Publications by authors named "Andreas Zirlik"

106 Publications

Proportion of patients eligible for statin therapy substantially varies between different cardiovascular disease risk calculators and guidelines used.

Int J STD AIDS 2021 Jul 7:9564624211029392. Epub 2021 Jul 7.

Heart Center Freiburg University, Department of Cardiology and Angiology I, Faculty of Medicine, 9174University of Freiburg, Freiburg, Germany.

Because people living with HIV (PLWH) have an elevated risk for cardiovascular disease (CVD), prevention of CVD should be integrated in to HIV care. In this study, we compared the agreement between three risk scores and evaluated the indication for statin therapy based on guidelines of the American Heart Association and European AIDS Clinical Society. This study is a cross-sectional, single-center study. All PLWH ≥ 30 years without CVD and statin therapy were consecutively enrolled. Agreement between CVD risk estimates was assessed using Cohen's kappa coefficient. Of 488 PLWH, 41.2% were female with a median age of 47.8 years. D:A:D-R classified the highest proportion of patients in the categories of high/very high risk for CVD (17.8%) compared to SCORE (4.7%) and FRS (13.7%). D:A:D-R and SCORE (κ = 0.11) as well as D:A:D-R and FRS (κ = 0.33) showed poor agreement. Based on different CVD risk equations and guidelines, indication for statin therapy ranged from 34.8% to 92.0% of patients. In conclusion, a high proportion of PLWH is at high risk for CVD likely underestimated by treating physicians. Inconsistencies in the evaluation of CVD risk and primary prophylaxis should be tackled by an interdisciplinary approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/09564624211029392DOI Listing
July 2021

Cardiac Magnetic Resonance Imaging Right Ventricular Longitudinal Strain Predicts Mortality in Patients Undergoing TAVI.

Front Cardiovasc Med 2021 7;8:644500. Epub 2021 May 7.

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

Right ventricular (RV) function predicts survival in numerous cardiac conditions, including left heart disease. The reference standard for non-invasive assessment of RV function is cardiac magnetic resonance imaging (CMR). The aim of this study was to investigate the association between pre-procedural CMR-derived RV functional parameters and mortality in patients undergoing transcatheter aortic valve implantation (TAVI). Patients scheduled for TAVI were recruited to undergo pre-procedural CMR. Volumetric function and global longitudinal and circumferential strain (GLS and GCS) of the RV and left ventricle (LV) were measured. The association with the primary endpoint (1-year all-cause mortality) was analyzed with Cox regression. Of 133 patients undergoing CMR, 113 patients were included in the analysis. Mean age was 81.8 ± 5.8 years, and 65% were female. Median follow-up was 3.9 [IQR 2.3-4.7] years. All-cause and cardiovascular mortality was 14 and 12% at 1 year, and 28 and 20% at 3 years, respectively. One-year all-cause mortality was significantly predicted by RV GLS [HR = 1.109 (95% CI: 1.023-1.203); = 0.012], RV ejection fraction [HR = 0.956 (95% CI: 0.929-0.985); = 0.003], RV end-diastolic volume index [HR = 1.009 (95% CI: 1.001-1.018); = 0.025], and RV end-systolic volume index [HR = 1.010 (95% CI: 1.003-1.017); = 0.005]. In receiver operating characteristic (ROC) analysis for 1-year all-cause mortality, the area under the curve was 0.705 (RV GLS) and 0.673 (RV EF). Associations decreased in strength at longer follow-up. None of the LV parameters was associated with mortality. RV function predicts intermediate-term mortality in TAVI patients while LV parameters were not associated with outcomes. Inclusion of easily obtainable RV GLS may improve future risk scores.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcvm.2021.644500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137844PMC
May 2021

Myeloid cell-specific Irf5 deficiency stabilizes atherosclerotic plaques in Apoe mice.

Mol Metab 2021 May 12;53:101250. Epub 2021 May 12.

University Heart Center, Department of Cardiology and Angiology I, University of Freiburg and Faculty of Medicine, 55 Hugstetter St, 79106, Freiburg, Germany. Electronic address:

Objective: Interferon regulatory factor (IRF) 5 is a transcription factor known for promoting M1 type macrophage polarization in vitro. Given the central role of inflammatory macrophages in promoting atherosclerotic plaque progression, we hypothesize that myeloid cell-specific deletion of IRF5 is protective against atherosclerosis.

Methods: Female ApoeLysmIrf5 and ApoeIrf5 mice were fed a high-cholesterol diet for three months. Atherosclerotic plaque size and compositions as well as inflammatory gene expression were analyzed. Mechanistically, IRF5-dependent bone marrow-derived macrophage cytokine profiles were tested under M1 and M2 polarizing conditions. Mixed bone marrow chimeras were generated to determine intrinsic IRF5-dependent effects on macrophage accumulation in atherosclerotic plaques.

Results: Myeloid cell-specific Irf5 deficiency blunted LPS/IFNγ-induced inflammatory gene expression in vitro and in the atherosclerotic aorta in vivo. While atherosclerotic lesion size was not reduced in myeloid cell-specific Irf5-deficient Apoe mice, plaque composition was favorably altered, resembling a stable plaque phenotype with reduced macrophage and lipid contents, reduced inflammatory gene expression and increased collagen deposition alongside elevated Mertk and Tgfβ expression. Irf5-deficient macrophages, when directly competing with wild type macrophages in the same mouse, were less prone to accumulate in atherosclerotic lesion, independent of monocyte recruitment. Irf5-deficient monocytes, when exposed to oxidized low density lipoprotein, were less likely to differentiate into macrophage foam cells, and Irf5-deficient macrophages proliferated less in the plaque.

Conclusion: Our study provides genetic evidence that selectively altering macrophage polarization induces a stable plaque phenotype in mice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.molmet.2021.101250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178123PMC
May 2021

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ehf2.13381DOI Listing
May 2021

Loss of autophagy protein ATG5 impairs cardiac capacity in mice and humans through diminishing mitochondrial abundance and disrupting Ca2+ cycling.

Cardiovasc Res 2021 Mar 22. Epub 2021 Mar 22.

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

Aims: Autophagy protects against the development of cardiac hypertrophy and failure. While aberrant Ca2+ handling promotes myocardial remodelling and contributes to contractile dysfunction, the role of autophagy in maintaining Ca2+ homeostasis remains elusive. Here, we examined whether Atg5 deficiency-mediated autophagy promotes early changes in subcellular Ca2+ handling in ventricular cardiomyocytes, and whether those alterations associate with compromised cardiac reserve capacity, which commonly precedes the onset of heart failure.

Methods And Results: RT-qPCR and immunoblotting demonstrated reduced Atg5 gene and protein expression and decreased abundancy of autophagy markers in hypertrophied and failing human hearts. The function of ATG5 was examined using cardiomyocyte-specific Atg5-knockout mice (Atg5-/-). Before manifesting cardiac dysfunction, Atg5-/- mice showed compromised cardiac reserve in response to β-adrenergic stimulation. Consequently, effort intolerance and maximal oxygen consumption were reduced during treadmill-based exercise tolerance testing. Mechanistically, cellular imaging revealed that Atg5 deprivation did not alter spatial and functional organization of intracellular Ca2+ stores or affect Ca2+ cycling in response to slow pacing or upon acute isoprenaline administration. However, high frequency stimulation exposed stunted amplitude of Ca2+ transients, augmented nucleoplasmic Ca2+ load and increased CaMKII activity, especially in the nuclear region of hypertrophied Atg5-/- cardiomyocytes. These changes in Ca2+ cycling were recapitulated in hypertrophied human cardiomyocytes. Finally, ultrastructural analysis revealed accumulation of mitochondria with reduced volume and size distribution, meanwhile functional measurements showed impaired redox balance in Atg5-/- cardiomyocytes, implying energetic unsustainability due to overcompensation of single mitochondria, particularly under increased workload.

Conclusion: Loss of cardiac Atg5-dependent autophagy reduces mitochondrial abundance and causes subtle alterations in subcellular Ca2+ cycling upon increased workload in mice. Autophagy-related impairment of Ca2+ handling is progressively worsened by β-adrenergic signalling in ventricular cardiomyocytes, thereby leading to energetic exhaustion and compromised cardiac reserve.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cvr/cvab112DOI Listing
March 2021

Deficiency of Endothelial CD40 Induces a Stable Plaque Phenotype and Limits Inflammatory Cell Recruitment to Atherosclerotic Lesions in Mice.

Thromb Haemost 2021 Feb 22. Epub 2021 Feb 22.

Department of Cardiology and Angiology I, University Heart Center Freiburg-Bad Krozingen, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Objectives:  The co-stimulatory CD40L-CD40 dyad exerts a critical role in atherosclerosis by modulating leukocyte accumulation into developing atherosclerotic plaques. The requirement for cell-type specific expression of both molecules, however, remains elusive. Here, we evaluate the contribution of CD40 expressed on endothelial cells (ECs) in a mouse model of atherosclerosis.

Methods And Results:  Atherosclerotic plaques of apolipoprotein E-deficient ( ) mice and humans displayed increased expression of CD40 on ECs compared with controls. To interrogate the role of CD40 on ECs in atherosclerosis, we induced EC-specific (BmxCre-driven) deficiency of CD40 in mice. After feeding a chow diet for 25 weeks, EC-specific deletion of CD40 (iEC-CD40) ameliorated plaque lipid deposition and lesional macrophage accumulation but increased intimal smooth muscle cell and collagen content, while atherosclerotic lesion size did not change. Leukocyte adhesion to the vessel wall was impaired in iEC-CD40-deficient mice as demonstrated by intravital microscopy. In accord, expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) in the vascular endothelium declined after deletion of CD40. In vitro, antibody-mediated inhibition of human endothelial CD40 significantly abated monocyte adhesion on ECs.

Conclusion:  Endothelial deficiency of CD40 in mice promotes structural features associated with a stable plaque phenotype in humans and decreases leukocyte adhesion. These results suggest that endothelial-expressed CD40 contributes to inflammatory cell migration and consecutive plaque formation in atherogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1397-1858DOI Listing
February 2021

Nicotinamide for the treatment of heart failure with preserved ejection fraction.

Sci Transl Med 2021 02;13(580)

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

Heart failure with preserved ejection fraction (HFpEF) is a highly prevalent and intractable form of cardiac decompensation commonly associated with diastolic dysfunction. Here, we show that diastolic dysfunction in patients with HFpEF is associated with a cardiac deficit in nicotinamide adenine dinucleotide (NAD). Elevating NAD by oral supplementation of its precursor, nicotinamide, improved diastolic dysfunction induced by aging (in 2-year-old C57BL/6J mice), hypertension (in salt-sensitive rats), or cardiometabolic syndrome (in ZSF1 obese rats). This effect was mediated partly through alleviated systemic comorbidities and enhanced myocardial bioenergetics. Simultaneously, nicotinamide directly improved cardiomyocyte passive stiffness and calcium-dependent active relaxation through increased deacetylation of titin and the sarcoplasmic reticulum calcium adenosine triphosphatase 2a, respectively. In a long-term human cohort study, high dietary intake of naturally occurring NAD precursors was associated with lower blood pressure and reduced risk of cardiac mortality. Collectively, these results suggest NAD precursors, and especially nicotinamide, as potential therapeutic agents to treat diastolic dysfunction and HFpEF in humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/scitranslmed.abd7064DOI Listing
February 2021

No antiarrhythmic effect of direct oral anticoagulants versus vitamin K antagonists in paroxysmal atrial fibrillation patients undergoing catheter ablation.

Int J Cardiol 2021 05 26;331:106-108. Epub 2021 Jan 26.

Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Austria; Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Limburg, the Netherlands.

Introduction: Direct oral anticoagulants (DOACs) are superior to vitamin K antagonists (VKAs) for the prevention of stroke in atrial fibrillation (AF) patients with elevated stroke risk. Possible antiarrhythmic effects of DOACs have been discussed. We analyzed impact of DOAC treatment on recurrence-free survival after AF catheter ablation.

Methods: Two-hundred and thirty-nine consecutive patients (median age 57 [IQR 48-64] years, 26.4% female) undergoing ablation for paroxysmal AF were included into this study. 68.6% of them received DOACs (DOAC group), 31.4% VKA (VKA group). The primary outcome was arrhythmia-free one-year survival.

Results: DOAC patients had lower BMI, shorter history of AF, less arterial hypertension, less vascular disease, less use of antiarrhythmics and consequently lower CHADS-VASc and HAS-BLED Scores. There was no difference in arrhythmia-free survival between DOAC and VKA groups (DOAC: 86.6%, VKA: 76.7%, p = 0.286).

Conclusions: Despite baseline characteristics favouring a better outcome of DOAC patients, arrhythmia-free survival was similar in both groups. Consequently, DOAC treatment did not have clinically relevant antiarrhythmic properties in these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2021.01.003DOI Listing
May 2021

Inhibition of macrophage proliferation dominates plaque regression in response to cholesterol lowering.

Basic Res Cardiol 2020 12 9;115(6):78. Epub 2020 Dec 9.

Department of Cardiology and Angiology I, University Heart Center Freiburg-Bad Krozingen and Faculty of Medicine, University of Freiburg, 55 Hugstetter St, 79106, Freiburg, Germany.

Statins induce plaque regression characterized by reduced macrophage content in humans, but the underlying mechanisms remain speculative. Studying the translational APOE*3-Leiden.CETP mouse model with a humanized lipoprotein metabolism, we find that systemic cholesterol lowering by oral atorvastatin or dietary restriction inhibits monocyte infiltration, and reverses macrophage accumulation in atherosclerotic plaques. Contrary to current believes, none of (1) reduced monocyte influx (studied by cell fate mapping in thorax-shielded irradiation bone marrow chimeras), (2) enhanced macrophage egress (studied by fluorescent bead labeling and transfer), or (3) atorvastatin accumulation in murine or human plaque (assessed by mass spectrometry) could adequately account for the observed loss in macrophage content in plaques that undergo phenotypic regression. Instead, suppression of local proliferation of macrophages dominates phenotypic plaque regression in response to cholesterol lowering: the lower the levels of serum LDL-cholesterol and lipid contents in murine aortic and human carotid artery plaques, the lower the rates of in situ macrophage proliferation. Our study identifies macrophage proliferation as the predominant turnover determinant and an attractive target for inducing plaque regression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00395-020-00838-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725697PMC
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm9103274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600032PMC
October 2020

Complications and mortality of cardiovascular emergency admissions during COVID-19 associated restrictive measures.

PLoS One 2020 24;15(9):e0239801. Epub 2020 Sep 24.

Division of Cardiology, Medical University of Graz, Graz, Austria.

While hospital admissions for myocardial infarction (MI) and pulmonary embolism (PE) are decreased during the COVID-19 pandemic, controversy remains about respective complication and mortality rates. This study evaluated admission rates, complications, and intrahospital mortality for selected life-threatening cardiovascular emergencies (MI, PE, and acute aortic dissection (AAD)) during COVID-19-associated restrictive social measures (RM) in Styria, Austria. By screening a patient information system for International Statistical Classification of Diseases and Related Health Problems (ICD) diagnosis codes covering more than 85% of acute hospital admissions in the state of Styria (~1.24 million inhabitants), we retrospectively identified patients with admission diagnoses for MI (I21, I22), PE (I26), and AAD (I71). Rates of complications such as cardiogenic shock and cardiopulmonary resuscitation, treatment escalations (thrombolysis for PE), and mortality were analyzed by patient chart review during 6 weeks following onset of COVID-19 associated RM, and during respective time frames in the years 2016 to 2019. 1,668 patients were included. Cumulative admissions for MI, PE and AAD decreased (RR 0.77; p<0.001) during RM compared to previous years. In contrast, intrahospital mortality increased by 65% (RR 1.65; p = 0.041), mainly driven by mortality following MI (RR 1.80; p = 0.042). PE patients received more frequently thrombolysis treatment (RR 3.63; p = 0.006), while rates of cardiogenic shock and cardiopulmonary resuscitation remained unchanged. Of 226 patients hospitalized during RM, 81 patients with suspected COVID-19 disease were screened for SARS-CoV-2 infection with only 5 testing positive. Thus, cumulative hospital admissions for cardiovascular emergencies decreased during COVID-19 associated RM while intrahospital mortality increased.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239801PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7514100PMC
October 2020

Pathogenic Autoimmunity in Atherosclerosis Evolves From Initially Protective Apolipoprotein B-Reactive CD4 T-Regulatory Cells.

Circulation 2020 Sep 24;142(13):1279-1293. Epub 2020 Jul 24.

Division of Vaccine Discovery (B.P., A.S.), La Jolla Institute for Immunology, CA.

Background: Throughout the inflammatory response that accompanies atherosclerosis, autoreactive CD4 T-helper cells accumulate in the atherosclerotic plaque. Apolipoprotein B (apoB), the core protein of low-density lipoprotein, is an autoantigen that drives the generation of pathogenic T-helper type 1 (T1) cells with proinflammatory cytokine secretion. Clinical data suggest the existence of apoB-specific CD4 T cells with an atheroprotective, regulatory T cell (T) phenotype in healthy individuals. Yet, the function of apoB-reactive T and their relationship with pathogenic T1 cells remain unknown.

Methods: To interrogate the function of autoreactive CD4 T cells in atherosclerosis, we used a novel tetramer of major histocompatibility complex II to track T cells reactive to the mouse self-peptide apo B (apoB) at the single-cell level.

Results: We found that apoB T cells build an oligoclonal population in lymph nodes of healthy mice that exhibit a T-like transcriptome, although only 21% of all apoB T cells expressed the T transcription factor FoxP3 (Forkhead Box P3) protein as detected by flow cytometry. In single-cell RNA sequencing, apoB T cells formed several clusters with mixed T signatures that suggested overlapping multilineage phenotypes with pro- and anti-inflammatory transcripts of T1, T helper cell type 2 (T2), and T helper cell type 17 (T17), and of follicular-helper T cells. ApoB T cells were increased in mice and humans with atherosclerosis and progressively converted into pathogenic T1/T17-like cells with proinflammatory properties and only a residual T transcriptome. Plaque T cells that expanded during progression of atherosclerosis consistently showed a mixed T1/T17 phenotype in single-cell RNA sequencing. In addition, we observed a loss of FoxP3 in a fraction of apoB T in lineage tracing of hyperlipidemic mice. In adoptive transfer experiments, converting apoB T failed to protect from atherosclerosis.

Conclusions: Our results demonstrate an unexpected mixed phenotype of apoB-reactive autoimmune T cells in atherosclerosis and suggest an initially protective autoimmune response against apoB with a progressive derangement in clinical disease. These findings identify apoB autoreactive T as a novel cellular target in atherosclerosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCULATIONAHA.119.042863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515473PMC
September 2020

Acute hyperglycaemia is not associated with the development of atrial fibrillation in healthy pigs.

Sci Rep 2020 07 17;10(1):11881. Epub 2020 Jul 17.

Department of Cardiology, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.

Development and progression of atrial fibrillation (AF) is driven by comorbidities such as arterial hypertension and diabetes mellitus. In animal models of chronic hyperglycaemia, progression of AF has been proposed to be triggered by oxidative stress, apoptosis and fibrosis. Acute glycosylation of CaMKII has been associated with increased susceptibility to arrhythmias in acute hyperglycaemia. However, the proarrhythmogenic effect of acute hyperglycaemia has not been investigated. Nine healthy, anesthetized pigs (54 ± 6 kg) were instrumented with electrophysiologic catheters and a multielectrode array on the epicardium of the left atrial anterior wall. Left and right atrial effective refractory periods (AERP), inducibility of AF and left atrial epicardial conduction velocities (CV) were measured at baseline (BL), increasing steps of blood glucose (200-500 mg/dL in steps of 100 mg/dL by glucose infusion) and repeated after normalisation of blood glucose levels (recovery). Serum electrolytes were kept constant during measurements by means of sodium and potassium infusion. There were no significant differences in AERP, CV or AF inducibility between BL and recovery. Heart rate remained constant regardless of blood glucose levels (BL: 103 ± 18 bpm, 500 mg/dL: 103 ± 18 bpm, r = 0.02, p = 0.346). Mean left as well as right AERP increased with higher glucose levels. CV increased with glucose levels (1.25 (1.04, 1.67) m/s at BL vs. 1.53 (1.22, 2.15) m/s at 500 mg/dL, r = 0.85, p = 0.034). Rate of AF inducibility in the left atrium remained constant throughout the whole protocol (AF episodes > 10 s: mean inducibility of 80% at BL vs. 69% at 500 mg/dL, p = 0.32, episodes > 30 s: 0% at BL vs. 0% at 500 mg/dL, p = 0.17). Our data imply that acute hyperglycaemia is associated with lower arrhythmogenic substrate and does not promote AF inducibility.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-68897-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367844PMC
July 2020

Renal Denervation in High-Risk Patients With Hypertension.

J Am Coll Cardiol 2020 06;75(23):2879-2888

Department of Internal Medicine, Saarland University Hospital, Homburg/Saar, Germany.

Background: Renal denervation (RDN) is under investigation for treatment of uncontrolled hypertension and might represent an attractive treatment for patients with high cardiovascular (CV) risk. It is important to determine whether baseline CV risk affects the efficacy of RDN.

Objectives: The purpose of this study was to assess blood pressure (BP) reduction and event rates after RDN in patients with various comorbidities, testing the hypothesis that RDN is effective and durable in these high-risk populations.

Methods: BP reduction and adverse events over 3 years were evaluated for several high-risk subgroups in the GSR (Global proSpective registrY for syMPathetic renaL denervatIon in seleCted IndicatIons Through 3 Years Registry), an international registry of RDN in patients with uncontrolled hypertension (n = 2,652). Comparisons were made for patients age ≥65 years versus age <65 years, with versus without isolated systolic hypertension, with versus without atrial fibrillation, and with versus without diabetes mellitus. Baseline cardiovascular risk was estimated using the American Heart Association (AHA)/American College of Cardiology (ACC) atherosclerosis cardiovascular disease (ASCVD) risk score.

Results: Reduction in 24-h systolic BP at 3 years was -8.9 ± 20.1 mm Hg for the overall cohort, and for high-risk subgroups, BP reduction was -10.4 ± 21.0 mm Hg for resistant hypertension, -8.7 ± 17.4 mm Hg in patients age ≥65 years, -10.2 ± 17.9 mm Hg in patients with diabetes, -8.6 ± 18.7 mm Hg in isolated systolic hypertension, -10.1 ± 20.3 mm Hg in chronic kidney disease, and -10.0 ± 19.1 mm Hg in atrial fibrillation (p < 0.0001 compared with baseline for all). BP reduction in patients with measurements at 6, 12, 24, and 36 months showed similar reductions in office and 24-h BP for patients with varying baseline ASCVD risk scores, which was sustained to 3 years. Adverse event rates at 3 years were higher for patients with higher baseline CV risk.

Conclusions: BP reduction after RDN was similar for patients with varying high-risk comorbidities and across the range of ASCVD risk scores. The impact of baseline risk on clinical event reduction by RDN-induced BP changes could be evaluated in further studies. (Global proSpective registrY for syMPathetic renaL denervatIon in seleCted IndicatIons Through 3 Years Registry; NCT01534299).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacc.2020.04.036DOI Listing
June 2020

Pathogenic Role of Air Pollution Particulate Matter in Cardiometabolic Disease: Evidence from Mice and Humans.

Antioxid Redox Signal 2020 08 15;33(4):263-279. Epub 2020 Jun 15.

Department of Cardiology and Angiology I, University Heart Center Freiburg, Freiburg, Germany.

Air pollution is a considerable global threat to human health that dramatically increases the risk for cardiovascular pathologies, such as atherosclerosis, myocardial infarction, and stroke. An estimated 4.2 million cases of premature deaths worldwide are attributable to outdoor air pollution. Among multiple other components, airborne particulate matter (PM) has been identified as the major bioactive constituent in polluted air. While PM-related illness was historically thought to be confined to diseases of the respiratory system, overwhelming clinical and experimental data have now established that acute and chronic exposure to PM causes a systemic inflammatory and oxidative stress response that promotes cardiovascular disease. A large body of evidence has identified an impairment of redox metabolism and the generation of oxidatively modified lipids and proteins in the lung as initial tissue response to PM. In addition, the pathogenicity of PM is mediated by an inflammatory response that involves PM uptake by tissue-resident immune cells, the activation of proinflammatory pathways in various cell types and organs, and the release of proinflammatory cytokines as locally produced tissue response signals that have the ability to affect organ function in a remote manner. In the present review, we summarize and discuss the functional participation of PM in cardiovascular pathologies and its risk factors with an emphasis on how oxidative stress, inflammation, and immunity interact and synergize as a response to PM. The impact of PM constituents, doses, and novel anti-inflammatory therapies against PM-related illness is also discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/ars.2020.8096DOI Listing
August 2020

Immunometabolism: a key target to improve microcirculation in ageing.

Cardiovasc Res 2020 04;116(5):e48-e50

Department of Cardiology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cvr/cvaa060DOI Listing
April 2020

Mitochondrial Mechanisms in Diabetic Cardiomyopathy.

Diabetes Metab J 2020 02;44(1):33-53

Division of Cardiology, Medical University of Graz, Graz, Austria.

Mitochondrial medicine is increasingly discussed as a promising therapeutic approach, given that mitochondrial defects are thought to contribute to many prevalent diseases and their complications. In individuals with diabetes mellitus (DM), defects in mitochondrial structure and function occur in many organs throughout the body, contributing both to the pathogenesis of DM and complications of DM. Diabetic cardiomyopathy (DbCM) is increasingly recognized as an underlying cause of increased heart failure in DM, and several mitochondrial mechanisms have been proposed to contribute to the development of DbCM. Well established mechanisms include myocardial energy depletion due to impaired adenosine triphosphate (ATP) synthesis and mitochondrial uncoupling, and increased mitochondrial oxidative stress. A variety of upstream mechanisms of impaired ATP regeneration and increased mitochondrial reactive oxygen species have been proposed, and recent studies now also suggest alterations in mitochondrial dynamics and autophagy, impaired mitochondrial Ca²⁺ uptake, decreased cardiac adiponectin action, increased O-GlcNAcylation, and impaired activity of sirtuins to contribute to mitochondrial defects in DbCM, among others. In the current review, we present and discuss the evidence that underlies both established and recently proposed mechanisms that are thought to contribute to mitochondrial dysfunction in DbCM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4093/dmj.2019.0185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7043970PMC
February 2020

Outcomes of transcatheter aortic valve implantations in high-volume or low-volume centres in Germany.

Heart 2020 10 18;106(20):1604-1608. Epub 2020 Feb 18.

Department of Cardiology and Angiology I, University Heart Center Freiburg, Medical Faculty, University of Freiburg, Freiburg, Germany

Objective: Transcatheter aortic valve implantation (TAVI) is the most common aortic valve replacement in Germany. Since 2015, to ensure high-quality procedures, hospitals in Germany and other countries that meet the minimum requirement of 50 interventions per centre are being certified to perform TAVI. This study analyses the impact of these requirements on case number and in-hospital outcomes.

Methods: All isolated TAVI procedures and in-hospital outcomes between 2008 and 2016 were identified by International Classification of Diseases (ICD) and the German Operation and Procedure Classification codes.

Results: 73 467 isolated transfemoral and transapical TAVI procedures were performed in Germany between 2008 and 2016. During this period, the number of TAVI procedures per year rose steeply, whereas the overall rates of hospital mortality and complications declined. In 2008, the majority of procedures were performed in hospitals with fewer than 50 cases per year (54.63%). Until 2014, the share of patients treated in low-volume centres constantly decreased to 5.35%. After the revision of recommendations, it further declined to 1.99%. In the 2 years after the introduction of the minimum requirements on case numbers, patients were at decreased risk for in-hospital mortality when treated in a high-volume centre (risk-adjusted OR 0.62, p=0.012). The risk for other in-hospital outcomes (stroke, permanent pacemaker implantation and bleeding events) did not differ after risk adjustment (p=0.346, p=0.142 and p=0.633).

Conclusion: A minimum volume of 50 procedures per centre and year appears suitable to allow for sufficient routine and thus better in-hospital outcomes, while ensuring nationwide coverage of TAVI procedures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/heartjnl-2019-316058DOI Listing
October 2020

Dysregulation of the Mitochondrial Proteome Occurs in Mice Lacking Adiponectin Receptor 1.

Front Endocrinol (Lausanne) 2019 13;10:872. Epub 2019 Dec 13.

Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany.

Decreased serum adiponectin levels in type 2 diabetes has been linked to the onset of mitochondrial dysfunction in diabetic complications by impairing AMPK-SIRT1-PGC-1α signaling via impaired adiponectin receptor 1 (AdipoR1) signaling. Here, we aimed to characterize the previously undefined role of disrupted AdipoR1 signaling on the mitochondrial protein composition of cardiac, renal, and hepatic tissues as three organs principally associated with diabetic complications. Comparative proteomics were performed in mitochondria isolated from the heart, kidneys and liver of mice. A total of 790, 1,573, and 1,833 proteins were identified in cardiac, renal and hepatic mitochondria, respectively. While 121, 98, and 78 proteins were differentially regulated in cardiac, renal, and hepatic tissue of 1 mice, respectively; only 15 proteins were regulated in the same direction across all investigated tissues. Enrichment analysis of differentially expressed proteins revealed disproportionate representation of proteins involved in oxidative phosphorylation conserved across tissue types. Curated pathway analysis identified HNF4, NRF1, LONP, RICTOR, SURF1, insulin receptor, and PGC-1α as candidate upstream regulators. In high fat-fed non-transgenic mice with obesity and insulin resistance, AdipoR1 gene expression was markedly reduced in heart (-70%), kidney (-80%), and liver (-90%) (all < 0.05) as compared to low fat-fed mice. NRF1 was the only upstream regulator downregulated both in 1 mice and in high fat-fed mice, suggesting common mechanisms of regulation. Thus, AdipoR1 signaling regulates mitochondrial protein composition across all investigated tissues in a functionally conserved, yet molecularly distinct, manner. The biological significance and potential implications of impaired AdipoR1 signaling are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2019.00872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923683PMC
December 2019

HDAC inhibition improves cardiopulmonary function in a feline model of diastolic dysfunction.

Sci Transl Med 2020 01;12(525)

Cardiovascular Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.

Heart failure with preserved ejection fraction (HFpEF) is a major health problem without effective therapies. This study assessed the effects of histone deacetylase (HDAC) inhibition on cardiopulmonary structure, function, and metabolism in a large mammalian model of pressure overload recapitulating features of diastolic dysfunction common to human HFpEF. Male domestic short-hair felines ( = 31, aged 2 months) underwent a sham procedure ( = 10) or loose aortic banding ( = 21), resulting in slow-progressive pressure overload. Two months after banding, animals were treated daily with suberoylanilide hydroxamic acid (b + SAHA, 10 mg/kg, = 8), a Food and Drug Administration-approved pan-HDAC inhibitor, or vehicle (b + veh, = 8) for 2 months. Echocardiography at 4 months after banding revealed that b + SAHA animals had significantly reduced left ventricular hypertrophy (LVH) ( < 0.0001) and left atrium size ( < 0.0001) versus b + veh animals. Left ventricular (LV) end-diastolic pressure and mean pulmonary arterial pressure were significantly reduced in b + SAHA ( < 0.01) versus b + veh. SAHA increased myofibril relaxation ex vivo, which correlated with in vivo improvements of LV relaxation. Furthermore, SAHA treatment preserved lung structure, compliance, blood oxygenation, and reduced perivascular fluid cuffs around extra-alveolar vessels, suggesting attenuated alveolar capillary stress failure. Acetylation proteomics revealed that SAHA altered lysine acetylation of mitochondrial metabolic enzymes. These results suggest that acetylation defects in hypertrophic stress can be reversed by HDAC inhibitors, with implications for improving cardiac structure and function in patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/scitranslmed.aay7205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065257PMC
January 2020

Position Paper on Lipid Therapy in Patients with Diabetes Mellitus.

Exp Clin Endocrinol Diabetes 2019 Dec 20;127(S 01):S97-S101. Epub 2019 Dec 20.

Medical Clinic I - Cardiology, Angiology and Internal Intensive Care Medicine, University Hospital Aachen, Aachen, Germany.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1018-9228DOI Listing
December 2019

Glucose lowering by SGLT2-inhibitor empagliflozin accelerates atherosclerosis regression in hyperglycemic STZ-diabetic mice.

Sci Rep 2019 11 29;9(1):17937. Epub 2019 Nov 29.

University Heart Center Freiburg-Bad Krozingen, Cardiology and Angiology I, University of Freiburg, Freiburg, Germany.

Diabetes worsens atherosclerosis progression and leads to a defect in repair of arteries after cholesterol reduction, a process termed regression. Empagliflozin reduces blood glucose levels via inhibition of the sodium glucose cotransporter 2 (SGLT-2) in the kidney and has been shown to lead to a marked reduction in cardiovascular events in humans. To determine whether glucose lowering by empagliflozin accelerates atherosclerosis regression in a mouse model, male C57BL/6J mice were treated intraperitoneally with LDLR- and SRB1- antisense oligonucleotides and fed a high cholesterol diet for 16 weeks to induce severe hypercholesterolemia and atherosclerosis progression. At week 14 all mice were rendered diabetic by streptozotocin (STZ) injections. At week 16 a baseline group was sacrificed and displayed substantial atherosclerosis of the aortic root. In the remaining mice, plasma cholesterol was lowered by switching to chow diet and treatment with LDLR sense oligonucleotides to induce atherosclerosis regression. These mice then received either empagliflozin or vehicle for three weeks. Atherosclerotic plaques in the empagliflozin treated mice were significantly smaller, showed decreased lipid and CD68 macrophage content, as well as greater collagen content. Proliferation of plaque resident macrophages and leukocyte adhesion to the vascular wall were significantly decreased in empagliflozin-treated mice. In summary, plasma glucose lowering by empagliflozin improves plaque regression in diabetic mice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-54224-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6884628PMC
November 2019

Inflammation in acute coronary syndrome: Expression of TLR2 mRNA is increased in platelets of patients with ACS.

PLoS One 2019 23;14(10):e0224181. Epub 2019 Oct 23.

Department of Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Background: Platelets are key components in atherogenesis and determine the course of its clinical sequelae acute coronary syndrome (ACS). Components of the innate immune system-the superfamily of TLR receptors-are present in platelets and represent a link between atherothrombosis and inflammation. We hypothesize that alteration in platelet TLR mRNA expression is a result of inflammation driving coronary atherosclerosis and may represent an alternative platelet activation pathway in ACS. TLR2-, TLR4- and TLR9- mRNA-expression was determined in ACS patients and compared to patients with invasive exclusion of atherosclerotic lesions of coronary arteries.

Methods: A total of fifty-four patients were enrolled in this clinical retrospective cohort single centre study. Total RNA from sepharose-filtered highly purified platelets was isolated using acid guanidinium thiocyanate-phenol-chloroform extraction and transcribed to cDNA using a first strand cDNA synthesis kit. To determine absolute copy numbers of TLR2, TLR4 and TLR9 we used plasmid based quantitative PCR with normalisation to an internal control.

Results: We found that mRNA expression levels of TLR2 but not TLR 4 and 9 are up-regulated in platelets of patients with ACS when compared to patients without coronary atherosclerosis.

Conclusion: Our results suggest elevated TLR2 mRNA expression in platelets as a biomarker reflecting the underlying inflammation in ACS and possibly severity of coronary atherosclerosis. Platelet TLR2 may represent a link between inflammation and atherothrombosis in ACS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0224181PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6808418PMC
March 2020

Association of soluble CD40L with short-term and long-term cardiovascular and all-cause mortality: The Ludwigshafen Risk and Cardiovascular Health (LURIC) study.

Atherosclerosis 2019 12 14;291:127-131. Epub 2019 Sep 14.

5th Medical Department, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, Germany. Electronic address:

Background And Aims: The CD40CD40 Ligand (CD40L) system has an important role in vascular inflammation. For this reason, we assessed the association of soluble CD40L with cardiovascular and all-cause mortality in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study.

Methods: Plasma levels of sCD40L were determined in 2759 persons using an enzyme immunoassay. Cox proportional hazard regressions were performed to evaluate the association between plasma concentration of sCD40 ligand and short-term (12 months) and long-term (10 years) mortality. Subpopulation analyses were conducted in seven different risk groups. Cox regression models were adjusted for traditional risk factors.

Results: The present study did not reveal significant association between sCD40L plasma levels and all-cause mortality, as well as cardiovascular mortality at one-year follow-up. In selected subgroups only, significant association between elevated sCD40L plasma levels and short-term all-cause and cardiovascular mortality could be observed. With regard to long-term all-cause and cardiovascular mortality analyses, no significant correlation with increased plasma levels of sCD40L could be detected, neither overall nor in any subgroup.

Conclusions: Soluble sCD40L is not associated with cardiovascular and all-cause mortality in this large cohort. Only in selected patient subgroups elevated levels of sCD40L correlate with short-term mortality but this correlation disappears in long-term analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.atherosclerosis.2019.09.004DOI Listing
December 2019

Predictors of survival in patients with acute coronary syndrome undergoing percutaneous coronary intervention of unprotected left main coronary artery stenosis.

Catheter Cardiovasc Interv 2020 07 11;96(1):E27-E33. Epub 2019 Sep 11.

Department of Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Objective: Aim of this study was to investigate predictors of survival in unstable patients with high SYNTAX-1-score.

Background: In significant unprotected left main coronary artery (ULMCA) stenosis, treatment options include percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG). While CABG is recommended for stable patients with ULMCA stenosis and a SYNTAX-1-score > 32, PCI may be preferable in unstable or high operative risk patients.

Methods: Retrospective single-center all-comers registry study.

Results: A total of 142 patients underwent ULMCA-PCI (~72.9 years, 23.2% females, 54.2% survival in 2-year follow-up), 84 of whom had a SYNTAX-1 > 32 (37.4 ± 12.8). Patients in the high-SYNTAX-1-group (score > 32) were more often in an acute condition compared to low-SYNTAX-2-group (score ≤ 32) including acute myocardial infarction (76.2% vs. 57.4%, p = .024), cardiogenic shock (48.2% vs. 14.8%, p = .001), or need for mechanical support (36.1% vs. 11.1%, p = .001). Survival was predicted by the acute condition including cardiogenic shock (OR 0.06 and 0.05) and myocardial infarction (OR 0.03 and 0.34) in both groups. Performance of the SYNTAX-1-score was limited in our patient collective in both groups (c-index 0.65 vs. 0.63) while SYNTAX-2-PCI-score performed better (c-index 0.67 vs. 0.67). EuroScore II had the best discriminative ability (c-index 0.87 vs. 0.78).

Conclusions: The majority of patients undergoing ULMCA-PCI presented in acute conditions with high SYNTAX-1-score, and is therefore underrepresented in clinical trials. Prognosis was best predicted by the acute condition and the EuroScore II. These data suggest that therapy in unstable patients should be guided by clinical condition over the anatomical SYNTAX-1-score.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ccd.28495DOI Listing
July 2020

Tumor Necrosis Factor Receptor-Associated Factor 5 Promotes Arterial Neointima Formation through Smooth Muscle Cell Proliferation.

J Vasc Res 2019 22;56(6):308-319. Epub 2019 Aug 22.

Department of Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Tumor necrosis factor (TNF) receptor-associated factors (TRAFs) are cytoplasmic adaptor proteins of the TNF/interleukin (IL)-1/Toll-like receptor superfamily. Ligands of this family such as TNFα, CD40L, and IL-1β promote chronic inflammatory processes such as atherosclerosis and restenosis, the latter being a common adverse reaction after vascular interventions. We previously reported overexpression of TRAF5 in murine and human atheromata and TRAF5-dependent proinflammatory functions in vitro. However, the role of TRAF5 in restenosis remains unsettled. To evaluate whether TRAF5 affects neointima formation, TRAF5-/-LDLR-/- and TRAF5+/+LDLR-/- mice consuming a high cholesterol diet (HCD) received wire-induced injury of the carotid artery. After 28 days, TRAF5-deficient mice showed a 45% decrease in neointimal area formation compared with TRAF5-compentent mice. Furthermore, neointimal vascular smooth muscle cells (vSMC) and macrophages decreased whereas collagen increased in TRAF5-deficient mice. Mechanistically, the latter expressed lower transcript levels of the matrix metalloproteinases 2 and 9, both instrumental in extracellular matrix degradation and vSMC mobilization. Additionally, TRAF5-specific siRNA interference rendered murine vSMC less proliferative upon CD40L stimulation. In accordance with these findings, fewer vSMC isolated from TRAF5-deficient aortas were in a proliferative state as assessed by Ki67 and cyclin B1 expression. In conclusion, TRAF5 deficiency mitigates neointima formation in mice, likely through a TRAF5-dependent decrease in vSMC proliferation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000501615DOI Listing
January 2020

The association of high-normal international-normalized-ratio (INR) with mortality in patients referred for coronary angiography.

PLoS One 2019 15;14(8):e0221112. Epub 2019 Aug 15.

Vth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Aims: The international-normalized-ratio (INR) is typically used to monitor patients on warfarin or related oral anticoagulant therapy. The aim of our study was to investigate the association of the INR with mortality in coronary artery disease (CAD) patients not on oral anticoagulant therapy.

Methods And Results: Between 1997 to 2000 the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study enrolled 3316 patients of German ancestry that had been referred for coronary angiography. We excluded patients on coumarin therapy (n = 222) and patients with an INR more than 5 standard deviations (SD) away from the mean (n = 30). During a median follow-up of 9.9 years, 884 patients died, 547 patients from cardiovascular causes. After adjustment for cardiovascular risk factors the INR was associated with all-cause mortality in all patients and the CAD positive group with HRs (95% CI) of 1.14(1.07-1.21) and 1.16(1.09-1.23) per 1-SD increase, respectively. Adjustment for NT-proBNP rendered the association insignificant.

Conclusion: In LURIC, the INR was positively associated with mortality in patients with prevalent CAD not on oral anticoagulant therapy as well as in patients without CAD. Adjustment for NT-proBNP abolished the association suggesting clinical or subclinical heart failure strongly contributing to increased INR and higher mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0221112PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6695160PMC
March 2020

Blood pressure changes after renal denervation are more pronounced in women and nondiabetic patients: findings from the Austrian Transcatheter Renal Denervation Registry.

J Hypertens 2019 11;37(11):2290-2297

Division of Cardiology, Department of Internal Medicine, Medical University Graz, Graz.

Objectives: Three recently published sham-controlled studies proved the efficacy of renal denervation (RDN) in hypertensive patients. The study presented here analyzed a nationwide multicentre registry database to clarify which patient subgroups benefit most from radiofrequency RDN.

Methods: This is a post hoc analysis from the multicentre Austrian Transcatheter Renal Denervation Registry hosted by the Austrian Society of Hypertension. We correlated change of SBP after RDN to sex and presence/absence of comorbidities. Univariable correlation and multiple linear regression analyses were performed.

Results: Two hundred and ninety-one patients (43% women, median age 64 years) undergoing RDN between April 2011 and September 2014 were included in this analysis. Mean baseline ambulatory 24 h BP (systolic/diastolic) was 150 ± 18/89 ± 14 mmHg and mean baseline office BP was 170 ± 16/94 ± 14 mmHg.After RDN, mean ambulatory 24 h BP reduction was 9 ± 19/6 ± 16 mmHg. The following features were associated with a good response to RDN: high baseline systolic ambulatory BP, high baseline diastolic office BP, female sex, absence of diabetes mellitus, and absence of peripheral artery disease. Multivariable analysis identified female sex and absence of diabetes mellitus as strongest predictors for ambulatory BP reduction, although those groups had the lowest baseline ambulatory BP.

Discussion: Ambulatory BP reductions after RDN were substantially more pronounced in female and in nondiabetic patients despite lower baseline BP. It is concluded that in terms of efficacy female patients and nondiabetic patients might benefit more from RDN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/HJH.0000000000002190DOI Listing
November 2019

Residual inflammatory risk in coronary heart disease: incidence of elevated high-sensitive CRP in a real-world cohort.

Clin Res Cardiol 2020 Mar 19;109(3):315-323. Epub 2019 Jul 19.

Department of Cardiology and Angiology I, University Heart Center Freiburg, Medical Faculty, University of Freiburg, Freiburg, Germany.

Background: Inflammation drives atherosclerosis and its complications. Anti-inflammatory therapy with interleukin 1 beta (IL-1β) antibody reduces cardiovascular events in patients with elevated high-sensitive C-reactive protein (hsCRP). This study aims to identify the share of patients with coronary heart disease (CHD) and residual inflammation who may benefit from anti-inflammatory therapy.

Methods: hsCRP and low-density lipoprotein (LDL) levels were determined in 2741 all-comers admitted to the cardiological ward of our tertiary referral hospital between June 2016 and June 2018. Patients without CHD, with acute coronary syndrome, chronic or recurrent systemic infection, use of immunosuppressant or anti-inflammatory agents, chronic inflammatory diseases, chemotherapy, terminal organ failure, traumatic injury and pregnancy were excluded.

Results: 856 patients with stable CHD were included. 42.7% of those had elevated hsCRP ≥ 2 mg/l. Within the group of patients with LDL-cholesterol < 70 mg/dl, 30.9% shared increased hsCRP indicating residual inflammation. After multivariate adjusted backward selection elevated Lipoprotein (a) (OR 1.61, p = 0.048), elevated proBNP (OR 2.57, p < 0.0001), smoking (OR 1.70, p = 0.022), and obesity (OR 2.28, p = 0.007) were associated with elevated hsCRP. In contrast, the use of ezetimibe was associated with normal hsCRP (OR 0.51, p = 0.014). In the subgroup of patients with on-target LDL-cholesterol < 70 mg/dl, backward selection identified elevated proBNP (OR 3.49, p = 0.007) as independent predictor of elevated hsCRP in patients with LDL-cholesterol < 70 mg/dl.

Conclusion: One-third of all-comers patients with CHD showed increased levels of hsCRP despite a LDL-cholesterol < 70 mg/dl potentially qualifying for an anti-inflammatory therapy. Elevated proBNP is an independent risk factor for hsCRP elevation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00392-019-01511-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042185PMC
March 2020
-->