, Amsterdam, Netherlands.

Objective: PTH can be oxidised in vivo, rendering it biologically inactive. Non-oxidised PTH (n-oxPTH) may therefore give a better image of the hormonal status of the patient. While vitamin D supplementation decreases total PTH (tPTH) concentration, the effect on n-oxPTH concentration is unexplored. We investigated the effect of vitamin D on n-oxPTH concentration in comparison to tPTH and compared the correlations between parameters of calcium, bone and lipid metabolism with n-oxPTH and tPTH.

Methods: N-oxPTH was measured in 108 vitamin D-insufficient (25(OH)D <75 nmol/L) hypertensive patients, treated with vitamin D (2800 IE daily) or placebo for 8 weeks in the Styrian Vitamin D Hypertension Trial (NCT02136771). We calculated the treatment effect and performed correlation analyses of n-oxPTH and tPTH with parameters of calcium, bone and lipid metabolism and oxidative stress.

Results: After treatment, compared to placebo, 25(OH)D concentrations increased, tPTH decreased by 9% (P < 0.001), n-oxPTH by 7% (P = 0.025) and the ratio of n-oxPTH/tPTH increased (P = 0.027). Changes in phosphate and HDL concentration correlated with changes in n-oxPTH, but not tPTH.

Conclusions: tPTH and n-oxPTH decrease upon vitamin D supplementation. Our study suggests that vitamin D supplementation reduces the oxidation of PTH, as we observed a small but significant increase in the non-oxidised proportion of PTH upon treatment. In addition, we found that changes in phosphate and HDL concentration showed a relationship with changes in n-oxPTH, but not tPTH. This may be explained by the biological activity of n-oxPTH. Further research should be carried out to establish the clinical relevance of n-oxPTH.
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http://dx.doi.org/10.1530/EC-19-0097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6499917PMC
May 2019

Exercise training in patients with a left ventricular assist device (Ex-VAD): rationale and design of a multicentre, prospective, assessor-blinded, randomized, controlled trial.

Eur J Heart Fail 2019 09 28;21(9):1152-1159. Epub 2019 Mar 28.

Department of Internal Medicine and Cardiology, Charité University Medicine Berlin, Berlin, Germany.

Aims: Left ventricular assist device (LVAD) therapy is a promising option for patients with advanced heart failure (HF), refractory to guideline-mandated medical treatment either as a bridge to heart transplantation or as lifelong therapy. Functional capacity improves after LVAD implantation but remains reduced in patients with long-term LVAD therapy. Exercise training (ET) improves functional capacity and quality of life (QoL) in HF and may provide incremental benefits in patients supported with LVAD therapy.

Methods: The primary objective of Ex-VAD is to investigate whether a 12-week supervised ET can improve peak oxygen uptake (peakVO ) measured by cardiopulmonary exercise testing (CPET) on an ergometer. The study is powered to demonstrate a group difference of 3 mL/min/kg in peakVO at week 12, with a power of 0.9 and a standard deviation of 5 mL/min/kg. After baseline assessments to determine whether ET is safe, 66 patients at six trial sites with advanced HF and LVAD therapy will be randomized 2:1 to supervised ET or to the control arm of usual care alone. Patients randomized to ET will perform supervised aerobic endurance and resistance ET (three times/week) for 12 weeks. At baseline and during follow-up, anthropometry, CPET, echocardiography (at rest and exercise), and QoL evaluation will be performed. Blood samples will be collected to examine cardiac-specific relevant biomarkers. Overall physical activity, training sessions, and adherence will be monitored and documented throughout the study using accelerometers and patient diaries.

Conclusions: The Ex-VAD trial will assess the effects of a supervised ET programme on peakVO and QoL in patients with LVAD. As LVAD therapy moves from crisis support to ambulatory functional enhancement, this trial will provide a rationale to improve functional capacity and, in perspective, cardiovascular outcomes in LVAD-supported patients with advanced HF.
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http://dx.doi.org/10.1002/ejhf.1431DOI Listing
September 2019

The endogenous cardiotonic steroid Marinobufagenin and decline in estimated glomerular filtration rate at follow-up in patients with arterial hypertension.

PLoS One 2019 28;14(2):e0212973. Epub 2019 Feb 28.

Department of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria.

Background: Marinobufagenin (MBG) is an endogenous cardiotonic steroid (CTS) that inhibits the Na+/K+-ATPase. Human MBG is significantly increased in end-stage renal disease and immunization against MBG attenuates cardiovascular fibrosis in a rat model of uremic cardiomyopathy. Mineralocorticoid antagonists (MRA) block MBG binding sites and decrease proteinuria in chronic kidney disease (CKD) patients. We therefore aimed to investigate the association of MBG and albuminuria, as a marker of renal damage, as well as MBG and decline of glomerular filtration rate (GFR).

Methods: The Graz endocrine causes of hypertension (GECOH) study is a single center study of adults routinely referred for screening of endocrine hypertension. Plasma MBG was measured by an enzyme-linked immunoassay, and in a post-hoc analysis, follow-up creatinine levels were obtained. Patients with proteinuria >3.5g/day at baseline were excluded from further evaluation.

Results: We measured MBG concentrations in 40 hypertensive subjects and excluded one patient due to pre-existing proteinuria. Plasma MBG was significantly correlated with albuminuria (Spearman ρ = .357; p = .028) and proteinuria (ρ = .336; p = .039). In linear regression analysis, the association remained significant after adjustment for age, sex, and BMI (β = .306; p = .036), and for mean systolic blood pressure (β = .352; p = .034). In follow-up analyses (N = 30), MBG was significantly associated with decline in GFR after adjustment for time-to-follow-up (β = -.374; p = .042).

Conclusion: The findings suggest that MBG plasma concentrations were associated with albuminuria as well as decline in kidney function. Whether MBG predicts hard renal endpoints warrants further investigations.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0212973PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394930PMC
November 2019

Diastolic stress test echocardiography in patients with suspected heart failure with preserved ejection fraction: a pilot study.

ESC Heart Fail 2019 02 19;6(1):146-153. Epub 2018 Nov 19.

Department of Internal Medicine and Cardiology, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany.

Aims: The purpose of this pilot study was to assess the potential usefulness of diastolic stress test (DST) echocardiography in patients with suspected heart failure with preserved ejection fraction (HFpEF).

Methods And Results: Patients with suspected HFpEF (left ventricular ejection fraction ≥ 50%, exertional dyspnoea, septal E/e' at rest 9-14, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) at rest < 220 pg/mL; n = 13) and a control group constituted from asymptomatic patients with arterial hypertension (n = 19) and healthy subjects (n = 18) were included. All patients were analysed by two-dimensional and Doppler echocardiography at rest and during exercise (DST) and underwent cardiopulmonary exercise testing and NT-proBNP analysis during exercise. HFpEF during exercise was defined as exertional dyspnoea and peak VO  ≤ 20.0 mL/min/kg. In patients with suspected HFpEF at rest, 84.6% of these patients developed HFpEF during exercise, whereas in the group of asymptomatic patients with hypertension and healthy subjects, the rate of developed HFpEF during exercise was 0%. Regarding the diagnostic performance of DST to detect HFpEF during exercise, an E/e' ratio >15 during exercise was the most accurate parameter to detect HFpEF (accuracy 86%), albeit a low sensitivity (45.5%). Nonetheless, combining E/e' with tricuspid regurgitation (TR) velocity > 2.8 m/s during exercise provided a significant increase in the sensitivity to detect patients with HFpEF during exercise (sensitivity 72.7%, specificity 79.5%, and accuracy 78%). Consistent with these findings, an increase of E/e' was significantly linked to worse peak VO , and the combination of an increase of both E/e' and TR velocity was associated with elevated NT-proBNP values during exercise.

Conclusions: The findings of this pilot study suggest that DST using E/e' ratio and TR velocity could be of potential usefulness to diagnose HFpEF during exercise in patients with suspected HFpEF at rest.
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http://dx.doi.org/10.1002/ehf2.12375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352885PMC
February 2019

Homoarginine/ADMA ratio and homoarginine/SDMA ratio as independent predictors of cardiovascular mortality and cardiovascular events in lower extremity arterial disease.

Sci Rep 2018 09 21;8(1):14197. Epub 2018 Sep 21.

Division of Angiology, Department of Internal Medicine, Medical University Graz, Graz, Austria.

Endothelial dysfunction plays a key role in development of atherosclerosis and lower extremity arterial disease (LEAD). Homoarginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are sensitive markers for endothelial dysfunction and independent risk factors for cardiovascular death. However, homoarginine may influence the proatherogenic effects of ADMA and SDMA suggesting homoarginine/ADMA ratio or homoarginine/SDMA ratio as further predictors for cardiovascular mortality. Therefore, we investigated the predictive value of homoarginine/ADMA ratio and homoarginine/SDMA ratio related to cardiovascular mortality and cardiovascular events in claudicant patients with LEAD. 151 patients with intermittent claudication were included in a prospective observational study (observation time 7.7 ± 2.5 years) with cardiovascular mortality as main outcome parameter and the occurrence of cardiovascular events as secondary outcome parameter. Homoarginine, ADMA and SDMA were measured by high-performance liquid chromatography at baseline. Low homoarginine/ADMA ratio and homoarginine/SDMA ratio were independently associated with higher cardiovascular mortality (HR 2.803 [95% CI 1.178-6.674], p = 0.020; HR 2.782 [95% CI 1.061-7.290], p = 0.037, respectively) and higher incidence of cardiovascular events (HR 1.938 [95% CI 1.015-3.700], p = 0.045; HR 2.397 [95% CI 1.243-4.623], p = 0.009, respectively). We observed that homoarginine/ADMA ratio and homoarginine/SDMA ratio are independent predictors for long-term cardiovascular mortality and events in claudicant patients with LEAD.
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http://dx.doi.org/10.1038/s41598-018-32607-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155043PMC
September 2018

Rationale and Plan for Vitamin D Food Fortification: A Review and Guidance Paper.

Front Endocrinol (Lausanne) 2018 17;9:373. Epub 2018 Jul 17.

Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium.

Vitamin D deficiency can lead to musculoskeletal diseases such as rickets and osteomalacia, but vitamin D supplementation may also prevent extraskeletal diseases such as respiratory tract infections, asthma exacerbations, pregnancy complications and premature deaths. Vitamin D has a unique metabolism as it is mainly obtained through synthesis in the skin under the influence of sunlight (i.e., ultraviolet-B radiation) whereas intake by nutrition traditionally plays a relatively minor role. Dietary guidelines for vitamin D are based on a consensus that serum 25-hydroxyvitamin D (25[OH]D) concentrations are used to assess vitamin D status, with the recommended target concentrations ranging from ≥25 to ≥50 nmol/L (≥10-≥20 ng/mL), corresponding to a daily vitamin D intake of 10 to 20 μg (400-800 international units). Most populations fail to meet these recommended dietary vitamin D requirements. In Europe, 25(OH)D concentrations <30 nmol/L (12 ng/mL) and <50 nmol/L (20 ng/mL) are present in 13.0 and 40.4% of the general population, respectively. This substantial gap between officially recommended dietary reference intakes for vitamin D and the high prevalence of vitamin D deficiency in the general population requires action from health authorities. Promotion of a healthier lifestyle with more outdoor activities and optimal nutrition are definitely warranted but will not erase vitamin D deficiency and must, in the case of sunlight exposure, be well balanced with regard to potential adverse effects such as skin cancer. Intake of vitamin D supplements is limited by relatively poor adherence (in particular in individuals with low-socioeconomic status) and potential for overdosing. Systematic vitamin D food fortification is, however, an effective approach to improve vitamin D status in the general population, and this has already been introduced by countries such as the US, Canada, India, and Finland. Recent advances in our knowledge on the safety of vitamin D treatment, the dose-response relationship of vitamin D intake and 25(OH)D levels, as well as data on the effectiveness of vitamin D fortification in countries such as Finland provide a solid basis to introduce and modify vitamin D food fortification in order to improve public health with this likewise cost-effective approach.
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http://dx.doi.org/10.3389/fendo.2018.00373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056629PMC
July 2018

Intermittent Fasting (Alternate Day Fasting) in Healthy, Non-obese Adults: Protocol for a Cohort Trial with an Embedded Randomized Controlled Pilot Trial.

Adv Ther 2018 Aug 25;35(8):1265-1283. Epub 2018 Jul 25.

Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.

Background/objectives: Alternate day fasting (ADF) is a subtype of intermittent fasting and is defined as a continuous sequence of a fast day (100% energy restriction, zero calories) and a feed day (ad libitum food consumption), resulting in roughly 36-h fasting periods. Previous studies demonstrated weight reductions and improvements of cardiovascular risk factors with ADF in obese subjects. However, rigorous data on potential endocrine, metabolic and cardiovascular effects, besides weight loss, are lacking. Therefore we aim to investigate the short- and mid- to long-term clinical and molecular effects of ADF in healthy non-obese subjects.

Methods: We will perform a prospective cohort study with an embedded randomized controlled trial (RCT) including 90 healthy subjects. Thirty of them will have performed ADF for at least 6 months (mid-term group). Sixty healthy subjects without a particular diet before enrolment will serve as the control group. These subjects will be 1:1 randomized to either continuing their current diet or performing ADF for 4 weeks. All subjects will undergo study procedures that will be repeated in RCT participants after 4 weeks. These procedures will include assessment of outcome parameters, dual-energy X-ray absorptiometry, measurement of endothelial function, an oral glucose tolerance test, 24-h blood pressure measurement, retinal vessel analysis, echocardiography and physical activity measurement by an accelerometer. Blood, sputum, buccal mucosa and faeces will be collected for laboratory analyses. Participants in the RCT will wear a continuous glucose monitor to verify adherence to the study intervention.

Planned Outcomes: The aim of this project is to investigate the effects of ADF on human physiology and molecular cellular processes. This investigation should gain in-depth mechanistic insights into the concept of ADF and form the basis for larger subsequent cohort recruitment and consecutive intervention studies.

Trial Registration: NCT02673515; registered 24 November 2015. Current protocol date/version: 7 February 2017/version 1.8.
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http://dx.doi.org/10.1007/s12325-018-0746-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096974PMC
August 2018

Age-dependent effects of homocysteine and dimethylarginines on cardiovascular mortality in claudicant patients with lower extremity arterial disease.

Heart Vessels 2018 Dec 26;33(12):1453-1462. Epub 2018 Jun 26.

Division of Angiology, Department of Internal Medicine, Medical University Graz, Auenbruggerplatz 15, 8036, Graz, Austria.

The association among serum homocysteine (HCY), symmetric dimethylarginine (SDMA), and asymmetric dimethylarginine (ADMA) is of interest in endothelial dysfunction, although the underlying pathology is not fully elucidated. We investigated the relationship of HCY with SDMA and ADMA regarding their long-time outcome and the age dependency of HCY, SDMA, and ADMA values in claudicant patients with lower extremity arterial disease. 120 patients were included in a prospective observational study (observation time 7.96 ± 1.3 years) with cardiovascular mortality as the main outcome parameter. Patients with intermittent claudication prior to their first endovascular procedure were included. HCY, SDMA, and ADMA were measured by high-performance liquid chromatography. Cutoff values for HCY (≤/>15 µmol/l), SDMA (≤/>0.75 µmol/l), and ADMA (≤/>0.8 µmol/l) differed significantly regarding cardiovascular mortality (p < 0.001, p < 0.001, p = 0.017, respectively). Age correlated significantly with HCY (r = 0.393; p < 0.001), SDMA (r = 0.363; p < 0.001), and ADMA (r = 0.210; p = 0.021). HCY and SDMA (r = 0.295; p = 0.001) as well as SDMA and ADMA (r = 0.380; p < 0.001) correlated with each other, while HCY and ADMA did not correlate (r = 0.139; p = 0.130). Patients older than 65 years had higher values of HCY (p < 0.001) and SDMA (p = 0.01), but not of ADMA (p = 0.133). In multivariable linear regression, age was the only significant independent risk factor for cardiovascular death (beta coefficient 0.413; 95% CI 0.007-0.028; p = 0.001). Age correlated significantly with HCY, SDMA, and ADMA. However, only age was an independent predictor for cardiovascular death. Older patients have higher values of HCY and SDMA than younger subjects suggesting age-adjusted cutoff values of HCY and SDMA due to strong age dependency.
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http://dx.doi.org/10.1007/s00380-018-1210-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267409PMC
December 2018

Mineralocorticoid Receptor Blockers and Aldosterone to Renin Ratio: A Randomized Controlled Trial and Observational Data.

Horm Metab Res 2018 May 3;50(5):375-382. Epub 2018 May 3.

Bad Gleichenberg Clinic, Bad Gleichenberg, Austria.

Current guidelines recommend to withdraw mineralocorticoid receptor (MR) blocker treatment for at least 4 weeks when measuring the aldosterone to renin ratio (ARR) as a screening test for primary aldosteronism (PA). We aimed to evaluate the effect of MR blocker treatment on ARR and its components, plasma aldosterone concentration (PAC), and direct renin concentration (DRC). First, we performed a post-hoc analysis of the effect of eplerenone on parathyroid hormone levels in primary hyperparathyroidism (EPATH) study, a randomized controlled trial (RCT) in 110 patients with primary hyperparathyroidism (pHPT). Patients were 1:1 randomly assigned to receive either 25 mg eplerenone once daily (up-titration after 4 weeks to 50 mg/day) or placebo for 8 weeks. Second, we measured the ARR in 4 PA patients from the Graz Endocrine Causes of Hypertension Study (GECOH) before and after MR blocker treatment. Ninety-seven participants completed the EPATH trial, and the mean treatment effect (95% confidence interval) for log(e)ARR was 0.08 (-0.32 to 0.48) ng/dl/μU/ml (p=0.694). The treatment effect was 0.71 (0.47 to 0.96; p<0.001) ng/dl for log(e)PAC and 0.64 (0.19 to 1.10; p=0.006) μU/ml for log(e)DRC, respectively. In the 4 PA patients, the ARR decreased from 11.24±3.58 at baseline to 2.70±1.03 (p=0.013) ng/dl/μU/ml after MR blocker treatment. In this study with limited sample size, MR blocker treatment did not significantly alter the ARR in pHPT patients but significantly reduced the ARR in PA patients. Diagnostic utility of ARR and its components for PA diagnostics under MR blocker treatment warrants further study.
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http://dx.doi.org/10.1055/a-0604-3249DOI Listing
May 2018

The Bone-Cardiovascular Axis: Mechanisms and Clinical Relevance.

Int J Endocrinol 2018 21;2018:9689106. Epub 2018 Feb 21.

Department of Health Sciences, Vrije Universiteit Amsterdam and the Amsterdam Public Health Research Institute, Amsterdam, Netherlands.

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http://dx.doi.org/10.1155/2018/9689106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841107PMC
February 2018

Zinc Inhibits Phosphate-Induced Vascular Calcification through TNFAIP3-Mediated Suppression of NF-B.

J Am Soc Nephrol 2018 06 13;29(6):1636-1648. Epub 2018 Apr 13.

Department of Internal Medicine and Cardiology, Charité- Universitätsmedizin Berlin, Berlin, Germany.

The high cardiovascular morbidity and mortality of patients with CKD may result in large part from medial vascular calcification, a process promoted by hyperphosphatemia and involving osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs). Reduced serum zinc levels have frequently been observed in patients with CKD, but the functional relevance of this remains unclear. We performed experiments in primary human aortic VSMCs; klotho-hypomorphic (), subtotal nephrectomy, and cholecalciferol-overload mouse calcification models; and serum samples from patients with CKD. In cultured VSMCs, treatment with zinc sulfate (ZnSO) blunted phosphate-induced calcification, osteo-/chondrogenic signaling, and NF-B activation. ZnSO increased the abundance of zinc-finger protein TNF--induced protein 3 (TNFAIP3, also known as A20), a suppressor of the NF-B pathway, by zinc-sensing receptor ZnR/GPR39-dependent upregulation of gene expression. Silencing of TNFAIP3 in VSMCs blunted the anticalcific effects of ZnSO under high phosphate conditions. mice showed reduced plasma zinc levels, and ZnSO supplementation strongly blunted vascular calcification and aortic osteoinduction and upregulated aortic Tnfaip3 expression. ZnSO ameliorated vascular calcification in mice with chronic renal failure and mice with cholecalciferol overload. In patients with CKD, serum zinc concentrations inversely correlated with serum calcification propensity. Finally, ZnSO ameliorated the osteoinductive effects of uremic serum in VSMCs. Zinc supplementation ameliorates phosphate-induced osteo-/chondrogenic transdifferentiation of VSMCs and vascular calcification through an active cellular mechanism resulting from GPR39-dependent induction of TNFAIP3 and subsequent suppression of the NF-B pathway. Zinc supplementation may be a simple treatment to reduce the burden of vascular calcification in CKD.
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http://dx.doi.org/10.1681/ASN.2017050492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054342PMC
June 2018

Vitamin D supplementation and lipoprotein metabolism: A randomized controlled trial.

J Clin Lipidol 2018 May - Jun;12(3):588-596.e4. Epub 2018 Mar 15.

Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria.

Background: Vitamin D deficiency is associated with an unfavorable lipid profile, but whether and how vitamin D supplementation affects lipid metabolism is unclear.

Objective: To examine the effects of vitamin D supplementation on lipid and lipoprotein parameters.

Methods: This is a post hoc analysis of the single-center, double-blind, randomized, placebo-controlled Styrian Vitamin D Hypertension Trial (2011-2014). Two hundred individuals with arterial hypertension and 25-hydroxyvitamin D concentrations of <75 nmol/L were randomized to 2800 IU of vitamin D daily or placebo for 8 weeks.

Results: One hundred sixty-three participants (62.2 [53.1-68.4] years of age; 46% women) had available lipid data and were included in this analysis. Vitamin D supplementation significantly increased total cholesterol, triglycerides, very-low-density lipoprotein (VLDL) triglycerides, low-density lipoprotein (LDL) triglycerides, high-density lipoprotein (HDL) triglycerides, apolipoprotein B (ApoB), LDL-ApoB, ApoCII, ApoCIII, phospholipids, and ApoE (P < .05 for all). Except for ApoCII and ApoCIII and HDL-triglycerides, all other treatment effects remained statistically significant after adjustment for multiple testing with the Benjamini and Hochberg false discovery rate method. There was a nonsignificant increase in LDL cholesterol. Furthermore, no significant effects were seen on free fatty acids, lipoprotein (a), ApoAI, ApoAII, VLDL cholesterol, VLDL-ApoB, HDL cholesterol, LDL diameter, and VLDL diameter.

Conclusions: The effects of vitamin D on lipid metabolism are potentially unfavorable. They require further investigation in view of the wide use of vitamin D testing and treatment.
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http://dx.doi.org/10.1016/j.jacl.2018.03.079DOI Listing
September 2019

Thermic sealing in femoral catheterization: First experience with the Secure Device.

Cardiol J 2019 3;26(3):233-240. Epub 2018 Apr 3.

Division of Cardiology, Medical University Graz, Austria.

Background: Devices currently used to achieve hemostasis of the femoral artery following percutaneous cardiac catheterization are associated with vascular complications and remnants of artificial materials are retained at the puncture site. The Secure arterial closure Device induces hemostasis by utilizing thermal energy, which causes collagen shrinking and swelling. In comparison to established devices, it has the advantage of leaving no foreign material in the body following closing. This study was designed to evaluate the efficacy and safety of the Secure Device to close the puncture site following percutaneous cardiac catheterization.

Methods: The Secure Device was evaluated in a prospective non-randomized single-center trial with patients undergoing 6 F invasive cardiac procedures. A total of 67 patients were enrolled and the device was utilized in 63 patients. Fifty diagnostic and 13 interventional cases were evaluated. Femoral artery puncture closure was performed immediately after completion of the procedure. Time to hemostasis (TTH), time to ambulation (TTA) and data regarding short-term and 30-day clinical follow-up were recorded.

Results: Mean TTH was 4:30 ± 2:15 min in the overall observational group. A subpopulation of patients receiving anticoagulants had a TTH of 4:53 ± 1:43 min. There were two access site complications (hematoma > 5 cm). No major adverse events were identified during hospitalization or at the 30 day follow-up.

Conclusions: The new Secure Device demonstrates that it is feasible in diagnostic and interventional cardiac catheterization. With respect to safety, the Secure Device was non-inferior to other closure devices as tested in the ISAR closure trial.
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http://dx.doi.org/10.5603/CJ.a2018.0035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086670PMC
April 2020