Aims/hypothesis
This post hoc analysis from the Diabetes Mellitus Insulin–Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 trial reports on extended long-term outcome in relation to ...glucose-lowering agents in patients with myocardial infarction and type 2 diabetes.
Methods
Patients were randomised as follows: group 1, insulin-based treatment; group 2, insulin during hospitalisation followed by conventional glucose control; and group 3, conventional treatment. Treatment according to the above protocol lasted 2.1 years. Using the total DIGAMI 2 cohort as an epidemiological database, this study presents mortality rates in the randomised groups, and mortality and morbidity rates by glucose-lowering treatment during an extended period of follow-up (median 4.1 and max 8.1 years).
Results
Follow-up data were available in 1,145 of the 1,253 patients. The mortality rate was 31% (72% cardiovascular) without significant differences between treatment groups. The total number of fatal malignancies was 37, with a trend towards a higher risk in group 1. The HR for death from malignant disease, compared with group 2, was 1.77 (95% CI 0.87–3.61;
p
= 0.11) and 3.60 (95% CI 1.24–10.50;
p
= 0.02) compared with group 3. Insulin treatment was associated with non-fatal cardiovascular events (OR 1.89 95% CI 1.35–2.63;
p
= 0.0002), but not with mortality (OR 1.30, 95% CI 0.93–1.81;
p
= 0.13). Metformin was associated with a lower mortality rate (HR 0.65, 95% CI 0.47–0.90;
p
= 0.01) and a lower risk of death from malignancies (HR 0.25, 95% CI 0.08–0.83;
p
= 0.02).
Conclusions/interpretation
Patients with type 2 diabetes and myocardial infarction have a poor prognosis. Glucose-lowering drugs appear to be of prognostic importance. Insulin may be associated with an increased risk of non-fatal cardiac events, while metformin seems to be protective against risk of death.
One of the objectives of the ESC-EORP EUROASPIRE V survey is to determine how well European guidelines on the management of dyslipidaemias are implemented in coronary patients.
Standardized methods ...were used by trained technicians to collect information on 7824 patients from 130 centers in 27 countries, from the medical records and at a visit at least 6 months after hospitalization for a coronary event. All lipid measurements were performed in one central laboratory. Patients were divided into three groups: on high-intensity LDL-C-lowering-drug therapy (LLT), on low or moderate-intensity LLT and on no LLT.
At the time of the visit, almost half of the patients were on a high-intensity LLT. Between hospital discharge and the visit, LLT had been reduced in intensity or interrupted in 20.8% of the patients and had been started or increased in intensity in 11.7%. In those who had interrupted LLT or had reduced the intensity, intolerance to LLT and the advice of their physician were reported as the reason why in 15.8 and 36.8% of the cases, respectively. LDL-C control was better in those on a high-intensity LLT compared to those on low or moderate intensity LLT. LDL-C control was better in men than women and in patients with self-reported diabetes.
The results of the EUROASPIRE V survey show that most coronary patients have a less than optimal management of LDL-C. More professional strategies are needed, aiming at lifestyle changes and LLT adapted to the need of the individual patient.
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•Most patients with established coronary artery disease have suboptimal lipid management.•More professional strategies are needed aiming at lifestyle changes and LLT adapted to the need of the individual patient.•The striking variability between countries and centers with several examples of well managed patients illustrates that the present conditions can be improved.
To explore if hypoglycaemic episodes during hospitalisation influence the subsequent prognosis in patients with diabetes and acute myocardial infarction.
Within the framework of the clinical trial ...DIGAMI 2 hypoglycaemic episodes (blood glucose <3.0 mmol/l with or without symptoms) were recorded in 1253 patients (mean age 68 years; 67% males) with type 2 diabetes and myocardial infarction. The patients were followed during a median of 2.1 years. A total of 947 patients were randomised to an initial insulin infusion while 306 received routinely used glucose lowering therapy.
Unadjusted and adjusted (age, sex, smoking, previous infarction, heart failure, renal function, diabetes duration, coronary interventions, pharmacological treatment and B-glucose at hospital admission) hazard ratios (HR) and 95% confidence intervals (CI) for total mortality and cardiovascular events (death, re-infarction or stroke) were related to hypoglycaemic episodes during the index hospitalisation.
During the first 24 hours hypoglycaemic episodes were noted in 111 (12%) insulin-treated (symptomatic 23%) and three (1.0%) routinely treated patients (symptomatic 33%). Symptomatic hypoglycaemia related to mortality (unadjusted HR 1.99; 95% CI 1.20 to 3.29; p = 0.0074) but this difference disappeared following adjustment (HR 1.09; 95% CI 0.64 to 1.87; p = 0.7403). Body weight (OR 0.97; 95% CI 0.95 to 0.98; p<0.0001) and diabetes duration (OR 1.03; 95% CI 1.01 to 1.05; p = 0.0085) were independent predictors of hypoglycaemia
Hypoglycaemia during the initial hospitalisation was not an independent risk factor for future morbidity or mortality in patients with type 2 diabetes and myocardial infarction. Such episodes were, however, more prevalent in patients at high risk for other reasons.
Dysglycemia, in this survey defined as impaired glucose tolerance (IGT) or type 2 diabetes, is common in patients with coronary artery disease (CAD) and associated with an unfavorable prognosis. This ...European survey investigated dysglycemia screening and risk factor management of patients with CAD in relation to standards of European guidelines for cardiovascular subjects.
The European Society of Cardiology's European Observational Research Programme (ESC EORP) European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EUROASPIRE) V (2016-2017) included 8,261 CAD patients, aged 18-80 years, from 27 countries. If the glycemic state was unknown, patients underwent an oral glucose tolerance test (OGTT) and measurement of glycated hemoglobin A
. Lifestyle, risk factors, and pharmacological management were investigated.
A total of 2,452 patients (29.7%) had known diabetes. OGTT was performed in 4,440 patients with unknown glycemic state, of whom 41.1% were dysglycemic. Without the OGTT, 30% of patients with type 2 diabetes and 70% of those with IGT would not have been detected. The presence of dysglycemia almost doubled from that self-reported to the true proportion after screening. Only approximately one-third of all coronary patients had completely normal glucose metabolism. Of patients with known diabetes, 31% had been advised to attend a diabetes clinic, and only 24% attended. Only 58% of dysglycemic patients were prescribed all cardioprotective drugs, and use of sodium-glucose cotransporter 2 inhibitors (3%) or glucagon-like peptide 1 receptor agonists (1%) was small.
Urgent action is required for both screening and management of patients with CAD and dysglycemia, in the expectation of a substantial reduction in risk of further cardiovascular events and in complications of diabetes, as well as longer life expectancy.
Abstract
Background
Plasma mannose, an emerging marker of insulin resistance (IR), is independently associated with coronary artery disease and cardiovascular (CV) events, not only in patients with ...altered glycaemic status, but also among those with normal glucose tolerance (NGT) 1, 2. Whether mannose is a predictor of future CV events is not known.
Purpose
To investigate the association of mannose with surrogate indexes of IR as well as with long-term prognosis in patients with and without dysglycaemia.
Methods
Fasting plasma mannose was measured by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS-MS) in 696 cases with a first myocardial infarction (MI) and 707 controls matched for age, gender and living area from the PAROKRANK study 3. Subjects free of known diabetes were further categorized as having either NGT (n=1045) or newly detected dysglycaemia (i.e., impaired glucose tolerance or type 2 diabetes; n=358) according to the results of an oral glucose tolerance test (OGTT). Surrogate indexes of IR and insulin secretion were calculated using glucose, insulin and C-peptide levels measured at 0, 30 and 120 minutes during the OGTT. The relationship between plasma mannose and different indexes was explored by fitting univariate and multivariate linear regression models. Kaplan-Meier functions were used to estimate crude survival across mannose quartiles. Unadjusted and adjusted Cox proportional hazards models were used to investigate the prognostic capacity of mannose, categorized as high (top quartile) vs low (lowest three quartiles), in relation to major adverse cardiac events (MACE) defined as CV death, MI and stroke during 10 years of follow-up. Secondary outcomes were single components of MACE and all-cause mortality.
Results
Mannose levels were associated with indexes of IR independently of BMI and other covariates in both the NGT and dysglycaemia subgroups. There was no difference in crude MACE-free survival between subjects with high and low mannose (log-rank p=0.10; Figure 1). However, high mannose remained as the only predictor of MACE in the overall population (Hazard ratio (HR): 1.58 (1.10-2.27); p=0.014) after multiple adjustments (Figure 2). This association was independent of the presence of dysglycaemia (interaction p between mannose category and dysglycaemia group=0.94) and IR expressed as HOMA-IR. High mannose also predicted MI, independently of the presence of a first MI (HR: 1.62 (1.00-2.62); p=0.050), while there was no significant association with the other secondary outcomes.
Conclusions
In a case-control setting of first MI, high mannose was the only significant predictor of future CV events, independently of traditional CV risk factors including a previous MI, glycaemic state and IR. Our findings expand the knowledge indicating that mannose might be used as a clinical tool for CV risk stratification.
Cardiovascular disease (CVD) is the main reason for premature death in patients with type 2 diabetes. Hyperglycemia, the hallmark of diabetes, has long been considered the link between diabetes and ...CVD, and many trials focused on preventing CVD manifestations by means of tight glucose control. However, diabetes is a multifactorial disease in which, e. g., insulin resistance, endothelial dysfunction, and factors such as hypertension and dyslipidemia contribute. Thus, treatment needs to be multifactorial and take cardiovascular aspects into account. Newer classes of drugs, originally launched for glucose lowering, among them dipeptidyl-peptidase (DPP)-4 inhibitors, sodium–glucose cotransporter (SGLT)-2 inhibitors, and glucagon-like peptide (GLP)-1 receptor agonists, have been studied in large cardiovascular outcome trials (CVOT). Several SGLT-2 inhibitors and GLP-1 receptor agonists are associated with a reduction of cardiovascular events (cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke). Although the mechanisms behind the effects are not fully understood, an important reason for the benefits of SGLT-2 inhibitors seems be a reduction in heart failure, while GLP-1 receptor agonists may retard the development of the atherosclerotic vascular disease or may be effective by stabilizing plaques. The outcomes of these studies have been taken into account in recently issued guidelines and an important task for diabetologists, cardiologists, and general practitioners is to incorporate the findings of these trials into clinical practice.
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