Summary. 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 ( ‡ 11AE6 fl) had a significantly higher risk of experiencing a myocardial infarction compared with patients within the lowest quintile (OR ¼ 2AE6, 95% CI 1AE3-5AE1) in a multivariate analysis that included sex, age, body mass index, hyperlipidaemia, hypertension, smoking and diabetes mellitus. Our results indicate that patients with preexisting coronary artery disease and an increased MPV ( ‡ 11AE6 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.

Background and Purpose-Increased mean platelet volume (MPV), indicating higher platelet reactivity, is associated with an increased risk of myocardial infarction. Higher levels of MPV have been found in patients with acute ischemic stroke than in control subjects. Data from smaller studies regarding an association between MPV and stroke severity and outcome have been controversial. If such an association exists, MPV might help to identify patients at increased risk of a severe course of acute cerebrovascular disease. Methods-Within a multicenter, cross-sectional study nested in a cohort, we analyzed the relation between MPV and stroke severity as determined by the modified Rankin Scale after 1 week in 776 patients with acute ischemic stroke or transient ischemic attack. By multivariate logistic regression modeling, we determined the influence of MPV on stroke severity, adjusting for potential confounding factors. Results-Patients within the highest quintile of MPV had a significantly higher risk of suffering a severe stroke, defined as modified Rankin Scale score of 3 to 6, compared with patients within the lowest quintile (odds ratioϭ2.6; 95% confidence interval, 1.6 to 4.1; PϽ0.001). This association remained significant after adjustment for possible confounding factors (odds ratioϭ2.2; 95% confidence interval, 1.2 to 4.0; Pϭ0.013). Conclusions-Our results indicate that an elevated MPV is associated with a worse outcome for acute ischemic cerebrovascular events independent of other clinical parameters.

BackgroundOnly limited data on the prevalence of iron deficiency (ID) and its correlation with clinical parameters are available in cancer. ID frequently contributes to the pathogenesis of anemia in patients with cancer and may lead to several symptoms such as impaired physical function, weakness and fatigue.Patients and methodsParameters of iron status and clinical parameters were evaluated in 1528 patients with cancer who presented consecutively within a four-month period at our center. One thousand fifty-three patients had solid tumors and 475 hematological malignancies.ResultsID [transferrin saturation (TSAT) < 20%] was noted in 645 (42.6%) of the 1513 patients with TSAT tests available and 500 (33.0%) were anemic. ID rates were highest in pancreatic (63.2%), colorectal (51.9%) and lung cancers (50.7%). Of the 409 iron-deficient patients in whom serum ferritin levels were available additionally to TSAT, 335 (81.9%) presented with functional ID (FID) (TSAT < 20%, serum ferritin ≥30 ng/ml) and 74 (18.1%) with absolute ID. In patients with solid tumors, prevalence of ID correlated with cancer stage at diagnosis (P = 0.001), disease status (P = 0.001) and ECOG performance status (P = 0.005).ConclusionsID was frequently noted in cancer and was associated with advanced disease, close proximity to cancer therapy, and poor performance status in patients with solid tumors.

Objective— An increased mean platelet volume (MPV), as an indicator of larger, more reactive platelets resulting from an increased platelet turnover, may represent a risk factor for overall vascular mortality, including myocardial infarction. We intended to identify patients at higher risk of dying from vascular disease in a large, hospital-based cohort. Methods and Results— A total of 206 554 first-ever admissions to the Allgemeines Krankenhaus Wien for determination of MPV between January 1996 and July 2003 were included. Primary end points were overall vascular mortality and death due to ischemic heart disease. Multivariate Cox regression adjusted for sex, age, and platelet count was applied for analysis. MPV values were categorized into quintiles, with the lowest quintile serving as the reference category. Compared with individuals with lower MPV (<8.7 fL), hazard ratios for overall vascular mortality gradually increased to 1.5 in the highest category (≥11.01 fL). The relationship of MPV to ischemic heart disease was even stronger and increased from 1.2 (8.71 to 9.60 fL category) to 1.8 in the highest category (≥11.01 fL). Conclusion— Our results indicate that patients with an increased MPV (≥11.01 fL) are at higher risk of death due to ischemic heart disease, with hazard ratios comparable to those reported for obesity or smoking.

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 <0.001) associated with allcause, cancer, hepatobiliary, and vascular mortalities. Hazard ratios (HRs) for men and women were similar in all categories. Among patients who presented with GGT above the reference category, those younger than 30 years had higher all-cause mortality rates than did older individuals (HR 1.5-3.3 vs HR 1-1.3 >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.

Abstract-Leptin, a protein encoded by the obese gene, is produced by adipocytes and released into the bloodstream. In obese humans, serum leptin levels are increased and correlate with the individual's body mass index and blood pressure. Elevated serum concentrations of endothelin-1 (ET-1), a potent vasoconstrictor and mitogen, were also observed in obese subjects. The pathomechanisms underlying this ET-1 increase in obesity are poorly understood. In the present study, we investigated the influence of the ob gene product leptin on the expression of ET-1 in human umbilical vein endothelial cells (HUVECs). Binding studies using 125 I-radiolabeled leptin revealed high-and low-affinity leptin binding sites on HUVECs (Kd1ϭ13.1Ϯ3.1 nmol/L and Kd2ϭ1390Ϯ198 nmol/L, respectively), mediating a time-and dose-dependent increase of ET-1 mRNA expression and protein secretion after incubation of HUVECs with leptin. This leptin-induced ET-1 expression was inhibited by preincubation of HUVECs with 0.75 mol/L antisense phosphorothioate oligonucleotides directed against the leptin receptor Ob-Rb. Furthermore, after incubation with leptin, increased nuclear staining of c-fos and c-jun, the major components of the transcription factor AP-1, and increased AP-1 DNA binding were observed. Transient transfection studies with ET-1 promoter constructs showed that leptin-induced promoter activity was abolished in the absence of AP-1 binding sites or by cotransfection with a plasmid overexpressing a mutated jun, which is able to bind c-fos but not DNA. Thus, leptin upregulates ET-1 production in HUVECs via a mechanism potentially involving jun binding members of the bZIP family. Key Words: endothelin Ⅲ obesity Ⅲ hypertension Ⅲ vasculature A lthough the association of obesity and hypertension is well established, 1 there is, however, scarce information about the underlying pathomechanisms. Recently, the adipocyte gained more attention, serving not only as a passive energy storage pool but also as an important source of endocrine-active peptides, thus leading to a novel concept of adipocyte function.One of the adipocyte-derived peptides involved in the control of body weight is the recently identified hormone leptin, 2 a protein encoded by the obese (ob) gene modulating lipid metabolism, 3 hematopoiesis, 4 pancreatic ␤-cell function, 5 and angiogenesis. 6,7 Mutation of the ob gene causes severe obesity in ob/ob mice, which can be reversed through administration of exogenous leptin. 8 -10 In contrast, serum leptin levels in obese humans are increased and correlate with their body mass index, 11 suggesting that obese subjects are resistant to endogenous leptin.Several alternate spliced isoforms of the leptin receptor (Ob-R) have been cloned (reviewed in Tartaglia 12 ) containing a single transmembrane domain and an extracellular domain homologous to the class I cytokine receptor family, but differing in the length of their cytoplasmic tail. The receptor with the full-length cytoplasmic domain (Ob-Rb, 302 amino acids) is predominantly expressed...

Summary. Introduction:The clinical relevance of decreased coagulation factor XII (FXII) plasma activity as a risk factor for both venous and arterial thrombosis is still discussed controversially. The current study evaluated the predictive value of FXII levels for all-cause mortality in a large Viennese patient cohort. Patients and methods: Individuals, whose FXII activity levels were determined for suspected coagulation disorders or thrombophilia screening between 1991-2003 were included in this study (n = 8936, 51% male, 49% female, median age 43 years). Death/survival was determined by record linkage with the Austrian Death Registry. The median observation period was 5 years covering a total of 46 400 person years; the death rate was 17.1%. For Cox regression analysis, FXII plasma activity was divided into 11 categories of 10% steps with the category of > 100% FXII serving as a reference category. Results: With decreasing FXII plasma activity, hazard ratios for all-cause mortality gradually increased linearly from 1.0 in the > 100% category to 1.5 (95% CI: 1.2-1.9) in the 80-90% category to 4.7 (95% CI: 3.4-6.5) in the 10-20% category. Similar results were obtained, when only vascular mortality or death as a result of ischemic heart disease was considered. No significant increase in all-cause mortality (HR: 1.4, 95%CI 0.7-2.8) was observed in the small group of FXII-deficient subjects [0-10% category (n = 58)]. Conclusions: This study first demonstrates a strong and almost linear association of FXII plasma activity between 90% and 10% with all-cause mortality in a large Viennese patient cohort. Interestingly, mortality rates are not increased when FXII activity is below 10%, resulting in a U-shaped survival curve.

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