Use of ADAM-C and CHA2DS2-VASc scores to predict complex aortic atheroma after brain ischemia: A prospective observational study.

BACKGROUND AND AIMS: Complex aortic atheroma (CAA) is a common cause of acute brain ischemia (BI), including ischemic stroke (IS) and transient ischemic attack (TIA), and is associated with recurrence. The CHA2DS2-VASc score is a useful tool for predicting stroke in patients with atrial fibrillation (AF), and can also predict cardiovascular events in other populations, including non-AF populations. The ADAM-C score is a new risk score for predicting the diagnostic yield of transesophageal echocardiography (TEE) after BI. We aimed to evaluate the ability of CHA2DS2-VASc and ADAM-C scores to predict CAA after BI. METHODS: This prospective, multicenter, observational study included 1479 patients aged over 18 years who were hospitalized for BI. CAA was defined as the presence of one or more of the following criteria: thrombus, ulcerated plaque, or plaque thickening ≥ 4 mm. RESULTS: CAA was diagnosed in 216 patients (14.6%). CHA2DS2-VASc and ADAM-C scores were significantly higher in the CAA group versus the non-CAA group (P < .0001 for both). The CHA2DS2-VASc and ADAM-C scores appear to be good predictors of CAA (AUC 0.699 [0.635, 0.761] and 0.759 [0.702, 0.814], respectively). The sensitivity, specificity, predictive positive value (PPV), and negative predictive value (NPV) of the scores for detecting CAA were 94%, 22%, 17%, and 96%, respectively, for a CHA2DS2-VASc score < 2, and 90%, 46%, 22%, and 96%, respectively, for an ADAM-C score < 3 CONCLUSIONS: CHA2DS2-VASc and ADAM-C scores are able to predict CAA after BI. CHA2DS2-VASc < 2 and ADAM-C < 3 both have an interesting NPV of 96%.

Prognostic impact of myocardial perfusion single photon emission computed tomography in patients with major extracardiac findings by computed tomography for attenuation correction.

BACKGROUND: Attenuation correction computed tomography (CT) contributes to an improvement in the diagnostic accuracy of myocardial perfusion imaging (MPI) by single photon emission tomography (SPECT). The aim of this study was to explore the prognosis of patients with major findings by CT according to the results of MPI. METHODS AND RESULTS: 1506 patients who underwent MPI by SPECT were retrospectively included. Attenuation correction CT images were systematically analyzed for major and minor abnormalities. 830 (55.1%) and 212 (14.1%) patients had minor and major extracardiac findings, respectively. Among patients with major extracardiac findings, the abnormality was previously unknown in 113 (53.3%) patients. 90 (41.9%) had abnormal MPI, 73 (34.4%) had a myocardial infarction scar, 55 (25.9%) had myocardial ischemia, and 38 (17.7%) patients had both myocardial infarction scar and myocardial ischemia. Among the 201 patients available for survival analysis, there were 67 (31.2%) deaths over a follow-up period of 3.2±1.3 years. There was no significant impact on survival arising from MPI, whatever the result. The results were the same among the 103 patients with previously unknown major extracardiac findings. CONCLUSION: Extracardiac findings by CT during MPI are frequent. Patients with major extracardiac findings have a poor mid-term outcome, whatever the results of the myocardial perfusion imaging. Extracardiac findings should be systematically checked when attenuation correction CT is performed.

Myocardial multilayer strain does not provide additional value for detection of myocardial viability assessed by SPECT imaging over and beyond standard strain.

BACKGROUND: The aim of this study was to evaluate the value of multilayer strain analysis to the assessment of myocardial viability (MV) through the comparison of both speckle tracking echocardiography and single-photon emission computed tomography (SPECT) imaging. We also intended to determine which segmental longitudinal strain (LS) cutoff value would be optimal to discriminate viable myocardium. METHODS: We included 47 patients (average age: 61 ± 11 years) referred to our cardiac imaging center for MV evaluation. All patients underwent transthoracic echocardiography with measures of LS, SPECT, and coronary angiography. RESULTS: In all, 799 segments were analyzed. We correlated myocardial tracer uptake by SPECT with sub-endocardial, sub-epicardial, and mid-segmental LS values with r = .514 P < .0001, r = .501 P < .0001, and r = .520 P < .0001, respectively. The measurements of each layer strain (sub-endocardial, sub-epicardial, and mid) had the same performance to predict MV viability as defined by SPECT with areas under curve of 0.819 [0.778-0.861, P < .0001], 0.809 [0.764-0.854, P < .0001], and 0.817 [0.773-0.860, P < .0001], respectively. The receiver-operating characteristic analysis yielded a cutoff value of -6.5% for mid-segmental LS with a sensitivity of 76% and specificity of 76% to predict segmental MV as defined by SPECT. CONCLUSIONS: Multilayer strain analysis does not evaluate MV with more accuracy than standard segmental LS analysis.

ADAM-C score: New risk score for predicting diagnostic yield of transesophageal echocardiography after cerebral ischemia.

BACKGROUND AND AIM: The clinical utility of transesophageal echocardiography (TEE) after brain ischemia (BI) remains a matter of debate. We aimed to evaluate the clinical impact of TEE and to build a score that could help physicians to identify which patients should better benefit from TEE. METHODS: This prospective, multicenter, observational study included patients over 18 years old, hospitalized for BI. TEE findings were judged discriminant if the results showed important information leading to major changes in the management of patients. Most patients with patent foramen ovale were excluded. Variables independently associated with a discriminant TEE were used to build the prediction model. RESULTS: Of the entire population (1479 patients), 255 patients (17%) were classified in the discriminant TEE group. Five parameters were selected as predictors of a discriminant TEE. Accordingly, the ADAM-C score could be calculated as follows: Score = 4 (if age ≥60) + 2 (if diabetes) + 2 (if aortic stenosis from any degrees) + 1 (if multi-territory stroke) + 2 (if history of coronary artery disease). At a threshold lower than 3, the sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of detecting discriminant TEE were 88% (95% CI 85-90), 44% (95% CI 41-47), 21% (95% CI 19-27), and 95% (95% CI 94-97), respectively. CONCLUSION: A simple score based on clinical and transthoracic echocardiographic parameters can help physicians to identify patients who might not benefit from TEE. Indeed, a score lower than 3 has an interesting NPV of 95% (95% CI 94-97).

Prevalence, treatment and control of hypertension in La Réunion: the RÉDIA population-based cohort study.

A better knowledge of prevalence, management and determinants of hypertension is needed in regions in epidemiological transition to adapt the strategies of public health screening and prevention, and to reduce the burden of cardiovascular diseases. We conducted a prospective cohort study including 4610 participants aged between 18 and 69 years and representative of the general population of La Réunion, a French overseas island located in the western Indian Ocean. The median time between inclusion and follow-up was 7.4 years. Blood pressure data at baseline and follow-up of 3087 participants were analyzed. We found a high prevalence of hypertension, especially in women (36.7% [34.5-39.0]) and in men (40.3% [37.6-43.0]) and in the under 30s (17.1% [14.0-20.5]), with an increase of 10% at follow-up. Treatment rates were very low in men (19.5% versus 39.1% in women) as was awareness of their condition (25.7% versus 44.6%). Blood pressure control rates were similar (18% at baseline and 34% at follow-up for both sexes). Diagnosis of hypertension at follow-up among subjects normotensive at baseline was independently associated with obesity at baseline (relative risk (RR) = 1.40 [1.12-1.75] for BMI between 27 and 30 kg/m2 and 1.72 [1.33-2.25] for BMI ≥30 kg/m2 as compared with BMI <27 kg/m2) and HbA1C (RR =1.12 [1.05-1.19] per %), suggesting a prominent role of insulin resistance in our population. Our study provides original data that cannot be assimilated to any existing model and should guide the implementation of original community-based programs in such countries.

A Holistic Approach to Cardiometabolic and Infectious Health in the General Population of Reunion Island: The REUNION Study.

INTRODUCTION: Reunion Island is a French overseas department in the South West Indian Ocean with a unique multi-ethnic population. Cardiovascular diseases are the most common chronic conditions with higher prevalences of hypertension and diabetes compared to mainland France. Moreover, Reunion Island is particularly exposed to vector-borne diseases such as chikungunya and dengue. Our objective is to describe the prevalence of cardiometabolic and infectious diseases in Reunion Island and explore causal mechanisms linking these diseases. METHODS: The REUNION study is an ongoing French prospective study. From January 2022, 2,000 consenting participants (18-68 years old) are being recruited from the general population according to polling lists and random generation of cellphone number. Baseline examination consists of (i) general health examination, assessment of cardiovascular risk factors, markers of subclinical atherosclerosis, bronchial obstruction, neuropathic and autonomic dysfunction, (ii) questionnaires to determine sociodemographic characteristics, diet, exposure to vector-borne diseases, mental health and cognitive functions, social inequalities in health and ethnic origins, (iii) biological sampling for determination of cardiovascular risk factors, seroprevalence of infectious diseases, innovative lipid biomarkers, advanced omics, composition of intestinal, periodontal and skin microbiota, and biobanking. CONCLUSIONS: The REUNION study should provide new insights into the prevalence of cardiometabolic and infectious diseases, as well as their potential associations through the examination of various environmental pathways and a wide range of health aspects.

Usefulness of initial glucose level to improve acute coronary syndrome diagnosis in the emergency department.

INTRODUCTION: The aim of the study was to analyse the incremental usefulness of high blood glucose level for non-ST elevation acute coronary syndrome (ACS) diagnosis in patients admitted to the emergency department (ED) for chest pain and suspected ACS. METHODS: A post hoc analysis of a prospective, observational study of 11 months duration was carried out. Initial glucose levels were analysed in 672 consecutive patients admitted to the ED with chest pain and suspected non-ST elevation ACS. A cut-off glucose level (>140 mg/dl) for high glucose level diagnosis was defined. Based on hospital diagnostic test results, patients were classified as having non-ST elevation ACS by two independent physicians. The association and performance of high glucose level for ACS diagnosis were studied by univariate and multivariate analysis and receiver operator characteristic (ROC) curves. RESULTS: Out of the 672 eligible patients who were recruited, 181 (26.9%) had a confirmed non-ST elevation ACS. The independent factors associated with a diagnosis of ACS were age, previous coronary artery disease, hyperlipidaemia, smoking status and glucose level >140 mg/dl (OR 1.98 95% CI 1.14 to 3.45). In addition to a predictive model that included the usual diagnostic tools for non-ST elevation ACS management, a glucose level >140 mg/dl added significant incremental information (p=0.03). However, the addition of blood glucose level >140 mg/dl to the conventional diagnostic tool resulted in small increases in the ability to classify ACS, as measured by the c-statistic (0.82, 95% CI 0.79 to 0.85). CONCLUSION: An initial serum glucose level >140 mg/dl is associated with non-ST elevation ACS in patients admitted to an ED for chest pain but added moderately to conventional tools used for ACS diagnosis. CLINICAL TRIAL NUMBER: NCT00714298.

Relationship between lipoprotein concentrations and short-term and 1-year mortality in intensive care unit septic patients: results from the HIGHSEPS study.

BACKGROUND: High-density lipoproteins (HDLs), particles characterized by their reverse cholesterol transport function, display pleiotropic properties, including anti-inflammatory and antioxidant functions. Moreover, all lipoproteins (HDLs but also low-density lipoproteins (LDLs)) neutralize lipopolysaccharides, leading to increased bacterial clearance. These two lipoproteins decrease during sepsis, and an association between low lipoprotein levels and poor outcome was reported. The goals of this study were to characterize the lipid profile of septic patients hospitalized in our intensive care unit (ICU) and to determine the relationship with the outcome. METHODS: A prospective observational study was conducted in a university hospital ICU. All consecutive patients admitted for septic shock or sepsis were included. Total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride levels were assessed at admission (day 1), at day 3, and at ICU discharge. When available, a prehospitalization lipid profile collected prior to the patient's hospitalization was compiled. Short-term and 1-year prognostic outcomes were prospectively assessed. RESULTS: A total of 205 patients were included. We found a decrease in HDL-C concentration between previous values and those at admission, followed by an additional decrease at day 3. At ICU discharge, the concentration was higher than that at day 3 but did not reach the concentration measured prior to hospitalization (prior HDL-C = 1.22 (1.04-1.57) mmol/l; day 1 HDL-C = 0.44 (0.29-0.70) mmol/l; day 3 HDL-C = 0.30 (0.25-0.48) mmol/l; and HDL-C at discharge = 0.65 (0.42-0.82) mmol/l). A similar trend was found for LDL-C (prior LDL-C = 2.7 (1.91-3.33) mmol/l; day 1 LDL-C = 1.0 (0.58-1.50) mmol/l; day 3 LDL-C = 1.04 (0.64-1.54) mmol/l; and LDL-C at discharge = 1.69 (1.26-2.21) mmol/l). Mixed models for repeated measures of lipoprotein concentrations showed a significant difference in HDL-C and LDL-C concentrations over time between survivors and nonsurvivors at day 28. An HDL-C concentration at admission of less than 0.4 mmol/l was associated with increased mortality at day 28 (log-rank test, p = 0.034) but not at 1 year (log-rank test, p = 0.24). An LDL-C concentration at admission of less than 0.72 mmol/l was associated with increased mortality at day 28 and at 1 year (log-rank test, p < 0.001 and p = 0.007, respectively). No link was found between prior lipid profile and mortality. CONCLUSIONS: We showed no relationship between the prehospitalization lipid profile and patient outcome, but low lipoprotein levels in the ICU were strongly associated with short-term mortality.

Additional prognostic value of physical examination, exercise testing, and arterial ultrasonography for coronary risk assessment in primary prevention.

BACKGROUND: The choice of noninvasive tests used in primary prevention of cardiovascular diseases must be based on medical evidence. The aim of this study was to assess the additional prognostic value, over conventional risk factors, of physical examination, exercise testing, and arterial ultrasonography, in predicting a first coronary event. METHODS: A prospective cohort study was conducted between 1996 and 2004 (n = 2,709), with follow-up in 2006 (response rate 96.6%). Participants had no history or symptoms of cardiovascular disease and had a standardized physical examination, a cardiac exercise testing, and carotid and femoral ultrasonography at baseline. Incident cases of definite coronary events were recorded during follow-up. RESULTS: Over the Framingham risk score, femoral bruit, positive exercise test, intima-media thickness >0.63 mm, and a femoral plaque provided significant additional information to the prediction model. The addition of the exercise test to the traditional risk factors, then the intima-media thickness and lastly the presence of femoral plaques, produces incremental increases in the area under the receiver operating characteristic curve (0.73-0.78, P = .02) and about a 50% increase in the positive predictive value (15.8%-31.4%), with no effect on the negative predictive value (96.4%-96.9%). CONCLUSION: Physical examination, exercise testing, and arterial ultrasonography provide incremental information on the risk of coronary event in asymptomatic adults. Exercise testing and femoral ultrasonography also improve the accuracy of the risk stratification.

Ceramide production associated with retinal apoptosis after retinal detachment.

BACKGROUND: During retinal detachment, premature apoptosis of photoreceptors and a loss of optimally corrected visual acuity occur. We hypothesized that retinal cell death and generation of ceramide, a pro-apoptotic lipid, would progress as a function of time following experimental retinal detachment, and undertook to define the appropriate temporal window. METHODS: Unilateral retinal detachment was induced in white New Zealand rabbits by subretinal injection of sodium hyaluronate. In experimental animals, we injected sphingosine-1-P into the vitreous 2 hours before retinal detachment. Both eyes were removed on days 1, 3 and 6 for histological and biochemical examination. The number of photoreceptors was counted in section, the level of apoptosis was assessed using the TUNEL assay, and the production of ceramide was analyzed in situ with immunohistochemistry. The concentration of ceramide was also determined on retinal homogenates using a diacylglycerol kinase assay. RESULTS: We confirmed that the average number of live photoreceptors decreased gradually after retinal detachment. In eyes pre-treated with sphingosine-1-P the number of apoptotic photoreceptors was significantly lower. The proportion of apoptotic photoreceptors (14%) remained constant as a function of time in the window studied. As compared to controls, the detached retina showed intense ceramide immunostaining that was prominent in the photoreceptors, but also present to a lesser extent in other retinal layers. The total concentration of intra-retinal ceramide increased by 40% on the first day and continued augmenting through the sixth day after retinal detachment. CONCLUSIONS: Retinal apoptosis during experimental retinal detachment is associated with in vivo production of ceramide.

Risk of neurological decompression sickness in the diver with a right-to-left shunt: literature review and meta-analysis.

OBJECTIVE: Literature review and meta-analysis to review the evidence of relationship between the presence of right-to-left shunts (RLSs) and the occurrence of neurological decompression sickness (DCS) in divers. DATA SOURCES: MEDLINE, Google Scholar, and Health Technology Assessment databases. STUDY SELECTION: Five case-control studies in which the prevalence of a RLS in a group of divers with neurological DCS was compared with that of a group of divers with no history of DCS, 3 cross-transversal studies in which the prevalence of RLS was measured in divers with neurological DCS, and 4 cross-transversal studies in which the prevalence of RLS was measured in divers with no history of DCS were reviewed. DATA EXTRACTION: Only case-control studies were retained for meta-analysis. DATA SYNTHESIS: This meta-analysis gathers 5 studies and 654 divers. The combined odds ratio of neurological DCS in divers with RLS was 4.23 (3.05-5.87). The meta-analysis including only large RLS found a combined odds ratio of 6.49 (4.34-9.71). CONCLUSIONS: Because of a low incidence of neurological DCS, increase in absolute risk of neurological DCS due to RLS is probably small. Thus, in recreational diving, the systematic screening of RLS seems unnecessary. In professional divers, because of a chronic exposition and unknown consequences of cerebral asymptomatic lesions, these results raise again the benefit of the transcranial Doppler in the screening and quantification of the RLS, independently of their location.

The Use of Transthoracic Echocardiogram to Quantify Pulmonary Vascular Resistance in Patients with Systemic Sclerosis.

OBJECTIVE: To explore the accuracy of tricuspid regurgitation velocity (TRV) to right ventricular outflow tract time-velocity integral (TVIRVOT) ratio by Doppler to determine pulmonary vascular resistance (PVR) in patients with systemic sclerosis (SSc). METHODS: Thirty-five consecutive adult patients with SSc, fulfilling the 2013 European League Against Rheumatism/American College of Rheumatology classification criteria, with sinus rhythm referred for right heart catheterization (RHC), were retrospectively included. All patients underwent a transthoracic echocardiogram (TTE) performed within 24 h of RHC. Patients with SSc were recruited regardless of disease activity, cardiac symptoms, and treatment regimen. Doppler measurements were compared to RHC measurements. A linear regression equation was generated to predict PVR by echocardiogram based on the TRV/TVIRVOT ratio. The accuracy of Doppler measurements for predicting PVR > 3 Wood units was assessed by computing the areas under the receiver-operating characteristic curves. RESULTS: There were 20 (57%) females in the study. The mean age was 65 ± 12 years. Mean and systolic pulmonary arterial pressures were 31 ± 8 and 53 ± 15 mmHg, respectively. There was a good correlation between TRV/TVIRVOT ratio assessed by Doppler and PVR measured by RHC (R = 0.743, p < 0.001). The equation generated by this analysis was the following: PVR by Doppler = 11.3 × (TRV/TVIRVOT) + 1.7. A cutoff value of 0.21 for TRV/TVIRVOT ratio provided the best sensitivity (86%) and specificity (86%) to determine PVR > 3 Wood units. CONCLUSION: Our study suggests that TTE using Doppler could be a useful and noninvasive tool for estimating PVR in patients with SSc.

Optimization of the use of B-type natriuretic peptide levels for risk stratification at discharge in elderly patients with decompensated heart failure.

BACKGROUND: In elderly patients hospitalized for decompensated heart failure, B-type natriuretic peptide (BNP) levels at discharge and the change in BNP during hospitalization may provide different information and may need to be taken into account simultaneously to best reflect the response to therapy. The aim of this study was to determine whether the most accurate risk stratification is obtained using BNP level after stabilization on treatment, the change in BNP under optimal treatment, or a combination of both markers. METHODS: This prospective cohort study included 157 consecutive patients aged >or=70 (mean, 83 years), hospitalized for decompensated heart failure. Clinical, radiologic, biologic, and ultrasonography data were collected on admission and at discharge. RESULTS: The median BNP level on admission was 1,057 pg/mL, and the mean change during hospitalization was -42%. Cardiac death or readmission were independently predicted by both predischarge BNP (best threshold: >360 pg/mL, HR 3.35 [1.94-5.75]) and the change in BNP levels (best threshold: -50%, HR 2.52 [1.59-4.01]). The highest event rate was observed in patients with both a predischarge BNP >or=360 pg/mL and a decrease <50% during hospitalization (HR 5.97 [2.98-11.94] compared with patients with a predischarge BNP <360 pg/mL and a decrease >or=50%, after adjustment for potential confounders). The remaining patients constituted an intermediate risk group (HR 3.13 [1.44-6.77]). CONCLUSION: Predischarge BNP and inhospital BNP change should not be interpreted independently from each other. The highest risk group includes patients with a high predischarge BNP level corresponding to more than the half of the BNP on admission. These patients would benefit from close monitoring for signs of decompensation.

Morphological study of fiber-reinforced post-bonding system-root dentin interface by evaluation of two bonding systems.

UNLABELLED: Morphological study of fiber post/bonding system/root dentin interface by evaluation of two bonding systems. OBJECTIVES: The aim of the study was to analyze the interfaces, and thus the seal, between root dentin and bonded fiber-reinforced posts. The interfaces were obtained by applying two enamel-dentin adhesive systems, a one-bottle system used after application of phosphoric acid and a self-etch system, both used with an adhesive cement. The interface was evaluated by SEM observation of the continuity of the hybrid layer and the morphology of the resin tags, in terms of length, density and presence of side branches, at the interface between the fiber-reinforced post, the bonding system and the root dentin. METHODS: Twenty-six anterior single-rooted teeth extracted for periodontal reasons were treated endodontically and then randomly separated into two groups of 13 teeth each: group 1: Excite DSC (Ivoclar Vivadent, Liechtenstein); group 2: AdheSE DC (Ivoclar Vivadent, Schaan, Liechtenstein). After preparation of the root canal and application of the adhesive, each specimen received a Postec translucent FRC post (Ivoclar Vivadent, Schaan, Liechtenstein) that was cemented in with Variolink II dual-curing luting composite (Ivoclar Vivadent, Schaan, Liechtenstein). The specimens were then prepared for SEM observation of the continuity of the hybrid layer and scoring of the morphology of the resin tags in each third of the root (at 1, 4.5 and 8mm from the coronal surface). RESULTS: There was no significant difference (at p<0.05) between the two groups in terms of continuity of the hybrid layer or morphology of the resin tags. The hybrid layer was present, unbroken and uniform in both the group where adhesive was used with a phosphoric acid total etch and the self-etch system group. Whatever the bonding system, the resin tags had side branches, and greater length and density in the cervical third than in the middle or apical thirds. Bubbles were found in the cement layer in most of the specimens. CONCLUSIONS: The one-bottle and self-etch bonding systems gave similar results in terms of interface morphology when a translucent fiber-reinforced post was cemented into the endodontically prepared roots.

Circulating Concentrations of Redox Biomarkers Do Not Improve the Prediction of Adverse Cardiovascular Events in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: Despite pathophysiological relevance and promising experimental data, the usefulness of biomarkers of oxidative stress for cardiac risk prediction is unclear. The aim of our study was to investigate the prognostic value of 6 biomarkers exploring different pathways of oxidative stress for predicting adverse cardiovascular outcomes in patients with type 2 diabetes mellitus beyond established risk factors. METHODS AND RESULTS: The SURDIAGENE (Survie, Diabete de type 2 et Genetique) prospective cohort study consecutively recruited 1468 patients with type 2 diabetes mellitus. Assays were performed at baseline, and incident cases of major adverse cardiovascular events (MACE)-first occurrence of cardiovascular death, nonfatal myocardial infarction, or stroke-were recorded during a median of 64 months. Advanced oxidation protein products, oxidative hemolysis inhibition assay, ischemia-modified albumin, and total reductive capacity of plasma were not associated with the risk of MACE in univariate analyses. Fluorescent advanced glycation end products and carbonyls were associated with MACE (hazard ratio=1.38 per SD, 95% confidence interval 1.24-1.54, P<0.001 and hazard ratio=1.15 per SD, 95% confidence interval 1.04-1.27, P=0.006, respectively) in univariate analysis, but when added to a multivariate predictive model including traditional risk factors for MACE, these markers did not significantly improve c-statistics or integrated discrimination index of the model. CONCLUSIONS: These plasma concentrations of 6 markers, which cover a broad spectrum of oxidative processes, were not significantly associated with MACE occurrence and were not able to improve MACE risk discrimination and classification beyond classical risk factors in type 2 diabetes mellitus patients.

A hemorrhagic transformation model of mechanical stroke therapy with acute hyperglycemia in mice.

Clinical benefit for mechanical thrombectomy (MT) in stroke was recently demonstrated in multiple large prospective studies. Acute hyperglycemia (HG) is an important risk factor of poor outcome in stroke patients, including those that underwent MT. The aim of this therapy is to achieve a complete reperfusion in a short time, given that reperfusion damage is dependent on the duration of ischemia. Here, we investigated the effects of acute HG in a mouse model of ischemic stroke induced by middle cerebral artery occlusion (MCAO). Hyperglycemic (intraperitoneal [ip] injection of glucose) and control (ip saline injection) 10-week male C57BL6 mice were subjected to MCAO (30, 90, and 180 min) followed by reperfusion obtained by withdrawal of the monofilament. Infarct volume, hemorrhagic transformation (HT), neutrophil infiltration, and neurological scores were assessed at 24 hr by performing vital staining, ELISA immunofluorescence, and behavioral test, respectively. Glucose injection led to transient HG (blood glucose = 250-390 mg/dL) that significantly increased infarct volume, HT, and worsened neurological outcome. In addition, we report that HG promoted blood-brain barrier disruption as shown by hemoglobin accumulation in the brain parenchyma and tended to increase neutrophil extravasation within the infarcted area. Acute HG increased neurovascular damage for all MCAO durations tested. HTs were observed as early as 90 min after ischemia under hyperglycemic conditions. This model mimics MT ischemia/reperfusion and allows the exploration of brain injury in hyperglycemic conditions.

Prognostic Values of Inflammatory and Redox Status Biomarkers on the Risk of Major Lower-Extremity Artery Disease in Individuals With Type 2 Diabetes.

OBJECTIVE: Inflammation and oxidative stress play an important role in the pathogenesis of lower-extremity artery disease (LEAD). We assessed the prognostic values of inflammatory and redox status biomarkers on the risk of LEAD in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: Plasma concentrations of tumor necrosis factor-α receptor 1 (TNFR1), angiopoietin-like 2, ischemia-modified albumin (IMA), fluorescent advanced glycation end products, protein carbonyls, and total reductive capacity of plasma were measured at baseline in the SURDIAGENE (Survie, Diabete de type 2 et Genetique) cohort. Major LEAD was defined as the occurrence during follow-up of peripheral revascularization or lower-limb amputation. RESULTS: Among 1,412 participants at baseline (men 58.2%, mean [SD] age 64.7 [10.6] years), 112 (7.9%) developed major LEAD during 5.6 years of follow-up. High plasma concentrations of TNFR1 (hazard ratio [95% CI] for second vs. first tertile 1.12 [0.62-2.03; P = 0.71] and third vs. first tertile 2.16 [1.19-3.92; P = 0.01]) and of IMA (2.42 [1.38-4.23; P = 0.002] and 2.04 [1.17-3.57; P = 0.01], respectively) were independently associated with an increased risk of major LEAD. Plasma concentrations of TNFR1 but not IMA yielded incremental information, over traditional risk factors, for the risk of major LEAD as follows: C-statistic change (0.036 [95% CI 0.013-0.059]; P = 0.002), integrated discrimination improvement (0.012 [0.005-0.022]; P < 0.001), continuous net reclassification improvement (NRI) (0.583 [0.294-0.847]; P < 0.001), and categorical NRI (0.171 [0.027-0.317]; P = 0.02). CONCLUSIONS: Independent associations exist between high plasma TNFR1 or IMA concentrations and increased 5.6-year risk of major LEAD in people with type 2 diabetes. TNFR1 allows incremental prognostic information, suggesting its use as a biomarker for LEAD.

Usefulness of in-hospital change in B-type natriuretic peptide levels in predicting long-term outcome in elderly patients admitted for decompensated heart failure.

The usefulness of repeated measures of B-type natriuretic peptide (BNP) in elderly subjects with decompensated heart failure to improve risk stratification remains poorly known. This prospective cohort study included 61 consecutive patients older than 70 years (mean age, 82.7 years) hospitalized for decompensated heart failure. Clinical, radiologic, biologic, and echographic data were collected at admission and at discharge. The median BNP level at admission was 1136 pg/mL and the mean change during the hospitalization was -32%. Cardiac death or readmission were best predicted by the change in BNP levels, with the poorest prognosis in patients who did not achieve a decrease of at least 40% (hazard ratio, 4.03; 95% confidence interval, 1.50-10.84 in multivariate analysis). Admission of an elderly patient for decompensated heart failure is a daily situation in clinical practice, in which 2 BNP measurements seem to provide reliable information on long-term prognosis.

Association between Fluorescent Advanced Glycation End-Products and Vascular Complications in Type 2 Diabetic Patients.

OBJECTIVES: Diabetes is a major health problem associated with hyperglycemia and chronically increased oxidative stress and enhanced formation of advanced glycation end-products (AGEs). The aim of this study was to determine whether oxidative plasma biomarkers in diabetic patients could be evidenced and associated with vascular complications. METHODS: Oxidative stress biomarkers such as thiols, ischemia-modified albumin (IMA), glycated albumin (GA), fructosamine, and AGEs were measured in 75 patients with poorly controlled type 2 diabetes (HbA1c > 7.5%) with (44) or without (31) vascular disease and in 31 nondiabetic controls. RESULTS: Most biomarkers of oxidation and glycation were significantly increased in diabetic patients in comparison with nondiabetics. Fructosamines, GA, IMA, and AGEs were positively correlated and levels of fluorescent AGEs were significantly increased in the plasma from patients presenting vascular complication. CONCLUSIONS: These results bring new evidence for the potential interest of glycated albumin, oxidative stress, and glycoxidation parameters in the monitoring of type 2 diabetic patients. Furthermore, it emphasizes fluorescent AGEs as a putative indicator for vascular event prediction in diabetic patients.

Ozone air pollution is associated with acute myocardial infarction.

BACKGROUND: Despite the diversity of the studied health outcomes, types and levels of pollution, and various environmental settings, there is substantial evidence for a positive link between urban air pollution and cardiovascular diseases. The objective of this study was to test the associations between air pollutants and the occurrence of acute myocardial infarction (AMI). METHODS AND RESULTS: Pollutant concentrations (SO2, NO2, and O3) were measured hourly as part of the automated air quality network. Since 1985, an AMI registry (the Toulouse MONICA Project) has been collecting data in the southwest of France. All cases of AMI and sudden and probable cardiac deaths are recorded for subjects 35 to 64 years of age. We studied the short-term exposure effect of pollution on the risk of AMI (from January 1, 1997, to June 30, 1999) using a case-crossover design method. We performed a conditional logistic regression analysis to calculate relative risks (RRs) and their 95% CIs. After adjustment for temperature, relative humidity, and influenza epidemics, the RRs (for an increase of 5 microg/m3 of O3 concentration) for AMI occurrence were significant for the current-day and 1-day-lag measurements (RR, 1.05; 95% CI, 1.01 to 1.08; P=0.009; and RR, 1.05; 95% CI, 1.01 to 1.09; P=0.007, respectively). Subjects 55 to 64 years of age with no personal history of ischemic heart disease were the most susceptible to develop an AMI (RR, 1.14; 95% CI, 1.06 to 1.23). NO2 and SO2 exposures were not significantly associated with the occurrence of AMI. CONCLUSIONS: Observational data confirm that short-term O3 exposure within a period of 1 to 2 days is related to acute coronary events in middle-aged adults without heart disease, whereas NO2 and SO2 are not.