Increased expression of NAMPT in PBMC from patients with acute coronary syndrome and in inflammatory M1 macrophages.

AIM: The aim of the present study were to elucidate the role of NAMPT in atherosclerosis, by examine NAMPT expression in peripheral blood mononuclear cells (PBMC) in patients with coronary artery disease (CAD) and healthy controls and by examining the regulation and effect of NAMPT on macrophage polarization, hypothesizing that it could influence the polarization to inflammatory and resolving macrophages. METHOD AND RESULTS: We analyzed RNA levels of NAMPT in PBMC from CAD and healthy controls and found NAMPT to be increased in PBMC from patients with acute coronary syndrome (n = 39) compared to healthy controls (n = 20) and patients with stable CAD (n = 22). Within the PBMC NAMPT was correlated to several inflammatory cytokines and the antioxidant enzyme superoxide dismutase 2. In vitro cell experiments revealed that NAMPT is increased both intracellular and extracellular in inflammatory M1 macrophages compared to in anti-inflammatory M2 macrophages. In addition, inhibiting NAMPT enzymatic activity inhibited M1 polarization in macrophages. CONCLUSION: Based on our in vivo and in vitro findings we suggest that NAMPT could contribute to systemic and plaque inflammation in atherosclerotic disorders at least partly through effect on macrophages.

Impact of newly diagnosed abnormal glucose regulation on long-term prognosis in low risk patients with ST-elevation myocardial infarction: A follow-up study.

BACKGROUND: Patients with acute myocardial infarction and newly detected abnormal glucose regulation have been shown to have a less favourable prognosis compared to patients with normal glucose regulation. The importance and timing of oral glucose tolerance testing (OGTT) in patients with acute myocardial infarction without known diabetes is uncertain. The aim of the present study was to evaluate the impact of abnormal glucose regulation classified by an OGTT in-hospital and at three-month follow-up on clinical outcome in patients with acute ST elevation myocardial infarction (STEMI) without known diabetes. METHODS: Patients (n = 224, age 58 years) with a primary percutanous coronary intervention (PCI) treated STEMI were followed for clinical events (all-cause mortality, non-fatal myocardial re-infarction, recurrent ischemia causing hospital admission, and stroke). The patients were classified by a standardised 75 g OGTT at two time points, first, at a median time of 16.5 hours after hospital admission, then at three-month follow-up. Based on the OGTT results, the patients were categorised according to the WHO criteria and the term abnormal glucose regulation was defined as the sum of impaired fasting glucose, impaired glucose tolerance and type 2-diabetes. RESULTS: The number of patients diagnosed with abnormal glucose regulation in-hospital and at three-month was 105 (47%) and 50 (25%), respectively. During the follow up time of (median) 33 (27, 39) months, 58 (25.9%) patients experienced a new clinical event. There were six deaths, 15 non-fatal re-infarction, 33 recurrent ischemia, and four strokes. Kaplan-Meier analysis of survival free of composite end-points showed similar results in patients with abnormal and normal glucose regulation, both when classified in-hospital (p = 0.4) and re-classified three months later (p = 0.3). CONCLUSIONS: Patients with a primary PCI treated STEMI, without previously known diabetes, appear to have an excellent long-term prognosis, independent of the glucometabolic state classified by an OGTT in-hospital or at three-month follow-up. TRIAL REGISTRATION: The trial is registered at http://www.clinicaltrials.gov, NCT00926133.

Activin A levels are associated with abnormal glucose regulation in patients with myocardial infarction: potential counteracting effects of activin A on inflammation.

OBJECTIVE: On the basis of the role of activin A in inflammation, atherogenesis, and glucose homeostasis, we investigated whether activin A could be related to glucometabolic abnormalities in patients with acute myocardial infarction (MI). RESEARCH DESIGN AND METHODS: Activin A measurement and oral glucose tolerance tests (OGTTs) were performed in patients (n = 115) with acute MI, without previously known diabetes, and repeated after 3 months. Release of activin A and potential anti-inflammatory effects of activin A were measured in human endothelial cells. Activin A effects on insulin secretion and inflammation were tested in human pancreatic islet cells. RESULTS: 1) In patients with acute MI, serum levels of activin A were significantly higher in those with abnormal glucose regulation (AGR) compared with those with normal glucose regulation. Activin A levels were associated with the presence of AGR 3 months later (adjusted odds ratio 5.1 [95% CI 1.73-15.17], P = 0.003). 2) In endothelial cells, glucose enhanced the release of activin A, whereas activin A attenuated the release of interleukin (IL)-8 and enhanced the mRNA levels of the antioxidant metallothionein. 3) In islet cells, activin A attenuated the suppressive effect of inflammatory cytokines on insulin release, counteracted the ability of these inflammatory cytokines to induce mRNA expression of IL-8, and induced the expression of transforming growth factor-ß. CONCLUSIONS: We found a significant association between activin A and newly detected AGR in patients with acute MI. Our in vitro findings suggest that this association represents a counteracting mechanism to protect against inflammation, hyperglycemia, and oxidative stress.

Increased levels of CRP and MCP-1 are associated with previously unknown abnormal glucose regulation in patients with acute STEMI: a cohort study.

BACKGROUND: Inflammation plays an important role in the pathophysiology of both atherosclerosis and type 2 diabetes and some inflammatory markers may also predict the risk of developing type 2 diabetes. The aims of the present study were to assess a potential association between circulating levels of inflammatory markers and hyperglycaemia measured during an acute ST-elevation myocardial infarction (STEMI) in patients without known diabetes, and to determine whether circulating levels of inflammatory markers measured early after an acute STEMI, were associated with the presence of abnormal glucose regulation classified by an oral glucose tolerance test (OGTT) at three-month follow-up in the same cohort. METHODS: Inflammatory markers were measured in fasting blood samples from 201 stable patients at a median time of 16.5 hours after a primary percutaneous coronary intervention (PCI). Three months later the patients performed a standardised OGTT. The term abnormal glucose regulation was defined as the sum of the three pathological glucose categories classified according to the WHO criteria (patients with abnormal glucose regulation, n = 50). RESULTS: No association was found between inflammatory markers and hyperglycaemia measured during the acute STEMI. However, the levels of C-reactive protein (CRP) and monocyte chemoattractant protein-1 (MCP-1) measured in-hospital were higher in patients classified three months later as having abnormal compared to normal glucose regulation (p = 0.031 and p = 0.016, respectively). High levels of CRP (≥ 75 percentiles (33.13 mg/L)) and MCP-1 (≥ 25 percentiles (190 ug/mL)) were associated with abnormal glucose regulation with an adjusted OR of 3.2 (95% CI 1.5, 6.8) and 7.6 (95% CI 1.7, 34.2), respectively. CONCLUSION: Elevated levels of CRP and MCP-1 measured in patients early after an acute STEMI were associated with abnormal glucose regulation classified by an OGTT at three-month follow-up. No significant associations were observed between inflammatory markers and hyperglycaemia measured during the acute STEMI.

Abnormal glucose regulation in patients with acute ST- elevation myocardial infarction-a cohort study on 224 patients.

BACKGROUND: A high prevalence of impaired glucose tolerance and unknown type 2-diabetes in patients with coronary heart disease and no previous diagnosis of diabetes have been reported. The aims of the present study were to investigate the prevalence of abnormal glucose regulation (AGR) 3 months after an acute ST-elevation myocardial infarction (STEMI) in patients without known glucometabolic disturbance, to evaluate the reliability of a 75-g oral glucose tolerance test (OGTT) performed very early after an acute STEMI to predict the presence of AGR at 3 months, and to study other potential predictors measured in-hospital for AGR at 3 months. METHODS: This was an observational cohort study prospectively enrolling 224 STEMI patients treated with primary PCI. An OGTT was performed very early after an acute STEMI and was repeated in 200 patients after 3 months. We summarised the exact agreement observed, and assessed the observed reproducibility of the OGTTs performed in-hospital and at follow up. The patients were classified into glucometabolic categories defined according to the World Health Organisation criteria. AGR was defined as the sum of impaired fasting glucose, impaired glucose tolerance and type 2-diabetes. RESULTS: The prevalence of AGR at three months was 24.9% (95% CI 19.1, 31.4%), reduced from 46.9% (95% CI 40.2, 53.6) when measured in-hospital. Only, 108 of 201 (54%) patients remained in the same glucometabolic category after a repeated OGTT. High levels of HbA1c and admission plasma glucose in-hospital significantly predicted AGR at 3 months (p < 0.001, p = 0.040, respectively), and fasting plasma glucose was predictive when patients with large myocardial infarction were excluded (p < 0.001). CONCLUSION: The prevalence of AGR in STEMI patients was lower than expected. HbA1c, admission plasma glucose and fasting plasma glucose measured in-hospital seem to be useful as early markers of longstanding glucometabolic disturbance. An OGTT performed very early after a STEMI did not provide reliable information on long-term glucometabolic state and should probably not be recommended.