Non-diabetic Acute Coronary Syndrome Patients Research Articles

Comparison of Safety and Effectiveness of Bivalirudin Between Diabetic and Nondiabetic Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention

Background: Recurrent thrombotic events remain significantly high in spite of the currently recommended dual antiplatelet (DAPT) and conventional antithrombotic heparin (± GPI/ glycoprotein IIb/IIIa inhibitor) in diabetic ACS patients after PCI compared with non-diabetic even this drug eluting stent (DES) era. Therefore, more potent antithrombotic therapies are warranted for this group of high-risk patients.Comparison of safety and efficacy of newer anticoagulant bivalirudin between diabetic and non-diabetic ACS patients undergoing PCI using bivalirudin versus heparin (± GPI) is less well defined in Bangladeshi population. Objective: To determine and compare the incidence of 30-day major adverse cardiac events (MACEs), stent thrombosis and hemorrhagic complications between diabetic and non-diabetic ACS patients undergoing PCI. Impact of antithrombotic strategy (bivalirudin vs. heparin ± GPI) on the 30- day post PCI clinical outcome was also evaluated and compared between diabetic and non-diabetic subgroup. Methods: In this randomized controlled study, 500 ACS patients aged 18-75 years (200diabetic and 300 non-diabetics) who underwent PCI from November 2018 to October 2019 at the department of cardiology, BSMMU, were randomly assigned, in an open-label fashion to treatment with bivalirudin alone, heparin alone, or heparin plus eptifibatide (GPI) in a 1:1:1 ratio. Among them, 200 patients received Bivalirudin with a loading dose of 0.75 mg/kg, followed by an infusion of 1.75 mg/kg/h for up to 4 hours, 153 patients received UFH with a bolus of 70-100 U/kg (targeted ACT: 200-250 s) and 147 patients got heparin plus eptifibatide as 60 IU/kg heparin along with 180 μg/kg eptifibatide i.v. boluses, followed by a 2 μg /kg /min eptifibatide infusion for 18 hr consistent with current guidelines.Other pre- and post-procedural medications got under current guidelines. Both diabetic and non-diabetic subjects were subdivided into bivalirudin and control group (heparin ± GPI). In diabetic cohort, 100 patients were in bivalirudin and 100 patients were in control group. Among non -diabetic patients, 100 were in bivalirudin and 200 were in control group. The outcome measures were 30-day hemorrhagic complications, stent thrombosis, and MACCEs [death, MI, target lesion revascularization (TLR), and stroke] according to diabetic status. The diabetic and non-diabetic subgroup was also analyzed for the same outcome measure according to antithrombotic strategy. Peri and post PCI clinical follow-up comprised checking office visits and telephone contacts. Results: According to diabetic status, net adverse clinical events (NACEs) were significantly higher in diabetic in comparison to non-diabetic (diabetic vs. non-diabetic, 15% vs. 7.6 %, P=0.008) and was associated with higher incidence of MACCEs (10.5% vs. 4.0%, P=0.004), cardiac death (4 % vs. 1 %, P=0.02) and BARC 2,3,5 grade bleeding events (9% vs. 4 %, P=0.02). In diabetic cohort, incidence of 30-day NACEs was significantly lower in bivalirudin than control group(bivalirudin vs. UFH ± GPI, 6 % vs. 24 %, P=0.004) and was associated with lower incidence of MACCEs (2% vs. 8.5%, P=0.03) and bleeding events (3 % vs. 15 %, P=0.003) whereas incidence of stent thrombosis (2 % vs. 3%, P =0.651) was comparable between the bivalirudin and control groups. There was a significant advantage in favor of bivalirudin treatment among insulin-treated patients with regard to cardiac death at 30-day (bivalirudin vs. control group, 0% vs. 16.6%, p = 0.03) compared with non-insulin treat diabetic patients. However, subgroup analysis of the nondiabetic patients showed that there was no significant difference in the incidence of 30-Day NACEs (4% vs. 9.5%, P=0.09) according anticoagulant status. Multivariate analysis showed that bivalirudin (HR: 0. 202, 95% CI: 0.078 – 0.519, P=0.009) was independent protective factor of 30-day NACEs for diabetic patients. Conclusion: Bivalirudin monotherapy is safer and more efficacious for diabetic ACS patients compared with non-diabetic ACS patients undergoing PCI. J Dhaka Med Coll. 2022; 31(1) : 126-136

Serum Lipoprotein Ratios as Markers for Insulin Resistance Among Non-Diabetic Acute Coronary Syndrome Patients with Impaired Fasting Glucose

Background: Insulin resistance is a major risk factor in the development of cardiovascular diseases and type 2 diabetes mellitus. Some studies concluded that serum lipoproteins levels and hence lipoprotein ratios were altered in patients with insulin resistance. Objective: To identify the possibility of using lipoprotein ratios as markers for insulin resistance. Methods: A cross sectional study conducted in Baghdad (Medical City) and in Maysan (Al Shaheed Al Sadir Teaching Hospital) from February to December 2020. Eighty-three male and 51 female in Coronary Care Unit and Internal Medicine Wards patients were selected in the study group. Results: Lipoprotein ratios were significantly higher in individuals with homeostatic model assessment for insulin resistance (HOMA-IR) ≥2.5 as compared to subjects with HOMA-IR <2.5. There was a statistically significant association between lipoprotein ratios and insulin resistance when HOMA-IR ≥2.5 (P less than 0.05). Fasting insulin correlated significantly with lipoprotein ratios. Conclusion: Serum lipoprotein ratios and the best one is triglyceride/high density lipoprotein cholesterol could be used as markers for insulin resistance. Keywords: Lipoprotein ratios, insulin resistance, diabetes Citation: Issa EF, Rasheed MK. Serum lipoprotein ratios as markers for insulin resistance among non-diabetic acute coronary syndrome patients with impaired fasting glucose. Iraqi JMS. 2022; 20(2): 239-244. doi: 10.22578/IJMS.20.2.11

English

BACKGROUND Hyperglycemia is a common finding during the admission of non-diabetic patients with acute coronary syndrome. It is very essential to differentiate this stress hyperglycemia from the hyperglycemia in latent diabetics whose diabetes may have been unmasked by the stress of acute coronary syndrome (ACS). We conducted this study to evaluate stress hyperglycemia in non-diabetic patients with ACS. METHODS We conducted this cross sectional study in the Department of Medicine, KIMS Hospital, Karad, over a period of one year. Non-diabetic patients with HbA1c < 6.5 admitted in our hospital with ACS were included in the study. We included a total of 100 patients in our study, their detailed history, clinical examination and lab evaluation was done. We divided the patients into two groups, Group A were normoglycaemic patients and Group B were acute phase hyperglycemic patients with blood sugars more than 160. Correlation between the blood sugar levels and outcome of the patients was done. RESULTS Mean age was 65.23 ± 21.05 years. No significant difference in risk factor distribution in the two groups was seen. (p > 0.05) We had 47 cases of unstable angina (UA – 47%) followed by 43 cases of STEMI (43 %) and 10 cases of NSTEMI (10 %). We observed a significant difference in the presence of complications in the two groups (p<0.001), Group B patients with hyperglycemia had more complications. Significant difference was seen between the presence of heart failure, arrhythmias and shock in the two groups, with group B having more incidences of these (p<0.05). Significant difference in the outcome of the two groups was seen (p = 0.012). We observed that out of 38 patients in Group B with hyperglycemia, there were 8 deaths (21.05%) as compared to 3 deaths (4.84%) in Group A patients. CONCLUSIONS We observed that the high prevalence (38%) of stress in non-diabetic ACS patients is responsible for significantly more complications, more chances of heart failure, arrhythmia, shock and more deaths. KEY WORDS Acute Coronary Syndrome, Stress Hyperglycemia, Non-Diabetic Patients, Outcome

Profile of Non-Diabetic patients with Microalbuminuria in Acute Coronary Syndrome: A hospital based study

Background and Aims: Microalbuminuria (MA) (urinary albumin excretion of 30-299 mg/d in a 24 hours collection or 30-299 μg/mg creatinine in a spot collection) is well accepted marker of micro and macrovascular damage in patients with diabetes mellitus and is considered as a surrogate marker for endothelial dysfunction in diabetic and non-diabetic patients. This study has been undertaken to investigate the prevalence of microalbuminuria among non-diabetic Acute Coronary Syndrome (ACS) patients.
 Methods: A hospital based cross-sectional study of 100 consecutive non-diabetic ACS patients was done. Traditional risk factors (like smoking, hypertension, dyslipidemia, obesity) of coronary artery disease were studied for the association with microalbuminuria in study subjects. Investigations were carried out in all the cases as per proforma and entered in the SPSS software for analysis.
 Results: The prevalence of microalbuminuria in non-diabetic ACS patients in the study was 73% which was statistically significant (p=0.04). A statistically significant higher prevalence of microalbuminuria was seen with different presentations of ACS; being highest (81.96%) in NSTEMI followed by STEMI (63.15%) and Unstable Angina (55%). It was found to be significant with the history of smoking (81.25%, p=0.013) and hypertension (82.25%, p=0.013). No significant association was found with age, body mass index (BMI) and dyslipidemia. A statistically significant higher prevalence of microalbuminuria was seen with increasing number of risk factors.
 Conclusion: There is increased prevalence of microalbuminuria in ACS patents. MA was associated with statistically higher number of cases with history of smoking and hypertension and presence of increasing number of risk factors.

Prevalence of undiagnosed diabetes mellitus in acute coronary syndrome patients: A hospital-based study

Introduction: Diabetes mellitus and cardiovascular disease are two widely connected entities. The prevalence of undiagnosed diabetes in and impact on survival of acute coronary syndrome (ACS) patients is largely unknown in our population. Aims and Objectives: To study the prevalence of undiagnosed diabetes mellitus in ACS patients and study short-term all-cause mortality in different diabetic and non-diabetic subgroups a hospital-based study. Materials and Methods: The study was conducted in the Post-graduate Department of Medicine at Government Medical College, Srinagar, Jammu and Kashmir, India. It was prospective observational study. It included all patients, admitted as ACS in Medicine Department in between the period from April 2014 to August 2015 with a diagnosis of acute coronary syndromes which include ST-elevation myocardial infarction (STEMI), non-STEMI, and unstable angina. Patients were categorized into five groups known Type 2 diabetes mellitus, prediabetes, first time detected diabetes, non-diabetic ACS patients, and stress-induced hyperglycemia. All-cause 30 days mortality was seen in all patient taken under study. Results: In our study, total of 693 ACS patients were enrolled. The mean age of patients was 61.20 ± 11.69 years. Males predominated in comparison to females with 4:1 ratio. 102 (14.7%) had undiagnosed (first time detected) diabetes. Diabetic and 1st time detected diabetic had double the mortality as compared to the normal and pre-diabetic group (10.8%, 8.8% vs. 5.8%). Conclusion: Undiagnosed diabetes in patients with ACS is not uncommon in our population. Diabetic status profoundly affects the short-term mortality of ACS patients.

Admission plasma glucose levels within the normal to mildly impaired range and the outcome of patients with acute coronary syndrome.

Elevated admission plasma glucose levels >140 mg/dl are associated with adverse clinical outcomes in both diabetic and non-diabetic patients admitted with acute coronary syndrome (ACS). We aimed to evaluate the association between admission plasma glucose levels <140 mg/dl and the outcome of non-diabetic patients admitted with acute coronary syndrome. The study population consisted of patients with acute coronary syndrome included in the Acute Coronary Syndrome Israeli Survey during 2000-2013. Diabetic patients were excluded. The primary endpoint was all-cause mortality at one year. The 452 0 patients had a mean age of 61.7±13.5 years and were stratified into four quartiles according to admission plasma glucose (60-94, 95-105, 106-119, 120-140 mg/dl). Patients with higher admission plasma glucose were older and included a higher percentage of smokers. In addition, the higher the glucose so also did they have a poorer risk factor profile including a higher body mass index, total and low-density lipoprotein cholesterol and triglyceride levels, and lower high-density lipoprotein cholesterol levels. During the first year 5.2% of patients died. A comparison of one-year mortality according to admission plasma glucose quartiles demonstrated a significant and progressive increase in mortality risk as admission plasma glucose rose (3.5%, 4.1%, 6.1%, 6.4%, respectively, p=0.001). However, this association lost its clinical significance following a multivariate analysis ( p=0.08). High admission plasma glucose levels within the normal to mildly impaired range are associated with increased one-year mortality in non-diabetic acute coronary syndrome patients. However, the higher glucose level is probably not the cause for the adverse outcome but rather a marker for high risk. Our findings support the definition of 140 mg/dl as the cutoff for clinically acceptable admission glucose levels in patients with acute coronary syndrome.

Serum lipoprotein ratios as markers of insulin resistance: a study among non-diabetic acute coronary syndrome patients with impaired fasting glucose.

Recent data suggest that insulin resistance can predict cardiovascular disease independently of the other risk factors, such as hypertension, visceral obesity or dyslipidaemia. However, the majority of available methods to evaluate insulin resistance are complicated to operate, expensive, and time consuming. This study was undertaken to assess whether serum lipoprotein ratios could predict insulin resistance in non-diabetic acute coronary syndrome (ACS) patients. Ninety non-diabetic patients with impaired fasting glucose admitted with a diagnosis of ACS were included in the study. At the time of admission fasting glucose and insulin concentrations were measured. The homeostatic model assessment-insulin resistance (HOMA-IR) was used for insulin resistance. The fasting serum total cholesterol (TC), triglycerides (TG) and high density lipoprotein cholesterol (HDL-C) levels were checked, and then TC/HDL-C and TG/HDL-C ratios were calculated. The areas under the curves (AUC) of the receiver operating characteristic (ROC) curves were used to compare the power of these serum lipoprotein ratios as markers. Lipoprotein ratios were significantly higher in patients with HOMA-IR index > 2.5 as compared to patients with index <2.5 (P < 0.05). Both TG/HDL-C and TC/HDL-C ratios were significantly correlated with HOMA-IR (P<0.05). The area under the ROC curve of the TG/HDL-C and TC/HDL-C ratio for predicting insulin resistance was 0.80 (95% CI, 0.67 to 0.93), 0.78 (95% CI, 0.65 to 0.91), respectively. The findings of this study demonstrate that serum lipoprotein ratios can provide a simple means of identifying insulin resistance and can be used as markers of insulin resistance and cardiovascular diseases risk in adult non-diabetic patients.

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.

Relationship between HbA1c levels and coronary artery severity in nondiabetic acute coronary syndrome patients

Relationship between HbA1c levels and coronary artery severity in nondiabetic acute coronary syndrome patients

Relationship between HbA1c levels and coronary artery severity in nondiabetic acute coronary syndrome patients

In this study, we aimed to investigate the relationship between HbA1c levels and the severity of coronary artery stenosis in patients with acute coronary syndrome (ACS) without diabetes mellitus. In this study, we included 65 patients (11 females, mean age: 57±11.42 years; 54 males, mean age: 54.56±8.51 years) who were diagnosed as acute myocardial infarction without diabetes mellitus. During hospitalization, fasting blood glucose, postprandial blood glucose and HbA1C were measured in each patient. Gensini score was used to assess the severity of coronary artery disease. Twenty patients (30.8%) had hypertension, 15 (23.1%) had impaired fasting glucose, 10 (15.3%) had combined impaired fasting and postprandial glucose, 28 had a low HDL cholesterol (45%), and 30 (46%) had abdominal obesity. Coronary angiography revealed one-vessel disease in 13 patients (20%), and two- and three-vessel disease in 52 patients (80%). There were no significant differences in terms of high-sensitive C-reactive protein (hs-CRP), total cholesterol, fasting glucose, and postprandial glucose (0.068, 0.974, 0.178, 0.677, respectively). There was no significant relation between the Gensini score and HbA1c levels (p=0.299), but there was a significant relation between the Gensini score and obesity (p=0.024). In our study, no significant relationship could be determined between the Gensini score and HbA1C, fasting and postprandial blood glucose levels, lipid profile, and hs-CRP levels in patients with nondiabetic ACSs.

A simple way to identify insulin resistance in non-diabetic acute coronary syndrome patients with impaired fasting glucose

Background and Objective:The incidence of coronary artery disease (CAD) is increasing in India. Recent data suggesting insulin resistance can predict cardiovascular disease independently of the other risk factors, such as hypertension, visceral obesity, or dyslipidemia, so a focus on the relation between acute coronary syndrome (ACS) and insulin resistance is relevant. Several studies addressing serum lipoprotein ratios as surrogates for insulin resistance have found promising results. We analyzed the association of lipoprotein ratios with the homeostatic model assessment of insulin resistance (HOMA-IR).Methods:One hundred non-diabetic patients with impaired fasting glucose admitted with a diagnosis of ACS were included in the study. Admission fasting glucose and insulin concentrations were measured. The HOMA-IR was used to calculate insulin resistance. The fasting serum total cholesterol (TC), triglycerides (TG), and high-density lipoprotein (HDL-C) levels are used to calculate following lipid ratios: TC/HDL-C and TG/HDL-C. The areas under the curves (AUC) of the receiver operating characteristic curves (ROC) were used to compare the power of these serum lipoprotein ratio markers.Results:Lipoprotein ratios were significantly higher in patients with HOMA Index >2 as compared to patients with Index <2. TG/HDL-C ratio and TC/HDL-C ratio were significantly correlated with HOMA-IR (P < 0.05) as obtained by Pearson's correlation analysis (r = 0.4459, P = 0.0012; r = 0.4815, P = 0.0004; r = 0.3993; P = 0.0041, respectively). The area under the ROC curve of the TG/HDL-C and TC/HDL-C ratios for predicting insulin resistance was 0.80 (95% CI, 0.67-0.93), 0.78 (95% CI, 0.65-0.91), respectively.Conclusion:A plasma TG/HDL-C ratio and TC/HDL-C ratio provide a simple means of identifying insulin resistant and can be used as the markers of insulin resistance and cardiovascular diseases risk in adult non-diabetic patients.

Platelet aggregability is modulated by eNOS locus in non-type 2 diabetic patients with acute coronary syndrome

Background and aim Platelet nitric oxide (NO) synthesis is compromised in patients with acute coronary syndrome (ACS), and platelet NO availability may be critically relevant in determining the extent of thrombosis in ACS patients. It has been demonstrated that an impaired responsiveness to the antiaggregatory effects of NO may affect platelet dysfunction in diabetic patients with ACS. Since NO availability may be genetically determined, we have investigated the role of endothelial nitric oxide synthase (eNOS) gene in influencing platelet aggregability in relation to the presence ( n = 247) or absence ( n = 883) of type 2 diabetes in ACS patients. Methods and results We have genotyped 1130 consecutive high risk ACS patients on dual antiplatelet therapy, previously investigated in relation to platelet function. eNOS 4a allele frequency was significantly higher in diabetic vs. non-diabetic patients ( p = 0.02). In non-diabetic patients the eNOS 4a allele significantly modulated platelet aggregability in response to arachidonic acid (AA), but not to collagen and adenosine diphosphate (ADP) stimulus, after Bonferroni correction for multiple testing. After adjustment for age, gender, smoking habit, hypertension and ejection fraction ≤40%, the eNOS 4a allele remained significantly and independently associated with platelet aggregability in response to AA stimulus [ β (SE) = 0.17 (0.07), p = 0.01]. When platelet aggregation values were considered according to the presence or absence of high residual platelet reactivity (RPR) eNOS 4a, but not −786C and 894T, allele was significantly associated with RPR by AA stimulus. The haplotype reconstruction analysis for eNOS gene showed that the −786C/894G/4a and −786C/894G/4b haplotypes significantly influenced platelet aggregation after AA stimulus. Conclusions Our study indicates that eNOS 4a allele, may be a determinant of higher platelet aggregability and residual platelet reactivity in non-diabetic ACS patients.

The Magnitude of the Variation in Glycemia: A New Parameter for Risk Assessment in Acute Coronary Syndrome?

The aim was to evaluate the relationship between the magnitude of the variation in the level of glycemia during hospitalization and in-hospital and long-term mortality and postdischarge endpoints in two groups of patients with acute coronary syndrome: those with and those without a previous diagnosis of diabetes. The study included 1210 patients admitted for acute coronary syndrome between May 2004 and July 2007. The study population was divided in two subgroups: patients with a previous diagnosis of diabetes (n=386) and nondiabetics (n=824). Each subgroup was further divided into four smaller groups according to the quartile of glycemia variation: diabetics (Q1: <46 mg/dl; Q2: 46-88 mg/dl; Q3: 88-164 mg/dl; Q4: >or=164 mg/dl) and nondiabetics (Q1: <14 mg/dl; Q2: 14-30 mg/dl; Q3: 30-60 mg/dl; Q4: >or=60 mg/dl). Patients were followed up for an average of 18 months after the occurrence of the acute coronary syndrome. In diabetic patients, there was no relationship between the magnitude of the glycemia variation and in-hospital or postdischarge endpoints. In nondiabetics, no significant difference was observed in in-hospital mortality or morbidity, but statistically significant clinical differences were found during follow-up. Multivariate regression analysis showed that Q4 versus Q1, age >or=70 years, and previous antiplatelet or angiotensin-converting enzyme inhibitor therapy were independent predictors of postdischarge endpoints in the nondiabetic group. In nondiabetic acute coronary syndrome patients, the magnitude of the variation in glycemia observed during hospitalization was a strong independent predictor of postdischarge clinical endpoints.

Inflammatory activity increases with haemoglobin A1c in patients with acute coronary syndrome

Objective. To study the relationship between inflammation, diabetes and HbA1c levels in patients with acute coronary syndrome (ACS). Design. Single-centre cross-sectional study comprising 688 consecutive patients with ACS (108 with diabetes) and 341 with stable coronary artery disease (SCAD) (51 with diabetes). High-sensitive C-reactive protein (hsCRP), albumin and fibrinogen concentrations, erythrocyte sedimentation rates (ESR) and leukocyte counts were measured. Results. hsCRP, fibrinogen and ESR levels were higher and albumin lower in ACS patients. ESR was higher, albumin lower and hsCRP borderline significantly higher (p=0.053) in ACS patient with diabetes compared to those without. All inflammatory markers were associated with HbA1c in all 688 ACS patients as well as in 540 non-diabetic ACS patients with normal HbA1c. In multivariate analyses, all inflammatory markers were independently associated with HbA1c in the entire ACS group, regardless of diabetes being present or not. When non-diabetic ACS patients were analyzed separately, only ESR and leukocyte counts were independently correlated with HbA1c. Conclusions. Patients with ACS had increased inflammatory activity, which increased with HbA1c levels in patients who neither had a history of diabetes nor HbA1c above normal, and was further exaggerated in the presence of diabetes.