H Ulmer

University of Innsbruck, Innsbruck, Tyrol, Austria

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Publications (117)469.78 Total impact

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    ABSTRACT: Background Elevated levels of fibroblast growth factor 23 (FGF23) are associated with incident heart failure in individuals with or without chronic kidney disease. We aimed to investigate the association between serum FGF23 concentrations and disease severity and long-term outcome in patients with stable heart failure.Materials and methodsSerum levels of C-term FGF23 (Ct-FGF23) concentrations, inorganic phosphate (Pi), parathormone (PTH), and 25-hydroxyvitamin D (25(OH)D) were measured in 208 patients with non-ischemic heart failure (age 48±15 years; 70% male; NYHA Class I 27.8%, NYHA Class II 43.4%, NYHA Class III/IV 28.8%; LV-EF 34±15%; eGFR ≥60ml/min/1.73m2 in 86%).ResultsMedian Ct-FGF23 levels were 18.2 RU/ml (7.5-40.8RU/ml). A dose-response relationship was found between median Ct-FGF23 levels and increasing NYHA class (I: 11.9 RU/ml, II: 15.8 RU/ml, III/IV: 38.8 RU/ml; p<0.001). Ct-FGF23 correlated with NTproBNP (r=0.307, p<0.001), central venous pressure, mean pulmonary arterial pressure, pulmonary capillary wedge pressure and inversely correlated with cardiac output after adjustment for renal function (eGFR) and Pi. LnCt-FGF23 was related with the combined endpoint of death or heart transplantation (hazard ratio 1.452 [1.029 to 2.048]; p=0.034) independent of Pi, PTH, 25(OH)D, age and sex.Conclusion The phosphatonin FGF23 is strongly associated with disease severity and long-term outcome in patients with non-ischemic heart failure and preserved renal function. Further studies are needed to evaluate the pathophysiologic role of FGF23 and its potential as a biomarker in heart failure.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 10/2014; · 3.37 Impact Factor
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    ABSTRACT: Aims Guidelines have been published for improving management of chronic heart failure (CHF). We examined the association between improved guideline adherence and risk for all-cause death in patients with stable systolic HF. Methods Data on ambulatory patients (2006–2010) with CHF and reduced ejection fraction (HF-REF) from the Austrian Heart Failure Registry (HIR Austria) were analysed. One-year clinical data and long-term follow-up data until all-cause death or data censoring were available for 1014 patients (age 65 [55–73], male 75%, NYHA class I 14%, NYHA II 56%, NYHA III/IV 30%). A guideline adherence indicator (GAI [0–100%]) was calculated for each patient at baseline and after 12 ± 3 months that considered indications and contraindications for ACE-I/ARB, beta blockers, and MRA. Patients were considered ΔGAI-positive if GAI improved to or remained at high levels (≥ 80%). ΔGAI50 + positivity was ascribed to patients achieving a dose of ≥ 50% of suggested target dose. Results Improvements in GAI and GAI50 + were associated with significant improvements in NYHA class and NT-proBNP (1728 [740–3636] to 970 [405–2348]) (p < 0.001). Improvements in GAI50 +, but not GAI, were independently predictive of lower mortality risk (HR 0.55 [95% CI 0.34–0.87; p = 0.01]) after adjustment for a large variety of baseline parameters and hospitalisation for heart failure during follow-up. Conclusions Improvement in guideline adherence with particular emphasis on dose escalation is associated with a decrease in long-term mortality in ambulatory HF-REF subjects surviving one year after registration.
    International Journal of Cardiology 07/2014; 175(1):83–89. · 6.18 Impact Factor
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    ABSTRACT: Cytoreductive surgery and platinum-based systemic therapy constitute the standard treatment of patients with advanced ovarian cancer. Aim of the present study was to evaluate whether the time interval from surgery to start of chemotherapy has an impact on clinical outcome. Data of 191 patients with advanced serous (FIGO III-IV) ovarian cancer from the prospective multicenter study OVCAD (OVarian CAncer Diagnosis) were analyzed. All patients underwent primary surgery followed by platinum-based chemotherapy. The 25%, 50%, and 75% quartiles of intervals from surgery to start of chemotherapy were 22, 28, and 38 days, respectively (range, 4-158 days). Preoperative performance status (P<0.001), extent of surgery (P<0.001), and perioperative complications (P<0.001) correlated with intervals from surgery to initiation of chemotherapy. Timing of cytotoxic treatment [≤28 days versus >28 days; hazard ratio (HR) 1.73 (95% confidence interval 1.08-2.78), P=0.022], residual disease [HR 2.95 (95% confidence interval 1.87-4.67), P<0.001], and FIGO stage [HR 2.26 (95% confidence interval 1.41-3.64), P=0.001] were significant prognostic factors for overall survival in multivariate analysis. While the interval from surgery to start of chemotherapy did not possess prognostic significance in patients without postoperative residual disease (n=121), it significantly correlated with overall survival in patients with postoperative residual disease [n=70, HR 2.24 (95% confidence interval 1.08-4.66, P=0.031]. Our findings suggest that delayed initiation of chemotherapy might compromise overall survival in patients with advanced serous ovarian cancer, especially when suboptimally debulked.
    Gynecologic Oncology 07/2013; · 3.69 Impact Factor
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    ABSTRACT: PURPOSE: The aim of this study was to compare postoperative pain between the open tension-free plug and patch (PP) technique and the totally extraperitoneal patch (TEP) hernioplasty. METHODS: One hundred and fifty-four male patients with unilateral inguinal hernia were randomized to undergo PP and TEP from 2005 to 2009. Pain assessment was conducted using the numerical rating scale (NRS) and the McGill Pain Questionnaire preoperatively, 6, 12 and 24 months postoperatively. All patients received the same analgesic regimen and documented pain in a NRS-based 4-week diary. RESULTS: Of the 154 patients 77 underwent TEP and 77 PP. Median follow-up was 3.8 years. One recurrent hernia was observed in the TEP and two in the PP group (p = 0.56). Median preoperative NRS scores were 2 and 2, 0.3 and 0.4 at 6 months, 0.1 and 0.3 at 12 months, 0.2 and 0.1 at 24 months postoperatively in the PP and TEP groups, respectively (p > 0.05). Data from the 4-week pain diaries revealed significant differences in pain intensity between the two different techniques from the second postoperative week (p < 0.05). Patients in the PP group required more additional analgesics on day four and five postoperatively (p = 0.037 and 0.015, respectively). CONCLUSIONS: Our data favor the TEP technique concerning postoperative pain as primary endpoint between tension-free PP and TEP hernia repair.
    Hernia 06/2013; 18(2). · 2.09 Impact Factor
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    ABSTRACT: BACKGROUND: Weather conditions influence symptoms in chronic stable coronary artery disease (CAD). Whether the ongoing climate change, with continuous and rapid temperature increases, also has an impact on the incidence and outcome of non-ST elevation (NSTEMI) and ST elevation (STEMI) myocardial infarctions referred for acute coronary angiography (CA) is less clear. METHODS: According to weather data from the Institute of Meteorology and Geophysics, Innsbruck University, the 2005/2006 winter was very cold (CW) and the 2006/2007 winter extraordinarily warm (WW). As the overall invasive management of patients with acute coronary syndromes did not change substantially within these winters, we compared patients referred for acute CA suffering an acute STEMI or NSTEMI, their risk factors and in-hospital mortality rates between these two consecutive winters. RESULTS: As expected, the average temperature was lower (- 1.6 vs. + 5.9°C; p < 0.001) and humidity was higher (82 vs. 79%; p < 0.012) in CW compared to WW, with no significant differences in other weather conditions (rainfall: 59 vs. 39 days; sunshine: 3.9 vs. 4.3 h/day; air pressure: 713.04 vs. 713.76 hPa). There were no differences in the number of overall CA (987 vs. 983) between these two winters, whereas the number of acute CA (12.9 vs. 10.4% of overall CA; p = 0.046) and the diagnosis of STEMI as an indication of acute CA (74.0% vs. 62.7%; p = 0.046) were higher in CW. Furthermore, patients in CW were younger (58.2 ± 12.4 vs. 61.7 ± 11.7 years; p < 0.03), had higher LDL cholesterol (134.8 ± 44.6 vs. 116.7 ± 36.0 mg/dl; p < 0.003) and were less frequently hypertensives (52.8 vs. 70.6%; p < 0.01). Other traditional risk factors were not different between WW and CW. In addition, there were no differences in in-hospital mortality rates in invasively diagnosed CAD, patients' nationalities (Austrians: 78.0 vs. 77.5%) and time from pain to arrival in the cath lab in STEMI patients (3.9 ± 3.5 vs. 3.8 ± 3.1 h). CONCLUSION: The average temperature increase of 7.5°C from the cold to the warm winter was associated with a decrease in acute coronary angiographies, in particular due to a lower incidence of STEMI referred for primary percutaneous intervention.
    Herz 06/2012; · 0.78 Impact Factor
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    ABSTRACT: To study the effects of a supervised exercise program on serum gamma-glutamyl transferase (GGT), glycemic control and cardiovascular risk factors in pre-diabetic patients with isolated impaired fasting glucose (IFG) and those with IFG plus impaired glucose tolerance (IGT).Out of 60 pre-diabetic patients (30 with isolated IFG and 30 with IFG + IGT) 24 were randomly assigned to the supervised exercise program (1 h twice a week) and 36 only obtained counselling on the risk of diabetes and its prevention. Patients have been followed over a 12-month period.The main findings were that patients with IFG + IGT had increased GGT levels at baseline (49.2±27.4 U/L) compared to subjects with isolated IFG (28.1±21.9 U/L) (p<0.01), and that GGT levels improved only after the supervised exercise intervention within the IFG + IGT subjects ( - 17.7±19.6 U/L). Similarly, baseline triglyceride levels were also higher in IFG + IGT patients (p<0.001) and there was a decrease through exercise intervention in these patients only (p<0.05).GGT is an unspecific marker of oxidative stress and both high plasma glucose and triglycerides levels may produce oxidative stress. Thus, patients with IFG + IGT seem to have higher levels of oxidative stress than those with isolated IFG. Based on the known association between GGT levels and cardiovascular risk factors, IFG + IGT patients may be at higher risk for the development of cardiovascular diseases. The specific effect of regular exercise on GGT in pre-diabetic patients may contribute to the understanding of the preventive effects related to exercise.
    Experimental and Clinical Endocrinology & Diabetes 05/2012; 120(8):445-50. · 1.76 Impact Factor
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    ABSTRACT: Einleitung: Ziel dieser retrospektiven Studie ist es, den Einfluß von Alter, Begleiterkrankungen, Frakturform, Operationszeitpunkt, Wahl des Implantats (kurzer oder langer Gammanagel) und Operationsverfahren auf Mobilisationsgrad, radiologischen Heilungsverlauf und mögliche Komplikationen nach operativer Stabilisierung von per- und subtrochantären Oberschenkelbrüchen mittels Gammanagel zu analysieren. Patienten und Methoden: Von 1992 bis 1997 wurden 96 Patienten mit isolierter per- oder subtrochantärer Oberschenkelfraktur mittels Gammanagel (Howmedica) operiert. Das Durchschnittsalter der Patienten zum Zeitpunkt der Verletzung betrug 72,5 (27–101) Jahre. 27 Patienten waren Männer, und 69 waren Frauen. Die Operation erfolgte durchschnittlich 1,19 (0–10) Tage nach dem Unfall. Die postoperativen Kontrollen erfolgten nach 3, 6 und 12 Monaten. Hierbei wurden jeweils Röntgenaufnahmen des Oberschenkels mit Hüftgelenk in 2 Ebenen durchgeführt und der Mobilisationsgrad der Patienten beurteilt. Ergebnisse: Begleiterkrankungen, Operationszeitpunkt, Frakturtyp, Operationsverfahren und Wahl des Implantats (kurzer oder langer Gammanagel) hatten keinen Einfluß auf den Grad der Mobilisation, auf den radiologischen Heilungsverlauf oder auf aufgetretene Komplikationen. Ältere Patienten ( > 70 Jahre) waren schlechter mobilisierbar (p < 0,001). Ein Jahr nach dem Unfall waren 97 % der Frakturen radiologisch geheilt. Bei 15 Patienten (18 %) kam es zu technischen Komplikationen bei der Verwendung des Gammanagels. Schlußfolgerungen: Per- und subtrochantäre Oberschenkelfrakturen können mit Hilfe des Gammanagels bei richtiger Handhabung stabil versorgt und die Patienten frühzeitig mobilisiert werden. Background: From 1992 through 1997 96 patients with per- or subtrochanteric femur fractures were treated with a Gamma nail. We retrospectively evaluated the influence of patient age, additional diseases, type of fracture, time of operation, type of implant (short/long Gamma nail) and surgical approach (open/closed reduction) on the mobility of the patients, healing of the fractures on radiographs, and possible complications. Patients and methods: The average patient age was 72.5 years (range 27 to 101). There were 27 male and 69 female patients. Surgery was performed 1.19 (0–10) days after injury. At 3, 6, and 12 months after surgery radiographs of the involved hip joint and femur were obtained and the degree of mobility was assessed. Results: Additional diseases, type of fracture, time of operation, type of implant (short/long Gamma nail) and surgical approach (open/closed reduction) did not influence mobility of the patients, healing of the fractures on radiographs or rate of complications. It was more difficult to mobilize older patients (P < 0.001). After 1 year 97 % of all fractures had healed on radiographs. In 15 patients (18 %) complications occurred due to technical errors using the Gamma nail. Discussion: With the Gamma nail stable osteosynthesis of per- and subtrochanteric femur fractures is obtained independently of the fracture classification. Patients can be mobilized immediately. Technical errors must be avoided.
    Der Chirurg 04/2012; 71(11):1380-1384. · 0.52 Impact Factor
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    ABSTRACT: Little is known about the associations of metabolic aberrations with malignant melanoma (MM) and nonmelanoma skin cancer (NMSC). To assess the associations between metabolic factors (both individually and combined) and the risk of skin cancer in the large prospective Metabolic Syndrome and Cancer Project (Me-Can). During a mean follow-up of 12 years of the Me-Can cohort, 1728 (41% women) incident MM, 230 (23% women) fatal MM and 1145 (33% women) NMSC were identified. Most NMSC cases (76%) were squamous cell carcinoma (SCC) (873, 33% women). Hazard ratios (HRs) were estimated by Cox proportional hazards regression for quintiles and standardized z-scores (with a mean of 0 and SD of 1) of body mass index (BMI), blood pressure, glucose, cholesterol, triglycerides and for a combined metabolic syndrome score. Risk estimates were corrected for random error in the measurements. Blood pressure per unit increase of z-score was associated with an increased risk of incident MM cases in men and women [HR 1·17, 95% confidence interval (CI) 1·04-1·31 and HR 1·18, 95% CI 1·03-1·36, respectively] and fatal MM cases among women (HR 2·39, 95% CI 1·58-3·64). In men, all quintiles for BMI above the reference were associated with a higher risk of incident MM. In women, SCC NMSC risk increased across quintiles for glucose levels (P-trend 0·02) and there was a trend with triglyceride concentration (P-trend 0·09). These findings suggest that mechanisms linked to blood pressure may be involved in the pathogenesis of MM. SCC NMSC in women could be related to glucose and lipid metabolism.
    British Journal of Dermatology 04/2012; 167(1):59-67. · 3.76 Impact Factor
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    ABSTRACT: We aimed to evaluate the clinical relevance of p53 and p73 isoforms that modulate the function of p53. This prospective multicentre study included 154 patients with stage III and IV serous ovarian cancer. A functional yeast-based assay and subsequent sequencing were performed to analyse the p53 mutational status. Expression of p53 and p73 isoforms was determined using RT-qPCR. Δ133p53 expression constituted an independent prognostic marker for recurrence-free (hazard ratio=0.571, P=0.016, 95% CI: 0.362-0.899) and overall survival (hazard ratio=0.365, P=0.004, 95% CI: 0.182-0.731) in patients with p53 mutant ovarian cancer (n=121). High Δ40p53 expression was associated with favourable tumour grading (P=0.037) and improved recurrence-free survival (33.4 vs 19.6 months, P=0.029), but not overall survival (43.1 vs 33.6 months, P=0.139), in patients with p53 wild-type cancer (n=33). Neither the p53 mutational status nor p73 isoform expression possessed prognostic significance in the examined ovarian cancer cases. Δ133p53 expression was associated with prognosis in the vast majority of ovarian cancer cases, that is, patients with p53 mutant advanced serous carcinomas. Thus, our findings underline the importance of considering the complex p53 regulatory network.
    British Journal of Cancer 11/2011; 105(10):1593-9. · 5.08 Impact Factor
  • European Journal of Cancer 09/2011; 47:3-3. · 4.82 Impact Factor
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    ABSTRACT: Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal hematopoietic stem cell disorders that are preferentially diagnosed in the elderly. Aberrant expression of the adhesion receptor CD44 correlates with poor prognosis in various neoplasms. To evaluate the prognostic impact of CD44 in MDS serum levels of soluble CD44 standard (solCD44s) were measured in 130 MDS patients (median age 68 years) using an enzyme-linked immunosorbent assay (ELISA). solCD44s levels were significantly elevated in MDS patients as compared to those of healthy donors (p<0.001) and were found to correlate with distinct FAB and WHO subtypes. The highest levels of solCD44s were found in patients with CMML, in RAEB and in patients with MDS transformed into secondary acute myeloid leukaemia (AML). In univariate analysis elevated levels of solCD44s (cut-off level>688.5ng/ml) correlated significantly with shorter overall survival in MDS patients (12 versus 39 months; p<0.001). In multivariate analysis solCD44s displayed prognostic significance independent of the International Prognosis Scoring System (IPSS). To test for refined prognostication, IPSS risk groups were split into two separate categories based on the solCD44s levels. Using this approach, MDS patients with a shorter survival were identified both in the IPSS low-risk (p=0.037) and in the IPSS intermediate-1-risk group (p=0.015). The CD44s-adjusted IPSS defines a cohort of MDS patients with unfavorable prognosis, which might be helpful in risk stratification and in therapeutic algorithms.
    Critical reviews in oncology/hematology 05/2011; 78(2):150-61. · 5.27 Impact Factor
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    ABSTRACT: The Vorarlberg Health Monitoring and Promotion Programme (VHM&PP), based on prospectively gathered, repeated routine health examination data from a cohort of more than 175,000 adults, is one of the largest ongoing population-based risk factor surveillance programmes worldwide. Among others, the so far widely unknown associations of serum uric acid (SUA) and gamma-glutamyltransferase (GGT) with cancer were investigated. Both SUA and GGT are known to be related to the metabolic syndrome and furthermore considered as markers of oxidative stress. After controlling for several confounding factors, it was found that elevated SUA levels were statistically significantly related to overall cancer mortality and several site-specific malignancies in both men and women. Additionally, a J-shaped effect of SUA levels on risk of overall cancer incidence appeared in men, with significantly increased cancer risk at high levels of SUA. Likewise, in accordance with some experimental evidence, among men and women elevated GGT increased cancer risk overall and for several lifestyle-related malignancies. On the basis of these findings, and considering the routine measurement in clinical practice, SUA and GGT might function as a valuable marker to identify patients with an increased risk to develop malignant diseases. KeywordsSerum uric acid–Gamma-glutamyltransferase–Cancer–Prospective cohort study–Epidemiology
    memo - Magazine of European Medical Oncology 04/2011; 4(1):50-54.
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    ABSTRACT: Due to increasing interest in indoor air quality (IAQ) monitoring for demand controlled ventilation (DCV) aiming at improved perceived air quality, health, energy and cost saving, the objective of this study has been the development of a sensor module based on a single microelectromechanical-system (MEMS) metal oxide semiconductor (MOS) gas sensor for IAQ monitoring as close as possible to the human sensory impression in indoor environments. Based on the results of a statistical evaluation on human induced volatile organic compounds (VOCs) in the ambient air of indoor environments correlating with human presence and perceived air quality, the performance of differently doped SnO2 thick film gas sensor materials has been investigated in laboratory and by means of field tests in order to find the most promising sensor material for IAQ monitoring based on the detection of changes of human induced VOCs in indoor air. Implementation of an empirical evaluation algorithm reversing proportionality of anthropogenic CO2 production and other bio-effluent generation allows prediction of CO2 equivalent units. Analytical instrumentation and reference sensors served to evaluate the effectiveness of the developed sensor module in real-life.
    Building and Environment 11/2010; · 2.70 Impact Factor
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    ABSTRACT: Risk factors for rare gynecological cancers are largely unknown. Initial research has indicated that the metabolic syndrome (MetS) or individual components could play a role. The Metabolic syndrome and Cancer project cohort includes 288,834 women. During an average follow-up of 11 years, 82 vulvar, 26 vaginal and 43 other rare gynecological cancers were identified. Hazard ratios (HRs) were estimated fitting Cox proportional hazards regression models for tertiles and standardized z-scores [with a mean of 0 and a standard deviation (SD) of 1] of body mass index (BMI), blood pressure, glucose, cholesterol, triglycerides and MetS. Risk estimates were corrected for random error in the measurement of metabolic factors. The MetS was associated with increased risk of vulvar [HR 1.78, 95% confidence interval (CI) 1.30-2.41) and vaginal cancer (HR 1.87, 95% CI 1.07-3.25). Among separate MetS components, 1 SD increase in BMI was associated with overall risk (HR 1.43, 95% CI 1.23-1.66), vulvar (HR 1.36, 95% CI 1.11-1.69) and vaginal cancer (HR 1.79, 95% CI 1.30-2.46). Blood glucose and triglyceride concentrations were associated with increased risk of vulvar cancer (HR 1.98, 95% CI 1.10-3.58 and HR 2.09, 95% CI 1.39-3.15, respectively). The results from this first prospective study on rare gynecological cancers suggest that the MetS and its individual components may play a role in the development of these tumors.
    Annals of Oncology 10/2010; 22(6):1339-45. · 6.58 Impact Factor
  • European Urology Supplements 04/2010; 9(2):297-297. · 3.37 Impact Factor
  • The Journal of Heart and Lung Transplantation 02/2010; 29(2). · 5.61 Impact Factor
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    ABSTRACT: Imatinib 400 mg/day is the standard treatment for patients with chronic phase chronic myeloid leukemia. Recent reports suggested higher and more rapid cytogenetic and molecular responses with higher doses of imatinib. In this prospective international, multicenter phase III study, 227 patients with pre-treated Philadelphia chromosome-positive, BCR-ABL-positive chronic myeloid leukemia were randomized to a standard-dose imatinib arm (400 mg/day) or a high-dose imatinib arm (800 mg/day for 6 months followed by 400 mg/day as maintenance therapy). In this planned interim analysis hematologic, cytogenetic and molecular responses as well as toxicity were evaluated. Compared to the standard-dose, high-dose imatinib led to higher rates of major and complete cytogenetic responses at both 3 months (major: 21% versus 37%, P=0.01; complete: 6% versus 25%, P<0.001) and 6 months (major: 34% versus 54%, P=0.009; complete: 20% versus 44%, P<0.001). This was paralleled by a significantly higher major molecular response rate at 6 months in the high-dose imatinib arm (11.8% versus 30.4%; P=0.003). At 12 months, the rates of major cytogenetic response (the primary end-point) were comparable between the two arms (57% versus 59%). In contrast to non-hematologic toxicities, grade 3/4 hematologic toxicities were more common in the high-dose arm. Cumulative complete cytogenetic response rates were higher in patients without dose reduction in the high-dose arm (61%) than in the patients with no dose reduction in the standard-dose arm (36%) (P=0.014). This is the first randomized phase III trial in patients with pre-treated chronic phase chronic myeloid leukemia demonstrating improvements in major cytogenetic response, complete cytogenetic response and major molecular response rates with high-dose imatinib therapy (ClinicalTrials.gov Identifier: NCT00327262).
    Haematologica 02/2010; 95(6):908-13. · 5.94 Impact Factor
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    ABSTRACT: Associations of C-reactive protein (CRP) concentration with risk of major diseases can best be assessed by long-term prospective follow-up of large numbers of people. We assessed the associations of CRP concentration with risk of vascular and non-vascular outcomes under different circumstances. We meta-analysed individual records of 160 309 people without a history of vascular disease (ie, 1.31 million person-years at risk, 27 769 fatal or non-fatal disease outcomes) from 54 long-term prospective studies. Within-study regression analyses were adjusted for within-person variation in risk factor levels. Log(e) CRP concentration was linearly associated with several conventional risk factors and inflammatory markers, and nearly log-linearly with the risk of ischaemic vascular disease and non-vascular mortality. Risk ratios (RRs) for coronary heart disease per 1-SD higher log(e) CRP concentration (three-fold higher) were 1.63 (95% CI 1.51-1.76) when initially adjusted for age and sex only, and 1.37 (1.27-1.48) when adjusted further for conventional risk factors; 1.44 (1.32-1.57) and 1.27 (1.15-1.40) for ischaemic stroke; 1.71 (1.53-1.91) and 1.55 (1.37-1.76) for vascular mortality; and 1.55 (1.41-1.69) and 1.54 (1.40-1.68) for non-vascular mortality. RRs were largely unchanged after exclusion of smokers or initial follow-up. After further adjustment for fibrinogen, the corresponding RRs were 1.23 (1.07-1.42) for coronary heart disease; 1.32 (1.18-1.49) for ischaemic stroke; 1.34 (1.18-1.52) for vascular mortality; and 1.34 (1.20-1.50) for non-vascular mortality. CRP concentration has continuous associations with the risk of coronary heart disease, ischaemic stroke, vascular mortality, and death from several cancers and lung disease that are each of broadly similar size. The relevance of CRP to such a range of disorders is unclear. Associations with ischaemic vascular disease depend considerably on conventional risk factors and other markers of inflammation. British Heart Foundation, UK Medical Research Council, BUPA Foundation, and GlaxoSmithKline.
    The Lancet 01/2010; 375(9709):132-40. · 39.21 Impact Factor
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    ABSTRACT: The contribution of natural killer (NK) cells to graft-versus-malignancy (GVM) effects following hematopoietic stem cell transplantation (HSCT) remains uncertain, particularly in the HLA-identical setting. A model considering missing HLA ligands to the donor's inhibitory killer cell immunoglobulin-like receptor (KIR), termed the missing KIR ligand model, has been established in T cell depleted bone marrow transplantation (BMT), but lacks validity in other cohorts with different treatment characteristics. We hypothesized that the impact of missing KIR ligands on relapse-free survival (RFS) and overall survival (OS) in T cell replete peripheral blood SCT (PBSCT) differs from that in the T cell depleted BMT setting, and retrospectively evaluated 100 consecutive, HLA-identical sibling transplantations for hematologic malignancies. In addition to KIR ligand status, we considered the donors' activating KIRs and grafted NK, T, and CD34(+) cell doses. Our findings demonstrate noninferiority for OS (P = .005) and RFS (P = .002) for the heterozygous HLA-C group KIR ligand status (C1/2; n = 47) compared with patients missing either C1 or C2 (n = 53). Similarly, OS (P = .031) and RFS (P = .034) of Bw4-positive patients was noninferior to that of patients missing a Bw4 ligand to KIR3DL1. By multivariate analysis, C1/2 heterozygous patients had a favorable risk ratio (RR) for relapse (RR = 0.28; P = .003), RFS (RR = 0.56; P = .046), and acute graft-versus-host disease grade II-IV (RR = 0.36; P = .05). Following reduced-intensity conditioning (RIC), but not standard-intensity conditioning, myeloablative (MA) transplantation, a grafted NK cell dose above the median (3.4 x 10(7)/kg) was associated with a lower risk of relapse (RR = 0.57; P = .003) and improved survival (RR = 0.78; P = .03). Overall, our findings support a role for NK alloreactivity in HLA-identical HSCT, but argue against a favorable impact of missing KIR ligands in the given setting. We conclude that the mechanism favoring the missing KIR ligand constellation in T cell depleted BMT may not operate in T cell replete PBSCT. The reasons for this differential effect remain unresolved.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 10/2009; 16(2):273-80. · 3.15 Impact Factor
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    ABSTRACT: Blood lipid levels as part of the metabolic syndrome are thought to be linked to cancer risk. Few epidemiological studies have addressed the association between serum triglyceride (STG) concentrations and cancer risk. Serum triglyceride concentrations were collected in a health investigation (1988-2003). The analyses included 156 153 subjects (71 693 men and 84 460 women), with 5079 incident cancers in men and 4738 cancers in women, and an average of 10.6 years of follow-up. All malignancies were ascertained from the population cancer registry. Multivariate Cox proportional hazard models stratified by age and sex were used to determine adjusted cancer risk estimates and 95% confidence interval (95% CI). In men and women combined, higher STG concentrations were associated with increased risk of lung (4th vs 1st quartile: HR, 1.94; 95% CI, 1.47-2.54), rectal (HR, 1.56; 95% CI, 1.00-2.44), and thyroid cancer (HR, 1.96; 95% CI, 1.00-3.84). Serum triglyceride concentrations were inversely associated with non-Hodgkin's lymphoma. In men, STG concentrations were inversely associated with prostate cancer and positively with renal cancer. In women, STG concentrations were positively associated with gynaecological cancers. Stratification by BMI revealed a higher risk of gynaecological cancers in overweight than in normal weight women. No other associations were found. Our findings support the hypothesis that STG concentrations are involved in the pathogenesis of lung, rectal, thyroid, prostate, and gynaecological cancers.
    British Journal of Cancer 09/2009; 101(7):1202-6. · 5.08 Impact Factor

Publication Stats

3k Citations
469.78 Total Impact Points


  • 1995–2014
    • University of Innsbruck
      • • Institute of Biochemistry
      • • Institut für Sportwissenschaft
      Innsbruck, Tyrol, Austria
  • 2012
    • Skåne University Hospital
      Malmö, Skåne, Sweden
  • 2006
    • University College Dublin
      • School of Public Health, Physiotherapy & Population Science
      Dublin, L, Ireland
  • 2005
    • Medizinische Universität Innsbruck
      • Department für Medizinische Statistik, Informatik und Gesundheitsökonomie
      Innsbruck, Tyrol, Austria