Hyperglycemia In Acute Coronary Syndrome Research Articles

Real-world evaluation of glucose-lowering therapies and the use of weight-adjusted variable rate intravenous insulin infusion in the management of hyperglycaemia in patients with acute coronary syndrome (REGULATE-ACS)

IntroductionAdmission hyperglycaemia in acute coronary syndromes (ACS) is a strong independent predictor of adverse clinical outcomes post-ACS. We examined the safety, efficacy, and feasibility of a modified, weight-adjusted variable rate intravenous insulin infusion (VRIII) and evaluated current practice of prescribing novel cardio-protective glucose-lowering therapies in patients presenting with acute hyperglycaemia across the ACS spectrum. MethodsREGULATE-ACS was an observational single-centre study of consecutive patients admitted with acute hyperglycaemia post-ACS between 2020 and 2021. Following updated local guidance on a modified VRIII, we evaluated its safety and efficacy in glycaemic control, cardio-metabolic complications including hypoglycaemia (blood glucose <3 mmol/L) and 30-day mortality. We also determined the prescription of glucose-lowering therapies pre-discharge. ResultsOut of 107 patients, mean age was 64.9 ± 12.2 years, 82% had known diabetes, and 15% newly diagnosed diabetes. 86.9% (n = 93) had an admission glucose ≥11 mmol/L. In patients treated with VRIII (n = 63/93, 67.7%), glucose improved from 17.5 to 9.0 mmol/L (IQR 7.1–12.1), which was 3 mmol/L lower (p = 0.03) than in patients not treated with VRIII (n = 30/93, 32.3%) where median glucose reduced from 12.6 to 12 mmol/L (IQR 8.6–13.9). No significant hypoglycaemia, arrhythmia or worsening pulmonary oedema associated with VRIII was found. Novel glucose-lowering therapies were initiated in 20/71 (28.2%) and 3/15 (20.0%) of patients with prior and newly diagnosed diabetes, respectively. ConclusionThis real-world analysis provides further support of efficacy, safety, and feasibility of a modified, weight-adjusted VRIII in managing acute hyperglycaemia in ACS. Despite established cardio-protective benefits of novel glucose-lowering therapies, <1/3 of eligible patients received such agents pre-discharge, demanding further research and awareness.

A novel form of glycolytic metabolism-dependent cardioprotection revealed by PKCα and β inhibition.

Acute hyperglycaemia at the time of a heart attack worsens the outcome for the patient. Acute hyperglycaemia is not limited to diabetic patients and can be due to a stress response in non-diabetics. This study suggests that the damaging cardiac effects of hyperglycaemia can be reversed by selective PKC inhibition. If PKCα/β isoforms are inhibited, then high glucose itself becomes protective against ischaemic damage. Selective PKC inhibition may therefore be a useful therapeutic tool to limit the damage that can occur during a heart attack by stress-induced hyperglycaemia. Hyperglycaemia has a powerful association with adverse prognosis for patients with acute coronary syndromes (ACS). Previous work shows that high glucose prevents ischaemic preconditioning and causes electrical and mechanical disruption via protein kinase C α/β (PKCα/β) activation. The present study aimed to: (i) determine whether the adverse clinical association of hyperglycaemia in ACS can be replicated in preclinical cellular models of ACS and (ii) determine the importance of PKCα/β activation to the deleterious effect of glucose. Freshly isolated rat, guinea pig or rabbit cardiomyocytes were exposed to simulated ischaemia after incubation in the presence of normal (5mm) or high (20mm) glucose in the absence or presence of small molecule or tat-peptide-linked PKCαβ inhibitors. In each of the four conditions, the following hallmarks of cardioprotection were recorded using electrophysiology or fluorescence imaging: cardiomyocyte contraction and survival, action potential stability and time to failure, intracellular calcium and ATP, mitochondrial depolarization, ischaemia-sensitive leak current, and time to Kir 6.2 opening. High glucose alone resulted in decreased cardiomyocyte contraction and survival; however, it also imparted cardioprotection in the presence of PKCα/β inhibitors. This cardioprotective phenotype displayed improvements in all of the measured parameters and decreased myocardium damage during whole heart coronary ligation experiments. High glucose is deleterious to cellular and whole-heart models of simulated ischaemia, in keeping with the clinical association of hyperglycaemia with an adverse outcome in ACS. PKCαβ inhibition revealed high glucose to show a cardioprotective phenotype in this setting. The results of the present study suggest the potential for the therapeutic application of PKCαβ inhibition in ACS associated with hyperglycaemia.

Stress Hyperglycaemia During Acute Coronary Syndrome of Non-Diabetic Patients

The risk of diabetes mellitus and coronary heart disease is high among South-Asian population. In this study, our objective was to measure blood glucose level during acute coronary syndrome of previously known non-diabetic patients that will give the information about the frequency of acute hyperglycemia in acute coronary syndrome (ACS) among Bangladeshi population. It is an observational cross sectional study performed in Rajshahi Medical College Hospital. A total of 248 non-diabetic subjects with ACS got admitted into hospital. FBS and standard OGTT within 3 days of ACS were done. This study was done to find out glucose abnormalities among ACS patients. Out of 248 study population, 135(54.44%) had glucose abnormalities. Male was 87.10% (216). Among male, IGT (prediabetic) was 31.94% (69) and diabetic 24.54% (53). Mean age (±SD) of our study population was 51.71±11.84 years. Normal glucose tolerance (NGT) was found in 45.6% (113) cases, IGT (prediabetic) and diabetic were detected among 30.6% (76) and 23.8% (59) cases respectively. Non-diabetic Bangladeshi patients showed a high prevalence of hyperglycemia in acute coronary syndrome (ACS). We should create awareness about a new risk factor- acute hyperglycemia during acute coronary syndrome and take appropriate and effective measures to reduce morbidity as well as mortality as a consequence of acute hyperglycemia during ACS with or without diabetes.TAJ 2012; 25: 30-34

Glycemic Status During Acute Coronary Syndrome of Non-Diabetic Patients

The risk of diabetes mellitus and coronary heart disease is high among South-Asian population. In this study, our objective was to measure blood glucose level during acute coronary syndrome of previously known nondiabetic patients that will give the information about the frequency of acute hyperglycemia in acute coronary syndrome (ACS) among Bangladeshi population. It is an observational cross sectional study performed in Rajshahi Medical College Hospital (RMCH). A total of 248 non-diabetic subjects with ACS got admitted into hospital. Fasting blood glucose (FBS) and standard oral glucose tolerance test (OGTT ) within 3 days of ACS were done. This study was done to find out glucose abnormalities among ACS patients. Out of 248 study population, 135 (54.44%) had glucose abnormalities. Male was 87.10% (216). Among male, IGT (prediabetic) was 31.94% (69) and diabetic 24.54% (53). Mean age (±SD) of our study population was 51.71±11.84 years. Normal glucose tolerance (NGT) was found in 45.6% (113) cases, IGT (prediabetic) and diabetic were detected among 30.6% (76) and 23.8% (59) cases respectively. Non-diabetic Bangladeshi patients showed a high prevalence of hyperglycemia in acute coronary syndrome (ACS). We should create awareness about a new risk factor- acute hyperglycemia during acute coronary syndrome and take appropriate and effective measures to reduce morbidity as well as mortality as a consequence of acute hyperglycemia during ACS with or without diabetes.KYAMC Journal Vol. 7, No.-1, Jul 2016, Page 697-699

Prognostic value of stress hyperglycemia in acute coronary syndrome in non-diabetic patients

Prognostic value of stress hyperglycemia in acute coronary syndrome in non-diabetic patients

Stress hyperglycemia in acute coronary syndrome and pulmonary disease

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Management of hyperglycemia in acute coronary syndrome. Issues and solutions

The role of hyperglycemia as an independent predictor of adverse course and prognosis of acute coronary syndrome (ACS) in patients with diabetes mellitus (DM) and without it [1] can hardly be overestimated. This relationship is thoroughly covered in the literature [2-- 13], and the discussions on the subject are underway. A simple summation of risks results in higher than expected rates of morbidity and mortality from CAD in DM patients, demonstrating a direct effect of hyperglycemia on the atherosclerotic process [14--16]. It is worth noting that in patients without DM hyperglycemia is associated with worse clinical outcomes and higher mortality from all causes compared with patients suffering from diabetes mellitus [17--21]. Increased blood sugar levels at the time of admission are usually seen as a reaction to stress in acute condition, but in some cases may serve as a marker of an existing though not yet diagnosed type 2 diabetes or impaired glucose tolerance (IGT) [22]. According to observational studies, hyperglycemia occurs in 32--38% of patients in hospitals [23, 24], 41% of severe patients with acute coronary syndrome[25], 44% of patients with heart failure [25] and 80% of patients after coronary intervention [26, 27].

The effects of intravenous insulin infusions on early mortality for patients with acute coronary syndromes who present with hyperglycaemia: A matched propensity analysis using data from the MINAP database 2008-2012.

In acute coronary syndrome, the use of intravenous insulin infusions (IVII) to control hyperglycaemia is based on limited evidence of survival benefit. To compare 7 day survival for patients receiving IVII compared with those receiving routine care to control admission hyperglycaemia (>=11 mmol/l) in acute coronary syndrome. We used matched propensity analysis to examine observational data from the MINAP database between 2008 and 2012. We matched 5974 pairs of patients. We separately examined outcomes for ST elevation (STEMI) and non ST segment elevation (NSTEMI) infarctions, and those without known diabetes and those with type 2 diabetes. Survival benefit from the use of IVII was seen only in patients with STEMI not known to have diabetes at admission (adjusted hazard ratio (HR) 0.77 (95% confidence interval (CI) 0.64-0.92), p=0.005). Those with STEMI and existing type 2 diabetes who received IVII showed similar outcomes to routine care (HR 0.99 (95% CI 0.80-1.23), p=0.931). In patients with NSTEMI IVII was associated with significantly worse adjusted 7 day survival outcome than routine care, regardless of diabetes status; for those without known diabetes, HR 1.50 (95% CI 1.04-2.16), p=0.029, and for those with type 2 diabetes, HR 1.35 (95% CI 1.08-1.70), p=0.010. As used in current clinical practice to treat hyperglycaemia in acute coronary syndromes, IVII appears to be of benefit only for patients with STEMI who are not known to have diabetes. IVII is associated with adverse early outcomes in patients with NSTEMI.

Evaluation of the procoagulant potential of endothelial microparticles CD144 (VE-Cadherin) positive in coronary syndrome patients

Background Apoptotic microparticles are responsible for almost all tissue factor activity of the plaque lipid core. We hypothesized that elevated levels of procoagulant microparticles could also circulate in the peripheral blood of patients with recent clinical signs of plaque disruption and thrombosis. The present study included 60 acute coronary syndrome (ACS) adult patients. Group I included 30 patients with diabetes mellitus who presented with ACS. Group II included 30 nondiabetic patients complaining of ACS and 25 healthy individuals as controls. ACS patients were further classified according to laboratory and radiological findings (troponin test and ECG) as follows: group A included 16 ST-segment elevation myocardial infarction (STEMI) patients, group B included 19 non-ST-segment elevation myocardial infarction (NSTEMI) patients, and group C included 25 patients with unstable angina. Traditional laboratory investigations and special laboratory assessments of CD144 fluorescein isothiocyanate by flow cytometry were performed.Results The present study found highly elevated CD144 percentages in diabetic ACS patients compared with healthy controls (P≤0.0001(, and highly elevated creatine kinase-MB (CK-MB), fasting sugar, total cholesterol, triglyceride, HDL, and LDL (P = 0.0001, 0.0001, 0.0002, 0.0002, 0.0001, and 0.0001, respectively). In contrast, nondiabetic ACS patients had significantly elevated CD144, CK-MB, total cholesterol, triglyceride, HDL, and LDL (P = 0.0001, 0.0001, 0.0001, 0.0021, 0.0001, and 0.0021, respectively), whereas fasting sugar and HbA1c did not change significantly. However, the patients in group B (NSTEMI) had significantly elevated CD144% in comparison with patients with unstable angina (group C) ( P = 0.05), but patients with group A (STEMI) had significantly elevated CK-MB compared with patients with unstable angina (group C) (P = 0.02).Conclusion The high levels of circulating microparticles of endothelial origin are increased in diabetic patients with coronary artery disease, suggesting an important role for endothelial injury in the prediction of ACS. Hyperglycemia in ACS is associated with enhanced local thrombin generation and platelet activation, as well as unfavorably altered clot features in patients with and without a previous history of diabetes.

Platelet Function and Hyperglycemia in Acute Coronary Syndrome

The literature provides strong evidence showing that platelet function is altered in patients with diabetes mellitus (DM) and that the platelet hyperactivation associated with hyperglycemia is produced by a number of thromboxane A2-independent pathways, such as those responsible for the release of adenosine diphosphatase, thrombin, epinephrine, and von Willebrand factor, among others. Being that they are independent of thromboxane A2, none of these platelet activation pathways are affected by the potential beneficial effect of the classical antiplatelet therapy with acetylsalicylic acid (ASA) or more modern compounds like clopidogrel. For this reason, the search for novel therapeutic approaches designed to control platelet reactivity, especially in diabetic individuals and not only in atherosclerosis not associated with DM, has been an object of interest in recent years, particularly if we take into consideration that diabetics have a certain resistance to the antiplatelet effect of ASA. Diabetic thrombocytopathy is due to the activation of multiple pathways that play a role in platelet function, the most relevant of which are the modification of platelet membrane components, the alteration of calcium and magnesium homeostasis (increasing and decreasing mobilization, respectively), increases in arachidonic acid metabolism and in thromboxane A2 synthesis, a decrease in prostacyclin and nitric oxide synthesis, and increased expression of certain adhesion molecules such as glycoprotein IIb/IIIa (GPIIb/IIIa) and P-selectin. The platelets of patients with DM, both type 1 and type 2, exhibit increased reactivity in early stages of the disease, and these phenomena are relevant because they contribute to the excessive rates of cardiovascular morbidity and mortality associated with this disease. Thus, the knowledge of these plateletrelated phenomena from the pathophysiological point of view, and of their eventual normalization, has been of great interest; in fact, the clinical practice guidelines on DM have incorporated, to a greater or lesser extent, recommendations concerning antiplatelet therapy. The platelets of diabetic patients express greater amounts of adhesion molecules such as activated GPIIb/IIIa, lysosomal GP53, thrombospondin, and P-selectin. In addition to supporting greater platelet aggregability, this may play a role in

Intensive management of hyperglycaemia in acute coronary syndromes. Study design and rationale of the BIOMArCS 2 glucose trial

Elevated admission plasma glucose is associated with increased mortality in patients who are admitted with an acute coronary syndrome. This may be mediated by increased inflammation, apoptosis and coagulation, and by a disturbed endothelial function that can be found in hyperglycaemic patients. Insulin has several characteristics that may potentially counteract these mechanisms. The BIOMArCS programme is a multi-centre initiative and currently consists of three different studies. The effects of acute coronary syndrome on acute biomarkers washout are studied in the BIOMArCS pilot and the value of biomarkers in predicting upcoming acute coronary syndrome events is studied in BIOMArCS 1. The third study (BIOMArCS 2 glucose), which will be presented here, investigates the effectiveness and safety of intensive glucose level control compared with conventional glucose management in patients with acute coronary syndrome and an admission plasma glucose of 7.8-16 mmol/l. In BIOMArCS 2 glucose, a total of 300 patients without insulin-treated diabetes mellitus will be randomized in a 1:1 ratio to either intensive or conventional glucose management on top of standard medical care. The primary endpoint is infarct size as expressed by the cardiac troponin T level 72 h after admission. To study the metabolic effects of insulin administration, we will investigate biomarker washout patterns of various metabolic mechanisms up to 7 days after admission. These markers will address inflammation, oxidative stress, hypercoagulability, endothelial activation and vasodilatation. Current acute coronary syndrome guidelines lack a clear strategy for hyperglycaemia treatment. This study will extend our knowledge on this matter as it may clarify mechanisms and generate hypotheses of if and how myocardial infarct size may be limited by glucose management at admission.

Hyperglycaemia in acute coronary syndromes: risk-marker or therapeutic target?

急性冠脉综合征患者入院时经常伴随高血糖现象；这种现象是一个预后不良的标志。使血糖迅速正常化的干预措施不能恰当应用并且疗效也不确切。在此，我们对高血糖与预后之间的关系进行了综述，对高血糖不仅仅反映了糖尿病前期状态的看法提供依据，并且我们还讨论了高血糖可能对急性心肌梗死过程产生不利影响的机制。最后，我们寻求胰岛素强化治疗改善预后的依据。

Postprocedural hyperglycemia in ST elevation myocardial infarction submitted to percutaneous coronary intervention: a prognostic indicator and a marker of metabolic derangement

Hyperglycemia in acute coronary syndrome is associated with an increased risk of death in patients without previously known diabetes but the prognostic role of postrevascularization hyperglycemia in these patients is so far incompletely elucidated. In 175 consecutive patients without previously known diabetes and with ST elevation myocardial infarction treated with primary angioplasty, we evaluated the relation between acute and chronic glucose dysmetabolism and early and late mortality and the relation between hyperglycemia and extension of myocardial damage [creatine phosphokinase-MB (CPK-MB), troponin I levels, ejection fraction], inflammation (leukocyte count, erythrocyte sedimentation rate, C-reactive protein) and prognostic biohumoral markers [N-terminal brain natriuretic peptide (NT-proBNP) and lactic acid]. Highest glucose levels were associated with higher Killip class, lower ejection fraction and increased values of CPK, CPK-MB, troponin I, proBNP, lactic acid, leukocytes and insulin. At multivariate logistic regression analysis, the following variables were independent predictors of intraintensive cardiac care unit mortality: postprocedural glycemia [odds ratio (OR) 8.79; 95% confidence interval (CI) 1.41-54.94; P = 0.020] and troponin I (OR 1.003; 95% CI 1.0004-1.006; P = 0.023) when adjusted for insulinemia [OR 0.98; 95% CI 0.92-1.06; P = not significant (NS)], HbA1c (OR 0.51; 95% CI 0.11-2.37; P = NS), ST elevation myocardial infarction location (OR 1.27; 95% CI 0.44-3.66; P = NS) and creatininemia (OR 1.48; 95% CI 0.90-2.45; P = NS). In ST elevation myocardial infarction patients without previously known diabetes submitted to percutaneous coronary intervention, glucose serum levels measured after mechanical revascularization were independent predictors of in-hospital mortality.

P-320 Current Management of Hyperglycaemia in Acute Coronary Syndromes, A National Survey

P-320 Current Management of Hyperglycaemia in Acute Coronary Syndromes, A National Survey

Hyperglycaemia in acute coronary syndromes: risk-marker or therapeutic target?

Patients with acute coronary syndrome (ACS) often have raised blood glucose concentrations when admitted to hospital; a marker for poorer prognosis. Interventions to rapidly normalise blood glucose inconsistently are applied...

Hyperglycemia Is Associated With Enhanced Thrombin Formation, Platelet Activation, and Fibrin Clot Resistance to Lysis in Patients With Acute Coronary Syndrome

OBJECTIVE—Acute hyperglycemia on admission for acute coronary syndrome worsens the prognosis in patients with and without known diabetes. Postulated mechanisms of this observation include prothrombotic effects. The aim of this study was to evaluate the effect of elevated glucose levels on blood clotting in acute coronary syndrome patients.RESEARCH DESIGN AND METHODS—We studied 60 acute coronary syndrome patients within the first 12 h after pain onset, including 20 subjects with type 2 diabetes, 20 subjects with no diagnosed diabetes but with glucose levels >7.0 mmol/l, and 20 subjects with glucose levels <7.0 mmol/l. We determined generation of thrombin-antithrombin complexes (TATs) and soluble CD40 ligand (sCD40L), a platelet activation marker, at the site of microvascular injury, together with ex vivo plasma fibrin clot permeability and lysis time.RESULTS—The acute coronary syndrome patients with no prior diabetes but elevated glucose levels had increased maximum rates of formation and total production of TATs (by 42.9%, P < 0.0001, and by 25%, P < 0.0001, respectively) as well as sCD40L release (by 16.2%, P = 0.0011, and by 16.3%, P < 0.0001, respectively) compared with those with normoglycemia, whereas diabetic patients had the highest values of TATs and sCD40L variables (P < 0.0001 for all comparisons). Patients with hyperglycemia, with no previously diagnosed diabetes, had longer clot lysis time (by ∼18%, P < 0.0001) similar to that in diabetic subjects, but not lower clot permeability compared with that in normoglycemic subjects.CONCLUSIONS—Hyperglycemia in acute coronary syndrome is associated with enhanced local thrombin generation and platelet activation, as well as unfavorably altered clot features in patients with and without a previous history of diabetes.