Publications by authors named "Renate Koppensteiner"

148 Publications

Platelet-to-Lymphocyte Ratio as Marker of Platelet Activation in Patients on Potent P2Y Inhibitors.

J Cardiovasc Pharmacol Ther 2022 Jan-Dec;27:10742484221096524

Department of Internal Medicine II, 27271Medical University of Vienna, Vienna, Austria.

A high platelet-to-lymphocyte ratio (PLR) has recently been associated with ischemic outcomes in cardiovascular disease. Increased platelet reactivity and leukocyte-platelet aggregate formation are directly involved in the progress of atherosclerosis and have been linked to ischemic events following percutaneous coronary intervention (PCI). In order to understand the relation of PLR with platelet reactivity, we assessed PLR as well as agonist-inducible platelet aggregation and neutrophil-platelet aggregate (NPA) formation in 182 acute coronary syndrome (ACS) patients on dual antiplatelet therapy with aspirin and prasugrel (n = 96) or ticagrelor (n = 86) 3 days after PCI. PLR was calculated from the blood count. Platelet aggregation was measured by multiple electrode aggregometry and NPA formation was determined by flow cytometry, both in response to ADP and SFLLRN. A PLR ≥91 was considered as high PLR based on previous data showing an association of this threshold with adverse ischemic outcomes. In the overall cohort and in prasugrel-treated patients, high PLR was associated with higher SFLLRN-inducible platelet aggregation (67 AU [50-85 AU] vs 59.5 AU [44.3-71.3 AU], = .01, and 73 AU [50-85 AU] vs 61.5 AU [46-69 AU], = .02, respectively). Further, prasugrel-treated patients with high PLR exhibited higher ADP- (15% [11%-23%] vs 10.9% [7.6%-15.9%], = .007) and SFLLRN-inducible NPA formation (64.3% [55.4%-73.8%] vs 53.8% [44.1%-70.1%], = .01) as compared to patients with low PLR. These differences were not seen in ticagrelor-treated patients. In conclusion, high PLR is associated with increased on-treatment platelet reactivity in prasugrel-treated patients, but not in patients on ticagrelor.
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http://dx.doi.org/10.1177/10742484221096524DOI Listing
April 2022

High-Density Lipoprotein Particle Subclasses in Statin-Treated Patients with Peripheral Artery Disease Predict Long-Term Survival.

Thromb Haemost 2022 04 18. Epub 2022 Apr 18.

Division of Angiology, Department of Medicine 2, Medical University of Vienna, Vienna, Austria.

Low-density lipoprotein-cholesterol reduction showed a strong reduction of cardiovascular (CV) event rates in CV disease. However, the residual risk of future CV events remains high, which especially extends to peripheral arterial disease (PAD). Nuclear magnetic resonance (NMR) spectroscopy offers a novel method for analysis of the lipoprotein spectrum. This study investigates lipoprotein subclasses using NMR spectroscopy and assesses implications for long-term survival in PAD. NMR spectroscopy was performed by Nightingale Inc., in 319 patients with stable PAD and well-controlled CV risk factors. Patients were followed-up for 10 years. During that period, 123 patients (38.5%) died, of those 68 (21.3%) were defined as CV deaths. Outcome data were analyzed by the Kaplan-Meier method and multivariable Cox-regression for lipoprotein particles. Small and medium high-density lipoprotein-particles (S-HDL-P and M-HDL-P) showed a significant inverse association with all-cause mortality in Cox-regression analyses after multivariable adjustment (S-HDL-P, hazard ratio [HR]: 0.71, 95% confidence interval [CI]: 0.57-0.88; M-HDL-P, HR: 0.72, 95% CI: 0.58-0.90) for each increase of one standard deviation. In contrast, cholesterol-rich X-large HDL-particles (XL-HDL-P) showed a positive association with all-cause mortality (HR: 1.51, 95% CI: 1.20-1.89). Only the association between XL-HDL-P and CV death sustained multivariable adjustment (HR: 1.49, 95% CI: 1.10-2.02), whereas associations for S-HDL-P and M-HDL-P were attenuated (HR: 0.76, 95% CI: 0.57-1.01; HR: 0.80, 95% CI: 0.60-1.06). This study shows a novel association for a beneficial role of S-HDL-P and M-HDL-P but a negative association with higher cholesterol-rich XL-HDL-P for long-term outcome in well-treated patients with PAD. Thus, these results provide evidence that NMR-measured HDL particles identify patients at high CV residual risk beyond adequate lipid-lowering therapy.
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http://dx.doi.org/10.1055/a-1827-7896DOI Listing
April 2022

Microvascular rarefaction in patients with cerebrovascular events.

Microvasc Res 2022 03 23;140:104300. Epub 2021 Dec 23.

Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria. Electronic address:

Capillary density rarefaction and endothelial dysfunction contribute to chronic hypoperfusion and cerebral small vessel disease. Previous animal experiments revealed spatiotemporal microvascular remodeling directing post-stroke brain reorganization. We hypothesized that microcirculatory changes during acute cerebrovascular events could be reflected systemically and visualized sublingually. In a prospective observational trial in vivo sublingual sidestream darkfield videomicroscopy was performed in twenty-one patients with either acute stroke (n = 13 ischemic, n = 1 ischemic with hemorrhagic transformation and n = 2 hemorrhagic stroke) or transitory ischemic attacks (n = 5) within 24 h after hospital admission and compared to an age- and sex-matched control group. Repetitive measurements were performed on the third day and after one week. Functional and perfused total capillary density was rarefied in the overall patient group (3060 vs 3717 μm/mm, p = 0.001 and 5263 vs 6550 μm/mm, p = 0.002, respectively) and in patients with ischemic strokes (2897 vs. 3717 μm/mm, p < 0.001 and 5263 vs. 6550 μm/mm, p = 0.006, respectively) when compared to healthy controls. The perfused boundary region (PBR), which was measured as an inverse indicator of glycocalyx thickness, was markedly related to red blood cell (RBC) filling percentage (regarded as an estimate of microvessel perfusion) in the overall patient group (r = -0.843, p < 0.001), in patients with ischemic strokes (r = -0.82, p = 0.001) as well as in healthy volunteers (r = -0.845, p < 0.001). In addition, there were significant associations between platelet count or platelet aggregation values (as measured by whole blood impedance aggregometry) and microvascular parameters in the overall patient collective, as well as in patients with ischemic strokes. In conclusion, cerebrovascular events are associated with altered systemic microvascular perfusion.
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http://dx.doi.org/10.1016/j.mvr.2021.104300DOI Listing
March 2022

Galectin-3 is linked to peripheral artery disease severity, and urinary excretion is associated with long-term mortality.

Atherosclerosis 2022 01 27;341:7-12. Epub 2021 Nov 27.

Division of Angiology, Medicine II, Medical University of Vienna, Vienna, Austria.

Background And Aims: Galectin-3 (Gal-3) is a biomarker involved in fibrosis and vascular inflammation. Gal-3 has been linked to chronic kidney disease (CKD) and patients with peripheral artery disease (PAD). Conflicting reports exist about the relevance of Gal-3 in PAD. The study aims to elucidate a possible link between serum and urinary Gal-3 and long-term survival in PAD patients without critical limb ischemia and mild to moderate CKD.

Methods: Galectin-3 (Gal-3) was measured in serum (n = 311) and urine (n = 266) of PAD patients (age 69 (62-77) years) by bead-based multiplex assay. Urinary Gal-3 concentration was normalized to urine creatinine (cr) levels. Mortality data were retrieved from the Austrian central death registry after a median observation period of 9.2 years. Survival analyses were performed by the Kaplan-Meier method and Cox-regression.

Results: Serum Gal-3 was higher in patients with claudication symptoms (p = 0.001) and correlated inversely with the patients' ankle-brachial index (R = -0.168, p = 0.009). Serum Gal-3 and urinary Gal-3 (uGal-3/cr) were associated with the estimated glomerular filtration rate (R = -0.359, p < 0.001; R = -0.285, p < 0.001). Serum Gal-3 was not linked to all-cause mortality [HR 1.17 (CI 0.96-1.42)] over 9.2 years. However, uGal-3/cr was associated with all-cause mortality [HR 1.60 (CI 1.31-1.95)]. This association sustained multivariable adjustment for cardiovascular risk factors and renal function [HR 1.71 (CI 1.35-2.17)].

Conclusions: This study is the first to show an association of uGal-3/cr and long-term mortality in patients with PAD. Gal-3 was not predictive of long-term mortality but seems to be a marker of PAD severity in patients without critical limb ischemia.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.11.016DOI Listing
January 2022

Angiogenin-A Proposed Biomarker for Cardiovascular Disease-Is Not Associated With Long-Term Survival in Patients With Peripheral Artery Disease.

Angiology 2021 10 29;72(9):855-860. Epub 2021 Mar 29.

Division of Angiology, Department of Internal Medicine II, 27271Medical University Vienna, Vienna, Austria.

We evaluated angiogenin as a prospective biomarker in peripheral artery disease (PAD) patients with and without claudication symptoms. A pilot study suggested an elevation of angiogenin in critical limb ischemia. However, in PAD patients, the predictive value of angiogenin has not yet been evaluated. For this purpose, 342 patients with PAD (age: 69 ± 10 years, 34.5% women) were followed-up for 7 years in a cross-sectional study. Angiogenin was measured by enzyme-linked immunosorbent assay. All-cause and cardiovascular mortality were analyzed by Cox regression. Angiogenin levels were higher in men ( = .001) and were associated with patient waist-to-hip ratio ( < .001), fasting triglycerides ( = .011), and inversely with estimated glomerular filtration rate ( = .009). However, angiogenin showed no association with age, characteristics of diabetes, markers of lipid metabolism, or C-reactive protein. Angiogenin did not correlate with markers of angiogenesis such as vascular endothelial growth factor, angiopoietin-2, or tie-2. Furthermore, angiogenin was not associated with PAD Fontaine stages or with patient ankle-brachial index in addition to all-cause mortality (hazard ratio [HR] = 1.09 [95% CI: 0.89-1.34]) or cardiovascular morality (HR = 1.05 [0.82-1.35]). These results suggest that angiogenin does not provide further information regarding outcome prediction in patients with PAD.
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http://dx.doi.org/10.1177/00033197211004393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436295PMC
October 2021

Glycocalyx as Possible Limiting Factor in COVID-19.

Front Immunol 2021;12:607306. Epub 2021 Feb 22.

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

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http://dx.doi.org/10.3389/fimmu.2021.607306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937603PMC
April 2021

Soluble urokinase-type plasminogen activator receptor predicts peripheral artery disease severity and outcomes.

Vasc Med 2021 02 15;26(1):11-17. Epub 2021 Jan 15.

Division of Angiology, Medicine II, Medical University Vienna, Vienna, Austria.

Soluble urokinase-type plasminogen activator receptor (suPAR) is associated with chronic kidney disease (CKD) severity and peripheral artery disease (PAD). We hypothesize an association of PAD severity and suPAR in patients without advanced CKD and further risk stratification according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. For study purposes, suPAR was measured in 334 PAD patients (34% women, age 69 (62-78) years, eGFR 68 ± 20 mL/min/1.72 m) by commercial ELISA. Patients were followed for 10 years to assess long-term all-cause survival by Cox regression. Higher suPAR levels were associated with lower ankle-brachial index ( = -0.215, = 0.001) in patients with PAD without media-sclerosis ( = 236). suPAR levels inversely correlated with decreased glomerular filtration rate ( = -0.476, < 0.001) and directly correlated with urinary albumin-to-creatinine ratio ( = 0.207, < 0.001). Furthermore, higher suPAR levels associated with a higher KDIGO risk score ( < 0.001). Baseline suPAR was significantly associated with all-cause mortality (HR 1.40 (95% CI 1.16-1.68), < 0.001) over 10 years. suPAR remained associated with mortality (HR 1.29 (1.03-1.61), = 0.026) after multivariable adjustment for age, sex, cardiovascular risk factors, and eGFR. Future research may define a standard role for suPAR assessment in PAD's work-up and treatment, especially in patients with CKD.
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http://dx.doi.org/10.1177/1358863X20982077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879231PMC
February 2021

Thromboangiitis Obliterans Biomarker Shifts in Different Acute Phase Stages: A Case Study.

Ann Vasc Surg 2021 May 21;73:509.e5-509.e9. Epub 2021 Jan 21.

Division of Angiology, Department of Medicine 2, Medical University of Vienna, Vienna, Austria.

Thromboangiitis obliterans (TAO) is a rare vasculopathy that is predominantly seen in young male smokers. Recently, new biomarkers have been shown to be useful in distinguishing TAO from acute phase TAO in an Asian study population. The present case study illustrates their application in a European patient during TAO exacerbation and their association with therapeutic performance.
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http://dx.doi.org/10.1016/j.avsg.2020.11.004DOI Listing
May 2021

GlycA for long-term outcome in T2DM secondary prevention.

Diabetes Res Clin Pract 2021 Jan 8;171:108583. Epub 2020 Dec 8.

Division of Angiology, Department of Medicine 2, Medical University of Vienna, Austria. Electronic address:

Aims: Glycosylated acetyls (GlycA), a systemic marker of inflammation, were associated both with incident type 2 diabetes mellitus (T2DM) and incident cardiovascular (CV) disease. This study evaluates the predictive value of GlycA for long-term survival in patients with T2DM and peripheral artery disease (PAD).

Methods: GlycA (mmol/l) levels were measured by nuclear magnetic resonance spectroscopy in a cross-sectional cohort of patients with PAD (n = 319). Both all-cause and CV mortality were evaluated after a follow-up of 9.0 (IQR 6.5-9.5) years. During the follow-up 117 patients died, of those 64 events were of CV origin (PAD-T2DM subgroup: all-cause mortality n = 60, CV-mortality n = 32).

Results: PAD-T2DM showed a tendency towards a worse CV risk factor profile and a higher percentage of known coronary artery disease (24.9% vs 43.5%, p < 0.001). GlycA levels were higher in PAD-T2DM (1.6 ± 0.2 vs. 1.53 ± 0.18, p = 0.002). GlycA predicted all-cause mortality after multivariable adjustment for traditional CV risk factors (HR for 1 SD increase 1.51, 95% confidence interval 1.03-2.19) in PAD-T2DM, while no association could be seen with CV-mortality (1.22, 0.73-2.06).

Conclusions: GlycA was capable of predicting long-term outcome in PAD patients with T2DM. Thus, GlycA might reflect the added inflammatory burden of T2DM in systemic atherosclerosis.
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http://dx.doi.org/10.1016/j.diabres.2020.108583DOI Listing
January 2021

Comparison of Light Transmission Aggregometry With Impedance Aggregometry in Patients on Potent P2Y12 Inhibitors.

J Cardiovasc Pharmacol Ther 2021 05 27;26(3):260-268. Epub 2020 Oct 27.

Department of Internal Medicine II, 27271Medical University of Vienna, Vienna, Austria.

Since data on the agreement between light transmission aggregometry (LTA) and multiple electrode aggregometry (MEA) in patients on the more potent P2Y inhibitors are missing so far, we investigated if the evaluation of the responsiveness to therapy by LTA can be replaced by MEA in 160 acute coronary syndrome (ACS) patients on dual antiplatelet therapy with aspirin and prasugrel or ticagrelor (n = 80 each). Cut-off values for high on-treatment residual platelet reactivity (HRPR) in response to adenosine diphosphate (ADP) or arachidonic acid (AA) were defined according to previous studies showing an association of HRPR with the occurrence of adverse ischemic outcomes. ADP- inducible platelet aggregation was 33% and 37% ( = 0.07) by LTA and 19 AU and 20 AU ( = 0.38) by MEA in prasugrel- and ticagrelor-treated patients, respectively. AA- inducible platelet aggregation was 2% and 3% by LTA and 15 AU and 16 AU by MEA, (all ≥ 0.3) in patients on prasugrel and ticagrelor, respectively. By LTA, HRPR ADP and HRPR AA were seen in 5%/5% and in 4%/ 13% of patients receiving prasugrel- and ticagrelor, respectively. By MEA, HRPR ADP and HRPR AA were seen in 3%/ 25% and 0%/24% of prasugrel- and ticagrelor-treated patients, respectively. ADP-inducible platelet reactivity by MEA correlated significantly with LTA ADP in prasugrel-treated patients (r = 0.4, < 0.001), but not in those receiving ticagrelor (r = 0.09, = 0.45). AA-inducible platelet aggregation by LTA and MEA did not correlate in prasugrel- and ticagrelor-treated patients. Sensitivity/specificity of HRPR by MEA to detect HRPR by LTA were 25%/99% for MEA ADP and 100%/79% for MEA AA in prasugrel-treated patients, and 0%/100% for MEA ADP and 70%/83% for MEA AA in ticagrelor-treated patients. In conclusion, on-treatment residual ADP-inducible platelet reactivity by LTA and MEA shows a significant correlation in prasugrel- but not ticagrelor-treated patients. However, in both groups LTA and MEA revealed heterogeneous results regarding the classification of patients as responders or non-responders to P2Y inhibition.
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http://dx.doi.org/10.1177/1074248420968706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010888PMC
May 2021

Vascular peroxidase 1 is independently associated with worse kidney function in patients with peripheral artery disease.

J Nephrol 2021 02 19;34(1):165-172. Epub 2020 Aug 19.

Division of Angiology, Department of Medicine II, Medical University and General Hospital of Vienna, Währinger Gürtel 18-20, Vienna, 1090, Austria.

Background: Oxidative stress is involved in cardiovascular disease such as peripheral artery disease (PAD). Vascular Peroxidase 1 (VPO1), a novel heme-containing peroxidase mainly expressed in the cardiovascular system, aggravates oxidative stress. Evidence in humans is limited. Current work aims to measure VPO1 in patients suffering from PAD, and to evaluate the association of VPO1 with conventional markers of cardiovascular risk factors (CVRF), including the estimated glomerular filtration rate (eGFR) and albuminuria categories.

Methods: This study is part of a longitudinal observational study. At baseline, 236 PAD-patients were included. VPO1 plasma levels (ng/mL) were measured by commercially available ELISA kits. A two-sided p level of < 0.05 was considered statistically significant.

Results: In the cross-sectional analysis (n = 236), VPO1 associated with ageing (p = 0.035) as well as with eGFR and albuminuria category, the markers of chronic kidney disease (CKD)-progression (p = 0.042). The longitudinal 18-months follow-up analysis (n = 152) demonstrated that baseline VPO1 predicts rapid kidney function decline (RKFD) (n = 49), defined as more than - 3 mL/min/1.73m eGFR loss per year, (OR per one SD VPO1 1.60 (1.11-2.30); p = 0.009). This association between VPO1 and kidney function withstood the multivariable adjustment for traditional CVRF including baseline eGFR and urine albumin-to-creatinine ratio (UACR), (adjOR per one SD VPO1 1.73 (1.14-2.61); p = 0.046).

Conclusion: This study is first to reveal that VPO1 is independently associated with declining kidney function in patients with PAD. VPO1 shows a tighter association to kidney function than to other CVRF. This finding points to VPO1 as a potential target protein to assess CKD-progression.
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http://dx.doi.org/10.1007/s40620-020-00818-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881961PMC
February 2021

Predictive power of novel and established obesity indices for outcome in PAD during a five-year follow-up.

Nutr Metab Cardiovasc Dis 2020 06 7;30(7):1179-1187. Epub 2020 Apr 7.

Division of Angiology, Department of Internal Medicine 2, Medical University of Vienna, Austria.

Background And Aims: Previous data show contradicting results regarding relevance of obesity on outcome in peripheral arterial disease (PAD). Thus, this study aims to evaluate the predictive power of obesity as measured by established and novel obesity indices (waist circumference WC, waist-hip ratio WHR, body-mass index BMI, body adiposity index BAI, visceral adiposity index VAI, weight-adjusted waist index WWI) in a PAD cohort.

Methods And Results: In 367 patients with diagnosed PAD anthropometric parameters were assessed at study inclusion in an observational study. Mortality data was retrieved from the central death registry after five years. Outcome analyses were performed by multivariable Cox-regression models. 57 PAD patients (15.5%) died during the follow-up, of those 36 were categorized as cardiovascular origin. Patients from the all-cause mortality group were older, more often diabetics with a worse glucose control and had worse renal function. Obesity indices were not significantly different between the event and control group. None of the evaluated risk factors predicted cardiovascular or all-cause death after multivariable adjustment for age, gender, LDL-C, serum creatinine, systolic blood pressure, CRP, smoking habits, diabetes status and previous history of peripheral revascularisation (all-cause WC 1.007 (0.983-1.031), WHR 1.772 (0.106-29.595), BMI 1.006 (0.939-1.078), BAI 1.002 (0.945-1.063), VAI 1.019 (0.895-1.161), WWI 1.085 (0.831-1.416); cv-death WC 1.007 (0.978-1.036), WHR 0.382 (0.006-25.338), BMI 1.004 (0.918-1.098), BAI 1.034 (0.959-1.116), VAI 1.036 (0.885-1.213), WWI 1.061 (0.782-1.441)).

Conclusion: Obesity as risk marker estimated by indices both for general and visceral adiposity, does not predict mortality in a secondary prevention cohort of PAD patients.
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http://dx.doi.org/10.1016/j.numecd.2020.03.019DOI Listing
June 2020

Peripheral arterial disease and type 2 diabetes: Older patients still exhibit a survival benefit from glucose control.

Diab Vasc Dis Res 2020 Mar-Apr;17(2):1479164120914845

Division of Angiology, Department of Medicine II, Medical University of Vienna, Vienna, Austria.

Objective: To investigate a possible beneficial effect of strict glycaemic control on all-cause mortality in patients with peripheral arterial disease and type 2 diabetes mellitus.

Methods: A total of 367 mainly older peripheral arterial disease patients [age: 69 (62-78) years, 34% women, Fontaine stage I-II] were categorized according to glycaemic control, that is, (a) no type 2 diabetes mellitus, (b) strict glucose control (HbA1c < 53 mmol/mol) and (c) lenient glucose control (HbA1c ⩾ 53 mmol/mol) at inclusion and by mean HbA1c over the first study year. Mortality was analysed using Kaplan-Meier and Cox-regression analyses after 7 years.

Results: The combination of type 2 diabetes mellitus and peripheral arterial disease reduced survival from 78.8% to 68.9% in comparison to patients without type 2 diabetes mellitus ( = 0.023). Patients with strict glucose control (75%) were associated with increased survival in comparison to patients with lenient glucose control (58.9%) stratified by mean HbA1c ( = 0.042). Baseline cardiovascular risk factors were similar in those type 2 diabetes mellitus patients. In this peripheral arterial disease cohort HbA1c (hazard ratio: 1.3, 1.04-1.63), age (hazard ratio: 1.7, 1.3-2.3) and C-reactive protein (hazard ratio: 1.5, 1.2-2.0) remained independent associates for mortality adjusted for cardiovascular risk factors and diabetes duration.

Conclusion: Older patients with peripheral arterial disease and type 2 diabetes mellitus still benefit from strict glucose control in a cohort of patients with similar distribution of cardiovascular risk factors.
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http://dx.doi.org/10.1177/1479164120914845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510380PMC
September 2020

Ticagrelor Inhibits Toll-Like and Protease-Activated Receptor Mediated Platelet Activation in Acute Coronary Syndromes.

Cardiovasc Drugs Ther 2020 02;34(1):53-63

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

Purpose: Since ticagrelor inhibits the cellular uptake of adenosine, thereby increasing extracellular adenosine concentration and biological activity, we hypothesized that ticagrelor has adenosine-dependent antiplatelet properties. In the current study, we compared the effects of ticagrelor and prasugrel on platelet activation in acute coronary syndrome (ACS).

Methods: Platelet surface expression of P-selectin and activated glycoprotein (GP) IIb/IIIa in response to adenosine diphosphate (ADP), the toll-like receptor (TLR)-1/2 agonist Pam3CSK4, the TLR-4 agonist lipopolysaccharide (LPS), the protease-activated receptor (PAR)-1 agonist SFLLRN, and the PAR-4 agonist AYPGKF were measured by flow cytometry in blood from 80 ticagrelor- and 80 prasugrel-treated ACS patients on day 3 after percutaneous coronary intervention. Residual platelet aggregation to arachidonic acid (AA) and ADP were assessed by multiple electrode aggregometry and light transmission aggregometry.

Results: ADP-induced platelet activation and aggregation, and AA-induced platelet aggregation were similar in patients on ticagrelor and prasugrel, respectively (all p ≥ 0.3). Further, LPS-induced platelet surface expression of P-selectin and activated GPIIb/IIIa did not differ significantly between ticagrelor- and prasugrel-treated patients (both p > 0.4). In contrast, Pam3CSK4-induced platelet surface expression of P-selectin and activated GPIIb/IIIa were significantly lower in ticagrelor-treated patients (both p ≤ 0.005). Moreover, SFLLRN-induced platelet surface expression of P-selectin and activated GPIIb/IIIa were significantly less pronounced in patients on ticagrelor therapy compared to prasugrel-treated patients (both p < 0.03). Finally, PAR-4 mediated platelet activation as assessed by platelet surface expression of activated GPIIb/IIIa following stimulation with AYPGKF was significantly lower in patients receiving ticagrelor (p = 0.02).

Conclusion: Ticagrelor inhibits TLR-1/2 and PAR mediated platelet activation in ACS patients more strongly than prasugrel.
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http://dx.doi.org/10.1007/s10557-019-06932-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093367PMC
February 2020

Sublingual microvasculature in diabetic patients.

Microvasc Res 2020 05 30;129:103971. Epub 2019 Dec 30.

Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria. Electronic address:

Diabetes is associated with micro- and macrovascular complications. The aim of the study was to investigate microvascular parameters (glycocalyx dimensions, perfused and total capillary density) in vivo in patients with type 1 and type 2 diabetes mellitus. In vivo sublingual videomicroscopy using sidestream darkfield - derived imaging was performed in 36 patients with diabetes mellitus (type 1: n = 20, type 2: n = 16) and compared to a control group of 36 healthy volunteers. Patients with HbA1c levels ≥ 8% had a significantly higher perfused boundary region (PBR; signifying the loss of glycocalyx dimensions) compared to patients with HbA1c levels < 8%, which was more pronounced in type 1 diabetes (2.08 μm [1.95-2.16 μm] vs.1.9 μm [1.66-1.94 μm], p = .029). Capillary density did not differ significantly between patients with diabetes and healthy controls. PBR was inversely related to RBC filling percentage and perfused capillary density in diabetic patients (r = -0.754, p < .001 and r = -0.505, p = .002, respectively) as well as in healthy volunteers (r = -0.701, p < .001 and r = -0.150, p = n.s.) signifying the association between glycocalyx dimensions and microvessel perfusion. Renal parameters were associated with microvascular perfusion in patients with type 2 diabetes (correlation between eGFR and perfused capillary density: r = 0. 568, p = .027/RBC filling percentage: r = 0.657, p = .008). In addition, the ratio of perfused/total capillary density correlated with CRP levels in type 2 diabetes (r = 0.682, p = .021). In conclusion, diabetes is associated with loss of glycocalyx density.
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http://dx.doi.org/10.1016/j.mvr.2019.103971DOI Listing
May 2020

Acute Limb Ischemia after Intake of the Phenylethylamine Derivate NBOMe.

Int J Environ Res Public Health 2019 12 12;16(24). Epub 2019 Dec 12.

Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, A-1090 Vienna, Austria.

: N-(2-methoxy) benzyl-phenethylamine (NBOMe) derivatives have a high affinity to the serotonin receptor 2A and emerged as new psychedelic agents. We report the case of a 30-year-old man admitted to the hospital because of acute ischemia of the left arm with clinical symptoms of pallor, pulselessness, paresthesia, and a motoric deficit. The patient had a history of schizophrenia and drug abuse and disclosed during the hospital stay the sublingual intake of a substance bought as 25I-NBOMe the night before the ischemic event. : Routine clinical diagnostics including among others color-coded duplex sonography and computed tomography angiography (CTA) were performed. The remainder of the drugs was analyzed using high performance liquid chromatography. : Initial color-coded duplex sonography of the upper left limb showed pathological flow profiles of the axillary, brachial, ulnar, and radial artery with a reduced diameter of the ulnar (0.9 mm) and radial (1.1 mm) artery. In consequence, peripheral vasospasm, distal arterial thrombosis, or arterial embolization was anticipated. As therapeutic measures, the patient immediately received intravenous systemic vasodilators (alprostadil) and therapeutic anticoagulation with low molecular weight heparin. Instant symptom improvement was observed within the first day after therapy initiation. The subsequently performed CTA of the heart and left arm showed no signs of thrombotic material. Treatment was continued for five days and the patient was released thereafter having completely normalized perfusion in his left arm. Outpatient treatment was continued with calcium-channel blockers, as the patient had also displayed arterial hypertension. Drug analysis retrieved a composition of the isomers 25I-NBOMe, 25C-NBOMe, and 25H-NBOMe as well as traces of pentylon. Conclusion: NBOMe ingestion implicates the risk of peripheral vasospasms with severe, limb-threatening ischemia.
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http://dx.doi.org/10.3390/ijerph16245071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950699PMC
December 2019

α-Hydroxybutyrate dehydrogenase is associated with atherothrombotic events following infrainguinal angioplasty and stenting.

Sci Rep 2019 12 3;9(1):18200. Epub 2019 Dec 3.

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

Besides clinical characteristics, easy-accessible laboratory markers could be of value to refine risk stratification in peripheral artery disease. In the current study, we investigated whether α-hydroxybutyrate dehydrogenase (HBDH) is associated with atherothrombotic events in 83 stable patients undergoing infrainguinal angioplasty and stenting. The primary endpoint was defined as the composite of the first occurrence of nonfatal myocardial infarction, nonfatal stroke or transient ischemic attack and cardiovascular death within 2 years after angioplasty and stenting, and occurred in 6 patients (7.2%). HBDH levels at baseline were significantly higher in patients who subsequently developed the primary endpoint (126 U/L [116-137 U/L] vs. 105 U/L [95-120 U/L]; p = 0.04). ROC curve analysis revealed that HBDH could distinguish between patients without and with future atherothrombotic events. A HBDH concentration ≥ 115 U/L was identified as the best threshold to predict the composite endpoint, providing a sensitivity of 83.3% and a specificity of 71.4%, and was therefore defined as high HBDH. High HBDH was seen in 28 patients (33.7%). Ischemic events occurred significantly more often in patients with high HBDH than in patients with lower HBDH levels (5 vs. 1 patients, p = 0.007). In conclusion, HBDH is associated with the occurrence of atherothrombotic events after infrainguinal angioplasty with stent implantation. Future trials are warranted to study the predictive role of HBDH for ischemic outcomes and to investigate underlying mechanisms.
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http://dx.doi.org/10.1038/s41598-019-54899-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890648PMC
December 2019

Protease-activated receptor-mediated platelet aggregation in acute coronary syndrome patients on potent P2Y inhibitors.

Res Pract Thromb Haemost 2019 Jul 22;3(3):383-390. Epub 2019 May 22.

Department of Internal Medicine II Medical University of Vienna Vienna Austria.

Background: Despite the increasing use of potent P2Y inhibitors, further atherothrombotic events still impair the prognosis of many acute coronary syndrome (ACS) patients. This may in part be attributable to intact platelet aggregation via the human thrombin receptors protease-activated receptor (PAR)-1 and PAR-4.

Objective: We studied PAR mediated platelet aggregation in ACS patients following percutaneous coronary intervention (PCI) with stent implantation in a cross-sectional study.

Methods: Platelet aggregation to ADP as well as to the PAR-1 agonist SFLLRN and the PAR-4 agonist AYPGKF was assessed by multiple electrode aggregometry in 194 ACS patients on dual antiplatelet therapy with aspirin and either prasugrel (n = 114) or ticagrelor (n = 80) 3 days after PCI.

Results: Based on the consensus cutoff value, high on-treatment residual platelet reactivity to ADP (HRPR ADP) was observed in only 2 prasugrel-treated patients. Both patients with HRPR ADP had also a normal response to SFLLRN and AYPGKF. Among the 112 prasugrel-treated patients with adequate P2Y inhibition, 50 patients (45%) still had a normal response to SFLLRN, and 70 patients (63%) still had a normal response to AYPGKF. Among the 80 ticagrelor-treated patients with adequate P2Y inhibition, 25 patients (31%) still had a normal response to SFLLRN, and 50 (63%) still had a normal response to AYPGKF.

Conclusion: Normal platelet aggregation via PAR-1 and PAR-4 is preserved in many patients with adequate P2Y inhibition by prasugrel and ticagrelor. The present findings may at least in part explain adverse ischemic events despite potent P2Y inhibition.
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http://dx.doi.org/10.1002/rth2.12213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6611376PMC
July 2019

Effects of -3 PUFA on endothelial function in patients with peripheral arterial disease: a randomised, placebo-controlled, double-blind trial.

Br J Nutr 2019 09;122(6):698-706

Department of Angiology, University Hospital Leipzig, Leipzig, Germany.

As only limited evidence is available for potential benefits of n-3 PUFA supplementation in patients with peripheral arterial disease (PAD), we studied the effects of 4 g n-3 PUFA on endothelial function and inflammatory markers. Seventy patients with stable PAD classified as Rutherford stage 2 or 3 and good control of cardiovascular factors were randomised to receive either 4 g n-3 PUFA or placebo daily for 3 months in a double-blind fashion. Primary endpoint was endothelial function assessed by flow-mediated vasodilation (FMD). In addition, ankle-brachial index, maximum and pain-free walking distances were determined. Lipid parameters including the omega-3 index reflecting n-3 PUFA intake as well as pro-inflammatory, endothelial and platelet activation markers were measured over the same time interval. After 3 months of treatment with 4 g n-3 PUFA daily, a significant improvement of FMD was observed compared with placebo (n-3 PUFA, median Δ 3·7 (interquartile range (IQR) -1·8, 7·1) % v. placebo, Δ -0·5 (IQR -6·5, 3·0) %, P = 0·01 between the groups). After a 3-month washout period, this benefit was not sustained (n-3 PUFA, median Δ 0·6 (IQR -2·2, 5·6) % v. placebo, Δ -0·9 (IQR -6·6, 6·7) %, P = 0·20). In response to n-3 PUFA, an improvement of lipid parameters with a pronounced increase in the omega-3 index was seen. No changes were found for other parameters. In conclusion, in patients with PAD, 4 g/d n-3 PUFA improved cardiovascular risk in PAD patients, which needs testing in large-scale trials.
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http://dx.doi.org/10.1017/S0007114519001582DOI Listing
September 2019

Thrombospondin-4 increases with the severity of peripheral arterial disease and is associated with diabetes.

Heart Vessels 2020 Jan 21;35(1):52-58. Epub 2019 Jun 21.

Division of Angiology, Department of Internal Medicine 2, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.

Thrombospondin-4 (TSP-4) is an extracellular matrix protein of the vessel wall. Despite bench evidence, its significance in the clinical setting of atherosclerosis is missing. TSP-4 (ng/ml) was measured in 365 PAD patientsusing a commercially available ELISA. PAD was diagnosed by the ankle-brachial index (ABI) and clinically graded using the Fontaine classification. TSP-4 levels were significantly higher in Fontaine II vs. Fontaine I (4.78 ± 0. 42, 4.69 ± 0.42, p = 0.043). TSP-4 significantly correlated with ABI (r = - 0.141, p = 0.023, n = 259) after the exclusion of mediasclerotic patients. Binary logistic regression analysis for Fontaine I vs. II showed an OR of 1.70 (1.02-2.82) in a multivariable model adjusted for traditional risk factors. Interestingly, TSP-4 levels were higher in patients with type 2 diabetes mellitus or prediabetes (DGT) compared with normal glucose tolerance (NGT) (4.76 ± 0.42 vs. 4.66 ± 0.41, p = 0.035). ANOVA for PAD and diabetes subgroups showed a linear increase with disease burden with the highest difference between Fontaine I-NGT and Fontaine II-DGT (4.59 ± 0.40, 4.79 ± 0.43, p = 0.015). TSP-4 levels increased with PAD severity and showed a former unknown association with diabetes. Thus, TSP-4 could be a novel marker of atherosclerotic activity, especially in the major subgroup of patients with concomitant diabetes.
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http://dx.doi.org/10.1007/s00380-019-01453-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942020PMC
January 2020

Functional capillary impairment in patients with ventricular assist devices.

Sci Rep 2019 04 11;9(1):5909. Epub 2019 Apr 11.

Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.

The implantation of continuous - flow ventricular assist devices (VAD) is suggested to evoke angiodysplasia contributing to adverse events such as gastrointestinal bleeding. We evaluated in vivo capillary density and glycocalyx dimensions to investigate possible systemic microvascular changes in patients with chronic heart failure and VAD support vs. standard medical treatment. Forty-two patients with VAD support were compared to forty-one patients with ischemic and non-ischemic chronic heart failure (CHF) on standard pharmacotherapy and to a group of forty-two healthy subjects in a prospective cross-sectional study. Sublingual microcirculation was visualized using Sidestream Darkfield videomicroscopy and functional and perfused total capillary densities were quantified. Patients with VAD implantation were followed for one year and bleeding events were recorded. Median time after VAD implantation was 18 months. Patients were treated with centrifugal-flow devices (n = 31) or axial-flow devices (n = 11). Median functional capillary density was significantly lower in patients with VAD therapy as compared to CHF patients (196 vs. 255/mm, p = 0.042, adjusted p-value). Functional and total capillary densities were 44% and 53% lower (both p < 0.001) in patients with VAD therapy when compared to healthy subjects. Cox regression analysis revealed loss of capillary density as a significant predictor of bleeding events during one -year follow-up of VAD patients (HR: 0.987, CI (95%): 0.977-0.998, p = 0.021 for functional and 0.992, CI (95%): 0.985-0.999, p = 0.03 for total capillary density). In conclusion, patients with VAD support exhibit capillary density rarefaction, which was associated with bleeding events. If confirmed independently, capillary impairment may be evaluated as novel marker of bleeding risk.
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http://dx.doi.org/10.1038/s41598-019-42334-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459831PMC
April 2019

YKL-40 levels increase with declining ankle-brachial index and are associated with long-term cardiovascular mortality in peripheral arterial disease patients.

Atherosclerosis 2018 07 9;274:152-156. Epub 2018 May 9.

Division of Angiology, Medicine II, Medical University Vienna, Spitalgasse 23, 1090, Vienna, Austria. Electronic address:

Background And Aims: YKL-40 is an inflammatory marker secreted by macrophages and is expressed in atherosclerotic plaques. YKL-40 increases in coronary artery disease (CAD) with poor coronary collateral vessel development. Higher levels are linked to reduced survival in CAD patients. Studies evaluating YKL-40 in patients with peripheral arterial disease (PAD) are scarce. This study aims to elucidate a possible link between YKL-40 and PAD severity as well as cardiovascular long-term mortality.

Methods: YKL-40 was measured at baseline in 365 elderly PAD patients (age 69 ± 10.4, 33.7% women, Fontaine stage I-II) by bead-based multiplex assay. Patients were followed for seven years to assess long-term cardiovascular and all-cause survival by Kaplan-Meier and Cox regression.

Results: YKL-40 levels were associated with declining ankle-brachial index (ABI) in PAD patients without Moenckeberg's mediasclerosis (R = -0.189, p=0.002). PAD patients with mediasclerosis exhibited higher YKL-40 levels (p=0.002). Baseline YKL-40 levels were significantly associated with cardiovascular mortality (HR 1.52 (1.21-1.91), p < 0.001) and all-cause mortality (HR 1.45 (1.20-1.75), p < 0.001) over a seven-year observation period. After multivariable adjustment for gender, patient age, known carotid artery disease, known coronary artery disease, smoking status, systolic blood pressure, HbA, low density lipoprotein cholesterol, estimated glomerular filtration rate, aspartate aminotransferase, and C-reactive protein, YKL-40 remained significantly associated with cardiovascular (HR 1.34 (1.02-1.75), p=0.033) and all-cause mortality (HR 1.25 (1.01-1.55), p=0.039).

Conclusions: Increased YKL-40 levels are independently associated with poor long-term cardiovascular survival in peripheral arterial disease patients. Furthermore, YKL-40 correlates with patients' ABI in PAD in the absence of mediasclerosis.
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http://dx.doi.org/10.1016/j.atherosclerosis.2018.05.006DOI Listing
July 2018

Angiopoietin-2 and Survival in Peripheral Artery Disease Patients.

Thromb Haemost 2018 04 4;118(4):791-797. Epub 2018 Apr 4.

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

Survival of peripheral arterial disease (PAD) patients increased over the last decade due to increased use of secondary preventive medication and rapid revascularization of PAD patients. Angiogenetic markers such as vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2) and its receptor Tie-2 might be useful markers to assess the residual risk for mortality in PAD patients. The aim of this study was to evaluate angiogenetic markers for the prediction of mortality in a PAD cohort. For this purpose, 366 patients (mean age: 69 ± 10 years) with PAD Fontaine stage I or II were included and followed up over a 5-year study period. Serum Ang-2, Tie-2 and VEGF levels were measured by bead-based multiplex assay. All-cause mortality and major cardiovascular events (MACE) including all-cause death, non-fatal stroke and non-fatal myocardial infarction were analysed by Kaplan-Meier and Cox regression analyses after 5 years. Ang-2 was associated with Tie-2 ( = 0.151,  = 0.006) and VEGF levels ( = 0.160,  = 0.002). However, only Ang-2 was linked to all all-cause mortality in PAD patients (hazard ratio [HR]: 1.55 [1.23-2.15],  = 0.008) even after adjustment for age and gender, haemoglobin A1c, low-density lipoprotein cholesterol, systolic blood pressure and glomerular filtration rate (HR: 1.44 [1.03-2.00],  = 0.032). Furthermore, an association of Ang-2 and MACE in PAD patients (HR: 1.36 (1.03-1.78),  = 0.028) was found. This result implies that Ang-2 might be used as an additional marker to stratify PAD patients to predict poor mid-term life expectancy.
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http://dx.doi.org/10.1055/s-0038-1636543DOI Listing
April 2018

Low Levels of High-Density Lipoprotein Cholesterol Are Linked to Impaired Clopidogrel-Mediated Platelet Inhibition.

Angiology 2018 Oct 26;69(9):786-794. Epub 2018 Feb 26.

1 Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.

Low high-density lipoprotein cholesterol (HDL-C) levels are an independent predictor of ischemic events in patients with atherosclerotic cardiovascular disease. This may in part be due to decreased clopidogrel-mediated platelet inhibition in patients with low HDL-C. We investigated the association of HDL-C with on-treatment platelet reactivity to adenosine diphosphate (ADP) in 314 patients on dual antiplatelet therapy with clopidogrel and aspirin undergoing angioplasty and stenting. Platelet P-selectin expression was assessed by flow cytometry, and platelet aggregation was determined by the VerifyNow P2Y assay and the Impact-R. High-density lipoprotein cholesterol levels were inversely associated with P-selectin expression and the VerifyNow P2Y assay (both P ≤ .01). Moreover, we found a positive correlation of HDL-C with surface coverage by the Impact-R ( P = .003). Patients with low HDL-C (≤35 mg/dL) exhibited a significantly higher P-selectin expression in response to ADP and higher platelet aggregation by the VerifyNow P2Y assay and the Impact-R than patients with normal HDL-C (>35 mg/dL; all P < .05). High on-treatment residual platelet reactivity by the VerifyNow P2Y assay occurred significantly more frequently in patients with low HDL-C levels than in those with normal HDL-C (47.4% vs 30.1%, P = .01). In conclusion, low HDL-C is linked to impaired clopidogrel-mediated platelet inhibition after angioplasty and stenting.
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http://dx.doi.org/10.1177/0003319718760074DOI Listing
October 2018

Circulating microRNAs identify patients at increased risk of in-stent restenosis after peripheral angioplasty with stent implantation.

Atherosclerosis 2018 02 16;269:197-203. Epub 2018 Jan 16.

Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria. Electronic address:

Background And Aims: Target lesion restenosis is the most frequent complication after angioplasty and stenting for peripheral artery disease (PAD). MicroRNAs (miRs) regulate crucial pathophysiological processes leading to in-stent restenosis and thrombosis. The aim of this study was to investigate the predictive value of 11 miRs for the composite endpoint of target lesion restenosis and atherothrombotic events (primary endpoint), and target vessel revascularization (TVR, secondary endpoint) in 62 consecutive PAD patients after infrainguinal angioplasty with stent implantation.

Methods: Circulating miRs were assessed using quantitative real-time polymerase chain reactions.

Results: Within the 2 years of follow-up, the primary endpoint occurred in 26 patients (41.9%), and 21 patients (33.9%) underwent TVR. miR-92a and miR-195 were identified as independent predictors of the primary endpoint after adjustment for age, sex and clinical risk factors with respective HR per 1 increase of standard deviation (1-SD) of 0.55 (95% CI: 0.34-0.88, p = 0.013) and HR per 1-SD of 0.40 (95% CI: 0.23-0.68, p = 0.001). MiR-195 independently predicted TVR with HR per 1-SD of 0.40 (95% CI: 0.22-0.75, p = 0.005). Adding miR-195 to clinical risk factors improved Harrell's C-index to 0.75 (95% CI: 0.66-0.85, p = 0.03) and was superior to a model with miR-92a (C-index: 0.70, 95% CI: 0.60-0.80, p for comparison =0 .012). Assessment of both miR-92a and miR-195 had no incremental value when compared to miR-195 alone (C-index: 0.79, 95% CI: 0.69-0.88, p = 0.313).

Conclusions: Circulating miR-195 predicts adverse ischemic events and TVR after infrainguinal angioplasty with stent implantation. MiR-195 could improve risk stratification after peripheral endovascular revascularizations.
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http://dx.doi.org/10.1016/j.atherosclerosis.2018.01.020DOI Listing
February 2018

Sublingual functional capillary rarefaction in chronic heart failure.

Eur J Clin Invest 2018 Feb 14;48(2). Epub 2017 Dec 14.

Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.

Background And Objective: Microcirculatory changes contribute to clinical symptoms and disease progression in chronic heart failure (CHF). A depression of coronary flow reserve is associated with a lower myocardial capillary density in biopsies. We hypothesized that changes in cardiac microcirculation might also be reflected by a systemic reduction in capillaries and visualized by sublingual videomicroscopy. The aim was to study in vivo capillary density and glycocalyx dimensions in patients with CHF vs healthy controls.

Methods: Fifty patients with ischaemic and nonischaemic CHF and standard treatment were compared to 35 healthy age-matched subjects in a prospective cross-sectional study. Sublingual microcirculation was visualized using a sidestream darkfield videomicroscope. Functional and perfused total capillary densities were compared between patients and controls. A reduced glycocalyx thickness was measured by an increased perfused boundary region (PBR).

Results: Median functional and total perfused capillary densities were 30% and 45% lower in patients with CHF (both P < .001). Intake of oral vitamin K antagonists was associated with significantly lower capillary densities (P < .05), but not independent of NT-proBNP. Dimensions of the glycocalyx were marginally lower in CHF patients than in healthy controls (<7% difference). However, PBR correlated significantly with inflammation markers (fibrinogen: r = .58; C-reactive protein: r = .42), platelet counts (r = .36) and inversely with measures of liver/renal function such as bilirubin (r = -.38) or estimated glomerular filtration rate (r = -.34) in CHF patients.

Conclusion: CHF patients have got a markedly lower functional and total perfused capillary density in sublingual microvasculature when compared to controls, indicating a systemic decrease in microcirculation.
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http://dx.doi.org/10.1111/eci.12869DOI Listing
February 2018

Decreased platelet inhibition by P2Y12 receptor blockers in anaemia.

Eur J Clin Invest 2018 Jan 7;48(1). Epub 2017 Dec 7.

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

Background: Anaemic patients undergoing angioplasty and stenting are at an increased risk of ischaemic events, which may be caused by an inadequate response to antiplatelet therapy with adenosine diphosphate (ADP) P2Y inhibitors. In the current study, we investigated the associations between anaemia and on-treatment platelet reactivity in clopidogrel-treated (group 1, n = 306) and prasugrel-/ticagrelor-treated (group 2, n = 109) patients undergoing elective and acute angioplasty with stent implantation, respectively.

Materials And Methods: Monocyte-platelet aggregate (MPA) formation was determined by flow cytometry in both groups. On-treatment residual platelet reactivity in response to ADP was assessed by light transmission aggregometry (LTA) in both groups, and by the VerifyNow P2Y assay and the Impact-R in group 1. P-selectin expression was measured by flow cytometry in group 2.

Results: In both groups, anaemia was associated with significantly higher MPA formation in response to ADP (both P ≤ .02). Moreover, by LTA maximal aggregation in response to ADP was significantly higher in patients with anaemia in both groups (both P < .05), and anaemic patients in group 1 had a significantly higher on-treatment platelet reactivity by the VerifyNow P2Y assay and the Impact-R than those without anaemia (both P < .001). In group 2, significantly higher platelet surface expression of P-selectin was seen in anaemia after stimulation with ADP (P = .02).

Conclusion: Anaemia is associated with decreased platelet inhibition by ADP P2Y receptor antagonists after elective and acute percutaneous interventions with stent implantation. However, due to inconsistencies between different platelet function tests additional data are needed to clarify the role of anaemia for platelet inhibition.
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http://dx.doi.org/10.1111/eci.12861DOI Listing
January 2018

Drug coated balloons in the superficial femoral artery.

J Cardiovasc Surg (Torino) 2018 Feb 20;59(1):60-69. Epub 2017 Sep 20.

Vascular Center Arnsberg Clinic, Arnsberg, Germany.

Despite the progress in endovascular treatment of patients with peripheral arterial disease, restenosis remains the major drawback, especially in patients with femoropopliteal lesions. To reduce neointimal proliferation and subsequent restenosis the use of antiproliferative drug eluting devices was implemented in the endovascular treatment of femoropopliteal disease. Aiming to use the favorable effects of these antiproliferative agents and to reduce foreign body exposure in affected arteries, drug coated balloons (DCB) have been developed. Up to now, several randomized controlled trials have consistently demonstrated the superiority of DCB over uncoated balloon angioplasty in the treatment of femoropopliteal lesions. Similarly, DCB appear to have favorable effects on vessel patency in the treatment of femoropopliteal in-stent restenosis. However, there still is a need for further studies, especially addressing different lesion characteristics as well as the combinations of particular treatment modalities.
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http://dx.doi.org/10.23736/S0021-9509.17.10214-4DOI Listing
February 2018

FABP4 and Cardiovascular Events in Peripheral Arterial Disease.

Angiology 2018 May 29;69(5):424-430. Epub 2017 Aug 29.

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

Fatty acid-binding protein 4 (FABP4) is a possible biomarker of atherosclerosis. We evaluated FABP4 levels, for the first time, in patients with peripheral artery disease (PAD) and the possible association between baseline FABP4 levels and cardiovascular events over time. Patients (n = 327; mean age 69 ± 10 years) with stable PAD were enrolled in this study. Serum FABP4 was measured by bead-based multiplex assay. Cardiovascular events were analyzed by FABP4 tertiles using Kaplan-Meier and Cox regression analyses after 5 years. Serum FABP4 levels showed a significant association with the classical 3-point major adverse cardiovascular event (MACE) end point (including death, nonlethal myocardial infarction, or nonfatal stroke) in patients with PAD ( P = .038). A standard deviation increase of FABP4 resulted in a hazard ratio (HR) of 1.33 (95% confidence interval [95% CI]: 1.03-1.71) for MACE. This association increased (HR: 1.47, 95% CI: 1.03-1.71) after multivariable adjustment ( P = .020). Additionally, in multivariable linear regression analysis, FABP4 was linked to estimated glomerular filtration rate ( P < .001), gender ( P = .005), fasting triglycerides ( P = .048), and body mass index ( P < .001). Circulating FABP4 may be a useful additional biomarker to evaluate patients with stable PAD at risk of major cardiovascular complications.
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http://dx.doi.org/10.1177/0003319717728226DOI Listing
May 2018

Disaggregation Following Agonist-Induced Platelet Activation in Patients on Dual Antiplatelet Therapy.

J Cardiovasc Transl Res 2017 Aug 19;10(4):359-367. Epub 2017 Apr 19.

Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Disaggregation as the difference between maximal and final platelet aggregation by light transmission aggregometry indicates the stability of platelet aggregates. We evaluated the extent of disaggregation after platelet stimulation with adenosine diphosphate (ADP), arachidonic acid (AA), collagen, epinephrine, and thrombin receptor-activating peptide (TRAP)-6 in 323 patients on dual antiplatelet therapy with daily aspirin and clopidogrel (group 1), prasugrel (group 2), or ticagrelor (group 3) therapy. All patients in group 1 underwent elective angioplasty and stenting, whereas all patients included in groups 2 and 3 suffered from acute coronary syndromes (STEMI or NSTEMI) and underwent urgent PCI. Significant differences between maximal and final platelet aggregation were observed with all agonists throughout the groups (all p<0.001). Disaggregation was highest using AA (clopidogrel 36.5%; prasugrel/ticagrelor 100%) and ADP (clopidogrel 21.7%; prasugrel/ticagrelor 100%). In contrast, low disaggregation was observed after platelet stimulation with collagen and TRAP-6 in clopidogrel-treated patients, and after platelet stimulation with collagen and epinephrine in prasugrel- and ticagrelor-treated patients. In conclusion, pathways of platelet activation that are not inhibited by standard antiplatelet therapy allow persisting platelet aggregation and may at least in part be responsible for adverse ischemic events.
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http://dx.doi.org/10.1007/s12265-017-9746-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585279PMC
August 2017
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