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Background: Females are generally less prone to cardiovascular (CV) events than males, but this protection is trumped by diabetes. The mechanism behind the increased relative risk in females with diabetes is not fully understood. Insulin resistance (IR) is suggested to be a more important contributor to CV morbidity in females than in males. We aim to investigate differences in the association between IR indexes (Homeostatic Model Assessment of IR - HOMA-IR, visceral adiposity index – VAI, and triglycerides/high-density lipoprotein-cholesterol - TG/HDL-C index), and a first non-fatal myocardial infarction (MI) across different glycaemic states. Methods: IR indexes were calculated in a population with (n = 696) and without (n = 707) a first non-fatal MI, free from known diabetes. MI cases were investigated at least six weeks after the event. All participants were categorized by an oral glucose tolerance test as having normal glucose tolerance, impaired fasting glucose, impaired glucose tolerance, or newly diagnosed diabetes. Comparison of proportion of glycaemic states by sex was tested by chi-square test. The associations between sex, a first non-fatal MI, IR indexes, and traditional CV risk factors were analysed by multivariate logistic regression models. Continuous variables were logarithmically transformed. Results: Of the total population 19% were females and 81% males, out of whom 47% and 50% had a first non-fatal MI, respectively. Compared with males, females were older, less often smokers, with lower body mass index and higher total cholesterol and high-density lipoprotein cholesterol levels. The proportion of glycaemic states did not differ between the sexes (p = 0.06). Females were less insulin resistant than males, especially among cases and with normal glucose tolerance. In logistic regression models adjusted for major CV risk factors including sex, the associations between VAI and TG/HDL-C index and a first non-fatal MI remained significant only in femal, QC 20240125

Background and Aim: The study ‘Periodontitis and Its Relation to Coronary Artery Disease’ (PAROKRANK) reported an association between periodontitis (PD) and the first myocardial infarction (MI). This follow-up study aims to test the hypothesis that those with PD—compared to periodontally healthy individuals—are at increased risk for cardiovascular (CV) events and death. Methods: A total of 1587 participants (age <75 years; females 19%) had a dental examination including panoramic radiographs between 2010 and 2014. PD was categorized as healthy (≥80% alveolar bone height), mild/moderate (79%–66%) or severe (<66%). A composite CV event (first of all-cause death, non-fatal MI or stroke and hospitalization following to heart failure) was investigated during a mean follow-up period of 9.9 years (range 0.2–12.5 years). Participants were divided into two groups: those with and without PD. The primary event rate, stratified by periodontal status at baseline, was calculated using the Kaplan–Meier method and Cox regression. Results: The number of events was 187 in the 985 periodontally healthy participants (19%) and 174 in the 602 participants with PD (29%; p < 0.0001). Those with PD had a higher likelihood for a future event (hazard ratio [HR] = 1.26; 95% CI: 1.01–1.57; p = 0.038), following adjustment for age, smoking and diabetes. Conclusion: The PAROKRANK follow-up revealed that CV events were more common among participants with PD, which supports the assumption that there might be a direct relation between PD and CV disease.

Background and Aim: The study ‘Periodontitis and Its Relation to Coronary Artery Disease’ (PAROKRANK) reported an association between periodontitis (PD) and the first myocardial infarction (MI). This follow-up study aims to test the hypothesis that those with PD—compared to periodontally healthy individuals—are at increased risk for cardiovascular (CV) events and death. Methods: A total of 1587 participants (age <75 years; females 19%) had a dental examination including panoramic radiographs between 2010 and 2014. PD was categorized as healthy (≥80% alveolar bone height), mild/moderate (79%–66%) or severe (<66%). A composite CV event (first of all-cause death, non-fatal MI or stroke and hospitalization following to heart failure) was investigated during a mean follow-up period of 9.9 years (range 0.2–12.5 years). Participants were divided into two groups: those with and without PD. The primary event rate, stratified by periodontal status at baseline, was calculated using the Kaplan–Meier method and Cox regression. Results: The number of events was 187 in the 985 periodontally healthy participants (19%) and 174 in the 602 participants with PD (29%; p < 0.0001). Those with PD had a higher likelihood for a future event (hazard ratio [HR] = 1.26; 95% CI: 1.01–1.57; p = 0.038), following adjustment for age, smoking and diabetes. Conclusion: The PAROKRANK follow-up revealed that CV events were more common among participants with PD, which supports the assumption that there might be a direct relation between PD and CV disease.

Not duplicate with DiVA 1828213QC 20240116

QC 20231121

QC 20231121

Background Plasma mannose, an emerging novel biomarker of insulin resistance, is associated with both diabetes mellitus and coronary atherosclerosis, but the relationship between mannose concentrations and myocardial infarction (MI) across different glycaemic states remains to be elucidated. The aim of this study was to investigate the independent association between mannose and a first MI in a group of subjects characterized according to their glycaemic state. Methods Fasting plasma mannose concentrations were analysed in 777 patients 6-10 weeks after a first myocardial infarction and in 770 matched controls by means of high-performance liquid chromatography coupled to tandem mass spectrometry. Participants without known diabetes mellitus were categorized by an oral glucose tolerance test (OGTT) as having normal glucose tolerance (NGT, n = 1045), impaired glucose tolerance (IGT, n = 246) or newly detected type 2 diabetes (T2DM, n = 112). The association between mannose and MI was investigated across these glycaemic states by logistic regression. Results Mannose levels increased across the glycaemic states (p < 0.0001) and were significantly associated with a first MI in the whole study population (odds ratio, OR: 2.2; 95% CI 1.4 to - 3.5). Considering the different subgroups separately, the association persisted only in subjects with NGT (adjusted OR: 2.0; 95% CI 1.2-3.6), but not in subgroups with glucose perturbations (adjusted OR: 1.8, 95% CI 0.8-3.7). Conclusions Mannose concentrations increased across worsening levels of glucose perturbations but were independently associated with a first MI only in NGT individuals. Thus, mannose might be a novel, independent risk marker for MI, possibly targeted for the early management of previously unidentified patients at high cardiovascular risk., QC 20221007

QC 20220907

QC 20231121

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 >= 6months, 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. [GRAPHICS] ., Funding Agencies|Bayer; Horizon Europe programme [101095479]; Swedish Heart and Lung Foundation [20220680]

Aims: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce mortality/morbidity in heart failure (HF). We explored the implementation of SGLT2i over time, and patient characteristics associated with their use, in a large, nationwide population with HF with reduced ejection fraction (HFrEF).Methods and results: Patients with HFrEF (ejection fraction <40%), no type 1 diabetes, estimated glomerular filtration rate (eGFR) <20 ml/min/1.73 m(2) and/or on dialysis, registered in the Swedish HF Registry between 1 November 2020 and 5 August 2022 were included. Independent predictors of use were investigated by multivariable logistic regressions. Of 8192 patients, 37% received SGLT2i. Use increased overall from 20.5% to 59.0% over time, from 46.2% and 12.5% to 69.8% and 55.4% in patients with and without type 2 diabetes, from 14.7% and 22.3% to 58.0% and 59.8% in eGFR <60 versus =60 ml/min/1.73 m(2), from 21.0% and 18.9% to 61.6% and 52.0% in males versus females, from 24.2% and 18.0% to 60.8% and 57.7% in patients with versus without recent HF hospitalization, from 26.1% and 19.8% to 54.7% and 59.6% in inpatients versus outpatients, and from 20.2% and 21.2% to 59.2% and 58.7% in those with HF duration <6 versus =6 months, respectively. Important characteristics associated with SGLT2i use were male sex, recent HF hospitalization, specialized HF follow-up, lower ejection fraction, type 2 diabetes, higher education level, use of other HF/cardiovascular interventions. Older age, higher blood pressure, atrial fibrillation and anaemia were associated with less use. Discontinuation rate at 6 and 12 months was 13.1% and 20.0%, respectively.Conclusions: Use of SGLT2i increased three-fold over 2 years. Although this indicates a more rapid translation of trial results and guidelines into clinical practice compared to previous HF drugs, further efforts are advocated to complete the implementation process while avoiding inequities across different patient, Funding Agencies|Swedish Heart and Lung Foundation; [20220680]

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 >= 6months, 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. [GRAPHICS] ., Funding Agencies|Bayer; Horizon Europe programme [101095479]; Swedish Heart and Lung Foundation [20220680]

Aims: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce mortality/morbidity in heart failure (HF). We explored the implementation of SGLT2i over time, and patient characteristics associated with their use, in a large, nationwide population with HF with reduced ejection fraction (HFrEF).Methods and results: Patients with HFrEF (ejection fraction <40%), no type 1 diabetes, estimated glomerular filtration rate (eGFR) <20 ml/min/1.73 m(2) and/or on dialysis, registered in the Swedish HF Registry between 1 November 2020 and 5 August 2022 were included. Independent predictors of use were investigated by multivariable logistic regressions. Of 8192 patients, 37% received SGLT2i. Use increased overall from 20.5% to 59.0% over time, from 46.2% and 12.5% to 69.8% and 55.4% in patients with and without type 2 diabetes, from 14.7% and 22.3% to 58.0% and 59.8% in eGFR <60 versus =60 ml/min/1.73 m(2), from 21.0% and 18.9% to 61.6% and 52.0% in males versus females, from 24.2% and 18.0% to 60.8% and 57.7% in patients with versus without recent HF hospitalization, from 26.1% and 19.8% to 54.7% and 59.6% in inpatients versus outpatients, and from 20.2% and 21.2% to 59.2% and 58.7% in those with HF duration <6 versus =6 months, respectively. Important characteristics associated with SGLT2i use were male sex, recent HF hospitalization, specialized HF follow-up, lower ejection fraction, type 2 diabetes, higher education level, use of other HF/cardiovascular interventions. Older age, higher blood pressure, atrial fibrillation and anaemia were associated with less use. Discontinuation rate at 6 and 12 months was 13.1% and 20.0%, respectively.Conclusions: Use of SGLT2i increased three-fold over 2 years. Although this indicates a more rapid translation of trial results and guidelines into clinical practice compared to previous HF drugs, further efforts are advocated to complete the implementation process while avoiding inequities across different patient, Funding Agencies|Swedish Heart and Lung Foundation; [20220680]

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 >= 6months, 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. [GRAPHICS] ., Funding Agencies|Bayer; Horizon Europe programme [101095479]; Swedish Heart and Lung Foundation [20220680]

El trabajo fin de máster How to Disappear Completely se adentra en un análisis de la desaparición, concebida como proceso, destino que cumplir y síntoma de renacimiento. Este estudio se presenta como un manual de instrucciones, y proporciona una guía sobre cómo desvanecer dejando el menor rastro posible. A través de un enfoque interdisciplinario, se examina cómo la desaparición puede convertirse en un acto de regeneración, reactivación y crecimiento espiritual., The Master thesis project How to Disappear Completely delves into an analysis of disappearance, conceived as a process, de stiny to fulfill and symptom of rebirth. This study is presented as an instruction manual, and provides a do-it-yourself guide on how to fade leaving as little trace as possible. Through an interdiscipli nary approach, it examines how disappearance can become an act of regeneration, reactivation and spiritual growth.

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 ide

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 ide

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 ide

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 ide

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 ide

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 ide

Aims: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce mortality/morbidity in heart failure (HF). We explored the implementation of SGLT2i over time, and patient characteristics associated with their use, in a large, nationwide population with HF with reduced ejection fraction (HFrEF).Methods and results: Patients with HFrEF (ejection fraction <40%), no type 1 diabetes, estimated glomerular filtration rate (eGFR) <20 ml/min/1.73 m(2) and/or on dialysis, registered in the Swedish HF Registry between 1 November 2020 and 5 August 2022 were included. Independent predictors of use were investigated by multivariable logistic regressions. Of 8192 patients, 37% received SGLT2i. Use increased overall from 20.5% to 59.0% over time, from 46.2% and 12.5% to 69.8% and 55.4% in patients with and without type 2 diabetes, from 14.7% and 22.3% to 58.0% and 59.8% in eGFR <60 versus =60 ml/min/1.73 m(2), from 21.0% and 18.9% to 61.6% and 52.0% in males versus females, from 24.2% and 18.0% to 60.8% and 57.7% in patients with versus without recent HF hospitalization, from 26.1% and 19.8% to 54.7% and 59.6% in inpatients versus outpatients, and from 20.2% and 21.2% to 59.2% and 58.7% in those with HF duration <6 versus =6 months, respectively. Important characteristics associated with SGLT2i use were male sex, recent HF hospitalization, specialized HF follow-up, lower ejection fraction, type 2 diabetes, higher education level, use of other HF/cardiovascular interventions. Older age, higher blood pressure, atrial fibrillation and anaemia were associated with less use. Discontinuation rate at 6 and 12 months was 13.1% and 20.0%, respectively.Conclusions: Use of SGLT2i increased three-fold over 2 years. Although this indicates a more rapid translation of trial results and guidelines into clinical practice compared to previous HF drugs, further efforts are advocated to complete the implementation process while avoiding inequities across different patient, Funding Agencies|Swedish Heart and Lung Foundation; [20220680]

Aims: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce mortality/morbidity in heart failure (HF). We explored the implementation of SGLT2i over time, and patient characteristics associated with their use, in a large, nationwide population with HF with reduced ejection fraction (HFrEF).Methods and results: Patients with HFrEF (ejection fraction <40%), no type 1 diabetes, estimated glomerular filtration rate (eGFR) <20 ml/min/1.73 m(2) and/or on dialysis, registered in the Swedish HF Registry between 1 November 2020 and 5 August 2022 were included. Independent predictors of use were investigated by multivariable logistic regressions. Of 8192 patients, 37% received SGLT2i. Use increased overall from 20.5% to 59.0% over time, from 46.2% and 12.5% to 69.8% and 55.4% in patients with and without type 2 diabetes, from 14.7% and 22.3% to 58.0% and 59.8% in eGFR <60 versus =60 ml/min/1.73 m(2), from 21.0% and 18.9% to 61.6% and 52.0% in males versus females, from 24.2% and 18.0% to 60.8% and 57.7% in patients with versus without recent HF hospitalization, from 26.1% and 19.8% to 54.7% and 59.6% in inpatients versus outpatients, and from 20.2% and 21.2% to 59.2% and 58.7% in those with HF duration <6 versus =6 months, respectively. Important characteristics associated with SGLT2i use were male sex, recent HF hospitalization, specialized HF follow-up, lower ejection fraction, type 2 diabetes, higher education level, use of other HF/cardiovascular interventions. Older age, higher blood pressure, atrial fibrillation and anaemia were associated with less use. Discontinuation rate at 6 and 12 months was 13.1% and 20.0%, respectively.Conclusions: Use of SGLT2i increased three-fold over 2 years. Although this indicates a more rapid translation of trial results and guidelines into clinical practice compared to previous HF drugs, further efforts are advocated to complete the implementation process while avoiding inequities across different patient, Funding Agencies|Swedish Heart and Lung Foundation; [20220680]

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 >= 6months, 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. [GRAPHICS] ., Funding Agencies|Bayer; Horizon Europe programme [101095479]; Swedish Heart and Lung Foundation [20220680]

Aims: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce mortality/morbidity in heart failure (HF). We explored the implementation of SGLT2i over time, and patient characteristics associated with their use, in a large, nationwide population with HF with reduced ejection fraction (HFrEF).Methods and results: Patients with HFrEF (ejection fraction <40%), no type 1 diabetes, estimated glomerular filtration rate (eGFR) <20 ml/min/1.73 m(2) and/or on dialysis, registered in the Swedish HF Registry between 1 November 2020 and 5 August 2022 were included. Independent predictors of use were investigated by multivariable logistic regressions. Of 8192 patients, 37% received SGLT2i. Use increased overall from 20.5% to 59.0% over time, from 46.2% and 12.5% to 69.8% and 55.4% in patients with and without type 2 diabetes, from 14.7% and 22.3% to 58.0% and 59.8% in eGFR <60 versus =60 ml/min/1.73 m(2), from 21.0% and 18.9% to 61.6% and 52.0% in males versus females, from 24.2% and 18.0% to 60.8% and 57.7% in patients with versus without recent HF hospitalization, from 26.1% and 19.8% to 54.7% and 59.6% in inpatients versus outpatients, and from 20.2% and 21.2% to 59.2% and 58.7% in those with HF duration <6 versus =6 months, respectively. Important characteristics associated with SGLT2i use were male sex, recent HF hospitalization, specialized HF follow-up, lower ejection fraction, type 2 diabetes, higher education level, use of other HF/cardiovascular interventions. Older age, higher blood pressure, atrial fibrillation and anaemia were associated with less use. Discontinuation rate at 6 and 12 months was 13.1% and 20.0%, respectively.Conclusions: Use of SGLT2i increased three-fold over 2 years. Although this indicates a more rapid translation of trial results and guidelines into clinical practice compared to previous HF drugs, further efforts are advocated to complete the implementation process while avoiding inequities across different patient, Funding Agencies|Swedish Heart and Lung Foundation; [20220680]

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 ide

Nowadays, development processes are also crucially embedded in diverse local and country contexts, with high diversity and heterogeneity of values, interests, policy ideas and discourses within the socio-economic infrastructure and policy networks of each society. Moreover, as the world cogitates about the post-2015 Sustainable Development Goals (SDG) Agenda, the importance of dealing with economic competitiveness, social inclusion, human rights and environmental protection were essential in the territorial level (UNDP, 2014). In these circumstances, the synergies between local development (LD) and Sustainable Human Development (SHD) will become more remarkable than ever before. The aim of this paper is to deepen the importance of the integrated territorial systems for SHD at the local level, based on the recognition that the SHD cannot be accomplished without the LD but neither without a coherent MLG setting., Hoy en día, los procesos de desarrollo están además insertados en distintos contextos locales y nacionales, caracterizados por una gran heterogeneidad de valores, intereses, ideas políticas y debates entre las infraestructuras socioeconómicas y redes políticas de cada sociedad. Además, a partir de las reflexiones en la Agenda de los Objetivos de Desarrollo Sostenible (ODS) post-2015, la importancia de enfrentar temáticas como la competitividad económica, la inclusión social, los derechos humanos y la protección ambiental fueron esenciales a nivel territorial (PNUD, 2014). En estas circunstancias, las sinergias entre el desarrollo local (DL) y el desarrollo humano sostenible (DHS) están haciéndose más notables. El objetivo de este artículo es profundizar en la importancia de los sistemas territoriales integrados para el DHS a nivel local, basado en la conciencia de que el DHS no puede lograrse sin el DL, pero tampoco sin un coherente ajuste de la gobernanza multinivel., Aujourd’hui, les processus de développement sont également insérés dans différents contextes locaux et nationaux, caractérisés par une grande variété de valeurs, d’intérêts, d’opinions politiques et de débats entre les infrastructures socio-économiques et les réseaux politiques de chaque société. Également, à partir des réflexions sur l’Agenda des Objectifs de Développement Durable (ODD) post-2015, l’importance d’aborder des questions comme la compétitivité économique, l’inclusion sociale, les droits humains et la protection environnementale furent essentiels dans le niveau territorial (PNUD, 2014). Dans ces circonstances, les synergies entre le Développement local (DL) et le Développement Humain Durable (DHD) sont devenus plus remarquables. Le but de cette article est d’examiner l’importance des systèmes territoriaux intégrés pour le DHS localement, sur la base de la prise de conscience de que le DHD ne peut être atteint sans le DL, mais pas sans un ensemble cohérent de gouvernance aux plusieurs niveaux.

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 >= 6months, 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. [GRAPHICS] ., Funding Agencies|Bayer; Horizon Europe programme [101095479]; Swedish Heart and Lung Foundation [20220680]

Aims: In patients with heart failure (HF), we aimed to assess (i) the time trends in N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing; (ii) patient characteristics associated with NT-proBNP testing; (iii) distribution of NT-proBNP levels, focusing on the subgroups with (WHFE) vs. without (NWHFE) a worsening HF event, defined as an HF hospitalization; and (iv) changes of NT-proBNP levels over time.Methods and results: NT-proBNP testing and levels were investigated in HF patients enrolled in the Swedish Heart Failure Registry (SwedeHF) linked with the Stockholm CREAtinine Measurements project from January 2011 to December 2018. Index date was the first registration in SwedeHF. Patterns of change in NT-proBNP levels before (in the previous 6 +/- 3 months) and after (in the following 6 +/- 3 months) the index date were categorized as follows: (i) <3000 ng/L at both measurements = stable low; (ii) <3000 ng/L at the first measurement and >= 3000 ng/L at the second measurement = increased; (iii) >= 3000 ng/L at the first measurement and <3000 ng/L at the second measurement = decreased; and (iv) >= 3000 ng/L at both measurements = stable high. Univariable and multivariable logistic regression models, expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs), were performed to assess the associations between (i) clinical characteristics and NT-proBNP testing and (ii) changes in NT-proBNP from 6 months prior to the index date and the index date and a WHFE. Consistency analyses were performed in HF with reduced ejection fraction (HFrEF) alone. A total of 4424 HF patients were included (median age 74 years, women 34%, HFrEF 53%), 33% with a WHFE. NT-proBNP testing increased over time, up to 55% in 2018, and was almost two-fold as frequent, and time to testing was less than half, in patients with WHFE vs. NWHFE. Independent predictors of testing were WHFE, higher heart rate, diuretic use, and preserved ejection f, Funding Agencies|Merck Co., Inc.

Background: We investigated eligibility for dapagliflozin and empagliflozin in a real-world heart failure (HF) cohort based on selection criteria of DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure), and EMPEROR (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Reduced Ejection Fraction and Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with APreserved Ejection Methods and Results: Selection criteria were applied to the Swedish HF registry outpatient population according to 3 scenarios: (i) a "trial scenario" applying all selection criteria; (ii) a "pragmatic scenario" applying the most clinically relevant criteria; and (iii) a "label scenario" following the regulatory agencies labels. Of the 49,317 patients, 55% had an ejection fraction of less than 40% and were assessed for eligibility based on DAPA-HF and EMPEROR-Reduced, 45% had ejection fraction of 40% or greater 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; and 32%, 59%, and 75% for EMPEROR-Preserved, respectively. The main selection criteria limiting eligibility were HF duration and N-terminal pro-B type natriuretic peptide levels. Eligible patients had more severe HF, more comorbidities, higher use of HF treatments and higher mortality and morbidity. Clinical Highlights: Large clinical trials for the approval of new drugs in heart failure often apply numerous selection criteria, limiting the generalizability of trial findings to real-world populations. We assessed eligibility for dapagliflozin and empagliflozin according to trial criteria, the more practical criteria usually applied in daily practice for treatment selection, and the criteria mandated by reg, Funding Agencies|AstraZeneca; Boehringer Ingelheim

Objective. To explore long-term cardiovascular outcomes and mortality in patients after a first myocardial infarction (MI) compared with matched controls in a contemporary setting. Methods. During 2010–2014 the Swedish study PAROKRANK recruited 805 patients <75 years with a first MI and 805 age-, gender-, and area-matched controls. All study participants were followed until 31 December 2018, through linkage with the National Patient Registry and the Cause of Death Registry. The primary endpoint was the first of a composite of all-cause death, non-fatal MI, non-fatal stroke, and heart failure hospitalization. Event rates in cases and controls were calculated using a Cox regression model, subsequently adjusted for baseline smoking, education level, and marital status. Kaplan–Meier curves were computed and compared by log-rank test. Results. A total of 804 patients and 800 controls (mean age 62 years; women 19%) were followed for a mean of 6.2 (0.2–8.5) years. The total number of primary events was 211. Patients had a higher event rate than controls (log-rank test p < .0001). Adjusted hazard ratio (HR) for the primary outcome was 2.04 (95% CI 1.52–2.73). Mortality did not differ between patients (n = 38; 4.7%) and controls (n = 35; 4.4%). A total of 82.5% patients and 91.3% controls were event-free during the follow up. Conclusions. In this long-term follow up of a contemporary, case-control study, the risk for cardiovascular events was higher in patients with a previous first MI compared with their matched controls, while mortality did not differ. The access to high quality of care and cardiac rehabilitation might partly explain the low rates of adverse outcomes.

Background: We investigated eligibility for dapagliflozin and empagliflozin in a real-world heart failure (HF) cohort based on selection criteria of DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure), and EMPEROR (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Reduced Ejection Fraction and Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with APreserved Ejection Methods and Results: Selection criteria were applied to the Swedish HF registry outpatient population according to 3 scenarios: (i) a "trial scenario" applying all selection criteria; (ii) a "pragmatic scenario" applying the most clinically relevant criteria; and (iii) a "label scenario" following the regulatory agencies labels. Of the 49,317 patients, 55% had an ejection fraction of less than 40% and were assessed for eligibility based on DAPA-HF and EMPEROR-Reduced, 45% had ejection fraction of 40% or greater 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; and 32%, 59%, and 75% for EMPEROR-Preserved, respectively. The main selection criteria limiting eligibility were HF duration and N-terminal pro-B type natriuretic peptide levels. Eligible patients had more severe HF, more comorbidities, higher use of HF treatments and higher mortality and morbidity. Clinical Highlights: Large clinical trials for the approval of new drugs in heart failure often apply numerous selection criteria, limiting the generalizability of trial findings to real-world populations. We assessed eligibility for dapagliflozin and empagliflozin according to trial criteria, the more practical criteria usually applied in daily practice for treatment selection, and the criteria mandated by reg, Funding Agencies|AstraZeneca; Boehringer Ingelheim

Objective. To explore long-term cardiovascular outcomes and mortality in patients after a first myocardial infarction (MI) compared with matched controls in a contemporary setting. Methods. During 2010–2014 the Swedish study PAROKRANK recruited 805 patients <75 years with a first MI and 805 age-, gender-, and area-matched controls. All study participants were followed until 31 December 2018, through linkage with the National Patient Registry and the Cause of Death Registry. The primary endpoint was the first of a composite of all-cause death, non-fatal MI, non-fatal stroke, and heart failure hospitalization. Event rates in cases and controls were calculated using a Cox regression model, subsequently adjusted for baseline smoking, education level, and marital status. Kaplan–Meier curves were computed and compared by log-rank test. Results. A total of 804 patients and 800 controls (mean age 62 years; women 19%) were followed for a mean of 6.2 (0.2–8.5) years. The total number of primary events was 211. Patients had a higher event rate than controls (log-rank test p < .0001). Adjusted hazard ratio (HR) for the primary outcome was 2.04 (95% CI 1.52–2.73). Mortality did not differ between patients (n = 38; 4.7%) and controls (n = 35; 4.4%). A total of 82.5% patients and 91.3% controls were event-free during the follow up. Conclusions. In this long-term follow up of a contemporary, case-control study, the risk for cardiovascular events was higher in patients with a previous first MI compared with their matched controls, while mortality did not differ. The access to high quality of care and cardiac rehabilitation might partly explain the low rates of adverse outcomes.

Aims/hypothesis: 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. Methods: 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. Results: 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. Conclusions/interpretation: Empagliflozin had predicted effects on the dysglycaemia but did not influence vari-ables expressing LV function, coronary flow reserve and ECV. An explanation may be that the LV function of the patients was within the normal range., QC 20230109

Objective. To explore long-term cardiovascular outcomes and mortality in patients after a first myocardial infarction (MI) compared with matched controls in a contemporary setting. Methods. During 2010-2014 the Swedish study PAROKRANK recruited 805 patients <75 years with a first MI and 805 age-, gender-, and area-matched controls. All study participants were followed until 31 December 2018, through linkage with the National Patient Registry and the Cause of Death Registry. The primary endpoint was the first of a composite of all-cause death, non-fatal MI, non-fatal stroke, and heart failure hospitalization. Event rates in cases and controls were calculated using a Cox regression model, subsequently adjusted for baseline smoking, education level, and marital status. Kaplan-Meier curves were computed and compared by log-rank test. Results. A total of 804 patients and 800 controls (mean age 62 years; women 19%) were followed for a mean of 6.2 (0.2-8.5) years. The total number of primary events was 211. Patients had a higher event rate than controls (log-rank test p < .0001). Adjusted hazard ratio (HR) for the primary outcome was 2.04 (95% CI 1.52-2.73). Mortality did not differ between patients (n = 38; 4.7%) and controls (n = 35; 4.4%). A total of 82.5% patients and 91.3% controls were event-free during the follow up. Conclusions. In this long-term follow up of a contemporary, case-control study, the risk for cardiovascular events was higher in patients with a previous first MI compared with their matched controls, while mortality did not differ. The access to high quality of care and cardiac rehabilitation might partly explain the low rates of adverse outcomes., QC 20220912

Background Mannose binding lectin (MBL) has been suggested to be associated with an impaired cardiovascular prognosis in dysglycaemic conditions, but results are still contrasting. Our aims are (i) to examine whether MBL levels differ between patients with an acute myocardial infarction (MI) and healthy controls and between subgroups with different glucose tolerance status, and (ii) to investigate the relation between MBL and future cardiovascular events. Methods MBL levels were assessed at discharge and after 3 months in 161 AMI patients without any previously known glucose perturbations and in 183 age- and gender-matched controls from the Glucose metabolism in patients with Acute Myocardial Infarction (GAMI) study. Participants were classified as having dysglycaemia, i.e. type 2 diabetes or impaired glucose tolerance, or not by an oral glucose tolerance test. The primary outcome was a composite of cardiovascular events comprising cardiovascular death, AMI, stroke or severe heart failure during 11 years of follow-up. Total and cardiovascular mortality served as secondary outcomes. Results At hospital discharge patients had higher MBL levels (median 1246 mu g/L) than three months later (median 575 mu g/L; p < 0.01), the latter did not significantly differ from those in the controls (801 mu g/L; p = 0.47). MBL levels were not affected by dysglycaemia either in patients or controls. Independent of glycaemic state, increasing MBL levels did not predict any of the studied outcomes in patients. In unadjusted analyses increasing MBL levels predicted cardiovascular events (hazard ratio HR: 1.67, 95% confidence interval CI 1.06-2.64) and total mortality (HR 1.53, 95% CI 1.12-2.10) in the control group. However, this did not remain in adjusted analyses. Conclusions Patients had higher MBL levels than controls during the hospital phase of AMI, supporting the assumption that elevated MBL reflects acute stress. MBL was not found to be independently associated with cardiovasc, QC 20220721

Background: We investigated eligibility for dapagliflozin and empagliflozin in a real-world heart failure (HF) cohort based on selection criteria of DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure), and EMPEROR (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Reduced Ejection Fraction and Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with APreserved Ejection Methods and Results: Selection criteria were applied to the Swedish HF registry outpatient population according to 3 scenarios: (i) a "trial scenario" applying all selection criteria; (ii) a "pragmatic scenario" applying the most clinically relevant criteria; and (iii) a "label scenario" following the regulatory agencies labels. Of the 49,317 patients, 55% had an ejection fraction of less than 40% and were assessed for eligibility based on DAPA-HF and EMPEROR-Reduced, 45% had ejection fraction of 40% or greater 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; and 32%, 59%, and 75% for EMPEROR-Preserved, respectively. The main selection criteria limiting eligibility were HF duration and N-terminal pro-B type natriuretic peptide levels. Eligible patients had more severe HF, more comorbidities, higher use of HF treatments and higher mortality and morbidity. Clinical Highlights: Large clinical trials for the approval of new drugs in heart failure often apply numerous selection criteria, limiting the generalizability of trial findings to real-world populations. We assessed eligibility for dapagliflozin and empagliflozin according to trial criteria, the more practical criteria usually applied in daily practice for treatment selection, and the criteria mandated by reg, Funding Agencies|AstraZeneca; Boehringer Ingelheim

Background: We investigated eligibility for dapagliflozin and empagliflozin in a real-world heart failure (HF) cohort based on selection criteria of DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure), and EMPEROR (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Reduced Ejection Fraction and Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with APreserved Ejection Methods and Results: Selection criteria were applied to the Swedish HF registry outpatient population according to 3 scenarios: (i) a "trial scenario" applying all selection criteria; (ii) a "pragmatic scenario" applying the most clinically relevant criteria; and (iii) a "label scenario" following the regulatory agencies labels. Of the 49,317 patients, 55% had an ejection fraction of less than 40% and were assessed for eligibility based on DAPA-HF and EMPEROR-Reduced, 45% had ejection fraction of 40% or greater 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; and 32%, 59%, and 75% for EMPEROR-Preserved, respectively. The main selection criteria limiting eligibility were HF duration and N-terminal pro-B type natriuretic peptide levels. Eligible patients had more severe HF, more comorbidities, higher use of HF treatments and higher mortality and morbidity. Clinical Highlights: Large clinical trials for the approval of new drugs in heart failure often apply numerous selection criteria, limiting the generalizability of trial findings to real-world populations. We assessed eligibility for dapagliflozin and empagliflozin according to trial criteria, the more practical criteria usually applied in daily practice for treatment selection, and the criteria mandated by reg, Funding Agencies|AstraZeneca; Boehringer Ingelheim

Background: We investigated eligibility for dapagliflozin and empagliflozin in a real-world heart failure (HF) cohort based on selection criteria of DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure), and EMPEROR (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Reduced Ejection Fraction and Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with APreserved Ejection Methods and Results: Selection criteria were applied to the Swedish HF registry outpatient population according to 3 scenarios: (i) a "trial scenario" applying all selection criteria; (ii) a "pragmatic scenario" applying the most clinically relevant criteria; and (iii) a "label scenario" following the regulatory agencies labels. Of the 49,317 patients, 55% had an ejection fraction of less than 40% and were assessed for eligibility based on DAPA-HF and EMPEROR-Reduced, 45% had ejection fraction of 40% or greater 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; and 32%, 59%, and 75% for EMPEROR-Preserved, respectively. The main selection criteria limiting eligibility were HF duration and N-terminal pro-B type natriuretic peptide levels. Eligible patients had more severe HF, more comorbidities, higher use of HF treatments and higher mortality and morbidity. Clinical Highlights: Large clinical trials for the approval of new drugs in heart failure often apply numerous selection criteria, limiting the generalizability of trial findings to real-world populations. We assessed eligibility for dapagliflozin and empagliflozin according to trial criteria, the more practical criteria usually applied in daily practice for treatment selection, and the criteria mandated by reg, Funding Agencies|AstraZeneca; Boehringer Ingelheim

Background and aim: Angiopoietin-like 3 (ANGPTL3) and 4 (ANGPTL4) are regulators of triglyceride storage and utilization. Bariatric surgery (BS) leads to profound changes in adipose tissue composition and energy metabolism. We evaluated the impact of BS on plasma levels of ANGPTL3 and ANGPTL4.Methods and results: Twenty-seven subjects affected by morbid obesity with or without type 2 diabetes (T2D) underwent Roux-en-Y gastric bypass (RYGB) and 18 patients with advanced T2D received Biliopancreatic Diversion (BPD). Fasting ANGPTL proteins levels, insulin sensitivity (evaluated by euglycemic hyperinsulinemic clamp), total bile acids (TBA) and free fatty acids (FFA) were measured at baseline and 1 year after surgery.Both surgical procedures resulted in the loss of fat mass, improved glucose control, and a -2-fold increase of insulin sensitivity. ANGPTL4 levels decreased significantly with both RYGB (26.6 +/- 0.6 to 24.4 +/- 0.3 ng/mL, p = 0.001) and BPD (27.9 +/- 1.5 to 24.0 +/- 0.5 ng/mL, p = 0.003). In contrast, ANGPTL3 concentrations did not change after RYGB but rose following BPD (225 +/- 20 to 300 +/- 15 ng/mL, p = 0.003). By multiple regression analysis, changes after BS in ANGPTL4 were independently associated with changes in blood glucose, (p = 0.0169) whereas changes in ANGPTL3 were associated with variations in FFA (p = 0.008) and insulin sensitivity (p = 0.043).Conclusion: Circulating ANGPTL4 is reduced by BS, probably due to the loss of fat mass and improved insulin sensitivity. Conversely, ANGPTL3 levels increased after BPD, but not after RYGB, presumably because of the metabolic changes induced by the malabsorptive effect of BPD.(c) 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Ital-ian Society of Human Nutritio

OBJECTIVE Coronary artery disease (CAD) is a major challenge in patients with type 2 diabetes (T2D). Coronary computed tomography angiography (CCTA) provides a detailed anatomic map of the coronary circulation. Proteomics are increasingly used to improve diagnostic and therapeutic algorithms. We hypothesized that the protein panel is differentially associated with T2D and CAD. RESEARCH DESIGN AND METHODS In CAPIRE (Coronary Atherosclerosis in Outlier Subjects: Protective and Novel Individual Risk Factors Evaluationda cohort of 528 individuals with no previous cardiovascular event undergoing CCTA), participants were grouped into CAD2 (clean coronaries) and CAD1 (diffuse lumen narrowing or plaques). Plasma proteins were screened by aptamer analysis. Two-way partial least squares was used to simultaneously rank proteins by diabetes status and CAD. RESULTS Though CAD1 was more prevalent among participants with T2D (HbA1c 6.7 6 1.1%) than those without diabetes (56 vs. 30%, P < 0.0001), CCTA-based atherosclerosis burden did not differ. Of the 20 top-ranking proteins, 15 were associated with both T2D and CAD, and 3 (osteomodulin, cartilage intermediate-layer protein 15, and HTRA1) were selectively associated with T2D only and 2 (epidermal growth factor receptor and contactin-1) with CAD only. Elevated renin and GDF15, and lower adiponectin, were independently associated with both T2D and CAD. In multivariate analysis adjusting for the Framingham risk panel, patients with T2D were “protected” from CAD if female (P 5 0.007), younger (P 5 0.021), and with lower renin levels (P 5 0.02). CONCLUSIONS We concluded that 1) CAD severity and quality do not differ between participants with T2D and without diabetes; 2) renin, GDF15, and adiponectin are shared markers by T2D and CAD; 3) several proteins are specifically associated with T2D or CAD; and 4) in T2D, lower renin levels may protect against CAD.

QC 20220215

QC 20211217

Aim To explore the early effects of dapagliflozin on myocardial function and metabolism in patients with type 2 diabetes without heart failure. Materials and Methods Patients with type 2 diabetes on metformin treatment were randomized to double-blind, 6-week placebo or dapagliflozin 10 mg daily treatment. Investigations included cardiac function and structure with myocardial resonance imaging; cardiac oxygen consumption, perfusion and efficiency with [C-11]-acetate positron emission tomography (PET); and cardiac and hepatic fatty acid uptake with [F-18]-6-thia-heptadecanoic acid PET, analysed by ANCOVA as least square means with 95% confidence intervals. Results Evaluable patients (placebo: n = 24, dapagliflozin: n = 25; 53% males) had a mean age of 64.4 years, a body mass index of 30.2 kg/m(2) and an HbA1c of 6.7%. Body weight and HbA1c were significantly decreased by dapagliflozin versus placebo. Dapagliflozin had no effect on myocardial efficiency, but external left ventricular (LV) work (-0.095 [-0.145, -0.043] J/g/min) and LV oxygen consumption were significantly reduced (-0.30 [-0.49, -0.12] J/g/min) by dapagliflozin, although the changes were not statistically significant versus changes in the placebo group. Change in left atrial maximal volume with dapagliflozin versus placebo was -3.19 (-6.32, -0.07) mL/m(2) (p = .056). Peak global radial strain decreased with dapagliflozin versus placebo (-3.92% [-7.57%, -0.28%]; p = .035), while peak global longitudinal and circumferential strains were unchanged. Hepatic fatty acid uptake was increased by dapagliflozin versus placebo (0.024 [0.004, 0.044] mu mol/g/min; p = .018), while cardiac uptake was unchanged. Conclusions This exploratory study indicates reduced heart work but limited effects on myocardial function, efficiency and cardiac fatty acid uptake, while hepatic fatty acid uptake increased, after 6 weeks of treatment with dapagliflozin.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.

Context: Pancreatic beta-cell glucose sensitivity is the slope of the plasma glucose-insulin secretion relationship and is a key predictor of deteriorating glucose tolerance and development of type 2 diabetes. However, there are no large-scale studies looking at the genetic determinants of beta-cell glucose sensitivity. Objective: To understand the genetic determinants of pancreatic beta-cell glucose sensitivity using genome-wide meta-analysis and candidate gene studies. Design: We performed a genome-wide meta-analysis for beta-cell glucose sensitivity in subjects with type 2 diabetes and nondiabetic subjects from 6 independent cohorts (n = 5706). Beta-cell glucose sensitivity was calculated from mixed meal and oral glucose tolerance tests, and its associations between known glycemia-related single nucleotide polymorphisms (SNPs) and genome-wide association study (GWAS) SNPs were estimated using linear regression models. Results: Beta-cell glucose sensitivity was moderately heritable (h2 ranged from 34% to 55%) using SNP and family-based analyses. GWAS meta-analysis identified multiple correlated SNPs in the CDKAL1 gene and GIPR-QPCTL gene loci that reached genome-wide significance, with SNP rs2238691 in GIPR-QPCTL (P value = 2.64 × 10−9) and rs9368219 in the CDKAL1 (P value = 3.15 × 10−9) showing the strongest association with beta-cell glucose sensitivity. These loci surpassed genome-wide significance when the GWAS meta-analysis was repeated after exclusion of the diabetic subjects. After correction for multiple testing, glycemia-associated SNPs in or near the HHEX and IGF2B2 loci were also associated with beta-cell glucose sensitivity. Conclusion: We show that, variation at the GIPR-QPCTL and CDKAL1 loci are key determinants of pancreatic beta-cell glucose sensitivity.

Aims Use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) in real-world heart failure (HF) is poorly characterised. In contemporary patients with HF and type 2 diabetes mellitus (T2DM) we assessed over time SGLT2i use, clinical characteristics and outcomes associated with SGLT2i use. Methods and results Type 2 diabetes patients enrolled in the Swedish HF Registry between 2016-2018 were considered. We performed multivariable logistic regression models to assess the independent predictors of SGLT2i use and Cox regression models in a 1:3 propensity score-matched cohort and relevant subgroups to investigate the association between SGLT2i use and outcomes. Of 6805 eligible HF patients with T2DM, 376 (5.5%) received SGLT2i, whose use increased over time with 12% of patients on treatment at the end of 2018. Independent predictors of SGLT2i use were younger age, HF specialty care, ischaemic heart disease, preserved kidney function, and absence of anaemia. Over a median follow-up of 256 days, SGLT2i use was associated with a 30% lower risk of cardiovascular (CV) death/first HF hospitalisation (hazard ratio 0.70, 95% confidence interval 0.52-0.95), which was consistent regardless of ejection fraction, background metformin treatment and kidney function. SGLT2i use was also associated with a lower risk of all-cause and CV death, HF and CV hospitalisation, and CV death/myocardial infarction/stroke. Conclusion In a contemporary HF cohort with T2DM, SGLT2i use increased over time, was more common with specialist care, younger age, ischaemic heart disease, and preserved renal function, and was associated with lower mortality and morbidity., Funding Agencies|AstraZenecaAstraZeneca; EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart grant [116074]; Swedish Research CouncilSwedish Research CouncilEuropean Commission [2019-01059]; Swedish Heart and Lung FoundationSwedish Heart-Lung Foundation

Context: Pancreatic beta-cell glucose sensitivity is the slope of the plasma glucose-insulin secretion relationship and is a key predictor of deteriorating glucose tolerance and development of type 2 diabetes. However, there are no large-scale studies looking at the genetic determinants of beta-cell glucose sensitivity. Objective: To understand the genetic determinants of pancreatic beta-cell glucose sensitivity using genome-wide meta-analysis and candidate gene studies. Design: We performed a genome-wide meta-analysis for beta-cell glucose sensitivity in subjects with type 2 diabetes and nondiabetic subjects from 6 independent cohorts (n = 5706). Beta-cell glucose sensitivity was calculated from mixed meal and oral glucose tolerance tests, and its associations between known glycemia-related single nucleotide polymorphisms (SNPs) and genome-wide association study (GWAS) SNPs were estimated using linear regression models. Results: Beta-cell glucose sensitivity was moderately heritable (h2 ranged from 34% to 55%) using SNP and family-based analyses. GWAS meta-analysis identified multiple correlated SNPs in the CDKAL1 gene and GIPR-QPCTL gene loci that reached genome-wide significance, with SNP rs2238691 in GIPR-QPCTL (P value = 2.64 × 10−9) and rs9368219 in the CDKAL1 (P value = 3.15 × 10−9) showing the strongest association with beta-cell glucose sensitivity. These loci surpassed genome-wide significance when the GWAS meta-analysis was repeated after exclusion of the diabetic subjects. After correction for multiple testing, glycemia-associated SNPs in or near the HHEX and IGF2B2 loci were also associated with beta-cell glucose sensitivity. Conclusion: We show that, variation at the GIPR-QPCTL and CDKAL1 loci are key determinants of pancreatic beta-cell glucose sensitivity.

Aims Use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) in real-world heart failure (HF) is poorly characterised. In contemporary patients with HF and type 2 diabetes mellitus (T2DM) we assessed over time SGLT2i use, clinical characteristics and outcomes associated with SGLT2i use. Methods and results Type 2 diabetes patients enrolled in the Swedish HF Registry between 2016-2018 were considered. We performed multivariable logistic regression models to assess the independent predictors of SGLT2i use and Cox regression models in a 1:3 propensity score-matched cohort and relevant subgroups to investigate the association between SGLT2i use and outcomes. Of 6805 eligible HF patients with T2DM, 376 (5.5%) received SGLT2i, whose use increased over time with 12% of patients on treatment at the end of 2018. Independent predictors of SGLT2i use were younger age, HF specialty care, ischaemic heart disease, preserved kidney function, and absence of anaemia. Over a median follow-up of 256 days, SGLT2i use was associated with a 30% lower risk of cardiovascular (CV) death/first HF hospitalisation (hazard ratio 0.70, 95% confidence interval 0.52-0.95), which was consistent regardless of ejection fraction, background metformin treatment and kidney function. SGLT2i use was also associated with a lower risk of all-cause and CV death, HF and CV hospitalisation, and CV death/myocardial infarction/stroke. Conclusion In a contemporary HF cohort with T2DM, SGLT2i use increased over time, was more common with specialist care, younger age, ischaemic heart disease, and preserved renal function, and was associated with lower mortality and morbidity., Funding Agencies|AstraZenecaAstraZeneca; EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart grant [116074]; Swedish Research CouncilSwedish Research CouncilEuropean Commission [2019-01059]; Swedish Heart and Lung FoundationSwedish Heart-Lung Foundation