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Vienna, Austria

Huelsmann M.,Medical University of Vienna | Neuhold S.,Medical University of Vienna | Resl M.,Medical University of Vienna | Strunk G.,University of Technology | And 8 more authors.
Journal of the American College of Cardiology | Year: 2013

Objectives The study sought to assess the primary preventive effect of neurohumoral therapy in high-risk diabetic patients selected by N-terminal pro-B-type natriuretic peptide (NT-proBNP). Background Few clinical trials have successfully demonstrated the prevention of cardiac events in patients with diabetes. One reason for this might be an inaccurate selection of patients. NT-proBNP has not been assessed in this context. Methods A total of 300 patients with type 2 diabetes, elevated NT-proBNP (>125 pg/ml) but free of cardiac disease were randomized. The "control" group was cared for at 4 diabetes care units; the "intensified" group was additionally treated at a cardiac outpatient clinic for the up-titration of renin-angiotensin system (RAS) antagonists and beta-blockers. The primary endpoint was hospitalization/death due to cardiac disease after 2 years. Results At baseline, the mean age of the patients was 67.5 ± 9 years, duration of diabetes was 15 ± 12 years, 37% were male, HbA1c was 7 ± 1.1%, blood pressure was 151 ± 22 mm Hg, heart rate was 72 ± 11 beats/min, median NT-proBNP was 265.5 pg/ml (interquartile range: 180.8 to 401.8 pg/ml). After 12 months there was a significant difference between the number of patients treated with a RAS antagonist/beta-blocker and the dosage reached between groups (p < 0.0001). Blood pressure was significantly reduced in both (p < 0.05); heart rate was only reduced in the intensified group (p = 0.004). A significant reduction of the primary endpoint (hazard ratio: 0.351; 95% confidence interval: 0.127 to 0.975, p = 0.044) was visible in the intensified group. The same was true for other endpoints: all-cause hospitalization, unplanned cardiovascular hospitalizations/death (p < 0.05 for all). Conclusions Accelerated up-titration of RAS antagonists and beta-blockers to maximum tolerated dosages is an effective and safe intervention for the primary prevention of cardiac events for diabetic patients pre-selected using NT-proBNP. (Nt-proBNP Guided Primary Prevention of CV Events in Diabetic Patients [PONTIAC]; NCT00562952). © 2013 by the American College of Cardiology Foundation.

Smolen J.S.,Medical University of Vienna | Braun J.,Rheumazentrum Ruhrgebiet | Dougados M.,University of Paris Descartes | Emery P.,University of Leeds | And 29 more authors.
Annals of the Rheumatic Diseases | Year: 2014

Background Therapeutic targets have been defined for diseases like diabetes, hypertension or rheumatoid arthritis and adhering to them has improved outcomes. Such targets are just emerging for spondyloarthritis (SpA). Objective To define the treatment target for SpA including ankylosing spondylitis and psoriatic arthritis (PsA) and develop recommendations for achieving the target, including a treat-to-target management strategy. Methods Based on results of a systematic literature review and expert opinion, a task force of expert physicians and patients developed recommendations which were broadly discussed and voted upon in a Delphi-like process. Level of evidence, grade and strength of the recommendations were derived by respective means. The commonalities between axial SpA, peripheral SpA and PsA were discussed in detail. Results Although the literature review did not reveal trials comparing a treat-to-target approach with another or no strategy, it provided indirect evidence regarding an optimised approach to therapy that facilitated the development of recommendations. The group agreed on 5 overarching principles and 11 recommendations; 9 of these recommendations related commonly to the whole spectrum of SpA and PsA, and only 2 were designed separately for axial SpA, peripheral SpA and PsA. The main treatment target, which should be based on a shared decision with the patient, was defined as remission, with the alternative target of low disease activity. Follow-up examinations at regular intervals that depend on the patient's status should safeguard the evolution of disease activity towards the targeted goal. Additional recommendations relate to extra-articular and extramusculoskeletal aspects and other important factors, such as comorbidity. While the level of evidence was generally quite low, the mean strength of recommendation was 9-10 (10: maximum agreement) for all recommendations. A research agenda was formulated. Conclusions The task force defined the treatment target as remission or, alternatively, low disease activity, being aware that the evidence base is not strong and needs to be expanded by future research. These recommendations can inform the various stakeholders about expert opinion that aims for reaching optimal outcomes of SpA.

Stadler M.,Hietzing Hospital Vienna | Stadler M.,Kings College London | Peric S.,Karl Landsteiner Institute of Metabolic Diseases and Nephrology | Strohner-Kaestenbauer H.,Karl Landsteiner Institute of Metabolic Diseases and Nephrology | And 9 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014

Context and Objective: We investigated long term mortality, requirement for renal replacement therapy (RRT), and incidence of other late diabetic complications in an observational cohort study of 641 people with type 1 diabetes (T1DM). Design: Prospective observational cohort study. Setting: The study was conducted at a Tertiary Diabetes Centre in Vienna, Austria. Patients: Acohort with all people with T1DM (n = 641,47%females, 30 ± 11 years) attending their annual diabetes review was created in 1983-1984. Biomedical data were collected. Main Outcome Measures: In 2013 we investigated mortality rates and incidence rates of RRT by record linkage with national registries and incidence of other major diabetes complications by questionnaire. Results: 156 (24%) patients died [mortality rate: 922 (95%CI: 778-1066) per 100 000 person years]. Fifty-five (8.6%) received RRT [incidence rate: 335 (95%CI: 246-423) per 100 000 person years]. The 380 questionnaires (78% return rate) recorded cardiac events, strokes, limb amputations, and/or blindness, affecting 21.8% of survivors. Mortality and incidence of RRT increased in each quartile of baseline HbA1c, with the lowest rates in the quartile with HbA1c≤6.5% (48 mmol/mol) (P < .05). Conclusions: In people with established type 1 diabetes who were observed for almost three decades, the overall mortality was 24% and the incidence of renal replacement therapy was 8.6%, with a 21.8% combined incidence rate of the other hard endpoints in the surviving people. A clear linear relationship between early glycemic control and the later development of end stage renal disease and mortality has been found. Copyright © 2014 by the Endocrine Society.

Clodi M.,Medical University of Vienna | Resl M.,Medical University of Vienna | Neuhold S.,Medical University of Vienna | Hulsmann M.,Medical University of Vienna | And 7 more authors.
European Journal of Preventive Cardiology | Year: 2012

Aims: Cardiovascular events are the most relevant events in patients with diabetes mellitus. We aimed to compare the predictive values of N-terminal pro-brain natriuretic peptide (NT-proBNP) and the state-of-the-art marker, albuminuria, for cardiac events in diabetic patients. Methods: In this prospective observational study we recruited 1071 patients with diabetes mellitus. NT-proBNP and albuminuria - defined as a urinary albumin/creatinine ratio >30 mg/g - were measured at baseline. Patients were followed during a mean observation period of 33.1 months. A total of 103 patients reached the defined endpoint (unplanned hospitalization due to a cardiac event or death). Results: The mean duration of diabetes was 15 ± 12 years and the mean HbA1c was 7.5 ± 3.1%. At baseline, 23.7% of the patients presented with albuminuria and 36.6% had plasma NT-proBNP values >125 pg/ml. Multiple Cox regression analysis including age, gender, duration of diabetes HbA1c, albuminuria, and lnNT-proBNP revealed that lnNT-proBNP (hazard ratio 2.314; 95% CI 1.914-2.798, p < 0.001) was a better predictor than albuminuria (HR 1.544; 95% CI 1.007-2.368, p = 0.047) or age (HR 1.030; 95% CI 1.008-1.053, p = 0.007). Calculating different Cox-models with (A) albuminuria, (B) NT-proBNP, or (C) both in the model revealed that the C-index was best if NT-proBNP was entered in the model (C-index for A 0.735, for B 0.809, and for C 0.786). Kaplan-Meier analysis demonstrated that albuminuria does not add substantial information if NT-proBNP is entered into the model. Conclusion: NT-proBNP was superior to albuminuria for predicting cardiac events. © 2011 The European Society of Cardiology.

Neuhold S.,Medical University of Vienna | Resl M.,Medical University of Vienna | Huelsmann M.,Medical University of Vienna | Strunk G.,Complexity Research Vienna | And 7 more authors.
European Journal of Clinical Investigation | Year: 2011

Background Patients with diabetes mellitus have a substantially increased risk of developing cardiovascular disease. However, the absolute risk greatly varies not only among patients, but the risk profile for an individual patient may also change over time. We investigated the prognostic role of repetitive measurements of Glycated haemoglobin A 1c (HbA 1c) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with longstanding diabetes. Materials and methods For this prospective, observational study data from 544 consecutive patients were collected between 2005 and 2008. HbA 1c and NT-proBNP were measured at baseline and after 1year. The median observation period was 40months. Endpoints were all-cause mortality, cardiac, cardiovascular and all-cause hospitalizations. Results N-terminal pro-B-type natriuretic peptide concentrations significantly increased from 230±385 to 280±449pgmL -1 (P<0·001); during the same time, HbA 1c significantly decreased from 7·6±1·5 to 7·3±1·2 (P<0·001). NT-proBNP was the best baseline predictor in a Cox regression model consisting of NT-proBNP, HbA 1c, age, gender and duration of diabetes for all endpoints (P<0·001). NT-proBNP at follow-up was the best predictor for the remaining period (P<0·001, all endpoints). HbA 1c at baseline and follow-up was predictive for all-cause hospitalizations (P=0·005 both). In a third model that investigated the plasticity of both markers, changes in HbA 1c concentration had no predictive value, but a change of NT-proBNP concentration was highly predictive (P=0·025 all-cause mortality, P<0·001 all other endpoints). Conclusions N-terminal pro-B-type natriuretic peptide and HbA 1c concentrations significantly diverged over a 1-year period. NT-proBNP was the most potent predictor of outcome at baseline and follow-up, and changes in NT-proBNP concentrations were linked to an altered risk profile, unlike changes in HbA 1c levels. © 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.

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