Vorarlberg Institute for Vascular Investigation and Treatment

Feldkirch, Austria

Vorarlberg Institute for Vascular Investigation and Treatment

Feldkirch, Austria
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Holiner I.,Academic Teaching Hospital | Holiner I.,University of Liechtenstein | Haslinger V.,Academic Teaching Hospital | Lutschg J.,Academic Teaching Hospital | And 9 more authors.
Pediatric Neurology | Year: 2013

The aim of this study was to evaluate the prevalence of diabetic peripheral neuropathy in children and adolescents with type 1 diabetes mellitus and examine whether the neurological examination validly diagnoses diabetic peripheral neuropathy as compared with the gold standard of nerve conduction velocity in these patients. Nerve conduction velocity was measured in an unselected consecutive series of patients aged 8-18 years who had been suffering from type 1 diabetes mellitus for at least 1 year. For the neurological examination, neuropathy disability scores and neuropathy sign scores were used. Of the 39 patients, six (15%) had clinically evident diabetic peripheral neuropathy, whereas nerve conduction velocity testing revealed diabetic peripheral neuropathy in 15 (38%) patients. Sensitivity and specificity of the neurological examination for the diagnosis of diabetic peripheral neuropathy were 40% and 100%, respectively. The corresponding positive and negative predictive values were 100% and 72.7%, respectively. This conclusions from this study are that in children and adolescents with type 1 diabetes mellitus, diabetic peripheral neuropathy is highly prevalent, but in the majority of patients it is subclinical. Sensitivity and negative predictive values of the neurological examination are low. Therefore, routine nerve conduction velocity measurement for the assessment of diabetic peripheral neuropathy appears to be warranted in these patients. © 2013 Elsevier Inc. All rights reserved.

Muendlein A.,Vorarlberg Institute for Vascular Investigation and Treatment | Muendlein A.,University of Liechtenstein | Gasser K.,Vorarlberg Institute for Vascular Investigation and Treatment | Gasser K.,University of Liechtenstein | And 22 more authors.
American Journal of Hematology | Year: 2014

The JAK2 V617F mutation is not only found in the majority of patients with myeloproliferative neoplasms (MPN), including essential thrombocythemia (ET), but also has been reported in individuals without overt MPN. A close relation of the JAK2 V617F mutation to atherothrombotic events has been described, at least in patients with MPN. The prevalence of the JAK2 V617F mutation and its clinical impact in coronary patients is unknown. To address this issue, DNA samples from 1,589 subjects undergoing coronary angiography with up to 11 years of follow up were genotyped using allele-specific real-time PCR assays. Prevalence of the JAK2 V617F mutation was 1.32% (n=21) in coronary patients. Two JAK2 V617F positive patients showed baseline platelet counts indicative for ET and a third patient developed ET during follow up, finally resulting in a percentage of 0.188% of ET cases. This corresponds to an up to fivefold accumulation of ET cases in coronary patients compared with the general population. Our study showed no impact of the JAK2 V617F mutation on future atherothrombotic events or overall survival (HR=1.04 [0.33-3.27]; P=0.949 and HR=0.35 [0.05-2.46]; P=0.288, respectively). Therefore, our data suggest that JAK2 V617F positive coronary patients are not at increased risk for future atherothrombotic complications. Routine mutation screening in coronary patients is, therefore, not warranted. However, number of ET cases appears to be accumulated in coronary patients. For this reason, we recommend JAK2 V617F testing only in coronary patients showing abnormal blood cell counts for further clarification. © 2013 Wiley Periodicals, Inc.

Rein P.,Vorarlberg Institute for Vascular Investigation and Treatment | Rein P.,Academic Teaching Hospital Feldkirch | Rein P.,University of Liechtenstein | Saely C.H.,Vorarlberg Institute for Vascular Investigation and Treatment | And 12 more authors.
Diabetes Care | Year: 2010

OBJECTIVE - The metabolic syndrome (MetS) and coronary artery disease (CAD) frequently coincide; their individual contribution to inflammation is unknown. RESEARCH DESIGN AND METHODS - We enrolled 1,010 patients undergoing coronary angiography. Coronary stenoses ≥50% were considered significant. The MetS was defined according to American Heart Association - revised National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS - C-reactive protein (CRP) did not differ between patients with significant CAD and subjects without significant CAD (P = 0.706) but was significantly higher in MetS patients than in those without MetS (P < 0.001). The MetS criteria low HDL cholesterol (P < 0.001), large waist (P < 0.001), high glucose (P < 0.001), and high blood pressure (P = 0.016), but not high triglycerides (P = 0.352), proved associated with CRP. When all MetS traits were considered simultaneously, only low HDL cholesterol proved independently associated with CRP (F = 44.19; P < 0.001). CONCLUSIONS - CRP is strongly associated with the MetS but not with coronary atherosclerosis. The association of the MetS with subclinical inflammation is driven by the low HDL cholesterol feature. © 2010 by the American Diabetes Association.

Muendlein A.,Vorarlberg Institute for Vascular Investigation and Treatment | Muendlein A.,University of Liechtenstein | Saely C.H.,Vorarlberg Institute for Vascular Investigation and Treatment | Saely C.H.,University of Liechtenstein | And 20 more authors.
PLoS ONE | Year: 2011

Background: Coronary artery disease (CAD) shares common risk factors with type 2 diabetes (T2DM). Variations in the transcription factor 7-like 2 (TCF7L2) gene, particularly rs7903146, increase T2DM risk. Potential links between genetic variants of the TCF7L2 locus and coronary atherosclerosis are uncertain. We therefore investigated the association between TCF7L2 polymorphisms and angiographically determined CAD in diabetic and non-diabetic patients. Methodology/Principal Findings: We genotyped TCF7L2 variants rs7903146, rs12255372, and rs11196205 in a cross-sectional study including 1,650 consecutive patients undergoing coronary angiography for the evaluation of established or suspected stable CAD. Significant CAD was diagnosed in the presence of coronary stenoses ≥50%. Variant rs7903146 in the total study cohort was significantly associated with significant CAD (adjusted additive OR = 1.29 [1.09-1.53]; p = 0.003). This association was strong and significant in T2DM patients (n = 393; OR = 1.91 [1.32-2.75]; p = 0.001) but not in non-diabetic subjects (OR = 1.09 [0.90-1.33]; p = 0.370). The interaction risk allele by T2DM was significant (pinteraction = 0.002), indicating a significantly stronger impact of the polymorphism on CAD in T2DM patients than in non-diabetic subjects. TCF7L2 polymorphisms rs12255372 and rs11196205 were also significantly associated with CAD in diabetic patients (adjusted additive OR = 1.90 [1.31-2.74]; p = 0.001 and OR = 1.75 [1.22-2.50]; p = 0.002, respectively). Further, haplotype analysis demonstrated that haplotypes including the rare alleles of all investigated variants were significantly associated with CAD in the whole cohort as well as in diabetic subjects (OR = 1.22 [1.04-1.43]; p = 0.013 and OR = 1.67 [1.19-2.22]; p = 0.003, respectively). Conclusions/Significance: These results suggest that TCF7L2 variants rs7903146 rs12255372, and rs11196205 are significantly associated with angiographically diagnosed CAD, specifically in patients with T2DM. TCF7L2 therefore appears as a genetic link between diabetes and atherosclerosis. © 2011 Muendlein et al.

Puig L.,Autonomous University of Barcelona | Strohal R.,Academic Teaching Hospital Feldkirch | Fuiman J.,Pfizer | Pedersen R.,Pfizer | And 6 more authors.
Journal of Dermatological Treatment | Year: 2014

Objective: To assess cardiometabolic biomarkers in patients with psoriasis before and after etanercept treatment. Methods: Patients with moderate-to-severe plaque psoriasis were randomized to etanercept 50mg once or twice weekly, double-blinded. Cardiometabolic biomarkers were assessed at baseline and after 12 weeks of treatment (n=273). Results: At baseline, 42% of patients had metabolic syndrome. Etanercept was not associated with any clinically relevant adverse effects on cardiometabolic biomarkers. In the once-weekly subgroup, significant mean percentage changes from baseline (p<0.05) were observed for the quantitative insulin-sensitivity check index (QUICKI; -2.2%), apolipoprotein (Apo) A1 (3.2%), Apo B:Apo A1 ratio (-3.5%), leptin (8.6%) and high-sensitivity C-reactive protein (hsCRP) (-65.5%); and in the twice-weekly subgroup for plasma insulin (15.9%), QUICKI (-2.7%), high-density lipoprotein cholesterol (HDL-C; 2.9%), apolipoprotein (Apo) A1 (2.8%), Apo B:Apo A1 (-4.6%) and hsCRP (-74.4%). Conclusion: Metabolic syndrome was common in these patients with moderate-to-severe psoriasis. Etanercept treatment may provide some potentially favorable modulation of insulin sensitivity, HDL-C, Apo A1 and Apo B:Apo A1 ratio. © 2014 Informa UK Ltd. All rights reserved.

PubMed | Drexel University, Vorarlberg Institute for Vascular Investigation and Treatment and University of Liechtenstein
Type: Comparative Study | Journal: The American journal of cardiology | Year: 2014

Chronic kidney disease increases cardiovascular risk and all-cause mortality. However, data on the predictive power of dynamic changes in kidney function are sparse. The aim of this research was to assess the predictive power of serial changes in kidney function on mortality and cardiovascular risk. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation at baseline and at follow-up in a high-risk population of 619 consecutive patients who underwent coronary angiography. The population was stratified into 3 groups with respect to decreases in eGFR: stable kidney function (no decrease in eGFR) versus a mild decline (decrease in eGFR >0 but <4 ml/min/1.73 m(2) per year) and a rapid decline in kidney function (decrease in eGFR 4 ml/min/1.73 m(2) per year). Mortality and nonfatal cardiovascular events were recorded over 4 years. Baseline coronary angiography revealed significant coronary stenoses (50%) in 368 patients (60%). Survival and event-free survival were significantly lower in patients with rapid decreases in eGFR compared with those with mild decreases (p <0.001 and p = 0.012, respectively) and stable kidney function (p <0.001 and p = 0.004, respectively). After multivariate adjustment in Cox regression analyses, the continuous variable decline in kidney function significantly predicted death (standardized adjusted hazard ratio 1.32, 95% confidence interval 1.03 to 1.70, p = 0.032) and the incidence of the composite end point death and nonfatal vascular events (hazard ratio 1.20, 95% confidence interval 1.01 to 1.43, p = 0.038). A 5 ml/min/1.73 m(2) decrease in eGFR independently conferred a 60% increase in mortality risk (p = 0.032). In conclusion, a rapid decline in kidney function is a powerful and independent new risk marker for death and vascular events.

PubMed | Vorarlberg Institute for Vascular Investigation and Treatment
Type: | Journal: BMC cancer | Year: 2012

The newly discovered metastasis-associated in colon cancer-1 (MACC1) gene is a key regulator of the HGF/MET pathway. Deregulation of HGF/MET signaling is reported as a prognostic marker for tumorigenesis, early stage invasion, and metastasis. High expression levels of MACC1 have been associated with colon cancer metastasis and reduced survival. Potential links between the genetic diversity of the MACC1 locus and overall survival are unknown. We therefore investigated the association between MACC1 tagging single nucleotide polymorphisms (SNPs) and overall survival in a large cohort of colorectal cancer patients.The study included 318 subjects with histopathologically proven colorectal cancer at the Academic Teaching Hospital Feldkirch, Austria. Survival data were provided by the federal agency for statistics in Austria. Genomic DNA was isolated from formalin-fixed paraffin-embedded specimens; six tagging SNPs (rs1990172, rs3114446, rs10275612, rs3095007, rs3095009, and rs7780032), capturing most of the common variants of the MACC1 locus, were genotyped by SNaPshot assays.Over a mean follow up period of 5.3 ( 1.0) years, 94 deaths were recorded. Carriers of the G-allele of SNP rs1990172 showed a significantly decreased overall survival (additive HR = 1.38 [1.05-1.82]; p = 0.023). Multivariate analysis adjusted for age and UICC tumor stage confirmed this result (HR = 1.49 [1.12-1.98]; p = 0.007). Other investigated genetic variants of the MACC1 gene were not significantly associated with overall survival (p-values > 0.05).For the first time, our study investigated the influence of MACC1 tagging polymorphisms on overall survival suggesting SNP rs1990172 as a predictor for reduced overall survival in colorectal cancer patients. Further studies will be required to validate our findings.

PubMed | Vorarlberg Institute for Vascular Investigation and Treatment
Type: Journal Article | Journal: European journal of preventive cardiology | Year: 2013

Exercise is a cornerstone of cardiovascular prevention. Because many individuals are not willing or not able to perform regular exercise, new methods of exercise (like eccentric exercise) are necessary. Eccentric endurance exercise is supposed to be less strenuous than concentric exercise but its effects on glucose and lipid metabolism in relation to energy expenditure are unclear.We randomly allocated 45 healthy sedentary individuals to one of two groups, each hiking upwards or downwards for 2 months, with a crossover for a further 2 months; for the opposite way, a cable car was used. The difference in altitude was 540 metres; the distance was covered between three and five times a week. Energy expenditure was assessed for each hiking period.Both eccentric and concentric endurance exercise improved glucose tolerance vs. baseline (by 4.1%, p = 0.136; 6.2%, p = 0.023, respectively). Of note, adjustment for energy expenditure per exercise unit (127 22 kcal/unit with eccentric and 442 78 kcal/unit with concentric exercise) revealed a significantly greater improvement of glucose tolerance per kilocalorie spent by eccentric than by concentric exercise (4-times more economical; 0.1123 mg h/dl/kcal vs. 0.0245 mg h/dl/kcal; p = 0.038). Also the decrease of low-density lipoprotein (LDL) cholesterol per kilocalorie spent was significantly stronger with eccentric exercise (0.0982 mg/dl/kcal vs. 0.0346 mg/dl/kcal, p = 0.014). Serum levels of C-reactive protein and creatine kinase activity were reduced in both groups.Eccentric endurance exercise economically improves glucose tolerance and LDL cholesterol. It therefore is a promising new exercise modality for individuals who are not able to participate in more strenuous exercise regimens.

PubMed | Vorarlberg Institute for Vascular Investigation and Treatment
Type: Journal Article | Journal: International journal of cardiology | Year: 2013

We prospectively evaluated to what extent pre-existing coronary artery disease (CAD) accounts for the increased vascular event risk of patients with type 2 diabetes (T2DM).Vascular events were recorded over 8 years in 750 consecutive patients whose baseline CAD state was verified angiographically.The baseline prevalence of CAD (87.8% vs. 80.4%; p=0.029) and of significant coronary stenoses 50% (69.5% vs. 58.4%; p=0.010) as well as the extent of CAD, i.e. the number of significant coronary stenoses (1.7 1.6 vs. 1.4 1.5; p=0.014) was higher in patients with T2DM (n=164) than in non-diabetic subjects. During follow-up, T2DM predicted vascular events (n=257) independently from the presence and extent of baseline CAD (HR 1.36 [1.03-1.81]; p=0.032); conversely, the presence and extent of baseline CAD predicted vascular events independently from T2DM (HRs 3.29 [1.93-5.64]; p<0.001 and 1.37 [1.23-1.53]; p<0.001, respectively). The relative risk increase conferred by T2DM was not significantly modulated by the presence of baseline CAD (p(interaction)=0.415). However, in absolute terms the risk increase conferred by T2DM was driven by an extremely high 53.5% event rate of patients with both T2DM and significant CAD at baseline; individuals with T2DM but without significant baseline CAD showed a significantly lower event rate (22.0%; p<0.001).T2DM and angiographically visualized coronary atherosclerosis are mutually independent predictors of vascular events. The overall risk increase conferred by T2DM is driven by accelerated progression of pre-existing atherosclerosis to clinical cardiovascular events; vascular risk is much lower in diabetic patients without pre-existing significant CAD.

PubMed | Vorarlberg Institute for Vascular Investigation and Treatment
Type: Journal Article | Journal: Vascular pharmacology | Year: 2013

Type 2 diabetes mellitus is an inflammatory disease and the mechanisms that underlie this disease, although still incompletely understood, take place in the adipose tissue of obese subjects. Concurrently, the prevalence of obesity caused by Western diets excessive energy intake and the lack of exercise escalates, and is believed to be causative for the chronic inflammatory state in adipose tissue. Overnutrition itself as an overload of energy may induce the adipocytes to secrete chemokines activating and attracting immune cells to adipose tissue. But also inflammation-mediating food ingredients like saturated fatty acids are believed to directly initiate the inflammatory cascade. In addition, hypoxia in adipose tissue as a direct consequence of obesity, and its effect on gene expression in adipocytes and surrounding cells in fat tissue of obese subjects appears to play a central role in this inflammatory response too. In contrast, revisiting diet all over the world, there are also some natural food products and beverages which are associated with curative effects on human health. Several natural compounds known as spices such as curcumin, capsaicin, and gingerol, or secondary plant metabolites catechin, resveratrol, genistein, and quercetin have been reported to provide an improved health status to their consumers, especially with regard to diabetes, and therefore have been investigated for their anti-inflammatory effect. In this review, we will give an overview about these phytochemicals and their role to interfere with inflammatory cascades in adipose tissue and their potential for fighting against inflammatory diseases like diabetes as investigated in vivo.

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