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Background Type 2 Diabetes is a major risk factor for cardiovascular (CV) mortality. Insulin resistance can be evaluated non-invasively by insulin sensitivity indices (ISI) such as the Mcauley index (MCAi), which is a function of the fasting insulin and triglycerides. Currently, the association between ISIs and ECG findings and all-cause and CV mortality is still not established in a large scale and heterogeneous population. Method In a prospective study of the Israel cohort on Glucose Intolerance, Obesity and Hypertension (GOH) second phase (1979–1982) 1830 men and women were followed until December-2016 for CV-mortality and December-2019 for all-cause mortality. ECGs were recorded and OGTTs performed during baseline. ISIs were categorized into quartiles and evaluated against ECG findings and all-cause and CV-mortality. Results Mean age at baseline was 52.0 ± 8.1 years, and 75 (15.2%) and 47 (25.3%) participants in the upper quartiles (Q2-4) and the lower quartile (Q1) of the MCAi, presented with Ischemic changes on ECG respectively (p = 0.02). Multivariable analysis showed higher odds for ECG ischemic changes, for individuals in Q1-MCAi (adjusted-OR = 1.7, 95% CI 1.02–2.8), compared with Q2-4-MCAi, which attenuated when excluding individuals with diabetes (adjusted-OR = 1.6, 95% CI 0.9–2.7, p = 0.09). Median follow up for all-cause and for cardiovascular mortality was 31 years and 37 years, respectively. Cox proportional-hazards regression showed an increased risk for all-cause mortality for individuals in Q1-MCAi (HR = 1.2, 95% CI 1.02–1.3) as well as an increased risk for CV-mortality (HR = 1.4, 95%CI 1.1–1.8) compared with Q2-4-MCAi. Individuals in Q4-Ln Homeostatic model assessment- Insulin Resistance (HOMA-IR) and Q1- Quantitative Insulin Sensitivity Check Index (QUICKI) also presented with increased risk for all-cause-mortality (HR = 1.2, 95%CI 1.04–1.4; and HR = 1.2, 95% CI 1.04–1.4, respectively). Other ISIs did not show significant associations with CV-mortality. Conclusion Higher insulin-resistance, according to the MCAi, associated with ECG-changes, and with greater risk for all-cause and CV-mortality over a 40-year follow-up. The MCAi may be considered as an early predictive and prognostic biomarker for CV-morbidity and mortality in adults.

ZusammenfassungIndividuelle Förderung gilt als Merkmal guten Unterrichts, wobei individuelle Förderung als Sammelbegriff zu verstehen ist und in bildungswissenschaftlichen, bildungspolitischen und schulpraktischen Auseinandersetzungen unterschiedlich genutzt wird. Grundsätzlich ist darauf zu verweisen, dass individuelle Förderung unterbeforscht ist. Dies gilt sowohl zur Umsetzung individueller Förderung im Allgemeinen wie auch zu konkreten schulbezogenen Maßnahmen im Speziellen. Mit dieser Studie wird die Maßnahme ‚Ergänzungsstunden‘ (NRW) untersucht. Die ‚Ergänzungsstunden‘ sind an nordrhein-westfälischen Gymnasien Pflichtstunden, die verstärkt zur individuellen Förderung genutzt werden sollen und an den einzelnen Schulen unterschiedlich eingesetzt werden können. Während die Perspektive der Lehrpersonen auf individuelle Förderung bereits untersucht wurde, liegen Daten von Schüler/innen nur in sehr geringem Maße vor. So ist nicht beforscht, wie Schüler/innen Maßnahmen individueller Förderung wahrnehmen und wie sie diese bewerten. Dies erscheint aber insofern als relevant, als dass Schüler/innen wichtige Impulse für Schulentwicklungsprozesse unterstützen können, wenn sie in die Evaluation solcher Angebote einbezogen werden. Diese Studie stellt einen ersten Versuch dar, diese Forschungslücke zu schließen. 62 Unter- und Mittelstufen-Schüler/innen (Jahrgangsstufe 6–8) eines Gymnasiums wurden in zehn Gruppendiskussionen zur Umsetzung der ‚Ergänzungsstunden‘ an ihrer Schule befragt. Die Daten wurden mittels qualitativer Inhaltsanalyse ausgewertet. Die Daten verdeutlichen, dass die Befragten die Angebote individueller Förderung differenziert einschätzen können. Aus den Äußerungen der Schüler/innen lassen sich Impulse für die Schul- und Unterrichtsentwicklung ableiten, aber auch Implikationen für die weitere schulische und wissenschaftliche Praxis beschreiben.

Der Artikel setzt sich aus wissenschaftstheoretischer Perspektive mit dem der deutschsprachigen erziehungswissenschaftlichen Transferforschung unterliegenden Transfermodell auseinander, das als Stundenglasmodell bezeichnet wird. Das Modell wird skizziert und vor dem Hintergrund wissenschaftstheoretischer Prämissen analytisch-deskriptiver Forschung und pragmatistischer Aktionsforschung problematisiert. Aus keiner dieser Perspektiven kann von einer Rationalisierung pädagogischer Praxis durch wissenschaftliches Wissen ausgegangen werden. Ausblickend wird vorgeschlagen, verstärkt auf alternative Transfermodelle zu fokussieren und für diese Modelle mittels Design-Based- Research-Projekten zu prüfen, ob sich überzeugende Begründungslinien für die Notwendigkeit von Wissenstransfer finden lassenn. (DIPF/Orig.), The paper discusses the transfer model that underlies the current German-speaking educational research discourse on knowledge transfer. This model, that can be described as an hourglass model, is sketched out. The problems of this model are expounded against the background of the epistemological premises of analytical descriptive research as well as of pragmatistic action research. From neither perspective is it plausible to assume that educational practice can be rationalized through scientific knowledge. Hence, it is proposed to focus on alternative transfer models. It is stated that design-based research projects studying such alternative transfer models could provide convincing rationales for the necessity of knowledge transfer. (DIPF/Orig.)

Background The association between insulin resistance and cancer-mortality is not fully explored. We investigated the association between several insulin sensitivity indices (ISIs) and cancer-mortality over 3.5 decades in a cohort of adult men and women. We hypothesized that higher insulin resistance will be associated with greater cancer-mortality risk. Methods A cohort of 1,612 men and women free of diabetes during baseline were followed since 1979 through 2016 according to level of insulin resistance (IR) for cause specific mortality, as part of the Israel study on Glucose Intolerance, Obesity and Hypertension (GOH). IR was defined according to the Mcauley index (MCAi), calculated by fasting insulin and triglycerides, the Homeostatic Model Assessment (HOMA), the Matsuda Insulin Sensitivity Index (MISI), and the Quantitative Insulin Sensitivity Check Index (QUICKI), calculated by plasma glucose and insulin. Results Mean age at baseline was 51.5 ± 8.0 years, 804 (49.9%) were males and 871 (54.0%) had prediabetes. Mean follow-up was 36.7±0.2 years and 47,191 person years were accrued. Cox proportional hazard model and competing risks analysis adjusted for age, sex, country of origin, BMI, blood pressure, total cholesterol, smoking and glycemic status, revealed an increased risk for cancer-mortality, HR = 1.5 (95% CI: 1.1–2.0, p = 0.005) for the MCAi Q1 compared with Q2-4. No statistically significant associations were observed between the other ISIs and cancer-mortality. Conclusion The MCAi was independently associated with an increased risk for cancer-mortality in adult men and women free of diabetes and should be further studied as an early biomarker for cancer risk.

Introduction: Assessment of urine output in hospitalized patients or those undergoing complex surgery is essential for preventing Acute Kidney Injury and increased mortality. Currently, measurements of urine output are made by visually inspecting the volume of urine that accumulates in a bag attached to a catheter which resides in the bladder by way of a manual urinometer. Several electronic urinometers have been tested but have not been clinically proven or accepted. We report preliminary results of a novel Electronic Urinometer (EU) and compared its accuracy to a conventional Manual Urinometer (MU). Methods: The study included 22 consecutive ICU patients whose urine output was collected with a foley catheter. Urine output was measured for all patients by EU as well as by MU. Both measurements were compared to analysis of the volume in a Graduated Cylinder (GC). Results: The EU was highly accurate in measurement of both urine volume and urine flow with an average deviation from GC 4 ± 3.0% vs 17 ± 23% for the MU (P

Background Peritoneal dialysis (PD) is increasingly used for the long-term management of hypervolemic refractory congestive heart failure (CHF) patients, in particular when complicated by renal insufficiency. While PD has many advantages over hemodialysis (HD) in those patients, there is a controversy concerning survival superiority of PD compared with HD in this population. The aim of the study was to define typical patient profile and to compare outcomes of patients with CHF and renal failure treated with HD or PD. Methods This retrospective cohort study enrolled CHF patients treated with chronic PD or HD between the years 2009-2018. Information at dialysis initiation included age, gender, body weight, blood pressure, cause of renal disease, comorbidities, hospitalisations, echocardiographic and laboratory parameters. Survival was compared between PD and HD patients using a Kaplan-Meier model and Cox regression analysis. Results CHF patients treated with PD had significantly higher eGFR and lower systolic blood pressure compared with HD treated patients. Median survival time was 13.32 (7.08, 23.28) months in the PD group and 19.68 (9.48, 39.24) months in the HD group, P = .013. After adjustment for confounders the mortality risk amongst PD and HD patients was not significantly different: adjusted HR for death in PD vs HD patients was 1.44, P = .35 for 1- year and 1.69, P = .10 for 2-year mortality. Number of hospitalisations was similar in both groups. Conclusions CHF patient profile was different in PD and HD. Two modalities were equally effective in the treatment of patients with CHF and renal failure considering different patient characteristics.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Introduction There are limited contemporary data regarding the association between improvement in cardiovascular fitness in heart failure patients who participate in a cardiac rehabilitation programme and the risk of subsequent hospitalisations. Methods The study population comprised 421 patients with heart failure who participated in our cardiac rehabilitation programme between the years 2009 and 2016. All were evaluated by a standard exercise stress test before initiation, and underwent a second exercise stress test on completion of 3 ± 1 months of training. Participants were dichotomised by fitness level at baseline, according to the percentage of predicted age and sex norms achieved. Each group was further divided according to its degree of functional improvement, between the baseline and the follow-up exercise stress test. Major improvement was defined as improvement above the median value in each group. The combined primary endpoint was cardiac hospitalisation or all-cause mortality. Results A total of 211 (50%) patients had low baseline fitness (Conclusion In heart failure patients participating in a cardiac rehabilitation programme, improved cardiovascular fitness is associated with reduced mortality or cardiac hospitalisation risk during long-term follow-up, independent of baseline fitness.

Metabolic hormones stabilize brain reward and motivational circuits, whereas excessive opioid consumption counteracts this effect and may impair metabolic function. Here we addressed the role of metabolic processes in the course of the agonist medication-assisted treatment for opioid use disorder (OUD) with buprenorphine or methadone. Plasma lipids, hemoglobin A1C, body composition, the oral glucose tolerance test (oGTT) and the Sweet Taste Test (STT) were measured in buprenorphine- (n = 26) or methadone (n = 32)- treated subjects with OUD. On the whole, the subjects in both groups were overweight or obese and insulin resistant; they displayed similar oGTT and STT performance. As compared to methadone-treated subjects, those on buprenorphine had significantly lower rates of metabolic syndrome (MetS) along with better values of the high-density lipoproteins (HDL). Subjects with- vs. without MetS tended to have greater addiction severity. Correlative analyses revealed that more buprenorphine exposure duration was associated with better HDL and opioid craving values. In contrast, more methadone exposure duration was associated with worse triglycerides-, HDL-, blood pressure-, fasting glucose- and hemoglobin A1C values. Buprenorphine appears to produce beneficial HDL- and craving effects and, contrary to methadone, its role in the metabolic derangements is not obvious. Our data call for further research aimed at understanding the distinctive features of buprenorphine metabolic effects vis-à-vis those of methadone and their potential role in these drugs’ unique therapeutic profiles.

Background Prolonged QTc interval observed in daily practice is often deemed to be drug induced and might result in drug discontinuation, with possible therapeutic consequences. However, whether clinically significant prolonged QTc may be due to within-individual variability occurs has yet to be described. Methods A retrospective cohort study documenting within-individual QTc variability in subjects attending annual routine medical evaluation. At each visit, QT interval was measured and corrected for heart rate using Bazett and three other commonly used formulae. Outcome measures were rates of ΔQTc ≥60 msec, absolute QTc ≥500 msec and QTc ≥25% from baseline. Results A total of 188 subjects [54 (29%)] females were recruited. Mean age at first ECG was 54 ± 12.8 years with mean time interval of 12.2 ± 1.1 months between measurements. Mean Bazett QTc was higher compared to the other 3 formulae: 412 ± 20 vs. 400 ± 16 msec. Using Bazett formula, 18/188 (9.6%) and 5/188 (2.7%) subjects showed at least one measurement with ΔQTc ≥60 msec and QTc ≥500 msec, respectively. Of the former, 5/18 (27.8%) showed QTc ≥25% prolongation. In multivariate analysis, QTc ≥500 msec was significantly associated with number of measurements (HR: 5.01, 95%CI: 1.21-20.78, p = .026) with no effect of other known confounders. Lower rates were demonstrated with the other three formulae. Conclusion In clinical practice, significant prolonged QTc may be attributed to within-individual variability, particularly when adjusting the QT interval with Bazett correction. This should be taken into consideration when decisions on changing current drug regimens are to be made.

The present study was designed to assess the role of jugular venous distension (JVD) as a predictor of short- and long-term mortality in a "real-life" setting. The independent association between the presence of admission JVD and the 30-day, 1- and 10-year mortality was assessed among 2,212 patients hospitalized with acute heart failure (HF) who were enrolled in the Heart Failure Survey in Israel (2003). Independent predictors of JVD finding in study patients included: the presence of significant hyponatremia (odds ratio [OR] 1.48; p = 0.03), reduced left ventricular ejection fraction ([LVEF] OR 1.24; p = 0.03), anemia (OR 1.3; p = 0.01), New York Heart Association III to IV (OR 1.34; p0.01) and age75 years (OR 1.32; p = 0.01). The presence of JVD versus its absence at the time of HF hospitalization was associated with increased 30-day mortality (7.2% vs 4.9%, respectively; p = 0.02), 1-year (33% vs 28%, respectively; p0.001), and greater 10-year mortality (91.8% vs 87.2%, respectively; p0.001). Consistently, interaction term analysis demonstrated that the presence of JVD at the time of the index HF hospitalization was independently associated with a significant increased risk for 10-year mortality, with a more pronounced effect among younger patients, patients with reduced LVEF, preserved renal function, and chronic HF. In conclusion, in patients admitted with HF, JVD is associated with specific risk factors and is independently associated with increased risk of both short- and long-term mortality. These findings can be used for improved risk assessment and management of this high-risk population.

About half of all patients with heart failure are diagnosed with heart failure preserved ejection fraction (HFpEF). Until now, studies have failed to show that medical treatment improves the prognosis of patients with HFpEF.To evaluate changes in exercise capacity of patients with HFpEF compared to those with heart failure with reduced ejection fraction (HFrEF) following an exercise training program.Patient data was retrieved from a multi-center registry of patients with heart failure who participated in a cardiac rehabilitation program. Patients underwent exercise testing and an echocardiogram prior to entering the program and were retested6 months later.Of 216 heart failure patients enrolled in the program, 170 were diagnosed with HFrEF and 46 (21%) with HFpEF. Patients with HFpEF had lower baseline exercise capacity compared to those with HFrEF. Participating in a 6 month exercise program resulted in significant and similar improvement in exercise performance of both HFpEF and HFrEF patients: an absolute metabolic equivalent (MET) change (1.45 METs in HFrEF patients vs. 1.1 in the HFpEF group, P = 0.3).An exercise training program resulted in similar improvement of exercise capacity in both HFpEF and HFrEF patients. An individualized, yet similarly structured, cardiac rehabilitation program may serve both heart failure groups, providing safety and efficacy.

The definition of myocardial infarction relies on elevated troponin levels. However, elevated levels of high sensitive cardiac troponin (hs-cTnT) assays have been reported in elderly patients without acute myocardial infarction. We sought to determine whether elevated hs-cTnT levels have a prognostic value in stable elderly subjects without any acute illness.The study cohort included residents of a nursing home who were asymptomatic without any acute medical problem. Serum hs-cTnT levels were measured, and participants were divided into high and low hs-cTnT groups. We measured hs-cTnT levels of young healthy volunteers as well and compared them with hs-cTnT levels of those nursing home residents.Fifty-seven nursing home residents and 14 young volunteers were included in the study. The average age of nursing home residents was 83 ± 14 years, compared with 37 ± 3 years of the volunteers. Levels of hs-cTnT were significantly higher in the elderly compared with the volunteers (0.02 ± 0.016 ng/mL vs 0.005 ± 0.0003 ng/mL; P .001); accordingly, we chose a cutoff of 0.02 ng/mL hs-cTnT and divided the 57 patients into 2 subgroups for further evaluation. After adjustment for age, gender, and glomerular filtration rate, the hs-cTnT was still an independent predictor of 1-year mortality (relative risk 2.04 [95% conficence interval, 2.009-29.45], P = .003).Mild elevations of hs-cTnT levels are common in elderly patients, and hs-cTnT level is an independent marker of mortality risk in this population. For patients older than 70 years, a different hs-cTnT cutoff is required (eg, higher than 0.014 ng/mL).

Purpose To examine the correlation between participation in a cardiac rehabilitation (CR) program and quality of life (QoL). Design A prospective study of patients with coronary artery disease (CAD). Methods Participants completed questionnaires before and after a 3-month CR program. Patients were surveyed using a cardiac history evaluation and the MacNew Heart Disease Health-Related QoL questionnaire. Findings Of those eligible, only 14% of the participants were women and 7% were of Arab ethnicity. Patients' QoL significantly improved following participation. Higher level of education was associated with improved QoL. Conversely, cardiac risk factor burden was associated with a decline in QoL. No association was found between cardiac risk stratification, age or religiosity and QoL. Conclusions Improved QoL after CR program participation should raise awareness of the significant benefits of CR among healthcare professionals. Clinical relevance CR for those patients with CAD should be implemented, with a focus on women and minorities.

Limited information exists on whether changes in medical practices over the study decades have affected the outcomes of acute coronary syndrome (ACS) patients who undergo early coronary artery bypass surgery (CABG) during index hospitalisation.Data on trends for early CABG referral and associated outcomes were obtained among 11,485 ACS patients enrolled in the biennial Acute Coronary Syndrome Israeli Surveys (ACSIS) 2000-2010.Among 11,485 patients, 566 (5%) were referred to early CABG. These patients displayed higher risk characteristics, including Killip classII, anterior myocardial infarction, greater left ventricular dysfunction, and more frequent use of mechanical ventilation and intra-aortic balloon pump (all p0.01). Nevertheless, mortality rates of patients referred to early CABG vs. treated with percutaneous coronary intervention (PCI) or medically, was similar (11.4% vs. 10.2%; log-rank p-value=0.40). There was a significant decline in the referral trend over the study decade (6.7% - 1.7%; p0.001). One year survival was similar between patients referred to early CABG during the late (years: 2006-2010) vs. early (years: 2000-2005) period (85.7% vs. 90%; log-rank p-value=0.15), whereas, among patients who didn't undergo early CABG, and underwent percutaneous coronary intervention (PCI) or medical management only, enrolment during the late periods was associated with a significant survival benefit (91.5% vs. 88.1%; log-rank p-value0.001).Over the study decade there was a significant decline in referral for early CABG, without a difference in the one-year mortality between the early and non-early CABG group.

Background: The perioperative assessment and management of elderly patients with hip fracture and significant aortic stenosis (AS) is an increasingly common clinical problem with little data available to guide perioperative management. Objectives: It was the aim of this study to examine the incidence of perioperative events in an elderly population of patients with severe AS undergoing repair of hip fracture as compared with controls without severe AS. Methods: Patients over the age of 70 with an echocardiographic diagnosis of severe AS defined as an aortic valve area ≤1.0 cm2 who underwent surgery for hip fracture repair were retrospectively identified. An age-matched group of patients without a history of AS who underwent surgical repair of hip fracture was the control group. The primary outcome of the incidence of postoperative cardiac events defined as death, acute coronary syndrome or pulmonary edema within 30 days was compared. Results: Thirty-two patients with AS (median age 84.5 years, range 72–94; 27 females and 5 males) and 88 controls (median age 86 years, range 80–95; 67 females and 21 males) were entered into the study. There were no significant differences between the AS group and controls for 30-day mortality (6.2 vs. 6.8%) or for the total cardiac event rate (18.7 vs. 11.8%). Conclusions: Our results demonstrate that elderly patients with severe AS can safely undergo repair of hip fractures with a mortality and morbidity comparable with a control population. These patients should not be denied surgery on the basis of their aortic valve disease.

Background In ST-elevation MI (STEMI) the culprit artery is usually occluded, whereas non-STEMI (NSTEMI) it is usually patent. The location of the ruptured plaque may influence MI type. We examine whether the distance from the coronary ostium to the culprit lesion is different in STEMI as compared to NSTEMI. Methods We selected patients who presented with an acute MI and underwent coronary angiography during hospitalization. The analysis included 754 patients of whom 514 had STEMI and 240 had NSTEMI. The distance from the coronary ostium to the site of thrombosis was measured. Results For both STEMI and NSTEMI patients the first 60 mm of the coronary artery contained 75% of the culprit lesions. There were no significant differences in median distances from the vessel ostium to the site of thrombosis as well. Conclusions The distance from coronary ostium to culprit lesion is similar in STEMI and NSTEMI. Culprit lesion location does not appear to influence the development of STEMI as opposed to NSTEMI.

Clinical echocardiographic assessment of left ventricular hypertrophy (LVH) is generally performed by measuring wall thickness alone (WT). The objective of this study was to compare the assessment of LVH using the measurement of WT to that using indexed LV mass. Hypertensive patients underwent echocardiography with the measurement of LV WT and LV mass. For each patient, the presence of LVH was assessed by both methods with WT compared to the gold standard of LV mass index. In all, 92 patients (51M/41F) were entered, and in only 55 patients (60%) were the two methods concordant. There was a tendency for WT to underestimate LVH in females (sensitivity 37%, specificity 79%) and overestimate LVH in males (sensitivity 88%, specificity 56%). The measurement of WT alone overestimates LVH in males and underestimates LVH in females and should not be used as a surrogate marker for increased LV mass.

Patients with renal dysfunction (RD) who present with acute myocardial infarction (AMI) are at a high risk for subsequent cardiovascular morbidity and mortality. We sought to evaluate changes in the short and long term mortality of AMI patients with RD compared to patients with normal renal function over the last decade.This study based on 4 bi-annually surveys was performed from 2002 to 2010 and included 9468 AMI patients, that were followed for 1year, of whom 2770 (29%) had reduced estimated GFR ([eGFR]60ml/min/m(2)). Among patients with reduced eGFR: 1251 patients (45%) were included in the 2002-2005 surveys (early period) and 1519 (55%) in the 2006-2010 surveys (late period).Patients with RD were more likely to have advanced cardiovascular disease, multiple comorbidities and higher in-hospital, 30-day, and 1-year mortality rates (8.1%,12.3% and 23% vs. 0.7%, 1.7% and 4%, respectively; all p0.001). Patients with RD enrolled during the late survey periods were more likely to undergo primary PCI and be discharged with current evidence based medical treatment. 1-year mortality rates were significantly lower among patients with RD who were enrolled during the late vs. early survey periods: 22% vs. 25% respectively; (Log-rank P-value0.001). Consistently, multivariate analysis showed that patients with RD who were enrolled during the late survey periods displayed a lower adjusted risk for 1-year mortality (HR 0.83; CI[0.70-0.94] P=0.01).Prognosis of patients with RD admitted with AMI has significantly improved over the last decade, possibly due to an improvement of pharmacological and non-pharmacological management.

While earlier studies indicated that cholesterol levels decrease significantly after an acute myocardial infarction (MI), a more recent study refuted this observation.To assess changes in plasma lipid levels after onset of acute MI, and determine important predictors of lipid dynamics.We prospectively measured lipid levels of patients who presented with an acute MI. Blood samples were drawn on admission to the hospital (day 1), after fasting at least 12 hours overnight (day 2), and on the 4th day of hospitalization (day 4).Of 67 acute MI patients, 30 were admitted for ST elevation MI (STEMI) and 37 for non-STEMI. Both total cholesterol and low density lipoprotein cholesterol (LDL-C) levels decreased significantly (by 9%) in the 24 hours after admission and by 13% and 17% respectively on day 4. High density lipoprotein cholesterol (HDL-C) levels as well as triglycerides did not change significantly. Independent predictors of LDL-C decrease were the presence of diabetes mellitus [odds ratio (OR) 6.73, P = 0.01), and elevated cardiac troponin T (cTnT) levels (OR 1.81, P0.04).LDL-C levels decrease significantly after an acute MI. The reduction is correlated with cTnT levels. Diabetes is a strong independent predictor of LDL-C decrease. In acute MI patients only measurements taken within 24 hours of onset should be used to guide selection of lipid-lowering medication.

Background: Diagnostic coronary angiography is oftenfol-lowed by coronary stenting. Therapy with aspirin and clopidogrel is currently the standard treatment for patients undergoing coronary stenting. Clopidogrel loading is usually given prior to the procedure. Some pretreated patients, however, are found to have triple-vessel disease (3 VD) or left main disease (LMD) that requires referral for coronary artery bypass graft (CABG) surgery. Surgery in patients pretreated with clopidogrel may be complicated by excessive bleeding or delayed to avoid that risk. Hypothesis: A risk factor-based formula may predict the likelihood that patients referred for coronary angiography will have 3VD or LMD. Methods: Consecutive patients (n= 2,180) referred for coronary angiography constitute the training subset (n = 1,296) used to build the model, and the validation subset (n = 884) used to test the model. Logistic regression models selected five variables showing strong associations with the presence of 3VD or LMD: age, gender, diabetes, hypercholesterolemia, and prior myocardial infarction (MI). A formula based on these variables and on the training subset was constructed to calculate the probability of 3 VD or LMD. Results: Applying this model to the validation subset predicted 3 VD or LMD with 79% sensitivity, 53% specificity, 45% positive predictive value, and 83% negative predictive value. Conclusions: This simple formula based on five clinical variables is helpful in predicting the likelihood that patients, referred for coronary angiography, will have 3 VD or LMD. Use of this formula can help decide in which patients clopidogrel loading prior to angiography should be avoided.

Objectives The aim of this research was to test the effects of vascular endothelial growth factor (VEGF)/angiopoietin-1 (Ang-1) on adult hypoperfused tissues. Background Angiopoietin-1 and VEGF act separately and synergistically in vascular development during embryogenesis. However, little is known regarding their relative roles in collateral development after chronic arterial obstruction and tissue ischemia in the adult. Methods Central and caudal ear arteries of 32 rabbits were ligated to induce ischemia. At two months, when flow was about 65% of pre-ligation values, we injected intradermally 109plaque-forming unit adenovirus with the following transgenes: Ang-1, VEGF, or a combination of both. Ear perfusion was followed up for four weeks, and vessel leakage was assessed by Evens Blue test. Results Before injection, flow was 65% of baseline, and endogenous VEGF levels in ischemic tissue were increased. Adenovirus-encoding VEGF gene (Ad.VEGF) at one week caused a visible inflammatory response associated with a 24% flow increase (p = 0.018). Adenovirus-encoding Ang-1 gene (Ad.Ang-1) increased flow 22% (p = 0.004) with no visible inflammation; Ad.VEGF caused three times as much vessel leakage as Ad.Ang-1 (142.5 ± 38 vs. 49.5 ± 9.8 ng Evens Blue/mg tissue; p Conclusions Exogenous Ang-1 enhances perfusion in hypoperfused tissues only in the presence of increased levels of endogenous VEGF. Overexpression of VEGF, however, after causing an inflammatory response, does not improve collateral blood flow.

Atherosclerosis is an inflammatory disease. One of the candidate inflammatory triggers is infection. To further characterize the interaction between infection, cytokine induction, and atherosclerosis, we tested the hypothesis that cytomegalovirus (CMV) infection induces the pro-inflammatory cytokine interleukin-6 (IL-6), which in turn induces "pro-atherosclerotic" changes in vascular endothelial cells (ECs). ELISA was used to determine the levels of monocyte chemoattractant protein-1 (MCP-1) in the supernatant of mouse and human ECs incubated with IL-6, and IL-6 levels in supernatants of splenocytes, derived from CMV-infected and uninfected mice, stimulated with mice CMV antigens. IL-6 induced, in a dose response fashion, MCP-1 expression in human ECs: 0, 2, 10, and 50 pg/ml IL-6 increased MCP-1 levels in EC conditioned medium from 1120+/-65 to 1148+/-105, 1395+/-40, and 2119+/-130 pg/ml, respectively (P0.001). IL-6 also induced MCP-1 expression in mouse ECs (P0.002). Importantly, IL-6 concentration in the supernatants of splenocytes stimulated with CMV antigens rose from undetectable levels in uninfected mice to 14.9+/-5 pg/ml in the infected mice (P0.04). These results suggest a previously unrecognized, but potentially important mechanism whereby CMV, and other pathogens, contribute to atherogenesis: T lymphocytes, clonally expanded in response to antigens presented by CMV infection, home to sites of vascular injury and locally release IL-6 when presented with either pathogen antigens that may be present in the plaque, or when they cross-react with host peptides homologous to the relevant pathogen antigens; IL-6 then triggers ECs to release MCP-1, which recruits more monocytes and T-cells into the vessel wall and thereby exacerbates local inflammation, and thus atherogenesis.

Although both vasopressin and stress have been implicated in the course of schizophrenia, it is unknown whether schizophrenic patients have altered stress-induced function of the vasopressinergic system. We examined the effects of acute metabolic stress induced by pharmacological doses (40 mg/kg) of 2-deoxyglucose (2DG) on plasma concentrations of vasopressin in 13 patients with schizophrenia (with no history of polydipsia and hyponatremia) and 12 healthy control subjects. Baseline vasopressin levels were lower in the schizophrenic patients and progressively increased in both groups throughout the 60 min following 2DG administration to a similar absolute amount, thus remaining lower in the schizophrenic group. Concomitantly, patients with schizophrenia had significantly higher 2DG-induced plasma homovanillic acid (HVA) and 5-hydroxyindoleacetic acid levels. Vasopressin responses correlated positively and significantly with the HVA responses in schizophrenics and with the pituitary-adrenal axis responses in controls. These results suggest two different patterns of neuroendocrine alterations in schizophrenia, namely a relatively normal vasopressin response to 2DG despite significantly decreased baseline levels and exaggerated responses of the peripheral dopaminegic and serotonergic systems in the face of normal baseline concentrations.

Inflammation plays a central role in atherogenesis. It was hypothesized that infection of apolipoprotein E-deficient mice with murine cytomegalovirus (MCMV) increases serum levels of proinflammatory cytokines, which may induce "proatherosclerotic" changes in endothelial cells (ECs). Serum samples were collected from uninfected and infected mice. ELISA was used to determine cytokine serum levels and monocyte chemoattractant protein-1 (MCP-1) levels in the supernatant of mouse ECs incubated with serum-containing medium. Serum samples from infected mice induced MCP-1 expression by ECs. These serum samples contain interferon (IFN)-gamma, whereas IFN-gamma was undetectable in serum samples from uninfected mice. Preincubating infected mouse serum with anti-IFN-gamma monoclonal antibody significantly decreased serum-induced EC expression of MCP-1. Thus, MCMV infection increases IFN-gamma serum levels, such serum can induce MCP-1 in ECs, and the serum-induced MCP-1 expression is due, at least in part, to IFN-gamma. If these changes in EC function also occur in vivo in response to infection, they could exacerbate atherogenesis.

Background —Antibodies to mycobacterial heat-shock protein (HSP) 65 have been reported to be associated with carotid artery thickening. We examined whether antibodies to human HSP60 are associated with the risk of coronary artery disease (CAD). Methods and Results —Blood samples from 391 patients (62% men, mean age 57 years) being evaluated for CAD by coronary angiography were tested for IgG antibodies to human HSP60 by ELISA. We found that 75% of the study subjects had anti-HSP60 antibodies. The prevalence of CAD was increased in seropositive compared with seronegative patients (68% versus 49%, P =0.0009). Mean titers of HSP60 antibodies were higher in CAD patients than in non-CAD patients ( P =0.008). No association between HSP60 antibodies and infection or inflammation was found. Importantly, HSP60 antibodies were related to disease severity. The prevalence of HSP60 antibodies was 76%, 80%, and 85% in patients with 1-, 2-, and 3-vessel disease, compared with 64% in patients without CAD ( P for trend=0.003). A similar association between increasing antibody titers and number of diseased vessels was also found ( P =0.03). Significant associations between antibodies to HSP60 and CAD severity persisted after adjustment for traditional risk factors by age, race, sex, smoking, diabetes, hypercholesterolemia, hypertension, and C-reactive protein levels. Adjusted OR for number of vessels diseased was 1.86 (95% CI 1.13 to 3.04). Conclusions —This is the first study demonstrating a significant association between human HSP60 antibodies and both the presence and severity of CAD.

Background Combined therapy with aspirin and clopidogrel is currently the standard treatment for patients undergoing coronary artery stenting. Some stented patients do not tolerate aspirin and are treated by clopidogrel only, the risk of major adverse clinical events (MACE) in such patients is unclear. Objective To assess the risk of MACE in stented patients treated by clopidogrel only. Methods We reviewed records of consecutive patients who underwent bare metal coronary stenting between 1999 and 2004, looking for patients that were treated by clopidogrel without aspirin. Our search revealed 43 such patients with adequate clinical follow-up for at least 1 year following the procedure. We collected information regarding stent thrombosis, acute MI, death or repeat PCI. Results Two patients (4.7%) were admitted due to acute MI within 30 days of stenting. Stent thrombosis was documented by coronary angiography and target vessel revascularization was performed. Conclusions Clopidogrel as a sole anti-platelet treatment after coronary stenting resulted in a relatively high percentage of subacute stent thrombosis. Even higher percentages may be expected when using drug eluting stents. More aggressive anti-platelet therapy may be needed in patients who cannot tolerate aspirin. PTCA alone may be preferable to stenting in such patients.