Dysglycaemia and cardiovascular disease. Aspects on screening, management, and prognosis

Background: Dysglycaemia, in this thesis defined as impaired glucose tolerance (IGT) or type 2 diabetes (T2DM), is a major risk factor for cardiovascular disease (CVD). International guidelines recommend screening for dysglycaemia and target-driven lifestyle and pharmacological management in people with high cardiovascular (CV) risk or established CVD for both men and women. New glucose-lowering drugs with proven CV benefit are now available. Aims: The overall aim of this doctoral thesis was to investigate the screening and management of patients with CVD or at high CV risk including gender differences and implementation of new cardioprotective glucose-lowering drugs by studying: - the prevalence of dysglycaemia according to different screening tools in patients without known diabetes (Study I) and by gender (Study II); - the value of new screening methods for dysglycaemia in these patients (Study III and IV); - the management of such patients as regards lifestyle habits, use of cardioprotective drugs, and treatment target attainment (Study I) including possible gender disparities (Study II); - gender differences in prognosis (Study II); - whether cardioprotection of the glucagon-like peptide-1 receptor agonist dulaglutide is dependent on metformin (Study V). Methods: Studies I, II, III and IV were based on the population from the EUROASPIRE V cross-sectional survey; Study II included data from EUROASPIRE IV and V. Both surveys included patients with established coronary artery disease recruited across Europe at least six months prior to the investigation. Data on clinical history, life-style advice and pharmacological treatment was based on validated questionnaires and standardised blood tests at a study visit. Study V is based on patients with T2DM at high CV risk from the randomised controlled trial REWIND. Results: Prevalence and screening for dysglycaemia: In Study I, 29% of the study population had dysglycaemia detected by screening, with 70% of them being identified by a two-hour postload glucose value (2hPG) during an oral glucose tolerance test (OGTT). Study II found that more women than men had IGT and more men had T2DM. Study III validated a diagnostic algorithm for T2DM based on the assessment of a one-hour postload glucose value (1hPG) during the OGTT, shortening the time needed for glycaemic classification in 79% of them. In Study IV, the diagnostic performance of different insulin resistance indexes was unsatisfactory compared with the yield of an OGTT. Management: Study I showed that multifactorial management after the coronary event was unsatisfactory, with poor adherence to recommended treatment targets for blood pressure, lipids and glycaemic control and a high prevalence of obesity, persistent smoking and limited physical activity. Study II highlighted how this management was particularly inadequate in women, possibly contributing to a worse prognosis compared with men in those with known T2DM. Study V found that CV protection with dulaglutide seems to be present irrespective of metformin treatment at baseline. Conclusions: There is a compelling need for implementation of screening for dysglycaemia in patients with CAD, and the OGTT should be the preferred method because it identifies more patients with dysglycaemia, which otherwise would be missed. Time might be mature to introduce an algorithm based on the 1hPG value to identify T2DM. Its prognostic implications should however be further investigated. Multifactorial management of these patients is in demand of a substantial improvement, especially in women, where deficient care may be associated with worse prognosis. The use of new glucose-lowering agents with cardiovascular efficacy should be prioritised regardless of background glucose-lowering therapy

Gender differences in screening for glucose perturbations, cardiovascular risk factor management and prognosis in patients with dysglycaemia and coronary artery disease : results from the ESC-EORP EUROASPIRE surveys

BackgroundGender 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.MethodsThe 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.ResultsKnown diabetes was more common among women (32.9%) than men (28.4%, pPeer reviewe

Effects of treatment for acromegaly on Bone Mineral Density (BMD): is Pegvisomant protective on lumbar BMD?

The abstract deals with the different effects of treatments for acromegaly on bon

Association between use of novel glucose-lowering drugs and COVID-19 hospitalization and death in patients with type 2 diabetes: a nationwide registry analysis

Aims Type 2 diabetes (T2DM) in patients with coronavirus disease-19 (COVID-19) is associated with a worse prognosis. We separately investigated the associations between the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and dipeptidyl peptidase-4 inhibitors (DPP-4i), and the risk of COVID-19 hospitalization and death. Methods and results Patients with T2DM registered in the Swedish National Patient Registry and alive on 1 February 2020 were included. 'Incident severe COVID-19' was defined as the first hospitalization and/or death from COVID-19. A modified Poisson regression approach was applied to a 1:1 propensity score-matched population receiving vs. not receiving SGLT2i, GLP-1 RA, and DPP-4i to analyse the associations between their use and (I) incident severe COVID-19 and (II) risk of 30-day mortality in patients hospitalized for COVID-19. Among 344 413 patients, 39 172 (11%) were treated with SGLT2i, 34 290 (10%) with GLP-1 RA, and 53 044 (15%) with DPP-4i; 9538 (2.8%) had incident severe COVID-19 by 15 May 2021. SGLT2i and DPP-4i were associated with a 10% and 11% higher risk of incident severe COVID-19, respectively, whereas there was no association for GLP-1 RA. DPP-4i was also associated with a 10% higher 30-day mortality in patients hospitalized for COVID-19, whereas there was no association for SGLT2i and GLP-1 RA. Conclusion SGLT2i and DPP-4i use were associated with a higher risk of incident severe COVID-19. DPP-4i use was associated with higher 30-day mortality in patients with COVID-19, whereas SGLT2i use was not. No increased risk for any outcome was observed with GLP-1 RA

Eligibility for vericiguat in a real-world heart failure population according to trial, guideline and label criteria:Data from the Swedish Heart Failure Registry

Aim: We investigated the eligibility for vericiguat in a real-world heart failure (HF) population based on trial, guideline and label criteria. Methods and results: From the Swedish HF registry, 23 573 patients with HF with reduced ejection fraction (HFrEF) enrolled between 2000 and 2018, with a HF duration ≥6 months, were considered. Eligibility for vericiguat was calculated based on criteria from (i) the Vericiguat Global Study in Subjects with Heart Failure and Reduced Ejection Fraction (VICTORIA) trial; (ii) European and American guidelines on HF; (iii) product labelling according to the Food and Drug Administration and European Medicines Agency. Estimated eligibility for vericiguat in the trial, guidelines, and label scenarios was 21.4%, 47.4%, and 47.4%, respectively. Prior HF hospitalization within 6 months was the criterion limiting eligibility the most in all scenarios (met by 49.1% of the population). In the trial scenario, other criteria meaningfully limiting eligibility were elevated N-terminal pro-B-type natriuretic peptide levels and nitrate use. In all scenarios, eligibility was higher among patients hospitalized for HF at baseline (44.3% vs. 21.4% [trial scenario] and 97.3% vs. 47.4% [guideline/label scenarios] for hospitalized vs. non-hospitalized patients). Overall, eligible patients were older, had more severe HF, more comorbidities, and consequently higher cardiovascular mortality and HF hospitalization rates compared with ineligible patients across all scenarios. Conclusion: In a large and contemporary real-world HFrEF cohort, we estimated that 21.4% of patients would be eligible for vericiguat according to the VICTORIA trial selection criteria, 47.4% based on guidelines and labelling. Eligibility for vericiguat translated into the selection of a population at high risk of morbidity/mortality.</p

Mannose as a biomarker of coronary artery disease: Angiographic evidence and clinical significance

Background High mannose has previously associated with insulin resistance and cardiovascular disease (CVD). Our objective is to establish whether mannose is associated with anatomical evidence of coronary artery disease (CAD). Methods Plasma mannose concentrations were measured by liquid chromatography/tandem mass spectrometry in a discovery cohort (n = 513) and a validation cohort (n = 221) of carefully phenotyped individuals. In both cohorts CAD was quantitated using state-of-the-art imaging techniques (coronary computed coronary tomography angiography (CCTA), invasive coronary angiography and optical coherence tomography). Information on subsequent CVD events/death was collected. Associations of mannose with angiographic variables and biomarkers were tested using univariate and multivariate regression models. Survival analysis was performed using the Kaplan-Meier estimator. Results Mannose was related to indices of CAD and features of plaque vulnerability. In the discovery cohort, mannose was a marker of quantity and quality of CCTA-proven CAD and subjects with a mannose level in the top quartile had a significantly higher risk of CVD events/death (p = 3.6e-5). In the validation cohort, mannose was significantly associated with fibrous cap thickness &lt; 65 \u3bcm (odds ratio = 1.32 per each 10 \u3bcmol/L mannose change [95% confidence interval, 1.05\u20131.65]) and was an independent predictor of death (hazard ratio for mannose 65vs &lt; 84.6 \u3bcmol/L: 4.0(95%CI, 1.4\u201311.3), p = 0.006)

Eligibility for dapagliflozin and empagliflozin in a real-world heart failure population

Background: We investigated eligibility for dapagliflozin and empagliflozin in a real-world heart failure (HF) cohort based on selection criteria of DAPA-HF, DELIVER, and EMPEROR trials. Methods and Results: Selection criteria were applied to the Swedish HF registry out-patient population according to three scenarios: (i) a “trial scenario” applying all selection criteria; (ii) a “pragmatic scenario” applying the most clinically relevant criteria; (iii) a “label scenario” following the regulatory agencies labels. Of 49,317 patients, 55% had ejection fraction (EF)&lt;40% and were assessed for eligibility based on DAPA-HF and EMPEROR-Reduced, 45% had EF≥40% and were assessed based on EMPEROR-Preserved and DELIVER. Eligibility using trial, pragmatic and label scenarios was: 35%, 61% and 80% for DAPA-HF; 31%, 55% and 81% for EMPEROR-Reduced; 30%, 61% and 74% for DELIVER; 32%, 59% and 75% for EMPEROR-Preserved. Main selection criteria limiting eligibility were HF duration and NT-proBNP. Eligible patients had more severe HF, more comorbidities, higher use of HF treatments and higher mortality/morbidity. Conclusions: In a real-world HF setting, eligibility for SGLT2i was similar whether selection criteria from DAPA-HF or EMPEROR-Reduced were applied in HFrEF, or EMPEROR-Preserved or DELIVER in HFpEF. These data might help stakeholders assessing the consequences of future trial eligibility

Extremes of both weight gain and weight loss are associated with increased incidence of heart failure and cardiovascular death: evidence from the CANVAS Program and CREDENCE

Abstract Background Obesity is an independent risk factor for cardiovascular disease (CVD) in patients with type 2 diabetes (T2D). However, it is not known to what extent weight fluctuations might be associated with adverse outcomes. We aimed at assessing the associations between extreme weight changes and cardiovascular outcomes in two large randomised controlled trials of canagliflozin in patients with T2D and high cardiovascular (CV) risk. Methods In the study populations of the CANVAS Program and CREDENCE trials, weight change was evaluated between randomization and week 52–78, defining subjects in the top 10% of the entire distribution of weight changes as gainers, subjects in the bottom 10% as losers and the remainder as stable. Univariate and multivariate Cox proportional hazards models were used to test the associations between weight changes categories, randomised treatment and covariates with heart failure hospitalisation (hHF) and the composite of hHF and CV death. Results Median weight gain was 4.5 kg in gainers and median weight loss was 8.5 kg in losers. The clinical phenotype of gainers as well as that of losers were similar to that of stable subjects. Weight change within each category was only slightly larger with canagliflozin than placebo. In both trials, gainers and losers had a higher risk of hHF and of hHF/CV death compared with stable at univariate analysis. In CANVAS, this association was still significant by multivariate analysis for hHF/CV death in both gainers and losers vs. stable (hazard ratio – HR 1.61 [95% confidence interval - CI: 1.20–2.16] and 1.53 [95% CI 1.14–2.03] respectively). Results were similar in CREDENCE for gainers vs. stable (adjusted HR for hHF/CV death 1.62 [95% CI 1.19–2.16]) Conclusions Extremes of weight gain or loss were independently associated with a higher risk of the composite of hHF and CV death. In patients with T2D and high CV risk, large changes in body weight should be carefully assessed in view of individualised management. Trials registration CANVAS ClinicalTrials.gov number: NCT01032629. CREDENCE ClinicalTrials.gov number: NCT0206579