| 1. |
- Becher, Peter M., et al.
(författare)
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Use of sodium-glucose co-transporter 2 inhibitors in patients with heart failure and type 2 diabetes mellitus : data from the Swedish Heart Failure Registry
- 2021
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 23:6, s. 1012-1022
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Ekerstad, Niklas, et al.
(författare)
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Clinical Frailty Scale classes are independently associated with 6-month mortality for patients after acute myocardial infarction
- 2022
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Ingår i: European Heart Journal. - : Oxford University Press. - 2048-8726 .- 2048-8734. ; 11:2, s. 89-98
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Data on the prognostic value of frailty to guide clinical decision-making for patients with myocardial infarction (MI) are scarce. To analyse the association between frailty classification, treatment patterns, in-hospital outcomes, and 6-month mortality in a large population of patients with MI.Methods and results: An observational, multicentre study with a retrospective analysis of prospectively collected data using the SWEDEHEART registry. In total, 3381 MI patients with a level of frailty assessed using the Clinical Frailty Scale (CFS-9) were included. Of these patients, 2509 (74.2%) were classified as non-vulnerable non-frail (CFS 1–3), 446 (13.2%) were vulnerable non-frail (CFS 4), and 426 (12.6%) were frail (CFS 5–9). Frailty and non-frail vulnerability were associated with worse in-hospital outcomes compared with non-frailty, i.e. higher rates of mortality (13.4% vs. 4.0% vs. 1.8%), cardiogenic shock (4.7% vs. 2.5% vs. 1.9%), and major bleeding (4.5% vs. 2.7% vs. 1.1%) (allP < 0.001), and less frequent use of evidence-based therapies. In Cox regression analyses, frailty was strongly and independently associated with 6-month mortality compared with non-frailty, after adjustment for age, sex, the GRACE risk score components, and other potential risk factors [hazard ratio (HR) 3.32, 95% confidence interval (CI) 2.30–4.79]. A similar pattern was seen for vulnerable non-frail patients (fully adjusted HR 2.07, 95% CI1.41–3.02).Conclusion: Frailty assessed with the CFS was independently and strongly associated with all-cause 6-month mortality, also after comprehensive adjustment for baseline differences in other risk factors. Similarly, non-frail vulnerability was independently associated with higher mortality compared with those with preserved functional ability.
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| 3. |
- Ferrannini, Giulia, et al.
(författare)
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Screening for Glucose Perturbations and Risk Factor Management in Dysglycemic Patients With Coronary Artery Disease-A Persistent Challenge in Need of Substantial Improvement : A Report From ESC EORP EUROASPIRE V.
- 2020
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 43:4, s. 726-733
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Dysglycemia, in this survey defined as impaired glucose tolerance (IGT) or type 2 diabetes, is common in patients with coronary artery disease (CAD) and associated with an unfavorable prognosis. This European survey investigated dysglycemia screening and risk factor management of patients with CAD in relation to standards of European guidelines for cardiovascular subjects.RESEARCH DESIGN AND METHODS: The European Society of Cardiology's European Observational Research Programme (ESC EORP) European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EUROASPIRE) V (2016-2017) included 8,261 CAD patients, aged 18-80 years, from 27 countries. If the glycemic state was unknown, patients underwent an oral glucose tolerance test (OGTT) and measurement of glycated hemoglobin A1c. Lifestyle, risk factors, and pharmacological management were investigated.RESULTS: A total of 2,452 patients (29.7%) had known diabetes. OGTT was performed in 4,440 patients with unknown glycemic state, of whom 41.1% were dysglycemic. Without the OGTT, 30% of patients with type 2 diabetes and 70% of those with IGT would not have been detected. The presence of dysglycemia almost doubled from that self-reported to the true proportion after screening. Only approximately one-third of all coronary patients had completely normal glucose metabolism. Of patients with known diabetes, 31% had been advised to attend a diabetes clinic, and only 24% attended. Only 58% of dysglycemic patients were prescribed all cardioprotective drugs, and use of sodium-glucose cotransporter 2 inhibitors (3%) or glucagon-like peptide 1 receptor agonists (1%) was small.CONCLUSIONS: Urgent action is required for both screening and management of patients with CAD and dysglycemia, in the expectation of a substantial reduction in risk of further cardiovascular events and in complications of diabetes, as well as longer life expectancy.
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| 4. |
- Fortin, Elena, et al.
(författare)
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Empagliflozin improves insulin sensitivity in patients with recent acute coronary syndrome and newly detected dysglycaemia : Experiences from the randomized, controlled SOCOGAMI trial
- 2023
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Ingår i: Cardiovascular Diabetology. - : Springer Nature. - 1475-2840 .- 1475-2840. ; 22:1, s. 208-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Empagliflozin reduces the risk of cardiovascular disease (CVD) in patients with type 2 diabetes (T2DM) and high cardiovascular risk via mechanisms which have not been fully explained. The mechanisms of such benefit have not been fully understood, and whether empagliflozin can be safely administered as first-line treatment in patients with CVD at the initial stages of glycaemic perturbations remains to be established. We investigated the effects of empagliflozin on insulin resistance, insulin sensitivity and β-cell function indexes in patients with a recent acute coronary event and newly detected dysglycaemia, i.e., impaired glucose tolerance (IGT) or T2DM. METHODS: Forty-two patients (mean age 67.5 years, 19% females) with a recent myocardial infarction (n = 36) or unstable angina (n = 6) and newly detected dysglycaemia were randomized to either empagliflozin 25 mg daily (n = 20) or placebo (n = 22). Patients were investigated with stress-perfusion cardiac magnetic resonance imaging before randomization, 7 months after the start of study drug and 3 months following its cessation. Indexes of insulin resistance, sensitivity and β-cell function were calculated based on glucose and insulin values from 2-hour oral glucose tolerance tests (OGTT) and fasting C-peptide. The differences in glucose, insulin, C-peptide, mannose levels and indexes between the two groups were computed by repeated measures ANOVA including an interaction term between the treatment allocation and the time of visit. RESULTS: After 7 months, empagliflozin significantly decreased glucose and insulin values during the OGTT, whereas C-peptide, mannose and HbA1c did not differ. Empagliflozin significantly improved insulin sensitivity indexes but did not impact insulin resistance and β-cell function. After cessation of the drug, all indexes returned to initial levels. Insulin sensitivity indexes were inversely correlated with left ventricular mass at baseline. CONCLUSIONS: Empagliflozin improved insulin sensitivity indexes in patients with a recent coronary event and drug naïve dysglycaemia. These findings support the safe use of empagliflozin as first-line glucose-lowering treatment in patients at very high cardiovascular risk with newly diagnosed dysglycaemia. TRIAL REGISTRATION NUMBER: EudraCT number 2015-004571-73.
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| 5. |
- Fortin, Elena, et al.
(författare)
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Plasma mannose as a novel marker of myocardial infarction across different glycaemic states : A case control study
- 2022
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Ingår i: Cardiovascular Diabetology. - : Springer Nature. - 1475-2840 .- 1475-2840. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 6. |
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| 7. |
- Jurga, Juliane, et al.
(författare)
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Pretreatment With P2Y12 Inhibitors in Patients With Chronic Coronary Syndrome Undergoing Percutaneous Coronary Intervention : A Report From the Swedish Coronary Angiography and Angioplasty Registry
- 2021
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Ingår i: Circulation. Cardiovascular Interventions. - : NLM (Medline). - 1941-7640 .- 1941-7632. ; 14:11, s. 1086-1093
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In patients with chronic coronary syndrome undergoing percutaneous coronary intervention, the optimal timing of P2Y12 inhibitors' administration is uncertain. We compared pretreatment versus treatment in the catheterization laboratory (In-Cathlab) in a real-world population.METHODS: In Swedish Coronary Angiography and Angioplasty Registry, all patients with chronic coronary syndrome undergoing coronary angiography and ad hoc percutaneous coronary intervention, between 2006 and 2017 were identified. Pretreatment was defined as P2Y12 inhibitor administration before coronary angiography, outside the catheterization laboratory. Outcomes were net adverse clinical events including death, myocardial infarction, stroke, or bleeding within 30 days of the index procedure and in-hospital bleeding.RESULTS: We included 26 814 patients, 8237 in the In-Cathlab, and 18 577 in the pretreatment group. In-Cathlab treatment compared with pretreatment was associated with lower risk for net adverse clinical event (4.2 versus 5.1%, adjusted hazard ratio 0.79 [0.63-0.99]), bleeding (2.3 versus 2.6%, adjusted hazard ratio, 0.76 [0.57-1.01]). and in-hospital bleeding (1.9 versus 2.1%, adjusted odds ratio, 0.70 [0.51-0.96]). The risk for death, myocardial infarction, or stroke did not significantly differ between the groups. Among the In-Cathlab treated patients, 41% received ticagrelor or prasugrel and 59% clopidogrel. Treatment with ticagrelor or prasugrel was associated with higher risk for net adverse clinical events (5.4% versus 3.4%, adjusted hazard ratio, 1.66 [1.12-2.48]), bleeding (3.4 versus 1.6%, adjusted hazard ratio, 2.14 [1.34-3.42]), and in-hospital bleeding (2.9 versus 1.2%, adjusted odds ratio, 2.24 [1.29-3.90]) but similar risk for death, myocardial infarction, or stroke, compared with clopidogrel.CONCLUSIONS: In patients with chronic coronary syndrome undergoing coronary angiography and ad hoc percutaneous coronary intervention, pretreatment with P2Y12 inhibitors, before arrival to the catheterization laboratory, was not associated with improved clinical outcomes but was associated with increased risk for bleeding. Our data support clopidogrel administration in the catheterization laboratory as the standard of care. Graphic Abstract: A graphic abstract is available for this article.
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| 8. |
- Lundin, Magnus, et al.
(författare)
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SOdium-glucose CO-transporter inhibition in patients with newly detected Glucose Abnormalities and a recent Myocardial Infarction (SOCOGAMI)
- 2022
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 193, s. 110141-
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 9. |
- Mellbin, Linda Garcia
(författare)
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Myocardial infarction and diabetes mellitus : studies on glucose lowering therapies and novel risk markers based on observations from the DIGAMI 2 trial
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Patients with myocardial infarction (MI) and type 2 diabetes (T2DM) and have a poor prognosis. Hyperglycemia is an independent risk predictor. The best tools for glucose control are debated. Important is identification of biomarkers to gain further pathophysiological insights and new therapeutic possibilities. Aims: In patients with acute MI and T2DM: 1. Explore the prognostic impact of hypoglycemia during hospitalization for MI; 2. Study the prognostic impact of glucose lowering treatment; 3. Investigate the relation between Copeptin and IGFBP-1 and their prognostic impact; and 4. Characterize MBL geno- and phenotypes and to investigate their prognostic importance. Study population: This thesis is based on epidemiological reports from the DIGAMI 2 trial comprising 1253 patients with T2DM and acute MI. DIGAMI 2 was a randomized trial with the primary aim to compare three glucose lowering strategies testing the hypothesis that insulin-based metabolic control reduces mortality. Hypoglycemia during hospitalization for acute MI: Hypoglycemic episodes were recorded in 153 patients (symptomatic = 45). Patients with hypoglycemia were older, had a longer duration of T2DM, a lower body weight and more often a history of heart failure. The mortality and cardiovascular morbidity did not differ between patients with or without hypoglycemia besides that patients who were symptomatic were at increased risk of death. This higher risk disappeared after adjustment for confounding factors. Glucose lowering treatment and prognosis: During the initial follow-up of 2.3 years the adjusted hazard ratio (HR) for non-fatal MI and stroke, in patients discharged alive (n=1181), was 1.73 (95% CI 1.26 2.37; p =0.0007) with insulin treatment, 0.81 (95% CI 0.57 1.14; p = 0.23) with sulphonylureas and 0.63 (95% CI 0.42 0.95; p = 0.03) with metformin. None of the glucose lowering treatments influenced mortality. The odds ratio for insulin on non-fatal cardiovascular events was 1.90 (95% CI 1.38-2.63; p=<0.0001) without influencing mortality after an extended follow-up period of 4.1 years. Metformin was associated with a lower mortality and a lower risk of death of malignancies. There were no difference in total or cardiovascular mortality between the randomized treatment groups but the risk of dying of malignancies was highest in patients randomized to long-term insulin. Novel risk markers and prognosis: Copeptin, a surrogate marker for vasopressin, was associated with IGFBP-1 (r = 0.53; p<0.001) in 393 patients participating in the biochemical program of DIGAMI 2. Both biomarkers were predictors of events (cardiovascular death, MI and stroke) in univariate analyses. In the final statistical model, adjusting for age and renal function, copeptin was the only independent predictor (HR 1.35; 95% CI: 1.16-1.57; p<0.001). Serum (S)-MBL, an activator of the complement system, was determined in 387 and MBL genotypes in 287 patients. Fifty four percent had high coding (median S-MBL=2658 ìg/l; IQR 1715 3829) and 46% low coding MBL genotype (median S-MBL=373ìg/l; IQR 100-765). S-MBL did not predict events. The risk of events was lower in patients with high genotype and S-MBL above median for their genotype (HR 0.49; 95%CI 0.26-0.92; p= 0.026) than among patients with low genotype and S-MBL below median for their genotype. This relation did, however, only reach borderline significance in adjusted analyses. Conclusions: Hypoglycemia during hospitalization is not an independent risk factor for mortality and cardiovascular morbidity in patients with T2DM and MI. It is more prevalent in patient at high risk for other reasons. Glucose lowering agents seem to impact cardiovascular morbidity, mortality and deaths from malignancies, a finding that deserves further evaluation. Copeptin may explain at least some of the prognostic impact ofIGFBP-1 in these patients an observation that may open for new therapeutic attempts. MBL did not have a significant impact on prognosis.
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| 10. |
- Meziani, Sara, et al.
(författare)
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Mannose-binding lectin does not explain the dismal prognosis after an acute coronary event in dysglycaemic patients : A report from the GAMI cohort
- 2022
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Ingår i: Cardiovascular Diabetology. - : Springer Nature. - 1475-2840 .- 1475-2840. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- 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 cardiovascular prognosis in patients with AMI regardless of glucose state.
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