Heinz Drexel

Publications (57)389.07 Total impact

• Article: [Lipids: diagnosis and therapy in type 2 diabetes.]

  Thomas C Wascher, Bernhard Paulweber, Hermann Toplak, Christoph Saely, Heinz Drexel
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  ABSTRACT: Hyper- and Dyslipidemia contribute to cardiovascular morbidity and mortality in diabetic patients. Pharmacological therapy with statins has convincingly shown to reduce cardiovascular risk in diabetic patients. The present article represents the recommendations of the Austrian Diabetes Association for the use of lipid-lowering drugs in diabetic patients according to current scientific evidence.
  Wiener klinische Wochenschrift 12/2012; · 0.81 Impact Factor
• Article: Association of a common genetic variant of the IGF-1 gene with event-free survival in patients with HER2-positive breast cancer.

  Axel Muendlein, Alois H Lang, Simone Geller-Rhomberg, Thomas Winder, Klaus Gasser, Heinz Drexel, Thomas Decker, Elisabeth Mueller-Holzner, Martina Chamson, Christian Marth, Michael Hubalek
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  ABSTRACT: PURPOSE: Insulin-like growth factor 1 (IGF-1) stimulates mitosis and inhibits apoptosis. High circulating IGF-1 levels are linked with an increased risk of colorectal and breast cancer. Recently, IGF-1 single nucleotide polymorphisms (SNPs), especially variant rs2946834, have been associated with poor clinical outcome in patients with colorectal cancer. In the present study, we aimed to investigate the influence of IGF1 polymorphisms associated with IGF-1 plasma levels on event-free survival in patients with HER2-positive breast cancer. METHODS: The present study included 161 consecutive white patients with HER2-positive breast cancer. Event-free survival was calculated as the time from cancer diagnosis to either relapse or death from any cause. Genomic DNA was extracted from archived formalin-fixed paraffin-embedded tumor tissue samples; five IGF-1 polymorphisms (rs2946834, rs6220, rs1520220, rs5742694, and rs5742678), all associated with IGF-1 levels, were genotyped by SNaPshot assays. RESULTS: Kaplan-Meier analysis showed a poorer clinical outcome for carriers of the rare allele of SNP rs2946834 (log-rank test, p = 0.020). Concordantly, in univariate Cox regression analyses, the rare allele of SNP rs2946834 was significantly associated with a decreased event-free survival (HR = 3.06 [1.14-8.22]; p = 0.027). Multivariate analysis adjusted for age and tumor stage confirmed this result (HR = 4.02 [1.36-11.90]; p = 0.012). Other investigated polymorphisms of the IGF1 gene were not significantly associated with event-free survival (all p values >0.05). CONCLUSIONS: This study provides first evidence that IGF1 rs2946834 polymorphism is associated with clinical outcome of HER2-positive breast cancer patients. Further studies are warranted to validate these findings.
  Journal of Cancer Research and Clinical Oncology 11/2012; · 2.56 Impact Factor
• Article: Phytochemicals and their impact on adipose tissue inflammation and diabetes.

  Andreas Leiherer, Axel Mündlein, Heinz Drexel
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  ABSTRACT: 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 diet's 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.
  Vascular Pharmacology 09/2012; · 1.99 Impact Factor
• Article: Bedeutung der Lipidtherapie bei Diabetes

  Christoph H. Saely, Heinz Drexel
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  ABSTRACT: Das LDL-Cholesterin spielt eine zentrale Rolle in der Pathogenese der Atherogenese, und die primär LDL-Cholesterin-senkenden Statine reduzieren das kardiovaskuläre Risiko bei Patienten mit Diabetes signifikant. Das LDL-Cholesterin ist deshalb in den aktuellen Leitlinien das primäre Ziel der Lipidtherapie. Es sollten alle Patienten mit Typ-2-Diabetes ein LDL-Cholesterin <100 mg/dl erreichen, Höchstrisikopatienten mit der Kombination von Diabetes und koronarer Herzerkrankung ein LDL-Cholesterin <70 mg/dl. In Anbetracht der überwältigenden Evidenz für die Wirksamkeit der Statintherapie sollte die Senkung des LDL-Cholesterins primär durch Statine erfolgen. Bei vielen Patienten ist für eine Senkung des LDL-Cholesterins unter 70 mg/dl eine Hochdosis-Statintherapie erforderlich. Charakteristisch für Patienten mit Typ-2-Diabetes ist eine Fettstoffwechselstörung mit hohen Triglyzeriden, niedrigem HDL-Cholesterin und kleinen, atherogenen LDL-Partikeln, welche ein herausragender Prädiktor für die Inzidenz kardiovaskulärer Ereignisse bei Patienten mit Diabetes ist. Zumindest für die Höchstrisikopatienten mit der Kombination Diabetes plus KHK erscheint deshalb – trotz der aktuell noch unvollständigen Datenlage – eine zusätzliche medikamentöse Therapie dieser diabetischen Dyslipidämie mit Nikotinsäure oder Fibraten eine erwägenswerte Option. LDL cholesterol plays a central role in atherogenesis and LDL lowering statin therapy significantly reduces cardiovascular risk in patients with diabetes. Therefore, LDL cholesterol in current guidelines is the primary target of lipid intervention. All patients with type 2 diabetes should reach an LDL cholesterol of <100 mg/dl, the very-high risk patients with both diabetes and coronary artery disease an LDL cholesterol <70 mg/dl. Given the overwhelming body of evidence for the efficacy of statin therapy with respect to cardiovascular event prevention, LDL cholesterol should primarily be lowered by statins. Many very-high risk patients will require high-dose statin therapy to meet the stringent treatment goal of LDL cholesterol <70 mg/dl. Importantly, patients with type 2 diabetes typically exhibit a pattern of dyslipidemia with high triglycerides, low HDL cholesterol, and small, atherogenic LDL particles, which is a strong predictor of vascular events in patients with diabetes. Despite the currently limited evidence from large clinical endpoint-trials additional treatment of this diabetic dyslipidemia with niacin or fibrates therefore appears a promising option at least in the very-high risk patients with the combination of diabetes and coronary artery disease. SchlüsselwörterDiabetes mellitus-Atherosklerose-Kardiovaskuläres Risiko-Klinische Studien-Lipide-Statine-Nikotinsäure-Fibrate KeywordsDiabetes mellitus-Atherosclerosis-Cardiovascular risk-Clinical trials-Lipids-Statins-Nicotinic acids-Fibrates
  Wiener Medizinische Wochenschrift 04/2012; 160(1):25-29.
• Article: Eccentric endurance exercise economically improves metabolic and inflammatory risk factors.

  Markus Zeppetzauer, Heinz Drexel, Alexander Vonbank, Philipp Rein, Stefan Aczel, Christoph H Saely
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  ABSTRACT: Introduction: 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.Methods: 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.Results: 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.Conclusion: 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.
  European journal of preventive cardiology. 04/2012;
• Article: Type 2 diabetes and the progression of visualized atherosclerosis to clinical cardiovascular events.

  Christoph H Saely, Philipp Rein, Alexander Vonbank, Kurt Huber, Heinz Drexel
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  ABSTRACT: BACKGROUND/OBJECTIVES: 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). METHODS: Vascular events were recorded over 8years in 750 consecutive patients whose baseline CAD state was verified angiographically. RESULTS: 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). CONCLUSIONS: 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.
  International journal of cardiology 04/2012; · 7.08 Impact Factor
• Article: Are AHSG polymorphisms directly associated with coronary atherosclerosis?

  Axel Muendlein, Nicole Stark, Philipp Rein, Christoph H Saely, Simone Geller-Rhomberg, Kathrin Geiger, Alexander Vonbank, Heinz Drexel
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  ABSTRACT: Fetuin-A (AHSG) has been proposed as a new cardiovascular risk factor. Fetuin-A levels as well as AHSG single nucleotide polymorphisms (SNPs) have been associated with intima media thickness and incident vascular events, respectively. However, the association between AHSG variants and angiographically determined coronary artery disease (CAD) has not been reported yet. Therefore, we aimed at investigating the association of AHSG SNPs with angiographically characterized coronary atherosclerosis. We genotyped AHSG variants rs4917, rs2248690, rs2518136, and rs2077119 in a cross-sectional study including 1,649 patients undergoing coronary angiography. Significant CAD was diagnosed in the presence of coronary stenoses ≥50%. Variant rs2077119 deviates significantly from Hardy-Weinberg equilibrium and was excluded from further analysis. Neither under an additive, nor under a recessive or dominant model of inheritance, the association between investigated AHSG variants and angiographically determined CAD reached statistical significance. Haplotypes derived from these AHSG variants also were not significantly associated with coronary lesions. Further, no significant associations between investigated SNPs and the extent or severity of CAD could be observed (all p-values>0.05). Our data do not support a significant direct association between AHSG variants rs4917, rs2248690, and rs2518136 and clinical atherosclerosis as exemplified by angiographically characterized coronary atherosclerosis.
  Clinica chimica acta; international journal of clinical chemistry 01/2012; 413(1-2):287-90. · 2.54 Impact Factor
• Article: The fate of fat: a response.

  Christoph H Saely, Veronika Drexel, Heinz Drexel
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  ABSTRACT: Brown adipose tissue (BAT) activity increases energy expenditure and therefore may facilitate weight loss. The principal physiological trigger for its activation is stimulation of the sympathetic nervous system by decreased ambient temperature. Also, direct pharmacological stimulation of the sympathetic nervous system activates BAT, but sympathomimetics up to now have had only very limited success as weight-lowering agents. More recently, components of other signaling pathways that trigger brown adipocyte development and activity have been investigated as potential treatment targets. These pharmacological options are far from the bedside since safety issues need to be clarified as well as the potentially important role of counter-regulatory energy-sparing mechanisms attenuating the negative energy balance achieved by BAT activation in the long term. However, BAT remains a very important candidate target for antiobesity treatment, a field in which alternative approaches have proved disappointing. Importantly, physical exercise is a nonpharmacological intervention which has the potential to activate BAT, promotes weight loss, has beneficial metabolic effects and may even slow the rate of aging.
  Gerontology 01/2012; 58(2):123-5. · 2.78 Impact Factor
• Article: A common variant of the MACC1 gene is significantly associated with overall survival in colorectal cancer patients.

  Alois H Lang, Simone Geller-Rhomberg, Thomas Winder, Nicole Stark, Klaus Gasser, Bernd Hartmann, Bertram Kohler, Ina Grizelj, Heinz Drexel, Axel Muendlein
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  ABSTRACT: 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.
  BMC Cancer 01/2012; 12:20. · 3.01 Impact Factor
• Article: Insulin resistance is associated with the metabolic syndrome and is not directly linked to coronary artery disease.

  Alexander Vonbank, Christoph H Saely, Philipp Rein, Stefan Beer, Johannes Breuss, Christian Boehnel, Heinz Drexel
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  ABSTRACT: Insulin resistance (IR) is the key feature of the metabolic syndrome (MetS). Its association with directly visualized coronary atherosclerosis is unclear. We hypothesised that insulin resistance is associated with both angiographically determined coronary artery disease (CAD) and with the MetS. In 986 consecutive patients undergoing coronary angiography for the evaluation CAD, IR was determined by the HOMA index; the MetS was defined according to NCEP-ATPIII criteria; and significant CAD was diagnosed when coronary stenoses ≥50% were present. HOMA IR scores were higher in MetS patients than in subjects without the MetS (4.9±6.4 vs. 2.2±2.0; p<0.001). HOMA IR did not differ significantly between patients with significant CAD and those who did not have significant CAD. When both, the presence of MetS and of significant CAD were considered, HOMA IR was significantly higher in patients with the MetS both among those who had significant CAD (4.9±6.8 vs. 2.2±1.8; p<0.001) and among those who did not have significant CAD (5.0±5.8 vs. 2.1±2.3; p<0.001), it did not differ significantly between patients with significant CAD and subjects without significant CAD among patients with the MetS nor among those without MetS. Similar results were obtained with the IDF definition of the MetS. IR is significantly associated with the MetS but not with angiographically determined CAD. IR may play a greater role in the eventual precipitation of thrombosis than in the gradual progression of atherosclerosis.
  Clinica chimica acta; international journal of clinical chemistry 02/2011; 412(11-12):1003-7. · 2.54 Impact Factor
• Article: Relation of albuminuria to angiographically determined coronary arterial narrowing in patients with and without type 2 diabetes mellitus and stable or suspected coronary artery disease.

  Philipp Rein, Alexander Vonbank, Christoph H Saely, Stefan Beer, Vlado Jankovic, Christian Boehnel, Johannes Breuss, Lorenz Risch, Peter Fraunberger, Heinz Drexel
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  ABSTRACT: Albuminuria is associated with atherothrombotic events and all-cause mortality in patients with and without diabetes. However, it is not known whether albuminuria is associated with atherosclerosis per se in the same manner. The present study included 914 consecutive white patients who had been referred for coronary angiography for the evaluation of established or suspected stable coronary artery disease (CAD). Albuminuria was defined as a urinary albumin/creatinine ratio ≥ 30 μg/mg. Microalbuminuria was defined as 30 to 300 μg albumin/mg creatinine, and macroalbuminuria as a urinary albumin/creatinine ratio of ≥ 300 μg/mg. The prevalence of stenoses of ≥ 50% was significantly greater in patients with albuminuria than in those with normoalbuminuria (66% vs 51%; p <0.001). Logistic regression analysis, adjusted for age, gender, diabetes, smoking, hypertension, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, C-reactive protein, body mass index, estimated glomerular filtration rate, and the use of angiotensin-converting enzyme inhibitors/angiotensin II antagonists, aspirin, and statins, confirmed that albuminuria was significantly associated with stenoses ≥ 50% (standardized adjusted odds ratio [OR] 1.68, 95% confidence interval [CI] 1.15 to 2.44; p = 0.007). The adjusted OR was 1.54 (95% CI 1.03 to 2.30; p = 0.034) for microalbuminuria and 2.55 (95% CI 1.14 to 5.72; p = 0.023) for macroalbuminuria. This association was significant in the subgroup of patients with type 2 diabetes (OR 1.66, 95% CI 1.01 to 2.74; p = 0.045) and in those without diabetes (OR 1.42, 95% CI 1.05 to 1.92; p = 0.023). An interaction term urinary albumin/creatinine ratio*diabetes was not significant (p = 0.579). In conclusion, micro- and macroalbuminuria were strongly associated with angiographically determined coronary atherosclerosis in both patients with and those without type 2 diabetes mellitus, independent of conventional cardiovascular risk factors and the estimated glomerular filtration rate.
  The American journal of cardiology 02/2011; 107(8):1144-8. · 3.58 Impact Factor
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  Available from: Alois Lang

  Article: Optimized allele-specific real-time PCR assays for the detection of common mutations in KRAS and BRAF.

  Alois H Lang, Heinz Drexel, Simone Geller-Rhomberg, Nicole Stark, Thomas Winder, Kathrin Geiger, Axel Muendlein
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  ABSTRACT: Mutations in the oncogenes KRAS and BRAF have been identified as prognostic factors in patients with colorectal diseases and as predictors of negative outcome in epidermal growth factor receptor-targeted therapies. Therefore, accurate mutation detection in both genes, KRAS and BRAF, is of increasing clinical relevance. We aimed at optimizing allele-specific real-time PCR assays for the detection of common mutations in KRAS and the BRAF Val600Glu mutation using allele-specific PCR primers for allelic discrimination and probes (TaqMan) for quantification. Each reaction mix contains a co-amplified internal control to exclude false-negative results. Allele-specific real-time PCR assays were evaluated on plasmid model systems providing a mutation detection limit of 10 copies of mutant DNA in proportions as low as 1% of the total DNA. Furthermore, we analyzed 125 DNA samples prepared from archived, formalin-fixed, paraffin-embedded colorectal carcinomas and compared results with those obtained from direct-sequence analysis. All mutations determined by sequence analysis could be recovered by allele-specific PCR assays. In addition, allele-specific PCR assays clearly identified three additional samples affected by a mutation. We propose these allele-specific real-time PCR assays as a low-cost and fast diagnostic tool for accurate detection of KRAS and BRAF mutations that can be applied to clinical samples.
  The Journal of molecular diagnostics: JMD 01/2011; 13(1):23-8. · 3.48 Impact Factor
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  Available from: Andreas Leiherer

  Article: Identification of hypoxia-induced genes in human SGBS adipocytes by microarray analysis.

  Kathrin Geiger, Andreas Leiherer, Axel Muendlein, Nicole Stark, Simone Geller-Rhomberg, Christoph H Saely, Martin Wabitsch, Peter Fraunberger, Heinz Drexel
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  ABSTRACT: Hypoxia in adipose tissue is suggested to be involved in the development of a chronic mild inflammation, which in obesity can further lead to insulin resistance. The effect of hypoxia on gene expression in adipocytes appears to play a central role in this inflammatory response observed in obesity. However, the global impact of hypoxia on transcriptional changes in human adipocytes is unclear. Therefore, we compared gene expression profiles of human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes under normoxic or hypoxic conditions to detect hypoxia-responsive genes in adipocytes by using whole human genome microarrays. Microarray analysis showed more than 500 significantly differentially regulated mRNAs after incubation of the cells under low oxygen levels. To gain further insight into the biological processes, hypoxia-regulated genes after 16 hours of hypoxia were classified according to their function. We identified an enrichment of genes involved in important biological processes such as glycolysis, response to hypoxia, regulation of cellular component movement, response to nutrient levels, regulation of cell migration, and transcription regulator activity. Real-time PCR confirmed eight genes to be consistently upregulated in response to 3, 6 and 16 hours of hypoxia. For adipocytes the hypoxia-induced regulation of these genes is shown here for the first time. Moreover in six of these eight genes we identified HIF response elements in the proximal promoters, specific for the HIF transcription factor family members HIF1A and HIF2A. In the present study, we demonstrated that hypoxia has an extensive effect on gene expression of SGBS adipocytes. In addition, the identified hypoxia-regulated genes are likely involved in the regulation of obesity, the incidence of type 2 diabetes, and the metabolic syndrome.
  PLoS ONE 01/2011; 6(10):e26465. · 4.09 Impact Factor
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  Available from: Alaa Othman

  Article: Bile acid metabolites in serum: intraindividual variation and associations with coronary heart disease, metabolic syndrome and diabetes mellitus.

  Carine Steiner, Alaa Othman, Christoph H Saely, Philipp Rein, Heinz Drexel, Arnold von Eckardstein, Katharina M Rentsch
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  ABSTRACT: Bile acids (BAs) regulate glucose and lipid metabolism. In longitudinal and case-control-studies, we investigated the diurnal variation of serum concentrations of the 15 major BAs as well as the biosynthetic precursor 7α-hydroxy-4-cholesten-3-one (C4) and their associations, respectively, with coronary artery disease (CAD), diabetes mellitus type 2 (T2DM), and non-diabetic metabolic syndrome (MetS). In hourly taken blood samples of four healthy probands, the intraindividual 24 h variation of C4, conjugated and unconjugated BAs ranged from 42% to 72%, from 23% to 91%, and from 49% to 90%, respectively. Conjugated BA concentrations mainly increased following food intake. Serum levels of C4 and unconjugated BAs changed with daytime with maxima varying interindividually between 20h00 and 1h00 and between 3h00 and 8h00, respectively. Comparisons of data from 75 CAD patients with 75 CAD-free controls revealed no statistically significant association of CAD with BAs or C4. Comparisons of data from 50 controls free of T2DM or MetS, 50 MetS patients, and 50 T2DM patients revealed significantly increased fasting serum levels of C4 in patients with MetS and T2DM. Multiple regression analysis revealed body mass index (BMI) and plasma levels of triglycerides (TG) as independent determinants of C4 levels. Upon multivariate and principle component analyses the association of C4 with T2DM and/or MetS was not independent of or superior to the canonical MetS components. In conclusion, despite large intra- and interindividual variation, serum levels of C4 are significantly increased in patients with MetS and T2DM but confounded with BMI and TG.
  PLoS ONE 01/2011; 6(11):e25006. · 4.09 Impact Factor
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  Available from: Thomas Winder

  Article: Single nucleotide polymorphisms of TCF7L2 are linked to diabetic coronary atherosclerosis.

  Axel Muendlein, Christoph H Saely, Simone Geller-Rhomberg, Gudrun Sonderegger, Philipp Rein, Thomas Winder, Stefan Beer, Alexander Vonbank, Heinz Drexel
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  ABSTRACT: 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. 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 (p(interaction) = 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). 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.
  PLoS ONE 01/2011; 6(3):e17978. · 4.09 Impact Factor
• Article: Brown versus white adipose tissue: a mini-review.

  Christoph H Saely, Kathrin Geiger, Heinz Drexel
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  ABSTRACT: Brown adipose tissue (BAT) is abundant in small mammals and in newborns and helps them to survive cold temperatures. In adults, it had long been considered to be absent or at least of no relevance. Recent investigations, however, have fuelled interest in adult BAT. We aimed at (1) summarizing structural and physiological characteristics of BAT versus white adipose tissue (WAT); (2) discussing the development of the two adipose tissue types; (3) reviewing the data available from human studies on BAT, and (4) discussing the impact of aging. We summarize recent descriptions of BAT and WAT based on the original literature and reviews in the field, with emphasis on human BAT. WAT and BAT have essentially antagonistic functions: WAT stores excess energy as triglycerides and BAT is specialized in the dissipation of energy through the production of heat. Considerable amounts of BAT are present in a substantial proportion of adult humans and relatively high quantities of BAT are associated with lower body weight. With increasing age, BAT decreases and body weight increases. Although the available cross-sectional data do not allow definite conclusions to be drawn concerning a causal relationship between loss of BAT and increasing body weight with advancing age or obesity-related metabolic disorders of older age, stimulation of BAT appears to be an attractive novel candidate target for the treatment of age-related obesity.
  Gerontology 12/2010; 58(1):15-23. · 2.78 Impact Factor
• Article: HDL cholesterol and residual risk of first cardiovascular events.

  Christoph H Saely, Alexander Vonbank, Heinz Drexel
  The Lancet 11/2010; 376(9754):1738; author reply 1738-9. · 38.28 Impact Factor
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  Available from: PubMed Central

  Article: Roles of the metabolic syndrome, HDL cholesterol, and coronary atherosclerosis in subclinical inflammation.

  Philipp Rein, Christoph H Saely, Stefan Beer, Alexander Vonbank, Heinz Drexel
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  ABSTRACT: The metabolic syndrome (MetS) and coronary artery disease (CAD) frequently coincide; their individual contribution to inflammation is unknown. We enrolled 1,010 patients undergoing coronary angiography. Coronary stenoses >or=50% were considered significant. The MetS was defined according to American Heart Association-revised National Cholesterol Education Program Adult Treatment Panel III criteria. 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). 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.
  Diabetes care 08/2010; 33(8):1853-5. · 8.09 Impact Factor
• Article: Post-challenge hyperglycaemia is strongly associated with future macrovascular events and total mortality in angiographied coronary patients.

  Harald Sourij, Christoph H Saely, Fabian Schmid, Robert Zweiker, Thomas Marte, Thomas C Wascher, Heinz Drexel
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  ABSTRACT: The prevalence of post-challenge hyperglycaemia in coronary patients is high. Until now, it is unclear whether post-challenge hyperglycaemia is associated with an increased risk for future macrovascular events in this clinically important patient population. We enrolled 1040 patients undergoing coronary angiography for the evaluation of suspected or established coronary artery disease. In patients without previously established diabetes mellitus, an oral glucose tolerance test (oGTT) was performed. Prospectively, mortality and macrovascular events were recorded over a mean follow-up period of 3.8 years. From our patients, 394 had normal glucose tolerance (NGT), 280 post-challenge hyperglycaemia (this subgroup includes both impaired glucose tolerance and post-challenge diabetes) and 366 had conventional diabetes. The incidence of macrovascular events was significantly higher in patients with post-challenge hyperglycaemia as well as in patients with conventional diabetes than in subjects with NGT (23.6 and 29.5% vs. 18.5%; P = 0.013 and P < 0.001, respectively). Adjusted hazard ratios were 1.46 (95% CI 1.03-2.07, P = 0.033) for patients with post-challenge hyperglycaemia and 1.73 (1.25-2.37, P = 0.001) for patients with conventional diabetes. Post-challenge hyperglycaemia is associated with future macrovascular events in patients undergoing coronary angiography for the evaluation of stable coronary artery disease (CAD). Oral glucose tolerance tests in this high-risk population thus identify patients with a particularly unfavourable prognosis.
  European Heart Journal 04/2010; 31(13):1583-90. · 10.48 Impact Factor
• Article: Serial decline of kidney function as a novel biomarker for the progression of atherothrombotic disease.

  Philipp Rein, Christoph H Saely, Axel Muendlein, Alexander Vonbank, Heinz Drexel
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  ABSTRACT: Impaired kidney function is associated with cardiovascular disease. However, from the available data it cannot be discerned which of the two entities presents first and entails the other. If renal dysfunction is first, a dynamic decline in the estimated glomerular filtration rate (eGFR) should predict vascular events and prove a useful biomarker for atherothrombotic disease. We therefore tested the hypothesis that a decrease in kidney function predicts future vascular events in a high-risk population of angiographically characterized coronary patients. We calculated the eGFR by the Mayo clinic quadratic equation at baseline and after two years in a high-risk population of 400 consecutive men undergoing coronary angiography, of whom 355 had coronary artery disease (CAD). Vascular events were recorded over six years. A serial decrease in kidney function from baseline to the follow-up visit two years later significantly predicted vascular events in the subsequent four years independently from the baseline eGFR with a standardized adjusted hazard ratio (HR) of 1.41 (1.13-1.76); p=0.003. This result proved robust after adjustment for age, BMI, hypertension, diabetes, LDL-C, HDL-C, smoking, and high-sensitivity C-reactive protein (HR=1.41 [1.12-1.78]; p=0.004). The predictive power of eGFR loss was confirmed even after further adjustment for the presence of CAD at baseline (HR=1.43 [1.12-1.81]; p=0.004). In this fully adjusted model a 10 ml/min/1.73 m2 decrease in eGFR independently conferred a 31% increase in cardiovascular event risk (p=0.004). A decline of eGFR over two years strongly, significantly, and independently predicts vascular events over the subsequent four years. Declining eGFR is a readily obtainable and inexpensive candidate new biomarker for the progression of atherothrombotic disease.
  Atherosclerosis 03/2010; 211(1):348-52. · 3.79 Impact Factor