Sprague Dawley rats from different vendors vary in the modulation of prepulse inhibition of startle (PPI) by dopamine, acetylcholine, and glutamate drugs.

RATIONALE: Rodent vendors are often utilized interchangeably, assuming that the phenotype of a given strain remains standardized between colonies. Several studies, however, have found significant behavioral and physiological differences between Sprague Dawley (SD) rats from separate vendors. Prepulse inhibition of startle (PPI), a form of sensorimotor gating in which a low-intensity leading stimulus reduces the startle response to a subsequent stimulus, may also vary by vendor. Differences in PPI between rat strains are well known, but divergence between colonies within the SD strain lacks thorough examination. OBJECTIVES: We explored intrastrain variation in PPI by testing SD rats from two vendors: Envigo and Charles River (CR). METHODS: We selected drugs acting on four major neurotransmitter systems that have been repeatedly shown to modulate PPI: dopamine (apomorphine; 0.5, 1.5, 3.0 mg/kg), acetylcholine (scopolamine; 0.1, 0.5, 1.0 mg/kg), glutamate (dizocilpine; 0.5, 1.5, 2.5 mg/kg), and serotonin (2,5-Dimethoxy-4-iodoamphetamine, DOI; 0.25, 0.5, 1.0 mg/kg). We determined PPI and startle amplitude for each drug in male and female Envigo and CR SD rats. RESULTS: SD rats from Envigo showed dose-dependent decreases in PPI after apomorphine, scopolamine, or dizocilpine administration, without significant effects on startle amplitude. SD rats from CR were less sensitive to modulation of PPI and/or more sensitive to modulation of startle amplitude, across the three drugs. CONCLUSIONS: SD rats showed vendor differences in sensitivity to pharmacological modulation of PPI and startle. We encourage researchers to sample rats from separate vendors before experimentation to identify the most suited source of subjects for their specific endpoints.

Association between metabolic syndrome, diabetes mellitus and prostate cancer risk.

BACKGROUND: The worldwide incidence of diabetes mellitus is rapidly increasing. There is recent interest in the influence of glucose metabolism on oncogenesis. We investigated the role of diabetes mellitus and the metabolic syndrome (MS) on prostate cancer development. METHODS: This study consisted of 11 541 men with coronary heart disease screened to participate in a secondary cardiac prevention trial. MS was defined according to modified NCEP/ATP III criteria. Multivariable regression analysis accounting for competing risks was performed using a modified Cox proportional hazard model in order to assess the association between diabetes, the MS and the subsequent development of prostate cancer. RESULTS: At baseline, subjects were classified into one of the four groups: (1) 6119 (53%) with neither diabetic mellitus nor MS, (2) 3376 (29%) with the MS but without diabetes, (3) 560 (5%) with diabetes mellitus but without MS and (4) 1486 (13%) with both conditions. Median follow-up was 12.7 years (range 0-15.7 years). During follow-up, 459 new cases of prostate cancer were recorded. The age-adjusted hazard ratio (HR) for prostate cancer was reduced in diabetic patients compared with those without diabetes, 0.54 and 95% confidence interval of 0.40-0.73. No significant association was noted between the presence of MS and prostate cancer development. On multivariate analysis, diabetes mellitus continued to protect against the development of prostate cancer, this was more pronounced in the absence of MS (HR=0.43, P=0.01 for diabetes in the absence of MS; HR=0.64, P=0.08 in the presence of MS). CONCLUSIONS: The results of this study indicate an inverse association between type 2 diabetes mellitus and prostate cancer risk.

Electrical nano-imprint lithography.

We present a novel technique called electrical nano-imprint lithography (e-NIL) for topographic and electrostatic patterning of thermoplastic electret films at the nanometer scale. This versatile parallel process consists of simultaneously transferring micro- or nano-patterns from a conductive mold into a thermoplastic electret film and injecting positive or negative electrical charges into the bottom of the imprinted patterns. As proof of concept, we used this e-NIL process to fabricate arrays of 5 µm and 300 nm wide topographic charged patterns into polymethylmethacrylate (PMMA) thin films coated on silicon wafers. We demonstrated that these patterned PMMA films, exhibiting thousands of topographically confined and electrostatically active sites, can be used for high-throughput directed assembly of colloidal nanoparticles.

Apoptosis is an innate defense function of macrophages against Mycobacterium tuberculosis.

Two different forms of death are commonly observed when Mycobacterium tuberculosis (Mtb)-infected macrophages die: (i) necrosis, a death modality defined by cell lysis and (ii) apoptosis, a form of death that maintains an intact plasma membrane. Necrosis is a mechanism used by bacteria to exit the macrophage, evade host defenses, and spread. In contrast, apoptosis of infected macrophages is associated with diminished pathogen viability. Apoptosis occurs when tumor necrosis factor activates the extrinsic death domain pathway, leading to caspase-8 activation. In addition, mitochondrial outer membrane permeabilization leading to activation of the intrinsic apoptotic pathway is required. Both pathways lead to caspase-3 activation, which results in apoptosis. We have recently demonstrated that during mycobacterial infection, cell death is regulated by the eicosanoids, prostaglandin E(2) (proapoptotic) and lipoxin (LX)A(4) (pronecrotic). Although PGE(2) protects against necrosis, virulent Mtb induces LXA(4) and inhibits PGE(2) production. Under such conditions, mitochondrial inner membrane damage leads to macrophage necrosis. Thus, virulent Mtb subverts eicosanoid regulation of cell death to foil innate defense mechanisms of the macrophage.

Increased insulin resistance and risk of incident cerebrovascular events in patients with pre-existing atherothrombotic disease.

BACKGROUND AND PURPOSE: Diabetes and the metabolic syndrome are known risk factors for ischaemic stroke. Our aim was to examine whether amongst patients with pre-existing atherothrombotic disease, increased insulin resistance is associated with incident cerebrovascular events. METHODS: Patients with stable coronary heart disease included in a secondary prevention trial were followed up for a mean of 6.2 years. Coronary heart disease was documented by a history of myocardial infarction > or =6 months and <5 years before enrollment and/or stable angina pectoris with evidence of ischaemia confirmed by ancillary diagnostic testing. Main exclusion criteria were insulin treated diabetes, hepatic or renal failure, and disabling stroke. Baseline insulin levels were measured in 2938 patients from stored frozen plasma samples and increased insulin resistance assessed using the homeostatic model assessment of insulin resistance (HOMA-IR), categorized into tertiles or quartiles. RESULTS: Crude rates of incident cerebrovascular events rose from 5.0% for HOMA-IR at the bottom tertile to 5.7% at the middle tertile, and 7.0% at the top tertile (P = 0.07). HOMA-IR at the top versus bottom tertile was associated with an unadjusted hazard ratio (HR) of 1.37 (95%CI, 0.94-1.98) and a 1-unit increase in the ln HOMA-IR was associated with a HR of 1.14 (95%CI, 0.97-1.35). In further analyses adjusting for potential confounders, or categorizing baseline HOMA-IR into quartiles, or excluding diabetic patients, we did not identify an increased risk for incident cerebrovascular events conferred by the top category. CONCLUSIONS: Increased insulin resistance did not predict incident cerebrovascular events amongst patients with pre-existing atherothrombotic disease.

Incidence and prognosis of non-Q-wave vs. Q-wave myocardial infarction following catheter-based reperfusion therapy.

BACKGROUND: The clinical importance of classifying myocardial infarction (MI) into non-Q-wave (NQWMI) vs. Q-wave (QWMI) subsets is controversial and might depend on the therapeutic reperfusion strategy employed. The prognostic implications of NQWMI development following primary percutaneous coronary intervention (PCI) have not been reported. AIM: To examine the incidence, determinants and prognostic implications of NQWMI vs. QWMI development following primary PCI. DESIGN: The ACSIS Registry, a 2-month nationwide survey conducted biennially, prospectively collects data from all MI admissions in Israel. METHODS: Outcomes were compared among patients managed by primary PCI who subsequently developed NQWMI vs. QWMI. Independent predictors of Q-wave development and 1-year mortality were determined by multivariate stepwise logistic regression analysis and Cox proportional hazard model, respectively. RESULTS: Of 4537 MI patients with ST-segment elevation on admission, 1230 (27%) were treated with primary PCI. A discharge diagnosis of NQWMI was made in 259 (21.1%) patients. The baseline features and PCI strategies employed were similar among NQWMI vs. QWMI patients, though peak creatine kinase levels were higher (median 795 U/l vs. 1681 U/l, P = 0.0001) and severe left ventricular ejection fraction (LVEF) impairment (<40%) more frequent (22.6% vs. 43.9%, P < 0.0001), in the latter group. Mortality at 1-year was significantly lower in NQWMI vs. QWMI patients (3.9% vs. 10.8%, P log-rank = 0.001). By Cox proportional hazard analysis, NQWMI vs. QWMI was an independent predictor of freedom from 1-year mortality [HR = 0.34 (95% CI: 0.15-0.79), P = 0.01]. DISCUSSION: The diagnosis of NQWMI after primary PCI is associated with an excellent prognosis independent of established prognosticators, including LVEF.

CD1-restricted T cells in host defense to infectious diseases.

CD1 has been clearly shown to function as a microbial recognition system for activation of T cell responses, but its importance for mammalian protective responses against infections is still uncertain. The function of the group 1 CD1 isoforms, including human CD1a, CDlb, and CDLc, seems closely linked to adaptive immunity. These CD1 molecules control the responses of T cells that are highly specific for particular lipid antigens, the best known of which are abundantly expressed by pathogenic mycobacteria such as Mycobacterium tuberculosis and Mycobacterium leprae. Studies done mainly on human circulating T cells ex vivo support a significant role for group I CD1-restricted T cells in protective immunity to mycobacteria and potentially other pathogens, although supportive data from animal models is currently limited. In contrast, group 2 CD1 molecules, which include human CD1d and its orthologs, have been predominantly associated with the activation of CD1d-restricted NKT cells, which appear to be more appropriately viewed as a facet of the innate immune system. Whereas the recognition of certain self-lipid ligands by CD d-restricted NKT cells is well accepted, the importance of these T cells in mediating adaptive immune recognition of specific microbial lipid antigens remains controversial. Despite continuing uncertainty about the role of CD 1d-restricted NKT cells in natural infections, studies in mouse models demonstrate the potential of these T cells to exert various effects on a wide spectrum of infectious diseases, most likely by serving as a bridge between innate and adaptive immune responses.

C-reactive protein distribution and correlates among men and women with chronic coronary heart disease.

BACKGROUND: C-reactive protein (CRP) elevated in inflammation is associated with atherosclerotic disease. We describe the distribution of CRP and its association with coronary heart disease (CHD) risk factors in a large CHD patient group. METHODS: This analysis comprises 2,723 male and 256 female CHD patients, included in the Bezafibrate Infarction Prevention (BIP) study. High sensitive CRP levels were determined in frozen plasma samples. RESULTS: CRP distribution, was normalized upon log transformation. Levels among women were higher than in men in the entire group (4.4 vs. 3.5 mg/l) and in each age group. Co-morbidities, smoking, lower education level, and use of cardiovascular drugs, were associated with elevated CRP levels in both sexes. The correlation between CRP and body mass index (BMI), insulin and glucose was stronger among women. The explained variability in CRP level was larger in women (20%) compared to men (13%). Among women, BMI explained 10% of CRP variability, whereas the contribution of each variable among men was significantly smaller. CONCLUSIONS: Among men and women with CHD, CRP level was correlated with traditional risk factors and to a lesser degree to manifestation of CHD. BMI is the main contributor to CRP variability, explained by these factors among women.

Cardiovascular risk factors and clinical presentation in acute coronary syndromes.

OBJECTIVE: To investigate the hypothesis that risk factors may be differently related to severity of acute coronary syndromes (ACS), with ST elevation used as a marker of severe ACS. DESIGN: Cross sectional study of patients with ACS. SETTING: 103 hospitals in 25 countries in Europe and the Mediterranean basin. PATIENTS: 10,253 patients with a discharge diagnosis of ACS in the Euro heart survey of ACS. MAIN OUTCOME MEASURES: Presenting with ST elevation ACS. RESULTS: Patients with ACS who were smokers had an increased risk to present with ST elevation (age adjusted odds ratio (OR) 1.84, 95% confidence interval (CI) 1.67 to 2.02). Hypertension (OR 0.65, 95% CI 0.60 to 0.70) and high body mass index (BMI) (p for trend 0.0005) were associated with less ST elevation ACS. Diabetes mellitus was also associated with less ST elevation, but only among men. Prior disease (infarction, chronic angina, revascularisation) and treatment with aspirin, beta blockers, or statins before admission were also associated with less ST elevation. After adjustment for age, sex, prior disease, and prior medication, smoking was still significantly associated with increased risk of ST elevation (OR 1.53, 95% CI 1.38 to 1.69), whereas hypertension was associated with reduced risk (OR 0.75, 95% CI 0.69 to 0.82). Obesity (BMI > 30 kg/m2 versus < 25 kg/m2) was independently associated with less risk of presenting with ST elevation among women, but not among men. CONCLUSION: Among patients with ACS, presenting with ST elevation is strongly associated with smoking, whereas hypertension and high BMI (in women) are associated with less ST elevation, independently of prior disease and medication.

[The treatment of acute myocardial infarction among new immigrants in Israel].

BACKGROUND: We hypothesized that recent immigrants presenting with a poor cardiac profile may have a worse outcome after acute myocardial infarction compared with veteran Israelis. METHODS: Of 1,490 consecutive acute myocardial infarction patients investigated in a 2-month survey conducted in 2002, 256 had immigrated since January 1990 and 1,234 were veteran Israelis. RESULTS: Recent immigrants were older with a higher percentage of women compared with veteran Israelis (mean age 67.5 vs. 63.6 years, and 30 vs. 21%, p<0.001 respectively). More recent immigrants had hypertension (60%), higher total cholesterol (201 mg/dl) and prior angina (40%) compared to counterparts (45%; 194 mg/dl; 30%, p<0.01 respectively). Previous coronary interventions (7.4%) and coronary bypasses (4.3%) had been performed less frequently in recent immigrants, compared with veteran Israelis (13.8 and 8.3%, p<0.03 respectively). There were no differences between the two groups regarding thrombolysis, primary PCI, coronary angiography, IIb/IIIa and Clopidogrel treatment. Higher 7-day (6.3 vs. 4.1%), 30 day (9.0 vs. 6.3%), 6-month (14.1 vs. 10.0%), p<0.05 and 1-year mortality (18.0 vs. 11.7%, p<0.006) were observed along recent immigrants compared to veteran Israelis, respectively. Trend for increased mortality among recent immigrants may be explained by significant age and gender differences and co morbidity. After multiple adjustment for age, sex, prior angina, hypertension, prior PCI, CABG and Killip class 1I+, mortality rates among recent immigrants were not different from veteran Israelis. CONCLUSION: In a national acute myocardial infarction survey, recent immigrants were found to have a more adverse coronary profile than veteran Israeli patients, but were treated comparably and exhibited the same short-term prognosis.

[Out-of-hospital resuscitation in Israel 2000].

The aim of the study was to evaluate the impact of pre-hospital cardio-pulmonary resuscitation, performed by mobile intensive cardiac care units of Magen David Adom (MDA) teams in the framework of a national survey conducted in the period February and March 2000. During the survey, MDA performed 539 resuscitations, 485 of which were performed by mobile intensive care units of MDA, and they constitute the study population of the present analysis. The average age of the patients was 70.5 years, and 68% were men. The mean response time of the mobile intensive care units was 10.3 minutes. In 14% of the cases, a bystander initiated basic cardiac life support before the arrival of the MDA team. Upon arrival of the resuscitation team, 242 patients (50%) had asystole, 19% ventricular tachycardia (VT)/ventricular fibrillation (VF), 13% pulseless electrical activity (PEA), and 18% had other severe arrhythmias. One hundred and ninety-nine patients (41%) were transferred alive to the hospital after successful resuscitation. Hospital summaries were obtained for 148 of these patients. The cause of cardiac arrest was cardiac in 64% of the cases and 48% of the patients who reached the hospital had a previous history of heart disease. Fifty-three patients (11%) were discharged alive from the hospital. Patients discharged alive were younger, more promptly resuscitated, 78% had a cardiac cause of death and 38% of them were in ventricular tachycardia/fibrillation when first seen by the resuscitation team. The rate of successful resuscitation to discharge in the sub-group with VT/VF was 21%, and only 4% for patients in asystole, which is in line with other studies. However, the rate of initiation of resuscitation by bystanders is low in Israel. These data may help the medical staff and the health policy providers in Israel.

Hospital and 1-year outcome after acute myocardial infarction in patients with diabetes mellitus and hypertension.

Hypertension (HT) and diabetes mellitus (DM) lead to structural and functional cardiac impairment and worsen the prognosis after myocardial infarction (MI). However, the prognosis of male or female patients with the coexistence of HT and DM after MI has not been clearly demonstrated. The study sample comprised 4317 consecutive patients with an acute MI from a prospective nationwide survey conducted in 1992, 1994 and 1996 in all 25 coronary care units operating in Israel. The in-hospital, 30-day and 1-year outcome of diabetic hypertensive patients (n=546) was compared with that of diabetic normotensive patients (n=547) and with that of nondiabetic hypertensive patients (n=1192) and nondiabetic normotensive subjects (n=2032). The crude in-hospital, 30-day and 1-year mortality rates of diabetic hypertensive patients (11.7, 16.5 and 27.6%, respectively) were significantly higher than those of the diabetic normotensive patients (9.5, 15.4 and 22.9%, respectively) and nondiabetic hypertensive patients (7.1, 11.6 and 17.6%, respectively). Kaplan-Meier survival curves showed increased mortality rates during the 1-year follow-up in diabetic hypertensive patients. Adjusted risk for 1-year mortality was increased in diabetic patients. However, the risk was similar in diabetic hypertensive and normotensive patients (hazard ratio (HR) 1.55, 95% confidence interval (CI) 1.25-1.93, and 1.62, 95% CI 1.29-2.04, respectively). Adjusted Kaplan-Meier survival curves of diabetic hypertensive patients converged with those of the diabetic normotensives. The existence of DM increases the 1-year mortality after MI by about 60%. However, controlled hypertension did not worsen the outcome of diabetic male or female patients after MI.

Sexual activity cardiological survey on members of the Israel Heart Society.

A nationwide telephone survey conducted under the auspices of the Israeli Heart Society examined cardiologists' knowledge of and attitudes towards sexual activity among cardiac patients with concomitant sexual dysfunction. The items covered demography, understanding of relevant mechanisms, drug effects and cardiovascular physiology during sexual activity, suitable interventions and sources of the cardiologists' knowledge. Compliance was excellent (364/379 [96%] responders). Attitudes and knowledge were similar among males and females: 74% underestimated the published frequency of erectile dysfunction in general and among cardiac patients specifically; 90% knew that beta-blockers cause erectile dysfunction but few responded correctly about other non-cardiac drugs; 77% try to cope with their patient's problematic sexual function, especially younger cardiologists who tended to be more up to date about it. Israeli cardiologists are motivated to assist these patients but demonstrate a general lack of adequate up to date knowledge on the epidemiological, physiological and pharmacological aspects of the problem.

Improved prognosis of patients presenting with clinical markers of spontaneous reperfusion during acute myocardial infarction.

OBJECTIVE: To describe the clinical features, management, and prognosis of patients presenting with clinical markers of spontaneous reperfusion (SR) during acute myocardial infarction (AMI). DESIGN: Cohort study. SETTING: National registry of 26 coronary care units. PATIENTS: 2382 consecutive patients with AMI. MAIN OUTCOME MEASURES: Patient characteristics, management, and mortality. RESULTS: The incidence of SR was 4% of patients (n = 98) compared with thrombolytic treatment (n = 1163, 49%), primary angioplasty (n = 102, 4%), and non-reperfusion (n = 1019, 43%). SR patients were more likely to develop less or no myocardial damage as indicated by a higher percentage of non-Q wave AMI (58% v 32%, 47%, and 44%, respectively, p < 0.0001), aborted AMI (25% v 9%, 8%, and 12%, p < 0.001), and lower peak creatine kinase (503 v 1384, 1519, and 751 IU, p < 0.0001). SR patients, however, were more likely to develop recurrent ischaemic events (35% v 17%, 12%, and 16%, respectively; p < 0.001) and subsequently were more likely to be referred to coronary angiography (67%), angioplasty (41%), or bypass surgery (16%, p < 0.001). Mortality at 30 days (1% v 8%, 7%, and 13%, respectively, p < 0.0001) and one year (6% v 11%, 12%, and 19%, p < 0.0001) was significantly lower for SR patients than for the other subgroups. By multivariate analysis, SR remained a strong determinant of 30 day survival (odds ratio (OR) 0.16, 95% confidence interval (CI) 0.01 to 0.74). At one year, the association between SR and survival decreased (OR 0.49, 95% CI 0.18 to 1.13). CONCLUSIONS: Clinical markers of SR are associated with greater myocardial salvage and favourable prognosis. The vulnerability of SR patients to recurrent ischaemic events suggests that they need close surveillance and may benefit from early intervention.

A prospective survey of the characteristics, treatments and outcomes of patients with acute coronary syndromes in Europe and the Mediterranean basin; the Euro Heart Survey of Acute Coronary Syndromes (Euro Heart Survey ACS).

AIMS: To better delineate the characteristics, treatments, and outcomes of patients with acute coronary syndromes (ACS) in representative countries across Europe and the Mediterranean basin, and to examine adherence to current guidelines. METHODS AND RESULTS: We performed a prospective survey (103 hospitals, 25 countries) of 10484 patients with a discharge diagnosis of acute coronary syndromes. The initial diagnosis was ST elevation ACS in 42.3%, non-ST elevation ACS in 51.2%, and undetermined electrocardiogram ACS in 6.5%. The discharge diagnosis was Q wave myocardial infarction in 32.8%, non-Q wave myocardial infarction in 25.3%, and unstable angina in 41.9%. The use of aspirin, beta-blockers, angiotensin converting enzyme inhibitors, and heparins for patients with ST elevation ACS were 93.0%, 77.8%, 62.1%, and 86.8%, respectively, with corresponding rates of 88.5%, 76.6%, 55.8%, and 83.9% for non-ST elevation ACS patients. Coronary angiography, percutaneous coronary interventions, and coronary bypass surgery were performed in 56.3%, 40.4%, and 3.4% of ST elevation ACS patients, respectively, with corresponding rates of 52.0%, 25.4%, and 5.4% for non-ST elevation ACS patients. Among patients with ST elevation ACS, 55.8% received reperfusion treatment; 35.1% fibrinolytic therapy and 20.7% primary percutaneous coronary interventions. The in-hospital mortality of patients with ST elevation ACS was 7.0%, for non-ST elevation ACS 2.4%, and for undetermined electrocardiogram ACS 11.8%. At 30 days, mortality was 8.4%, 3.5%, and 13.3%, respectively. CONCLUSIONS: This survey demonstrates the discordance between existing guidelines for ACS and current practice across a broad region in Europe and the Mediterranean basin and more extensively reflects the outcomes of ACS in real practice in this region.

Sulfonylureas are not associated with increased mortality in diabetics treated with thrombolysis for acute myocardial infarction.

BACKGROUND: Sulfonylurea compounds may impair ischemic preconditioning and endogenous fibrinolysis. Increased mortality has been reported in diabetics receiving these drugs prior to admission for acute myocardial infarction when treated by direct angioplasty. Although thrombolytics are currently employed far more frequently than direct angioplasty the effect of sulfonylureas on mortality in the setting of thrombolysis has not been previously addressed. METHODS: Two hundred forty five diabetics treated with either accelerated t-PA or streptokinase in a national, multi-center, randomized comparison of argatroban vs. heparin (n=1200) were grouped by anti-diabetic treatment prior to hospitalization, and their outcomes were compared by retrospective analysis. RESULTS: Baseline characteristics were similar in all groups (sulfonylureas: n=121, oral medications other than sulfonylureas: n=17, insulin: n=28, diet alone: n=79). Sulfonylurea use was not associated with increased mortality or adverse event rates. By logistic regression analysis with diet treatment as reference, only prior insulin use was associated with higher risk for mortality at 30 days and 1 year (odds ratios 4.5 and 5.22, respectively, p<0.05). CONCLUSIONS: Sulfonylureas use prior to admission is not associated with adverse outcomes in diabetics treated with thrombolytics for myocardial infarction. Since direct angioplasty may increase mortality in patients taking these drugs, a randomized trial is needed to specifically compare different strategies of acute reperfusion in diabetics.Abbreviated abstract. Increased mortality has been reported in diabetics using sulfonylureas when treated for myocardial infarction by direct angioplasty. No study has specifically addressed the effect of these drugs on outcomes in the setting of thrombolysis. In a retrospective analysis of 245 diabetics treated with thrombolysis in a randomized comparison of argatroban vs. heparin, outcomes were compared in relation to anti-diabetic therapy prior to admission. Sulfonylurea use did not adversely affect prognosis, which was worst among diabetics previously treated with insulin. In conclusion, sulfonylureas do not worsen outcomes of diabetics treated with current thrombolytic regimens in comparison with other anti-diabetic treatments.

A prospective study of plasma fibrinogen levels and the risk of stroke among participants in the bezafibrate infarction prevention study.

PURPOSE: Plasma fibrinogen has emerged as an important predictor of cardiovascular disease, but few data are available on its association with stroke. We sought to determine if plasma fibrinogen is a marker of increased risk or a direct causative risk factor for stroke. SUBJECTS AND METHODS: Patients from the Bezafibrate Infarction Prevention Study, a placebo-controlled, randomized clinical trial of secondary prevention of coronary heart disease by lipid modification with bezafibrate retard (400 mg daily), were studied. Plasma fibrinogen levels were measured at baseline and yearly thereafter. Stroke, a prospectively monitored endpoint, was systematically assessed regarding stroke type, subtype, and functional outcome. RESULTS: Mean baseline fibrinogen levels were significantly higher in patients subsequently having a cerebrovascular event (140 strokes, 36 transient ischemic attacks; mean follow-up, 6.2 years) than in patients who did not (375 vs. 349 mg/dL, P <0.0001). Fibrinogen levels did not differ significantly by the type, subtype, or severity of the cerebrovascular event. Risk of ischemic stroke increased from 3.3% in the lowest tertile (baseline fibrinogen <314 mg/dL) to 7.% in the middle tertile (fibrinogen 314 to 373 mg/dL) to 10% in the upper tertile (fibrinogen >373 mg/dL, P <0.001). Adjusting for age, blood pressure, and other covariates, fibrinogen levels in the upper tertile were associated with more than a twofold increase in risk of ischemic stroke compared with in the lowest tertile (hazard ratio = 2.6; 95% confidence interval: 1.5 to 4.3). We did not find fibrinogen change from baseline to be related to subsequent ischemic stroke events. CONCLUSION: Plasma fibrinogen is a strong predictor of, rather than a direct causative factor for, subsequent stroke among patients at increased risk owing to manifest coronary heart disease.