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Type 2 diabetes is one of the fastest-growing health emergencies of the twenty-first century, in part due to its association with cardiovascular and renal disease. Successful implementation of evidence-based guidelines for the management of patients with diabetes and pre-diabetes has been shown to improve patient outcomes by controlling risk factors for cardiovascular and renal disease. Recommendations include the early introduction of lifestyle adjustments, supported by pharmacological tools. Despite the availability of regularly updated, evidence-based guidelines, guideline implementation in clinical practice is low. As a result, people living with type 2 diabetes are not consistently receiving ideal clinical care. Improving guideline adherence has the potential to improve quality of life and longevity in patients with type 2 diabetes. This article introduces Guardians For Health, a global initiative that aims to improve guideline adherence by simplifying patient management and encouraging patient participation in the implementation of guidelines for type 2 diabetes. Guardians For Health is supported by a global community of implementers, with tools to support decision-making and quality assurance. Through achieving better guideline adherence, Guardians For Health hopes to achieve its vision to “stop early mortality by reducing cardiovascular and kidney complications in people with type 2 diabetes”.

Objectives. To assess whether the use of cardioprotective therapies for type 2 diabetes varies by gender and whether the risk of cardiovascular events is higher in women versus men in the REWIND trial, including an international type 2 diabetes patient population with a wide range of baseline risk. Design. Gender differences in baseline characteristics, cardioprotective therapy, and the achieved clinical targets at baseline and two years were analyzed. Hazards for cardiovascular outcomes (fatal/nonfatal stroke, fatal/nonfatal myocardial infarction, cardiovascular death, all-cause mortality, and heart failure hospitalization), in women versus men were analyzed using two Cox proportional hazard models, adjusted for randomized treatment and key baseline characteristics respectively. Time-to-event analyses were performed in subgroups with or without history of cardiovascular disease using Cox proportional hazards models that included gender, subgroup, randomized treatment, and gender-by-subgroup interactions. Results. Of 9901 participants, 46.3% were women. Significantly fewer women than men had a cardiovascular disease history. Although most women met treatment targets for blood pressure (96.7%) and lipids (72.8%), fewer women than men met the target for cardioprotective therapies at baseline and after two years, particularly those with prior cardiovascular disease, who used less renin-angiotensin-aldosterone system inhibitors, statins, and aspirin than men. Despite these differences, women had lower hazards than men for all outcomes except stroke. No significant gender and cardiovascular disease history interactions were identified for cardiovascular outcomes. Conclusions. In REWIND, most women met clinically relevant treatment targets, but in lower proportions than men. Women had a lower risk for all cardiovascular outcomes except stroke. Clinical trials.gov registration number: NCT01394952

Objective: To evaluate whether estimates of risk of future cardiovascular events and death and established or unknown diabetes are significantly associated with calcified carotid artery atheromas (CCAAs) on panoramic radiographs (PRs). The main focus was on men and women without previous myocardial infarction (MI). Methods: The PAROKRANK (Periodontitis and its Relation to Coronary Artery Disease) study included patients with a first MI and matched control subjects. In this substudy, 738 patients (138 women) and 744 control subjects (144 women) with available PRs were assessed for CCAA. Cardiovascular risk estimates were determined according to the Framingham Risk Score (FRS) and Systematic COronary Risk Evaluation (SCORE). Established and previously unknown diabetes was also determined. Results: CCAA was detected on PRs in 206 control subjects (28%) and 251 patients (34%). FRS was significantly associated with CCAA among control subjects (P = .04) and patients (P = .001). SCORE was associated with CCAA among control subjects (P < .01) but not patients (P = .07). Among men, FRS and SCORE were associated with CCAA in both control subjects and patients. Diabetes was not significantly associated with CCAA after adjustments. Conclusions: Elevated cardiovascular risk scores were associated with CCAA on PRs among control subjects. Diabetes was not independently associated with CCAA, possibly owing to selection bias.

Aims Prevention guidelines have identified the management of obese patients as an important priority to reduce the burden of incident and recurrent cardiovascular disease. Still, studies have demonstrated that over 80% of patients with coronary heart disease (CHD) fail to achieve their weight target. Here, we describe advice received and actions reported by overweight CHD patients since being discharged from hospital and how weight changes relate to their risk profile. Methods and results Based on data from 10 507 CHD patients participating in the EUROASPIRE IV and V studies, we analysed weight changes from hospital admission to the time of a study visit ≥6 and Conclusions The management of obesity remains a challenge in the secondary prevention of CHD despite a beneficial effect of weight loss on risk factor prevalences and quality of life. Cardiac rehabilitation programmes should include weight loss interventions as a specific component and the incremental value of telehealth intervention as well as recently described pharmacological interventions need full consideration.

For many years, clinical studies could not show that lowering glucose in patients with type 2 diabetes leads to better macrovascular outcomes. In the past few years, new data have shown that treatment with two classes of dugs developed as "glucose-lowering agents," SGLT2 inhibitors and GLP-1 receptor agonists, can reduce macrovascular and renal complications. These studies have prompted debate about the main aim of type 2 diabetes management. In this review, three eras of diabetes management are described according to the treatment recommendations, such as the ADA/EASD consensus, moving from a pure glucocentric view into the present cardio-renal outcome-oriented approach, this has been endorsed by major diabetes and cardiology societies. While in the first era normalizing HbA1c was the only focus (e.g., UK Prospective Diabetes Study), failing to show a reduction in cardiovascular morbidity and mortality, further studies analyzing the pros and cons of intensified control such as ACCORD, VADT, ADVANCE recognized that treatment intensification was associated with weight gain and hypoglycemia, thereby potentially reducing the benefits of glycemic control. Therefore, the focus in the second area was on controlling HbA1c without these unwanted effects. The consistent beneficial results of several cardiovascular outcome trials with SGLT2 inhibitors and GLP-1 receptor agonists showing significantly improved cardio-renal outcomes, induced a paradigm shift: a change from (only) control of HbA1c to an organ-protective approach with the main focus now on cardio-renal risk; this is now considered as the third era. Recent data indicating beneficial effects of glucose-lowering agents in particular SGLT2 inhibitors even in subjects without diabetes, improving hospitalization for heart failure and renal outcomes might reveal another new era, which could then be considered a fourth era. While current international guidelines call for this paradigm shift, registry data show that we are still far from translating this objective into real-world practice.

Aims Despite the high use of cardioprotective medications, the risk factor control in patients with coronary heart disease (CHD) is still inadequate. Guidelines identify healthy lifestyles as equally important in secondary prevention as pharmacotherapy. Here, we describe reasons for poor lifestyle adherence from the patient’s perspective. Methods and results In the EUROASPIRE IV and V surveys, 16 259 CHD patients were examined and interviewed during a study visit ≥6 months after hospital discharge. Data gathering was fully standardized. The Brief Illness Perception questionnaire was completed by a subsample of 2379 patients. Half of those who were smoking prior to hospital admission, were still smoking; 37% of current smokers had not attempted to quit and 51% was not considering to do so. The prevalence of obesity was 38%. Half of obese patients tried to lose weight in the past month and 61% considered weight loss in the following month. In relation to physical activity, 40% was on target with half of patients trying to do more everyday activities. Less than half had the intention to engage in planned exercise. Only 29% of all patients was at goal for all three lifestyle factors. The number of adverse lifestyles was strongly related to the way patients perceive their illness as threatening. Lifestyle modifications were more successful in those having participated in a cardiac rehabilitation and prevention programme. Patients indicated lack of self-confidence as the main barrier to change their unhealthy behaviour. Conclusion Modern secondary prevention programmes should target behavioural change in all patients with adverse lifestyles.

Objective To compare the benefits and harms of drug treatments for adults with type 2 diabetes, adding non-steroidal mineralocorticoid receptor antagonists (including finerenone) and tirzepatide (a dual glucose dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist) to previously existing treatment options. Design Systematic review and network meta-analysis. Data sources Ovid Medline, Embase, and Cochrane Central up to 14 October 2022. Eligibility criteria for selecting studies Eligible randomised controlled trials compared drugs of interest in adults with type 2 diabetes. Eligible trials had a follow-up of 24 weeks or longer. Trials systematically comparing combinations of more than one drug treatment class with no drug, subgroup analyses of randomised controlled trials, and non-English language studies were deemed ineligible. Certainty of evidence was assessed following the GRADE (grading of recommendations, assessment, development and evaluation) approach. Results The analysis identified 816 trials with 471 038 patients, together evaluating 13 different drug classes; all subsequent estimates refer to the comparison with standard treatments. Sodium glucose cotransporter-2 (SGLT-2) inhibitors (odds ratio 0.88, 95% confidence interval 0.83 to 0.94; high certainty) and GLP-1 receptor agonists (0.88, 0.82 to 0.93; high certainty) reduce all cause death; non-steroidal mineralocorticoid receptor antagonists, so far tested only with finerenone in patients with chronic kidney disease, probably reduce mortality (0.89, 0.79 to 1.00; moderate certainty); other drugs may not. The study confirmed the benefits of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing cardiovascular death, non-fatal myocardial infarction, admission to hospital for heart failure, and end stage kidney disease. Finerenone probably reduces admissions to hospital for heart failure and end stage kidney disease, and possibly cardiovascular death. Only GLP-1 receptor agonists reduce non-fatal stroke; SGLT-2 inhibitors are superior to other drugs in reducing end stage kidney disease. GLP-1 receptor agonists and probably SGLT-2 inhibitors and tirzepatide improve quality of life. Reported harms were largely specific to drug class (eg, genital infections with SGLT-2 inhibitors, severe gastrointestinal adverse events with tirzepatide and GLP-1 receptor agonists, hyperkalaemia leading to admission to hospital with finerenone). Tirzepatide probably results in the largest reduction in body weight (mean difference −8.57 kg; moderate certainty). Basal insulin (mean difference 2.15 kg; moderate certainty) and thiazolidinediones (mean difference 2.81 kg; moderate certainty) probably result in the largest increases in body weight. Absolute benefits of SGLT-2 inhibitors, GLP-1 receptor agonists, and finerenone vary in people with type 2 diabetes, depending on baseline risks for cardiovascular and kidney outcomes ( https://matchit.magicevidence.org/230125dist-diabetes ). Conclusions This network meta-analysis extends knowledge beyond confirming the substantial benefits with the use of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing adverse cardiovascular and kidney outcomes and death by adding information on finerenone and tirzepatide. These findings highlight the need for continuous assessment of scientific progress to introduce cutting edge updates in clinical practice guidelines for people with type 2 diabetes. Systematic review registration PROSPERO CRD42022325948.

Established dysglycaemia (impaired glucose tolerance [IGT] or type 2 diabetes [T2DM]) is a risk factor for further cardiovascular events in patients with coronary artery disease. Sodium-glucose cotransporter 2 inhibitors reduce this risk. The aim of the present investigation was to test the hypothesis that empagliflozin exerts beneficial effects on myocardial function in patients with a recent acute coronary syndrome and newly detected dysglycaemia.Forty-two patients (mean age 67.5 years, 81 % male) with recent myocardial infarction (n = 36) or unstable angina (n = 6) and newly detected IGT (n = 27) or T2DM (n = 15) were randomised to 25 mg of empagliflozin daily (n = 20) or placebo (n = 22) on top of ongoing therapy. They were investigated with oral glucose tolerance tests, stress-perfusion cardiac magnetic resonance imaging (CMR) and echocardiography at three occasions: before randomisation, after seven months on study drug and three months following cessation of such drug. Primary outcome was a change in left ventricular (LV) end-diastolic volume (LVEDV) and secondary outcomes were a change in a) systolic and diastolic LV function; b) coronary flow reserve; c) myocardial extracellular volume (ECV) in non-infarcted myocardium; d) aortic pulse wave velocity.Empagliflozin induced a significant decrease in fasting and post load glucose (p 0.05) and body weight (p 0.01). Empagliflozin did not influence LVEDV, LV systolic or mass indexes, coronary flow reserve, ECV or aortic pulse wave velocity. Echocardiographic indices of LV diastolic function (E/e' and mitral E/A ratio) were not influenced. No safety concerns were identified.Empagliflozin had predicted effects on the dysglycaemia but did not influence variables expressing LV function, coronary flow reserve and ECV. An explanation may be that the LV function of the patients was within the normal range.

In the REWIND trial, dulaglutide reduced cardiovascular (CV) risk versus placebo in patients with type 2 diabetes (T2D) in both the 'established CV disease' (CVD) and 'CV risk factor' subgroups. The SUSTAIN 6 and PIONEER 6 trials of semaglutide used different criteria for established CVD than REWIND. This post hoc analysis assessed the effect of semaglutide on major adverse cardiovascular events (MACE) in a pooled population of SUSTAIN 6 and PIONEER 6 patients, re-categorized into CV risk subgroups using the REWIND CVD criteria. In the pooled analysis (n = 6480), a lower percentage of patients were in the established CVD subgroup, when using the REWIND CVD criteria, compared with the original trial CVD criteria (66.5% versus 83.8%, respectively). After re-categorization, the risk of MACE was significantly lower with semaglutide versus placebo in the established CVD subgroup (hazard ratio [HR], 95% confidence interval [CI]: 0.74 [0.59, 0.92]) and non-significantly lower in the CV risk factor subgroup (HR, 95% CI: 0.84 [0.55, 1.28]) (P-interaction=0.60). These results suggest that the CV effects of semaglutide may extend to patients with T2D across the CV risk continuum. This article is protected by copyright. All rights reserved.

Background Gender disparities in the management of dysglycaemia, defined as either impaired glucose tolerance (IGT) or type 2 diabetes (T2DM), in coronary artery disease (CAD) patients are a medical challenge. Recent data from two nationwide cohorts of patients suggested no gender difference as regards the risk for diabetes-related CV complications but indicated the presence of a gender disparity in risk factor management. The aim of this study was to investigate gender differences in screening for dysglycaemia, cardiovascular risk factor management and prognosis in dysglycemic CAD patients. Methods The study population (n = 16,259; 4077 women) included 7998 patients from the ESC-EORP EUROASPIRE IV (EAIV: 2012–2013, 79 centres in 24 countries) and 8261 patients from the ESC-EORP EUROASPIRE V (EAV: 2016–2017, 131 centres in 27 countries) cross-sectional surveys. In each centre, patients were investigated with standardised methods by centrally trained staff and those without known diabetes were offered an oral glucose tolerance test (OGTT). The first of CV death or hospitalisation for non-fatal myocardial infarction, stroke, heart failure or revascularization served as endpoint. Median follow-up time was 1.7 years. The association between gender and time to the occurrence of the endpoint was evaluated using Cox survival modelling, adjusting for age. Results Known diabetes was more common among women (32.9%) than men (28.4%, p Conclusions Guideline-recommended risk factor control is poorer in dysglycemic women than men. This may contribute to the worse prognosis in CAD women with known diabetes.

Digital, Objective Recent European Guidelines for Diabetes, Prediabetes and Cardiovascular Diseases introduced a shift in managing patients with type 2 diabetes at high risk for or established cardiovascular (CV) disease by recommending GLP-1 receptor agonists and SGLT-2 inhibitors as initial glucose-lowering therapy. This is questioned since outcome trials of these drug classes had metformin as background therapy. In this post hoc analysis, the effect of dulaglutide on CV events was investigated according to the baseline metformin therapy by means of a subgroup analysis of the Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial. Research design and methods Patients in REWIND (n = 9901; women: 46.3%; mean age: 66.2 years) had type 2 diabetes and either a previous CV event (31%) or high CV risk (69%). They were randomized (1:1) to sc. dulaglutide (1.5 mg/weekly) or placebo in addition to standard of care. The primary outcome was the first of a composite of nonfatal myocardial infarction, nonfatal stroke, and death from cardiovascular or unknown causes. Key secondary outcomes included a microvascular composite endpoint, all-cause death, and heart failure. The effect of dulaglutide in patients with and without baseline metformin was evaluated by a Cox regression hazard model with baseline metformin, dulaglutide assignment, and their interaction as independent variables. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by a Cox regression model with adjustments for factors differing at baseline between people with vs. without metformin, identified using the backward selection. Results Compared to patients with metformin at baseline (n = 8037; 81%), those without metformin (n = 1864; 19%) were older and slightly less obese and had higher proportions of women, prior CV events, heart failure, and renal disease. The primary outcome occurred in 976 (12%) participants with baseline metformin and in 281 (15%) without. There was no significant difference in the effect of dulaglutide on the primary outcome in patients with vs. without metformin at baseline [HR 0.92 (CI 0.81–1.05) vs. 0.78 (CI 0.61–0.99); interaction P = 0.18]. Findings for key secondary outcomes were similar in patients with and without baseline metformin. Conclusion This analysis suggests that the cardioprotective effect of dulaglutide is unaffected by the baseline use of metformin therapy., Ciencias Médicas y de la Salud

This study is aimed at investigating gender differences in the medical management of patients with coronary heart disease (CHD). Analyses were based on the ESC EORP EUROASPIRE V (European Survey Of Cardiovascular Disease Prevention And Diabetes) survey. Consecutive patients between 18 and 80 years, hospitalized for a coronary event, were included in the study. Information on cardiovascular medication intake at hospital discharge and at follow-up (≥ 6 months to 0.01) at discharge and follow-up respectively. However, a statistically significant difference was found in the use of statins at follow-up, in disfavor of women (82.8% vs. 77.7%; P 0.01). Furthermore, women were less likely than men to have received a CABG (20.4% vs. 13.2%; P

Background and Purpose: Covert brain infarcts are associated with cognitive decline. It is not known whether therapies that prevent symptomatic stroke prevent covert infarcts. COMPASS compared rivaroxaban with and without aspirin with aspirin for the prevention of stroke, myocardial infarction, and vascular death in participants with stable vascular disease and was terminated early because of benefits of rivaroxaban 2.5 mg twice daily plus aspirin over aspirin. We obtained serial magnetic resonance imagings and cognitive tests in a consenting subgroup of COMPASS patients to examine treatment effects on infarcts, cerebral microbleeds, and white matter hyperintensities. Methods: Baseline and follow-up magnetic resonance imagings were completed in 1445 participants with a mean (SD) interval of 2.0 (0.7) years. Whole-brain T1, T2 fluid-attenuated inversion recovery, T2* sequences were centrally interpreted by blinded, trained readers. Participants had serial measurements of cognition and function. The primary end point was the proportion of participants with incident covert infarcts. Secondary end points were the composite of clinical stroke and covert brain infarcts, cerebral microbleeds, and white matter hyperintensities. Results: At baseline, 493 (34.1%) participants had infarcts. Incident covert infarcts occurred in 55 (3.8%) participants. In the overall trial rivaroxaban plus aspirin reduced ischemic stroke by 49% (0.7% versus 1.4%; hazard ratio [95% CI], 0.51 [0.38–0.68]). In the magnetic resonance imaging substudy the effects of rivaroxaban+aspirin versus aspirin were: covert infarcts: 2.7% versus 3.5% (odds ratio [95% CI], 0.77 [0.37–1.60]); Covert infarcts or ischemic stroke: 2.9% versus 5.3% (odds ratio [95% CI], 0.53 [0.27–1.03]). Incident microbleeds occurred in 6.6% of participants and 65.7% of participants had an increase in white matter hyperintensities volume with no effect of treatment for either end point. There was no effect on cognitive tests. Conclusions: Covert infarcts were not significantly reduced by treatment with rivaroxaban and aspirin but estimates for the combination of ischemic stroke and covert infarcts were consistent with the effect on ischemic stroke in the overall trial. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01776424.

Background The optimal screening strategy for dysglycaemia, including type 2 diabetes (T2DM) and impaired glucose tolerance (IGT), in patients with coronary artery disease (CAD) is debated. Purpose We tested the hypothesis that measures of insulin resistance by homeostasis model assessment (HOMA) indexes may constitute accurate screening methods in a CAD population. Methods Insulin, C-peptide, glycated haemoglobin A1c (HbA1c) and an oral glucose tolerance test (OGTT) were centrally assessed in 3534 CAD patients without known dysglycaemia from the EUROASPIRE V survey. Three different HOMA indexes were calculated: HOMA-IR, HOMA2 based on insulin (HOMA2-ins), and HOMA2 based on C-peptide (HOMA2-Cpep). Dysglycaemia was diagnosed based on the two-hour postload glucose (2hPG) value obtained from the OGTT. Information on study participants was obtained by standardised visits. The optimal thresholds of the three HOMA indexes for dysglycaemia diagnosis were obtained by the maximum value of Youden's J statistic on receiver operator characteristics curves. The diagnostic performance of such thresholds was tested for both T2DM (i.e. in reference to a 2hPG value ≥11 mmol/L) and dysglycaemia (i.e. in reference to 2hPG value ≥7.8 mmol/L) and their correlation with several clinical parameters was assessed by Spearman's coefficients. Results The mean age of the patients was 63 years and 25% were women. Fifty-four percent of the patients had central obesity, 18% were current smokers, mean blood pressure was 133/80 mmHg and mean LDL-cholesterol 2.4 mmol/L. The OGTT revealed that 41% were dysglycaemic (IGT = 24% and T2DM = 16%). Mean insulin, C-peptide and HOMA indexes were significantly higher in patients with vs. without newly detected dysglycaemia (all p Conclusion Screening for dysglycaemia in CAD patients by insulin, C-peptide, HOMA-IR, HOMA2-ins and HOMA2-Cpep had insufficient diagnostic performance to detect dysglycaemia with reference to the yield of an OGTT, which should still be prioritized. Further studies are warranted to assess whether measures of insulin resistance might be better markers of unfavourable metabolic derangement beyond dysglycaemia. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): European Society of CardiologyErling-Perssons Stiftelse

Cardiovascular diabetology 21, 50 (2022). doi:10.1186/s12933-022-01481-0, Published by BioMed Central, London

Aims This study aims to provide an overview on contemporary gender differences in the risk factor control of coronary heart disease (CHD) patients. Methods and results Analyses were based on the cross-sectional ESC (European Society of Cardiology) EORP (EurObservational Research Programme) EUROASPIRE V (European Survey of Cardiovascular Disease Prevention and Diabetes) survey including data on CHD patients across 27 European countries. Men and women between 18 and 80 years old, hospitalized for a first or recurrent coronary event were included in the study. Data were available for 8261 patients of which 25.8% women. Overall, women had a worse risk factor control compared with men. Whereas women were more likely to be non-smokers (79.3% vs. 87.2%; P 0.05). Moreover, a lower proportion of women reached low-density lipoprotein cholesterol (LDL-C) target levels (31.4% vs. 22.1%; P Conclusion The risk factor control of CHD women is substantial worse compared with men despite little gender differences in cardiovascular medication intake. Further actions are needed to increase the awareness of the worse risk factor control in female CHD patients.

Type 2 diabetes represents a major threat to global health mainly because of its strong link to atherosclerotic vascular disease. From position 15 among the 20 leading causes of loss of disability-adjusted life-years in 2000, type 2 diabetes climbed to position 8 in 2016. The fact that ischemic heart disease and stroke, conditions for which diabetes is a major risk factor, hold the two leading positions confirms that diabetes is an important threat to health (1). Combining this information with a predicted increase in adults living with diabetes from 9.3% of the global population (463 million) in 2019 to 10.9% (700 million) in 2045, the majority with type 2 diabetes, further underlines that this menace is truly of an immense magnitude. In addition, impaired glucose tolerance (IGT) has been shown to be a risk factor for cardiovascular disease. The proportion of IGT is estimated to increase from 7.5% (374 million) of the adult population in 2019 to 8.6% (548 million) in 2045, with the largest increase in low- to middle-income countries. Of great concern is that about one-half of people with type 2 diabetes are undiagnosed, varying from 38% in high-income countries to 67% in low-income countries, limiting the possibility to prevent the development of diabetes-related complications. Diabetes already puts a strain on health economics; diabetes-related expenditure was estimated to be US$760 billion in 2019 and is expected to increase to US$845 billion in 2045 (2), with costs associated with cardiovascular complications dominating (3). Cardiovascular complications of diabetes were unknown until the Nobel Prize–awarded discovery of insulin a century ago allowed people with diabetes to survive longer (4). Not until the 1960s–1970s did the first reports on an increased cardiovascular risk associated with diabetes make their appearance from several research groups (5–8). One of the first long-term …

OBJECTIVE We examined the impact of acarbose, an α-glucosidase inhibitor, on incident diabetes and regression to normoglycemia in 6,522 Acarbose Cardiovascular Evaluation (ACE) trial participants in China who had impaired glucose tolerance (IGT) and coronary heart disease (CHD). RESEARCH DESIGN AND METHODS Participants were randomly assigned to acarbose or placebo and followed with four monthly fasting plasma glucose (FPG) tests and annual oral glucose tolerance tests. Incident diabetes was defined as two successive diagnostic FPG levels ≥7 mmol/L or 2-h plasma glucose (PG) levels ≥11.1 mmol/L while taking study medication or a masked adjudicated confirmation of this diagnosis. Regression to normoglycemia was defined as FPG RESULTS Incident diabetes was less frequent with acarbose compared with placebo (3.2 and 3.8 per 100 person-years, respectively; rate ratio 0.82 [95% CI 0.71, 0.94], P = 0.005), with no evidence of differential effects within the predefined subgroups after accounting for multiple testing. Regression to normoglycemia occurred more frequently in those randomized to acarbose compared with placebo (16.3 and 14.1 per 100 person-years, respectively; 1.16 [1.08, 1.25], P < 0.0001). This effect was greater in participants not taking an ACEi or ARB (1.36 [1.21, 1.53], Pinteraction = 0.0006). The likelihood of remaining in normoglycemic regression did not differ between the acarbose and placebo groups (P = 0.41). CONCLUSIONS Acarbose reduced the incidence of diabetes and promoted regression to normoglycemia in Chinese people with IGT and CHD.

Summary Background Cardiovascular outcome trials have suggested that glucagon-like peptide 1 (GLP-1) receptor agonists might reduce strokes. We analysed the effect of dulaglutide on stroke within the researching cardiovascular events with a weekly incretin in diabetes (REWIND) trial. Methods REWIND was a multicentre, randomised, double-blind, placebo-controlled trial done at 371 sites in 24 countries. Men and women (aged ≥50 years) with established or newly detected type 2 diabetes whose HbA1c was 9·5% or less (with no lower limit) on stable doses of up to two oral glucose-lowering drugs with or without basal insulin therapy were eligible if their body-mass index was at least 23 kg/m2. Participants were randomly assigned (1:1) to weekly subcutaneous injections of either masked dulaglutide 1·5 mg or the same volume of masked placebo (containing the same excipients but without dulaglutide). Randomisation was done by a computer-generated random code with an interactive web response system with stratification by site. Participants, investigators, the trial leadership, and all other personnel were masked to treatment allocation until the trial was completed and the database was locked. During the treatment period, participants in both groups were instructed to inject study drug on the same day at around the same time, each week. Strokes were categorised as fatal or non-fatal, and as either ischaemic, haemorrhagic, or undetermined. Stroke severity was assessed using the modified Rankin scale. Participants were seen at 2 weeks, 3 months, 6 months, and then every 3 months for drug dispensing and every 6 months for detailed assessments, until 1200 confirmed primary outcomes accrued. The primary endpoint was the first occurrence of any component of the composite outcome, which comprised non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular or unknown causes. All analyses were done according to an intention-to-treat strategy that included all randomly assigned participants, irrespective of adherence. The trial is registered with ClinicalTrials.gov , number NCT01394952 . Findings Between Aug 18, 2011, and Aug 14, 2013, we screened 12 133 patients, of whom 9901 with type 2 diabetes and additional cardiovascular risk factors were randomly assigned to either dulaglutide (n=4949) or an equal volume of placebo (n=4952). During a median follow-up of 5·4 years, cerebrovascular and other cardiovascular outcomes were ascertained and adjudicated. 158 (3·2%) of 4949 participants assigned to dulaglutide and 205 (4·1%) of 4952 participants assigned to placebo had a stroke during follow-up (hazard ratio [HR] 0·76, 95% CI 0·62–0·94; p=0·010). Dulaglutide reduced ischaemic stroke (0·75, 0·59–0·94, p=0·012) but had no effect on haemorrhagic stroke (1·05, 0·55–1·99; p=0·89). Dulaglutide also reduced the composite of non-fatal stroke or all-cause death (0·88, 0·79–0·98; p=0·017) and disabling stroke (0·74, 0·56–0·99; p=0·042). The degree of disability after stroke did not differ by treatment group. Interpretation Long-term dulaglutide use might reduce clinically relevant ischaemic stroke in people with type 2 diabetes but does not affect stroke severity. Funding Eli Lilly and Company.

An oral glucose tolerance test (OGTT) combining fasting (FPG) and 2-hour plasma glucose (2hPG) is the most sensitive method for detecting type 2 diabetes (T2DM). Since it is considered time-consuming, we aim at validating a previously proposed screening algorithm based on a 1-hour plasma glucose (1hPG) with a 12 mmol/L threshold.Nine-hundred-eighteen patients with coronary artery disease (CAD) without known T2DM from the EUROASPIRE V cross-sectional survey underwent an OGTT. The reference for T2DM was 2hPG ≥ 11.1 mmol/L. T2DM diagnosis by HbA1c ≥ 6.5%(48 mmol/mol), FPG ≥ 7.0 mmol/L, and 1hPG ≥ 12 mmol/L were compared with the outcome of 2hPG.Mean FPG, HbA1c and 2hPG were 6.1 mmol/L, 5.6%(38 mmol/mol) and 7.8 mmol/L respectively. Ninety-six patients (10%) were diagnosed with T2DM according to 2hPG. Using this definition, in the group with FPG 6.5 mmol/L and 1hPG 12 only 5 (1%) were misdiagnosed as false negatives. All patients with a FPG 8.0 mmol/L and 1hPG 15.0 mmol/L were identified as having T2DM. According to the algorithm, in 79% of patients T2DM could be excluded by combining FPG 6.5 mmol/L and 1hPG 12 mmol/L.T2DM Screening by means of an algorithm combining FPG and 1hPG limits the demand of a 2hOGTT in 79% of CAD patients without known T2DM. HbA1c did not add to the information derived from this algorithm.

Aims Low testosterone has been associated with cardiovascular disease in men but with contradictory findings. Testosterone bind to the androgen receptor and polymorphisms of the receptor gene such as CAG repeat length may affect transcriptional activity, possibly mitigating testosterone effects. The aims were to study the CAG repeat length and testosterone levels at four time points following a myocardial infarction (MI) and to analyse possible relationships between CAG repeat length and cardiovascular prognosis. Methods and results Male patients admitted for acute MI (n = 122) from the Glucose in Acute Myocardial Infarction study were included. Blood samples were drawn at four time points (day after admission, at discharge, and at 3 and 12 months post-infarction) for assessment of testosterone levels. Patients were followed for a median of 11.6 years. Cox regression analyses were performed for CAG repeat length by one unit increment and by > vs. ≤median for cardiovascular events and all-cause mortality. Median CAG repeat length was 20. There was no difference in testosterone levels at each time point when dividing the cohort into ≤ vs. >CAG repeat median (=20). There was no association between CAG repeat length either as a continuous or categorical variable in unadjusted and age-adjusted Cox analyses for cardiovascular events. While CAG >20 was associated with all-cause mortality in unadjusted analyses (hazard ratio 2.19, 95% confidence interval 1.13–4.22; P = 0.02), it did not remain significant following adjustment for age. Conclusion CAG repeat length was not associated with testosterone levels or prognosis in men with acute MI.

Purpose of Review To describe the INTERASPIRE scientific protocol—an international survey of secondary prevention of coronary heart disease (CHD). Recent Findings This international survey is being conducted through National Societies of Cardiology in selected countries from each of the six WHO regions and has the following overall aims: (i) describe prevalence of cardiometabolic and renal risk factors together with biomarkers in CHD patients; (ii) describe current risk factor management through lifestyle changes and cardioprotective drug therapies; (iii) provide an objective assessment of clinical implementation of preventive care by comparison with the lifestyle and risk factor targets defined in international and national guidelines; (iv) investigate the reasons for variation in preventive cardiology practice between regions and countries; and (v) promote the principles of best preventive cardiology practice. Summary This international survey will provide a unique picture of CHD patients; their cardiometabolic, renal and biomarker status; lifestyle and therapeutic management; and the quality of preventive care provided in all WHO regions.

Aims Recent European guidelines recommend in patients with atherosclerotic cardiovascular disease to achieve a reduction of low-density lipoprotein-cholesterol of at least 50% if the baseline low-density lipoprotein-cholesterol level is between 1.8 and 3.5 mmol/L. Systematic reviews have associated a given statin/dose combination with a fixed percentage low-density lipoprotein-cholesterol response. Algorithms for detecting cases and estimating the prevalence of familial hypercholesterolaemia often rely on such fixed percentage reductions. Methods and results We used data from 915 coronary patients participating in the EUROASPIRE V study in whom atorvastatin or rosuvastatin therapy was initiated at hospital discharge and who were still using these drugs at the same dose at a follow-up visit 6 or more months later. Pre and on-treatment low-density lipoprotein-cholesterol levels were compared across the full low-density lipoprotein-cholesterol range. The prevalence of FH was estimated using the Dutch Lipid Clinic Network criteria, once using observed pre-treatment low-density lipoprotein-cholesterol and once using imputed pre-treatment low-density lipoprotein-cholesterol by following the common strategy of applying fixed correction factors to on-treatment low-density lipoprotein-cholesterol. Inter-individual variation in the low-density lipoprotein-cholesterol response to a fixed statin and dose was considerable, with a strong inverse relation of percentage reductions to pre-treatment low-density lipoprotein-cholesterol. The percentage low-density lipoprotein-cholesterol response was markedly lower at the left end of the pre-treatment low-density lipoprotein-cholesterol range especially for levels less than 3 mmol/L. The estimated prevalence of familial hypercholesterolaemia was 2% if using observed pre-treatment low-density lipoprotein-cholesterol and 10% when using imputed low-density lipoprotein-cholesterol. Conclusion The inter-individual variation in the percentage low-density lipoprotein-cholesterol response to a given dose of a statin is largely dependent on the pre-treatment level: the lower the pre-treatment low-density lipoprotein-cholesterol level the smaller the percentage low-density lipoprotein-cholesterol reduction. The use of uniform correction factors to estimate pre-treatment low-density lipoprotein-cholesterol is not justified.

Provision and participation in formal external continuing medical education (CME) is costly. Employer or state support of CME is the exception rather than the rule. The medical industry has supported both providers and consumers of educational activities, leading to concerns of commercial bias. Recent medical industry initiatives in Europe to improve the transparency of the relationship between industry and the profession, including the field of medical education, have had the paradoxical effect of the industry playing an increasingly direct role in the provision of physician education. Funding of medical professional society annual congresses has been directly and indirectly jeopardized. Acknowledging that there are areas of cooperation in the field of education between the medical profession and the medical industry from which both can benefit, we argue that medical education requires an objective approach that the primary fiduciary duty of medical industry companies precludes. Medical professional societies, as not-for-profit organizations whose core mission is the development and promotion of best practice, are best placed to guide and deliver medical education to their members. (C) 2019 Published by Elsevier Inc.

This paper intends to describe and analyse the introduction, development and practice of environmental auditing in Ukraine and how it is affected by the EU-Ukraine integration process. Environmental auditing in Ukraine has combined features of both command-and-control and marked-based policy tools, which reflects a complex combination of influences from its Soviet past and international practices adopted as part of its transition to a market economy. Consequently, there are two types of environmental auditing: mandatory and voluntary, which, although based on different normative documents and having different objectives, largely rely on the same practitioners - environmental auditors. Environmental auditing in countries undergoing political and economic transition, like Ukraine, has not been studied before. A theoretical framework was developed for this purpose, consisting of 1) 'shift of policy paradigms' theory, 2) 'collective action' theory and 3) 'community of practice' theory. Several qualitative methods were used for data collection: literature review, semi-structure open-ended interviews, and participant/non-participant observations. The gathered data are summarised in a three-stage development of environmental auditing in Ukraine as preliminary (1991–2004), foundation (2004–2010) and stagnation (2010–2015) stages. Future EU-Ukraine integration will affect environmental auditing in Ukraine as the supremacy of European Law is accepted, mandatory and voluntary environmental auditing practices will follow different paths.

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.

Advances in the development of innovative medical devices and telehealth technologies create the potential to improve the quality and efficiency of diabetes care through collecting, aggregating, and interpreting relevant health data in ways that facilitate more informed decisions among all stakeholder groups. Although many medical societies publish guidelines for utilizing these technologies in clinical practice, we believe that the methodologies used for the selection and grading of the evidence should be revised. In this article, we discuss the strengths and limitations of the various types of research commonly used for evidence selection and grading and present recommendations for modifying the process to more effectively address the rapid pace of device and technology innovation and new product development.