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Because of long-term immunosuppression, solid organ transplant recipients are at increased risk for keratinocyte cancer. We matched solid organ transplant patients (n = 150), cases with keratinocyte cancers and tumor-free controls, considering the most important risk factors for keratinocyte cancer in solid organ transplant recipients. Using whole exome data of germline DNA from this patient cohort, we identified several genetic loci associated with the occurrence of multiple keratinocyte cancers. We found one genome-wide significant association of a common single nucleotide polymorphism located in EXOC3 (rs72698504). In addition, we found several variants with a p-value of less than 10−5 associated with the number of keratinocyte cancers. These variants were located in the genes CYB561, WASHC1, PITRM1-AS1, MUC8, ABI3BP, and THBS2-AS1. Using whole exome sequencing data, we performed groupwise tests for rare missense variants in our dataset and found robust associations (p < 10−6, Burden Zeggini test) between MC1R, EPHA8, EPO, MYCT1, ADGRG3, and MGME1 and keratinocyte cancer. Thus, overall, we detected genes involved in pigmentation/UV protection, tumor suppression, immunomodulation, intracellular traffic, and response to UV as genetic risk factors for multiple keratinocyte cancers in solid organ transplant recipients. We also grouped selected genes to pathways and found a selection of genes involved in the “cellular response to UV” to be significantly associated with multiple keratinocyte cancers.

In Osterreich sind rund 744.000 Erwerbstatige Schichtarbeiter. Da der Mensch eine tageszyklische Spezies ist, lost die Schichtarbeit Storungen der zirkadianen Rhythmik aus. Ziel der Studie ist es, den Zusammenhang zwischen Schichtarbeit, Ubergewicht und Hypogonadismus aufzuzeigen. Im Rahmen eines Mannergesundheitstages wurden bei Mitarbeitern des osterreichischen Bundesministeriums fur Inneres Serumtestosteron, PSA und, mittels bioelektrischer Impedanzanalyse, die Korperzusammensetzung bestimmt. Die Teilnehmer mussten in einem Fragebogen angeben, ob sie Schichtdienst leisten und ob sie an Schlafstorungen („shift work sleep disorder“), leiden. Ein Testosteronmangel wurde mit einem Wert 25 definiert. Bei 36 Mannern konnten die Daten ausgewertet werden, 12 davon leisteten Schichtdienst. Bei unserer Studie mit alteren Teilnehmern hatten fast 60 % der Probanden mit Schichtdienst verminderte T‑Spiegel (Testosteronspiegel) mit einem um ~25 % niedrigeren Gesamt‑T. Personen mit Schlafstorungen hatten deutlich niedrigere T‑Werte. Die Parameter fur die Korperzusammensetzung, wie Korpergewicht, BMI und Fettanteil, zeigten bei der Gruppe der Schichtarbeiter hohere Werte. Bei ~30 % fand sich ein erhohter PSA-Wert. Diese Ergebnisse spiegeln wider, dass Schichtarbeit mit einem deutlich hoheren PSA assoziiert ist. Das Prostatakarzinomrisiko steigt um ~2,8 %/5 Jahre, und im Schnitt haben Schichtarbeiter ein relatives Risiko von ~1,2 (95 %-KI: 1,1–1,5). Schichtarbeit ist ein Risikofaktor fur Adipositas, Hypogonadismus und Prostatakarzinom. Ein Grosteil der Beschaftigten toleriert allerdings Schichtarbeit ohne Probleme, wobei Schlafstorungen ursachlich zu einer verminderten Toleranz und niedrigeren Testosteronspiegel fuhren konnen.

The risk of keratinocyte cancer is determined by intrinsic and extrinsic factors, which also influence skin aging. Few studies have linked skin aging and UV exposure with the incidence of non-melanoma skin cancer (NMSC). We evaluated signs of actinic skin damage and aging, individual UV burden, and melanocortin-1 receptor (MC1R) variants. A total of 194 organ transplant recipients (OTR) who suffered from NMSC were compared to 194 tumor-free controls matched for gender, age, type of transplanted organ, post-transplantation (TX) period, and immunosuppressive therapy. Compared with the cases, the controls scored higher in all skin aging scores and there were no differences in UV burden except for intentional whole-body UV exposure for specific UV scenarios and periods of life in favor of cases. The number of NMSCs correlated with all types of skin aging scores, the extent of intentional sun exposure, older age, longer post-TX period, shorter interval from TX to first NMSC, and specific MC1R risk groups. Multivariable models revealed a 7.5-fold risk of developing NMSC in individuals with actinic keratosis; 4.1- or 3.6-fold in those with green or blue eyes, respectively; and a 1.9-fold increased risk in the MC1R medium- + high-risk group. In the absence of skin aging contributing to NMSC development, certain MC1R risk types may identify OTR at risk for high tumor burden.

Introduction. We aim to investigate the effect of vitamin D on metabolic parameters in a population with prediabetes and to detect possible sex differences. Methods. In 621 patients with diagnosed prediabetes, glucose, lipid, and anthropometric parameters were measured. Furthermore, the interaction of 25-OH-vitamin D (25-hydroxyvitamin D) with metabolic and glucose metabolism parameters was analysed in the total prediabetic population, as well as after stratification by sex (female vs. male prediabetic subgroup), by logistic regression. Results. 25-OH-vitamin D was negatively related to cholesterol, BMI, fatty liver index, insulin, and HOMA-IR. Especially in the male prediabetic cohort, 25-OH-vitamin D levels negatively correlated with total cholesterol levels (r = −0.17, p = 0.001 ), with triglycerides (r = −0.17, p = 0.001 ), and with HbA1c levels (r = −0.14, p = 0.010 ). Only in the female cohort with prediabetes, we found a negative correlation of 25-OH-vitamin D levels with systolic (r = −0.18, p = 0.005 ) and diastolic blood pressures (r = −0.23, p < 0.001 ). Conclusion. In this study, in females with prediabetes, 25-OH-vitamin D was notably related to a more favourable metabolic profile, including lower total cholesterol and higher HDL cholesterol levels. On the contrary, in men with prediabetes, there was a stronger association between 25-OH-vitamin D and cholesterol-HDL quotient, as well as fatty liver index was observed in the male prediabetic subgroup. Therefore, sex differences should be considered in future studies on vitamin D and glucose tolerance status.

Summary Background Testosterone plays an important role in the regulation of glucose metabolism. While earlier studies have shown that it has a protective effect in males, unfavorable effects of testosterone on glucose metabolism have been reported in females; however, whether there is a sex-specific relationship between testosterone and glucose metabolism in patients with prediabetes has not been investigated in detail hitherto. Methods This cross-sectional analysis investigated 423 males and 287 females with diagnosed prediabetes. Detailed assessment of their metabolic profiles was performed, including a 2‑h oral glucose tolerance test (OGTT), HbA1c levels, calculation of insulin resistance with homeostatic model assessment for insulin resistance (HOMA-IR), assessment of lipid metabolism, anthropometric parameters and the fatty liver index (FLI). By using Spearman’s correlation test, we investigated the sex-specific relationship between testosterone and metabolism in the prediabetic individuals. Results In the present study, prediabetic females (mean age 58.6 years, confidence interval [CI: 57.6 y; 59.5 y]) were characterized by lower fasting plasma glucose levels (104.2 mg/dl [CI: 103.0 mg/dl; 105.4 mg/dl] vs. 106.9 mg/dl [CI: 106.0 mg/dl; 107.8 mg/dl]) and a lower FLI (49.5 [CI: 45.7; 53.2] vs. 58.8 [CI: 55.8; 61.8]), but presented with a higher risk of developing manifest type 2 diabetes in the next 10 years (FINDRISK score: 17.6 [CI: 17.1; 18.1] vs. 16.1 [CI: 15.7; 16.5]) when compared to prediabetic males (mean age: 58.04 years [CI: 57.0 y; 59.1 y]). Testosterone was negatively related to insulin resistance (HOMA-IR: Spearman’s ρ: −0.33, p p p Conclusion The increase of testosterone levels in males was related to a more favorable glucose metabolism, including lower HbA1c, lower stimulated glucose levels and higher insulin sensitivity; however, in prediabetic females, testosterone was not related to glucose metabolism.

Introduction Fractures of the proximal femur are a significant cause of mortality and morbidity in the elderly population. Yet predictive marker of unfavourable prognosis are still lacking. Calcium phosphate product is a marker of osteo-renal dysregulation. This study investigated the role of serum calcium phosphate product (SCPP) levels as a prognostic parameter for outcome in those patients. Patients and methods A total of 3577 consecutive patients with diagnosed fractures of the proximal femur were included in our study (72.5% females). SCPP was divided into tertiles: 2 /l 2 , 1.93–2.38 mmol 2 /l 2 and >2.39 mmol 2 /l 2 . Data collection was performed prospectively and statistical evaluation was performed retrospectively. Results Mean follow up in our study group was 11.0 ± 0.3 months. The mean age of our study group was 79.0 years (SEM ±14 years). To facilitate analysis, patients were divided in two groups: ≤84 years (64.4%) and ≥85 years (35.6%), and mortality n = 445). In our study population higher SCPP levels ad admission were associated with a markedly elevated mortality. In a multivariate logistic regression model adjusted for age and sex, plasma creatinine and haemoglobin at admission caused a 1.3 (CI: 1.01–1.6) for SCPP 1.93–2.38 mmol 2 /l 2 , and a 1.6 (CI: 1.2–2.0) for SPP >2.39 mmol 2 /l 2 fold increase in overall mortality compared to patients with baseline SCPP levels ( 2 /l 2 ) as reference category. Conclusion Those findings in our study population with 3577 patients over a period of 20 years proved to be, that serum Ca levels may be a good predictor for mortality in patients with fracture of the proximal femur. Further studies are required to evaluate whether these high risk patients might benefit from specific therapeutic measurements. This prognostic factor may help to increase the outcome of elderly patients with a fracture of the proximal femur.

Burnout and work-related stress symptoms of anxiety disorder and depression cause prolonged work absenteeism and early retirement. Hence, reliable identification of patients under risk and monitoring of treatment success is highly warranted. We aimed to evaluate stress-specific biomarkers in a population-based, “real-world” cohort (burnouts: n = 40, healthy controls: n = 26), recruited at a preventive care ward, at baseline and after a four-month follow up, during which patients received medical and psychological treatment. At baseline, significantly higher levels of salivary cortisol were observed in the burnout group compared to the control group. This was even more pronounced in midday- (p

Bite wounds are among the commonest types of trauma to which man is the subject. They account for 5 % of the total traumatic wounds evaluated in the emergency department (ED) and approximately 1 % of all the ED visits. Early estimation of infection risk, adequate antibiotic therapy and if indicated surgical treatment are the cornerstones of successful cure of bite wounds. A total of 5248 consecutive trauma patients were collected prospectively and analysed retrospectively over a period of 15 years in this study at a level I trauma centre, Department of Trauma Surgery, Medical University of Vienna, Austria. The mean age was 33.8 years (range 0–97), 2620 (49.9 %) were male and 2628 (50.1 %) were female individuals. In our study population, a total of 2530 dog bites (48.2 %), 930 cat bites (17.8 %), 357 other animal bites (6.8 %), 426 human bites (8.1 %) and 1005 human self-bites (19.2 %) have been observed. A total of 995 wounds (19.0 %) have been infected. Surgery was done in 132 wounds (2.5 %). We could show a six times higher infection rate of cat bites compared to dog bites. Human bites showed a total infection rate of 8.2 %. Observed infection rate of puncture wounds and wounds greater than 3 cm was 1.5 times higher than for all other wounds in the present study. Total infection rates within 24 h to antibiotic administration was 29.3 %, compared to 65.0 %

Introduction Hip fractures are a significant cause of mortality and morbidity in the elderly. This study investigated the relationship between initial haemoglobin (Hb) levels and a prognostic parameter for outcome in those patients. Patients and methods A total of 3595 consecutive patients with diagnosed hip fractures were included in our study (72.2% females). Anaemia was defined according to WHO criteria, with according subgroups mild, moderate and severe anaemia. Data collection was performed prospectively and statistical evaluation was performed retrospectively. Results Mean follow up in our study group was 11.2±0.3 months. The mean age of our study group was 78.5 years (SEM±0.2 years). To facilitate analysis, patients were divided in two groups: ≤84 years (60.1%) and ≥85 years (39.9%). Mortality n =439). In our study population lower Hb levels ad admission were associated with a markedly elevated short-term mortality. In a multivariate logistic regression model adjusted for age and sex, mild anaemia at admission caused a 1.5 (CI: 1.1–1.9), moderate anaemia a 2.6 (95 CI: 2.0–3.4), and severe anaemia a 3.6 (CI: 1.8–6.9) fold increase in three months mortality compared to patients without anaemia. Total lymphocyte count (1.2±0) did not show any differences between the subgroups. Conclusion Those findings in our study population with 3595 patients over a period of twenty years have proven that initial Hb levels are a useful and cost effective parameter to predict mortality in elderly patients with a hip fracture. This prognostic factor may help to increase the outcome of elderly patients with a hip fracture.

Zusammenfassung 2014 wurden in Zusammenarbeit von zwei großen internationalen Expertengruppen Empfehlungen zur Bestimmung von Autoantikörpern gegen zelluläre Antigene, herkömmlich als antinukleäre Antikörper bezeichnet, herausgegeben. Die Empfehlungen wurden in einer 25 Punkte umfassenden Tabelle zusammengefasst und in einer weiteren Tabelle jene Muster beschrieben, die von einem Autoimmunlabor erkannt werden sollten. Internationale Empfehlungen haben für zertifizierte Labore Gültigkeit und erfordern ein Überdenken des analytischen Vorgehens. Die österreichische Arbeitsgruppe für Autoimmundiagnostik (http://www.easi-network.com) hat sich auf einen Konsens geeinigt, wie im deutschen Sprachraum diese 2014 veröffentlichten Empfehlungen umgesetzt werden könnten.

Endurance sports are enjoying greater popularity, particularly among new target groups such as the elderly. Predictors of future physical capacities providing a basis for training adaptations are in high demand. We therefore aimed to estimate the future physical performance of elderly marathoners (runners/bicyclists) using a set of easily accessible standard laboratory parameters. To this end, 47 elderly marathon athletes underwent physical examinations including bicycle ergometry and a blood draw at baseline and after a three-year follow-up period. In order to compile a statistical model containing baseline laboratory results allowing prediction of follow-up ergometry performance, the cohort was subgrouped into a model training (n = 25) and a test sample (n = 22). The model containing significant predictors in univariate analysis (alanine aminotransferase, urea, folic acid, myeloperoxidase and total cholesterol) presented with high statistical significance and excellent goodness of fit (R2 = 0.789, ROC-AUC = 0.951±0.050) in the model training sample and was validated in the test sample (ROC-AUC = 0.786±0.098). Our results suggest that standard laboratory parameters could be particularly useful for predicting future physical capacity in elderly marathoners. It hence merits further research whether these conclusions can be translated to other disciplines or age groups.

The purpose of this study was to determine whether different forms of stabilization for open femur fractures can be performed without influencing outcome, in particular infection and delayed unions/nonunions. Although the traditional management of these injuries is external fixation, a trend toward definitive stabilization techniques has evolved in the current literature. All open fractures of the femur shaft and the distal femur presenting to our urban Level I trauma center during a 10 year period were reviewed. A total of 40 patients (41 fractures) were initially treated at the above institution within 6 h of injury. All patients underwent emergent wound irrigation, debridement, and antibiothic theraphy. The method of fracture immobilization was left to the discretion of the attending trauma surgent. Study population consited of 12 (29 %) GI, 10 (25 %) GII, and 19 (46 %) GIII fractures. Initially, fracture management was performed with external fixation (EF) 19 (43.2 %), intramedullary nailing (IM) 18 (38.6 %), plating (PL) 3 (6.8 %), screw fixation (SF) 1 (2.3 %) and without treatment 4 (9.1 %). In all, 3 (6.8 %) fractures were complicated by infection, 7 (15.9 %) had implant failure, and 5 (11.4 %) developed delayed union. Using external fixation in acute fracture treatment for open femur fractures is a safe and effective surgical technique. Based on our results, external fixation might be superior to intramedullary nailing or plating when evaluating outcome parameters and complications.

Background and Aim Recent studies revealed a link between hypovitaminosis D3 and the risk for hyperglycemia. Further mechanistic and interventional investigations suggested a common reason for both conditions rather than a causal relationship. Exposure to sunlight is the most relevant source of vitamin D3 (25(OH)D), whereas adipose tissue is able to store relevant amounts of the lipophilic vitamin. Since running/bicycling leads to increased out-door time and alters physiological response mechanisms, it can be hypothesized that the correlation between hypovitaminosis D3 and hyperglycemia might be disturbed in outdoor athletes. Methods 47 elderly marathoners/bicyclists and 47 age/sex matched controls were studied in a longitudinal setting at baseline and after three years. HbA1c as a surrogate for (pre-)diabetic states was quantified via HPLC, 25(OH)D levels were measured by means of chemiluminescent assays. Physical performance was assessed by ergometry. Results When adjusted for seasonal variations, 25(OH)D was significantly higher in athletes than in controls. 25(OH)D levels inversely correlated with triglycerides in both groups, whereas only in controls an association between high BMI or low physical performance with hypovitaminosis D3 had been found. Likewise, the presence of hypovitaminosis D3 at baseline successfully predicted hyperglycemia at the follow up examinations within the control group (AUC = 0.85, 95% CI [0.74, 0.96], p < .001, statistically independent from BMI), but not in athletes. Conclusion Our data suggest that mechanisms of HbA1c elevation might differ between athletes and controls. Thus, intense physical activity must be taken into account as a potential pre-analytic confounder when it is aimed to predict metabolic risk by vitamin D3 levels.

Autoimmunerkrankungen sind eine klinisch heterogene Gruppe von Erkrankungen, die den Hausarzt oft vor differentialdiagnostische Herausforderungen stellen. Mit Ausnahme der rheumatoiden Arthritis, die mit einer Pravalenz von ca. 1 % der Bevolkerung zu den haufigen Autoimmunerkrankungen zahlt, sind systemische Autoimmunerkrankungen in der allgemeinmedizinischen Praxis so selten, dass der niedergelassene Arzt fur Allgemeinmedizin meist wenig Erfahrung mit den einzelnen Krankheitsbildern hat. Bei entsprechender klinischer Symptomatik und mit gezielten Fragestellungen konnen bestimmte Autoantikorper die Verdachtsdiagnose stutzen. Die osterreichische Gruppe der Europaischen Autoimmun Standardisierungsinitiative (EASI, European Autoimmunity Standardisation Initiative) hat es sich zum Ziel gesetzt, im vorliegenden und 2009 publizierten Leitfaden, dem Allgemeinmediziner einen Wegweiser durch den Dschungel der Biomarker fur Autoimmunerkrankungen zu bieten.

BACKGROUND Low serum butyrylcholinesterase activity was associated with all-cause and cardiovascular mortality in a community-based study; however, there are no data from investigations of the long-term effects of butyrylcholinesterase on mortality in patients with diagnosed coronary artery disease (CAD). We therefore assessed the effect of butyrylcholinesterase activity on the outcomes of patients with CAD. METHODS AND RESULTS We prospectively included 720 patients in our study: 293 patients with stable CAD and 427 patients with acute coronary syndrome. During a median follow-up of 11.3 years corresponding to 6469 overall person-years, 278 deaths (38.6%) were recorded. We detected a significant and independent protective effect of butyrylcholinesterase on all-cause mortality [adjusted hazard ratio (HR) for a 1-SD increase, 0.62; 95% CI, 0.54–0.71; P < 0.001] and cardiovascular mortality (adjusted HR, 0.64; 95% CI, 0.54–0.76; P < 0.001) in a Cox proportional hazards regression analysis. The 10-year survival rates were 42%, 74%, and 87% in the first, second, and third tertiles of butyrylcholinesterase activity. The presentation of CAD affected the effect of butyrylcholinesterase on mortality (P for interaction = 0.012), with a stronger association found in patients with stable CAD (adjusted HR, 0.56; 95% CI, 0.45–0.70; P < 0.001). CONCLUSIONS Our study demonstrates a strong inverse association between butyrylcholinesterase activity and long-term outcome in patients with known CAD. Because butyrylcholinesterase added predictive information after adjustment for established cardiovascular risk factors, additional underlying pathophysiological mechanisms and the potential applicability of butyrylcholinesterase activity for secondary risk prediction needs to be addressed in future studies.

Accurate assessment of injury severity is critical for decision making related to the prevention, triage, and treatment of several injured patients. Early estimation of mortality risk of critically injured patients is mandatory for adequate therapeutic strategies. Current risk stratification relies on clinical diagnosis and scoring systems. In our study, we hypothesized whether a simple laboratory test, the CK/CK-MB ratio, could help improving risk prediction in severely traumatized patients.In a 9-year period, 328 nonselected trauma patients were included in our retrospective study at a Level I Trauma Center up to September 2002. Data for this study were obtained from our computerized trauma database, established in September 1992.In our study population, we could show a negative correlation between Injury Severity Score (ISS) and leukocytes. A positive correlation was detected for liver enzymes and CK-MB. The correlation between ISS and Na(+) was significant. No correlation between ISS, K(+), and Hb/Ht could be observed. Exitus was associated with ISS, alteration in thrombocytes, CK, CK-MB, CRP, Crea, and Na(+).In our study population, CK-MB levels showed a significant correlation with overall surveillance in polytraumatized patients. In our opinion, this might suggest that CK-MB levels could be taken as an indirect predictor for survival. Our findings need to be proven in further prospective clinical trials.

Eur J Clin Invest 2012; 42 (5): 463–469 Abstract Background Myeloperoxidase (MPO) is involved in a multitude of inflammatory processes involving oxidative modification of soluble components and cellular surfaces. Thus, MPO plays a key role in promoting atherosclerosis via oxidative stress by modification of both high- and low-density lipoprotein and production of other bioactive molecules. A polymorphism (MPO 463G>A, rs2333227) results in different expression rates of MPO. We aimed to assess whether MPO could be of clinical use as a risk marker for vascular disease in a high-risk group. Material and methods Plasma MPO levels of 406 patients suffering from peripheral arterial disease (PAD) were measured on an Abbott Architect i2000sr and grouped into patients with high (>115 ng/mL) and low (< 115 ng/mL) MPO levels. Genotyping of rs2333227 was performed on an ABI TaqMan 7900HT RT-PCR thermocycler. Results The relative risk of major adverse cardiovascular events (MACE) for patients with high plasma MPO is 1·2 (95%CI: 1·038–1·377, P A is not an independent risk factor for MACE in patients suffering from PAD.

Introduction Vitamin D deficiency, as reflected by low 25-hydroxyvitamin D blood levels (25D), is a prevalent correctable risk factor for death in most populations around the globe. The evidence ranges from numerous association studies and meta-analyses thereof, over Mendelian randomization studies, to randomized controlled trials (RCTs). However, most studies reported to date were performed in rather older populations and some of the largest association studies may have been confounded by increased vitamin D supplementation at old age, especially in women, and by the use of vitamin D2, which is fully measured by 25D immunoassays but biologically considerably less active. In addition, cause-specific mortalities and the impact of age on the 25D association with the risk of death have not been reported in detail, yet. Methods Data of all patients who had a 25D measurement at the Department of Laboratory Medicine, General Hospital of Vienna between 1991 and 2011 were retrieved and matched with the Austrian national register of deaths. First 3 years of mortality since 25D measurement were excluded in the analyses. Fine-Gray regression models adjusting for competing risks were used to estimate the survival time in dependence on 25D, adjusting for sex, age, year and month of blood draw. 25D was represented using a spline with 5 knots placed on the corresponding 1/6th quantiles. Age group (0– Results Data from 78,581 patients (mean age = 51.0 years, men 31.5%) were used for analyses. During 20 years (median = 10.5) of follow-up, 11877 deaths were observed. Among these patients, 25D ≤ 10 nmol/L had 2-3 fold increased risk of death ( Conclusions Our survival data from a large cohort, covering all age groups, from a population with minimal vitamin D supplementation at old age and negligible intake of vitamin D2, confirm a strong association of vitamin D deficiency (25D

Elevated coagulation factor VIII activity has been associated with increased risk for both venous and arterial thrombosis. The current study evaluated the influence of Factor VIII levels and interactions with gender on all cause mortality in a large Austrian cohort.During 1991 and 2003, 11203 individuals, first ever request for laboratory analyses of FVIII: C, ageor =18 years, were included in this study. The median observation period was 5 years covering a total of 46000 person-years. The death rate was 17.1%.Compared to individuals within the reference category (FVIII: C94%) hazard ratios gradually increased from 1.4 (95% CI: 1.1-1.8) in the 152-170% category (5th decile) to finally 4.4 (95% CI: 3.5-5.5) in the313% category (highest decile, all p0.05). The association between FVIII: C levels and mortality remained essentially unchanged when considering non-cancer mortality, all cause vascular mortality or mortality due to ischemic heart disease. Compared to males females with elevated FVIII: C had a worse outcome resulting in higher hazard ratios reaching 6.8 (95% CI: 4.6-9.9) within the highest decile compared to males (HR: 3.4 (95% CI: 2.6-4.5)).In our large patient cohort we might be able to demonstrate for the first time that FVIII: C plasma activity is strongly associated with all cause mortality. Additionally, FVIII: C appears to interact with gender. Especially in women FVIII: C might help identifying high-risk cohorts, which might benefit from individualized prevention strategies.

This study set out to identify the effects of recreational and endurance exercise on subclinical evidence of atherosclerosis in young adults.Cardiovascular disease risk factors and intima-media thickness determination by B-mode ultrasonography of 150 subjects were correlated to endurance exercise, recreational exercise, and sedentary lifestyle. The subjects comprised 20- to 40-year-old men and women without cardiovascular disease. This cross-sectional, case-control study analyzed data on the laboratory parameters and information collected from a risk factor questionnaire.The athletes, both endurance and recreational groups, have significantly superior values with respect to physiognomy, lipid profile, and inflammatory markers in relation to the nonexercising study population (all P0.05). Detailed analysis showed markedly reduced values for relative body fat (relative reduction 14.3%), low-density lipoprotein (10.6%), and triglycerides (13.5%) and a 50% reduction of hs-C-reactive protein. In the univariate and multivariate comparison of athletic (n = 100) and nonathletic (n = 50) groups, exercise did not show to exert a significant influence on vascular wall parameters (for all, P0.05).Exercise, in recreational and endurance form, between the ages of 20 and 40 years exerts a preventive influence on cardiovascular risk factors but seems to fail to affect early, atherosclerotic vascular wall changes.

SummaryIm Vergleich zu anderen Labortests weisen Gerinnungstests eine relativ große Fehleranfälligkeit und eine größere analytische Variabilität auf, was nicht zuletzt mit der relativ komplexen Präanalytik zusammenhängt. Daher mehrere Richtlinien erschienen, die helfen sollen, die Präanalytik in der Hämostaseologie zu standardisieren. Obwohl die publizierten Richtlinien zweifellos wertvolle Anhaltspunkte für die tägliche Laborpraxis darstellen, handelt es sich in einigen Bereichen um Maximalkriterien, die sich technisch und logistisch im diagnostischen Alltag nicht immer vollständig umsetzen lassen.In diesem Übersichtsartikel sollen häufige Problemfelder in der Präanalytik der Routine-Gerinnungstests diskutiert werden. Da die Stabilität von Gerinnungstests wie z. B. der Prothrombinzeit und der partiellen Thromboplastinzeit stark von lokalen Faktoren abhängen (z. B. Röhrchentyp, Hersteller, Reagenzien und Analysesysteme) wird empfohlen, dass jedes Labor auf Basis der Richtlinien detaillierte Verfahrensanweisungen für die Ein-sender entwickelt, um die präanalytische Variabilität zu vermindern.

Background: C-reactive protein (CRP), an acute-phase protein, is a sensitive systemic marker of inflammation and acute-phase reactions. Testing CRP concentrations at hospital admission may provide information about disease risk and overall survival. Methods: All first-ever transmittals to the department of medical and chemical laboratory diagnostics for determination of low-sensitivity CRP (n = 274 515, 44.5% male, median age 51 years) between January 1991 and July 2003 were included [median follow-up time: 4.4 years (interquartile range, 2.3–7.4 years)]. The primary endpoint was all-cause mortality. Multivariate Cox regression adjusted for sex and age was applied for analysis. Results: Compared to individuals within the reference category (CRP 80 mg/L, all P 60 years: 1.7–3.7). Interestingly, both short- and long-term mortality were associated with increasing CRP concentrations (>80 mg/L: HR 22.8 vs 1.4). Conclusion: Measurement of low-sensitivity CRP at hospital admission allowed for the identification of patients at increased risk of unfavorable outcome. Our findings indicate that close attention should be paid to hospitalized patients with high CRP not only because of very substantial short-term risk, but also long-term excess risk, the basis for which needs to be determined.

Aims Blood d-dimer testing has been proposed as diagnostic marker with high sensitivity for exclusion of acute aortic dissection (AAD). We performed a systematic review and validated the findings in a prospective patient cohort. Methods and results We searched MEDLINE, EMBASE, CINAHL, and BIOSIS from inception until January 2007 using a combination of search terms for aortic dissection and d-dimer. Study type, type of assay used, predefined cut-off level, result of d-dimer testing, sensitivity, and specificity were abstracted. In 16 identified studies (437 patients), the reported cut-off values ranged from 0.1 to 0.9 µg/mL. d-Dimer testing provided high sensitivity (0.97 95% CI 0.94–0.98) and negative likelihood ratio (0.06 95% CI 0.02–0.13). In our cohort of 65 patients (36 male, 55%; median age 59 years, IQR 49–67) with proven AAD, d-dimer levels scattered from 0.24 to 137.88 µg/mL (median 3.47; IQR 1.55–14.49). Mean NPV for the different cut-off levels ranged from 92 % for a cut-off level of 0.9 µg/mL to 100% for a cut-off level of 0.1 µg/mL in our study population. Conclusion Current evidence supports a routine measurement of d-dimer in excluding AAD. A d-dimer

Summary. Background: Meningococcal disease may present as sepsis, meningitis or a combination of both. Impaired fibrinolysis and massive elevation of the plasminogen activator inhibitor-1 (PAI-1) is a characteristic feature of meningococcal sepsis. We and others have reported an association between mortality and the functional 4G/5G promoter polymorphism of the PAI-1 gene in children with meningococcal sepsis. Objective: Multicenter study to investigate the association of the 4G/5G PAI-1 polymorphism and disseminated intravascular coagulation (DIC) in children with meningococcal disease in a Central European population. Patients/Methods: Blood samples and clinical information of 326 previously healthy children with meningococcal infection were collected from 95 pediatric hospitals in Germany, Switzerland, Italy, and Austria from 2000 to 2002. Results: DIC, defined as platelet counts below 100 G L−1, increased D-dimer levels and prolonged prothrombin time, was significantly associated with the 4G4G genotype [31 of 63 (49%) vs. 55 of 175 (31%), P = 0.014], resulting in a hazard ratio (HR) of 1.5 (95% confidence interval 1.1–2.1) to develop DIC. Carriers of the 4G4G genotype showed significantly lower platelet counts (183 G L−1 vs. 227 G L−1, P = 0.009) on admission. Fibrinogen and C-reactive protein levels were not associated with the PAI-1 4G/5G polymorphism, nor were white blood cell counts. Conclusions: Our data show a correlation between the 4G4G genotype of the PAI-1 gene and development of DIC in meningococcal infection.

Background: Increased gamma glutamyltransferase (GGT) is associated with cardiovascular disease. To date, however, few studies with sufficient sample size and follow-up have investigated the association of GGT with all-cause mortality. Methods: The relation of GGT to the risk of death was examined in a cohort of 283 438 first attendants (inpatients or outpatients) of the Vienna General Hospital with request for GGT analysis as part of a routine screening panel and was monitored for up to 13 years. To evaluate GGT as a predictor, Cox proportional hazards models were calculated, which were adjusted for age and sex. Results: In both men and women, GGT above the reference category (GGT ≥9 U/L in women, ≥14 U/L in men) was significantly (P 80 years, respectively). Conclusions: GGT is associated with mortality in both men and women, especially in patients younger than 30 years, and even high-normal GGT is a risk factor for all-cause mortality.

Introduction The acute phase reactant fibrinogen plays a critical role in the coagulation system and inflammation. Recently several polymorphisms have been described regulating basal and peak fibrinogen expression. We evaluated the role of a frequent promoter polymorphism in the beta chain of the fibrinogen gene (− 148 C/T) in a human in vivo model of experimental endotoxemia. Material and methods Healthy volunteers received 2 ng/kg endotoxin (LPS, n = 73) as a bolus infusion over 2 min. Blood samples were collected by venipunctures into EDTA anticoagulated vacutainer tubes before LPS infusion. For determination of the fibrinogen promoter polymorphism, we developed a new mutagenic separated polymerase chain reaction assay. Results Carriers of the − 148 T allele had significantly lower TNFα expression throughout the whole time course of LPS stimulation and Interleukin-6 levels were trendwise lower, however only basal levels reached statistical significance. No effects were observed on markers of coagulation activation (D-Dimer, Prothrombin F1 + 2). Conclusion Our findings indicate, that the common − 148 C/T polymorphism is associated with differences in the TNFα release in response to systemic LPS infusion in humans, and add to current evidence that gene-sequence changes in beta-fibrinogen locus can alter the ability of the host to respond to endotoxin.

Clinical implications of subclinical hypothyroidism (SCH) are still matter of intense debate, resulting in the controversial discussion whether subclinical hypothyroidism should be treated. We performed a cohort study to evaluate the impact of subclinical hypothyroidism on vascular and overall mortality. Between 02/1993 and 03/2004, a total of 103,135 persons attending the General Hospital Vienna with baseline serum thyrotropin (TSH, thyroid-stimulating hormone) and free thyroxin (fT4) measurements could be enrolled in a retrospective cohort study. Subclinical hypothyroidism was defined by elevated TSH ranging from 4.5 to 20.0 mIU/L and normal fT4 concentration (0.7–1.7 ng/dL). Overall and vascular mortality as primary endpoints were assessed via record linkage with the Austrian Death Registry. A total of 80,490 subjects fulfilled inclusion criteria of whom 3934 participants (3.7 %) were classified as SCH (868 males and 3066 females, median age 48 years). The mean follow-up among the 80,490 subjects was 4.1 years yielding an observation period of 373,301 person-years at risk. In a multivariate Cox regression model adjusted for age and gender TSH levels showed a dose-dependent association with all-cause mortality. The association between SCH and overall or vascular mortality was stronger in men below 60 years compared to older males or females. Our data support the hypothesis that SCH might represent an independent risk factor for overall and vascular mortality, especially in men below 60 years. Whether this group would benefit from replacement therapy should be evaluated in interventional studies.

Background: C-reactive protein (CRP) plays a major role in the immune system and is an independent risk marker of cardiovascular disease. However, CRP’s role in atherogenesis as innocent bystander, causative, or even protective agent, remains unresolved. The +1444C/T alteration in the CRP gene has been reported to determine basal CRP concentrations. We hypothesized that this alteration may also be associated with the degree of inflammatory response and coagulation activation in a well-standardized model of systemic inflammation.Methods: We administered 2 ng/kg endotoxin [Escherichia coli bacterial lipopolysaccharide (LPS)] intravenously to stimulate inflammation in 91 healthy young Caucasian male paid volunteers (age range, 19–40 years). Participants were confined to bed rest and fasted for 8.5 h after LPS infusion. We collected blood samples before LPS infusion and at 0, 2, 6, and 24 h after LPS infusion to measure inflammation markers [interleukin 6 (IL6), tumor necrosis factor-α (TNFα)], temperature, and coagulation markers (prothrombin fragment F1+2, D-dimer). We analyzed the CRP 3′ untranslated variant with a mutagenic separated PCR assay.Results: Basal concentrations of high-sensitivity CRP were ∼40% lower in +1444CC alteration carriers than in T homozygous (TT) allele carriers (P = 0.04). In contrast, basal IL6 concentrations were 2-fold higher in wild-type C homozygous (CC) than in TT individuals (P = 0.01). In response to the LPS challenge, CC individuals had 4-fold higher peak TNFα concentrations (P 2.5-fold higher peak IL6 concentrations (P Conclusions: Genetic factors regulating CRP concentrations also modulate the individual response to endotoxin-stimulated inflammation.

An earlier study reported that a common polymorphism in the 5' untranslated region of the epidermal growth factor (EGF) gene is associated with increased risk for cutaneous malignant melanoma (MM) and Breslow thickness. Since then, several independent studies have reported conflicting results that have challenged this hypothesis. However, none of the previous studies examined survival as the primary outcome. We therefore sought to study the association between this polymorphism and survival. One hundred and thirty patients diagnosed with MM with a Breslow thickness of >1.5 mm were included in this study. In our collective, the G/G genotype represented a significant risk factor for both shorter disease-free period (hazard ratio of 2.246, 95% CI: 1.06-4.78, P=0.036) and overall MM-specific survival (hazard ratio of 3.8, 95% CI: 1.5-9.5, P=0.004) compared with the A/A genotype, while the heterozygous A/G genotype showed an intermediate risk. In the present study, we demonstrate for the first time that the EGF A61G polymorphism is associated with survival. Our data suggest that this polymorphism is a potential marker for disease severity that predicts earlier progression of MM.

Background: Anti-cardiolipin antibodies have been associated with both arterial and venous thrombosis, but their overall impact on all-cause or vascular mortality is unknown. In this study, we evaluated the influence of anti-cardiolipin antibodies on all-cause and vascular mortality. Methods: All individuals who fulfilled the inclusion criteria (completeness of data, no admission from an intensive care unit, unique identification with name and date of birth) and whose anti-cardiolipin antibodies were measured between October 2002 and February 2004 were included in this study (n = 4756; 64% female; median age, 46 years). Death/survival and cause of death were obtained from the Austrian Death Registry. The median observation period was 1.5 years, and the study comprised 7189 person-years. Results: During the study period, 184 patients (3.9%) died. There were no associations between either anti-cardiolipin IgM or IgG antibodies and both vascular death and noncancer mortality as outcome variables in a Cox regression analysis adjusted for age and sex. In contrast, the risk of cancer-related mortality was increased 2.6-fold. Conclusions: Anti-cardiolipin antibodies are associated with cancer mortality, likely as an epiphenomenon of malignancy, but they are not predictive of vascular mortality or noncancer mortality. Hence, although a clear association between anti-cardiolipin antibodies and (mostly nonfatal) vascular events has been described in the literature, our data indicate that this finding is not necessarily associated with an increase in vascular mortality.

Heme oxygenase-1 (HO-1) has been demonstrated to play an important role in the regulation of signaling systems, which are involved in the control of cell cycle progression and apoptosis. Recently, a (GT)n dinucleotide repeat polymorphism in the HO-1 promoter was shown to modulate HO-1 gene expression. Short (25 GT) repeats are associated with an increased HO-1 upregulation after stimulation than are longer repeats. Malignant melanoma (MM) is the most serious cutaneous malignancy with high tendency to aggressive growth and resistance to apoptosis. Therefore, we sought to study the influence of this polymorphism on the progression of MM. We determined the HO-1 promoter genotype in 152 patients with MM and 398 healthy controls and studied their association in regard to susceptibility to MM, Breslow thickness and disease-free survival. In our study, the homozygous short allele with25 (GT)n repeats (S/S) was found more frequently in the melanoma group compared to the healthy control population (21 and 12%, respectively). The calculated risk for acquiring primary MM in S/S carriers was 2-fold higher compared to those with L-allele types (95% confidence interval: 1.2-2.4, p = 0.03). Additionally, the S/S genotype was significantly associated with primary tumors with deeper Breslow thickness compared to L-allele (25 repeats) carriers (mean Breslow thickness: 4.0 +/- 2.9 mm versus 3.1 +/- 1.7 mm, p = 0.03). These data suggest that HO-1 might render a higher risk for MM in S/S genotype individuals and could represent an important candidate gene in the pathogenesis and growth of malignant melanoma.

Background: Amiloride-sensitive epithelial sodium channels (ENaCs) are important candidates in the development of hypertension, which is a major risk factor for stroke. Two single-nucleotide polymorphisms (SNPs) in the gene that encodes the ENac α-subunit (αENaC) have been identified. We evaluated those SNPs for a possible association with ischemic cerebrovascular events (ICEs). Methods and Results: We genotyped 1399 patients with ICEs [median age, 70 years; interquartile range, 58–78 years; 745 (53%) men] and 1076 control individuals without vascular disease [47 (39–58) years; 557 (52%) men] for the SNPs Trp493Arg and Ala663Thr. The SNP frequencies at nucleotide 3977 (Trp493Arg) in the αENaC gene were significantly different in patients and controls. Carriers of 493Arg had a 1.78-fold increased risk (95% confidence interval, 1.02–3.12) for ICEs compared with Trp/Trp carriers. Interaction analysis revealed that the relative risk was even higher in women in the lowest age tertile [adjusted odds ratio, 3.26 (1.10–9.72)]. Conclusions: Carriers of the 493Arg allele are at increased risk for ICEs compared with Trp/Trp carriers. The effect is independent of traditional vascular risk factors and is particularly evident in younger women. The Trp493Arg variant in αENaC may represent an important candidate genetic susceptibility factor in the development of ICEs.

SummaryThe chemokine fractalkine (FKN) recruits leukocytes into lesions of the arterial wall, which may lead to restenosis after stenting. FKN also regulates proliferation of smooth muscle cells, another mechanism pivotal to neointimal thickening. We assessed the hypothesis that functionally important polymorphisms of the FKN receptor CX3CR1 influence restenosis after coronary stenting. Three hundred and sixty-five patients undergoing coronary stenting were genotyped for the CX3CR1 polymorphisms V249I and T280M. Restenosis occurred in 25% of patients, and recurrent (> 1) restenosis at the target lesion in 8%.The allele I249 was associated with an increased risk of restenosis (adjusted odds ratio 2.4, 95% confidence interval: 1.3–4.2,P = 0.003) and recurrent restenosis (odds ratio 2.7,95% confidence interval:1.3–5.9,P = 0.011).Particularly, patients with I249 lacking the allele M280 were at an elevated risk of restenosis (P = 0.006) and, accordingly, the haplotype containing I249 but not M280 was more frequent in patients with restenosis (P = 0.001). In conclusion, the CX3CR1 I249 allele is associated with an increased risk of restenosis while the CX3CR1 M280 allele might counteract the harmful influence of I249.These findings show the importance of the chemokine FKN and genetic variations of its receptor for restenosis after coronary stenting. Recognition of these inherited risk modifiers may help to individualize treatment of coronary stenosis.

SummarySeveral lines of evidence suggest that the chemokine fractalkine (FKN) and its receptor CX3CR1 contribute to the accumulation of leukocytes in the atherosclerotic plaque. The M280 allele of the CX3CR1T280M polymorphism modulates leukocyte recruitment and is associated with lower prevalence of cardiovascular disease. The influence of V249I, another CX3CR1 poly-morphism, is discussed controversially. We investigated the association of the alleles M280 and I249 of CX3CR1 with coronary artery disease (CAD) and with acute coronary syndrome (ACS). Additionally, we assessed their association with the soluble ligand FKN and inflammatory activation measured by high-sensitivity C-reactive protein (hsCRP). The genotypes of the V249I and T280M polymorphisms were determined in 1152 patients with suspected CAD. 720 (62.5%) individuals showed significant CAD with an ACS prevalence of 59.3%. Using multivariate regression, we found a harmful influence of I249 (adjusted OR=1.8, P

We performed a multicenter case-control study to evaluate the impact of the glycoprotein 1b alpha (-5)T/C Kozak polymorphism on the risk of ischemic cerebrovascular events. The genetic analysis in 1399 patients (745 men; median age, 70 years; interquartile ratio, 58-78) and 1066 control subjects (549 men; median age, 47 years; interquartile ratio, 39-59) was carried out with mutagenically separated polymerase chain reaction. Homozygous C/C genotype carriers had a 3.5-fold increased risk for ischemic cerebrovascular events (95% confidence interval, 1.5-7.9, P = 0.003) over T/T or T/C genotype carriers together. The effect was independent of well-established atherosclerotic risk factors. Our findings could be explained by the reported gene dose effect of the Kozak polymorphism on the density of the glycoprotein 1b alpha/IX/V receptors on platelets. According to our data, the (-5)C Kozak allele may represent a candidate genetic susceptibility factor for ischemic cerebrovascular events.

Heme oxygenase-1 (HO-1) has been demonstrated to exert potent anti-oxidant and anti-inflammatory effects in the context of atherosclerotic vascular disease, and therefore was referred to as a potential vascular protective factor. A (GT)n dinucleotide repeat polymorphism in the HO-1 promoter has been shown to modulate HO-1 gene expression. Short ( or =25) repeat (class L) alleles after adjustment for potentially confounding factors. Genotype distributions of S/S, S/L and L/L in patients were 9.8% (n=39), 45.1% (n=180) and 45.1% (n=180), which was similar to the distribution in controls with 11.5% (n=46), 44.5% (n=177) and 44.0% (n=175). In the presence of vascular risk factors, the HO-1 genotype became functionally relevant: in patients without hyperlipidemia the S/S genotype exerted a protective effect on the development of ischaemic cerebrovascular events (OR 0.2; 95% CI 0.1-0.6), while this effect was no longer present in hyperlipidemic patients. Short (

Background: Interleukin 6 (IL-6) is a pleiotropic cytokine that plays an essential role in the pathogenesis of acute and chronic infections. As the role of the IL-6 G(−174)C polymorphism in determining serum concentrations of IL-6 is controversial, we studied the genotype-specific IL-6 response in a well-standardized model of systemic inflammation. Methods: A total of 76 healthy young males (age range, 19–35 years) received a single bolus of 2 ng/kg endotoxin [lipopolysaccharide (LPS)] intravenously. Plasma IL-6 was measured by enzyme immunoassay at 0, 2, 6, and 24 h after LPS infusion, and the IL-6 promoter genotype was analyzed by a mutagenic separated PCR assay. Results: IL-6 increased 300-fold 2 h after LPS challenge and returned almost to normal within 24 h. Neither basal IL-6 nor the IL-6 response to LPS was significantly affected by the IL-6 promoter genotype. Conclusions: The IL-6 G(−174)C promoter polymorphism does not significantly influence basal concentrations of IL-6 or peak IL-6 in human endotoxemia.

Background and purpose: Elevated plasma levels of interleukin-6 (IL-6) are associated with an increased risk and worse outcome of acute vascular events. A common G/C promoter polymorphism at nt (−174) of the IL-6 gene has been shown to affect basal IL-6 levels. Consequently, the IL-6 genotype may be associated with risk and outcome of ischemic stroke (IS). We investigated the statistical association between this polymorphism and cerebrovascular events, as well as the clinical outcome in patients with symptoms before the age of 60. Methods: We examined 214 patients of 60 years or less with acute ischemic stroke or transient ischemic attack (TIA) and 214 age- and sex-matched healthy control subjects for the (−174) IL-6 G/C polymorphism by mutagenic separated polymerase chain reaction (MS PCR). Clinical severity of the vascular event was evaluated by validated scales at predefined points of time. Results: In the total group of patients, the genotype and allele frequencies in the patient group (38% GG, 45% GC, 17% CC; allelic frequency: 60% G, 40% C) did not differ significantly from the control group. However, individuals homozygous for the (−174)G variant had significantly worse scores on the NIH Stroke Scale (NIHSS) already on admission and 1 week after the event. Also, patients with severe disability 1 week and 3 months after the event (Rankin Scale (RS) 4 or 5; NIH Stroke Scale≥6) were significantly more often carriers of the GG genotype. In a multivariate analysis, the IL-6 (−174)GG genotype was significantly associated with severe disability after 1 week (RS 4–5; odds ratio (OR)=3.2, 95% CI: 1.5–6.6; p=0.002; NIHSS≥6; OR=4.2, 95% CI: 1.6–11.1). Conclusions: The (−174)GG-genotype of the IL-6 gene is associated with severe stroke in young patients with acute cerebrovascular events. Further studies with larger patient groups are warranted to confirm these findings.

Arterial and venous thromboses, with their clinical manifestations such as stroke, myocardial infarction (MI), or pulmonary embolism, are the major causes of death in developed countries. Several studies in twins and siblings have shown that genetic factors contribute significantly to the development of these diseases. Since the advent of molecular genetics in medicine, it has been a focus of interest to elucidate the role of mutations in various candidate genes and their impact on hemostatic disorders such as arterial and venous thromboses. In this article, we review the current knowledge of the contribution of polymorphisms in coagulation factors to the development of thrombotic diseases. We show that in arterial thrombosis, results are controversial. Only for factor XIII 34Leu a protective effect on the development of myocardial infarction has been demonstrated in several studies. No other single polymorphism in a coagulation factor could be confirmed as a relevant risk factor, although there is evidence for a role of factor V Arg506Gln, factor VII Arg353Gln, and vWF Thr789Ala polymorphisms in patient subgroups. Further studies will be necessary to confirm the value of testing for genetic polymorphisms in arterial thrombosis. A large body of data is available on the role of factor V Arg506Gln and the prothrombin G20210A mutation in venous thrombosis. Some papers already recommend diagnosis and treatment strategies. We will discuss these recent publications on venous thrombosis in our review.

Summary. A frequent polymorphism in the factor XIII (FXIII) A-subunit gene, leading to a Val to Leu amino acid exchange at position 34, suggested to affect clot stability, has been associated with a decreased risk for venous thromboembolism and myocardial infarction. Its role in the development of stroke is still under investigation. Ninety-four patients with primary arterial intracerebral haemorrhage (mean age ± standard deviation: 69 ± 14 years; 48 men, 46 women), 718 patients with ischaemic stroke (63 ± 14 years; 395 men, 323 women) and 369 healthy control subjects (59 ± 14 years; 299 men, 170 women) were analysed for FXIII Val34Leu. No differences in genotype distribution between all three groups were observed. Also, no significant differences in the genotype distribution were found between subgroups of patients stratified according to age, sex, aetiology, history of hypertension, antiplatelet or anticoagulant medication and other vascular risk factors. In contrast to previously reported findings in smaller collectives, our data suggest that an association of the FXIII Val34Leu polymorphism with a decreased risk of ischaemic stroke or an increased risk of intracerebral haemorrhage is highly unlikely. Thus, screening for the FXIII Val34Leu polymorphism will not contribute significantly to the risk prediction of cerebrovascular disease.

Elevated plasma cell membrane glycoprotein 1 (PC-1) expression and the frequent PC-1 K121Q polymorphism have recently been associated with insulin resistance. Since insulin resistance represents an important risk factor for atherosclerotic vascular disease and myocardial infarction, we investigated the involvement of the PC-1 K121Q polymorphism in the development of myocardial infarction. We analyzed two independent series of cardiovascular patients at a defined end-point of atherosclerotic vascular disease (those having suffered myocardial infarction) for the PC-1 K121Q mutation by a newly developed mutagenic separated PCR assay. In both patient groups the presence of the Q allele was significantly associated with younger age at the time of first myocardial infarction, suggesting a more rapid progression of endothelial dysfunction. In a multivariate analysis carriers of the 121Q allele from Vienna and from Central Germany exhibited a 2.6- and a 4.2-increased odds, respectively, for suffering myocardial infarction within the first tertile of age (

After rupture of an arteriosclerotic plaque in a coronary artery, platelets play a crucial role in the subsequent thrombus formation, leading to myocardial infarction. An increased mean platelet volume (MPV), as an indicator of larger, more reactive platelets, may represent a risk factor for myocardial infarction. However, this hypothesis is still controversial and most studies addressing the role of MPV were performed comparing patients suffering from myocardial infarction with healthy controls. We intended to identify patients at high risk of suffering myocardial infarction in a group of patients with known coronary artery disease. One hundred and eighty-five consecutive patients with stable coronary artery disease were compared with 188 individuals who had suffered myocardial infarction. Patients within the highest quintile of MPV (> or = 11.6 fl) had a significantly higher risk of experiencing a myocardial infarction compared with patients within the lowest quintile (OR = 2.6, 95% CI 1.3-5.1) in a multivariate analysis that included sex, age, body mass index, hyperlipidaemia, hypertension, smoking and diabetes mellitus. Our results indicate that patients with pre-existing coronary artery disease and an increased MPV (> or = 11.6 fl) are at higher risk of myocardial infarction. These patients can be easily identified during routine haematological analysis and could possibly benefit from preventive treatment.

Atherosclerosis often presents as a complex systemic disease that is strongly influenced by lifestyle factors, but also by the genetic background. The sequence variant rs1333049 affects the expression of ANRIL, a noncoding RNA transcript playing a key role in the regulation of inflammatory processes. We thus aimed to replicate the predictive value of genetic information on this variant regarding the development of cardiovascular events in an Austrian high-risk cohort.Nine hundred and eighty-eight patients from an angiologic outpatient ward at a large University hospital were genotyped by means of the 5'-nuclease assay. Relative risk ratios were assessed for carriers of different alleles. Statistical independence of genetic information was evaluated in multivariable analysis including known risk markers.In patients carrying the [G]-allele, metabolic parameters (serum low-density lipoprotein, total cholesterol) significantly decreased during the initial 6 months of the observation period (P 0.01). Likewise, homozygous [C]-allele carriers were at a higher risk of suffering myocardial infarction (relative risk = 2.681, 95% confidence interval 1.418-5.070). In contrast, we found no interaction between rs1333049 genotype and progression of carotid atherosclerosis or stroke.These results are in line with the previous findings, suggesting that genetic information on the rs1333049 variant might be a useful predictor of adverse cardiac events. Thus, we could successfully replicate the predictive value of the 9p21 risk allele in an Austrian cohort.

Detection of chimerism by PCR analysis of short tandem repeats (STR) in blood samples of patients who received allogeneic bone marrow transplantation (BMT) has proved to be an important method for early detection of relapse. The prerequisite for this type of analysis is knowledge of donor and recipient pretransplantation genotypes. In some cases, recipient cells from time points prior to BMT are not available and the pretransplant fingerprint cannot be determined. As BM recipients only alter their genotype in blood cells, we attempted to identify patient's pretransplantation genotypes after transplantation in mouthwash samples that contain easily accessible epithelial cells. Of 17 patients who had undergone BMT between one week and 45 months prior to analysis, DNA was isolated from mouthwash cell pellets or from epithelial cells obtained from mouthwashes. PCR analysis of STR loci in the von Willebrand and the tyrosine hydroxylase genes were performed. Even though the mouthwash cell pellets contained about 75% epithelial cells (presumably of recipient origin) and only about 25% leukocytes (presumably of donor origin), three of five patients showed donor genotype and only two patients exhibited chimeric DNA patterns, when cellular DNA was obtained by boiling of mouthwash cell pellets. Following phenol/chloroform extraction, eight of 10 DNA samples exhibited a chimeric pattern, while two of 10 DNAs showed only donor genotype. Of three patients, epithelial cells were attached to magnetic beads prior to DNA isolation. Even this DNA contained donor and recipient material. From our results it appears that blood cells serve as preferential DNA source in mouthwash samples and cannot be removed by epithelial cell separation.