1. |
- Becher, Peter M., et al.
(author)
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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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In: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 23:6, s. 1012-1022
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Journal article (peer-reviewed)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.
(author)
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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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In: European Heart Journal. - : Oxford University Press. - 2048-8726 .- 2048-8734. ; 11:2, s. 89-98
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Journal article (peer-reviewed)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.
(author)
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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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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 43:4, s. 726-733
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Journal article (peer-reviewed)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.
(author)
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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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In: Cardiovascular Diabetology. - : Springer Nature. - 1475-2840. ; 22:1, s. 208-
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Journal article (peer-reviewed)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.
(author)
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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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In: Cardiovascular Diabetology. - : Springer Nature. - 1475-2840. ; 21:1
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Journal article (peer-reviewed)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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7. |
- Jurga, Juliane, et al.
(author)
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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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In: Circulation. Cardiovascular Interventions. - : NLM (Medline). - 1941-7640 .- 1941-7632. ; 14:11, s. 1086-1093
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Journal article (peer-reviewed)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.
(author)
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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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In: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 193, s. 110141-
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Journal article (peer-reviewed)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
(author)
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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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Doctoral thesis (other academic/artistic)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.
(author)
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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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In: Cardiovascular Diabetology. - : Springer Nature. - 1475-2840. ; 21:1
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Journal article (peer-reviewed)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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11. |
- Nyström, Thomas, et al.
(author)
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Oxygen Therapy in Myocardial Infarction Patients With or Without Diabetes : A Predefined Subgroup Analysis From the DETO2X-AMI Trial.
- 2019
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 42:11, s. 2032-2041
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To determine the effects of oxygen therapy in myocardial infarction (MI) patients with and without diabetes.RESEARCH DESIGN AND METHODS: In the Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction (DETO2X-AMI) trial, 6,629 normoxemic patients with suspected MI were randomized to oxygen at 6 L/min for 6-12 h or ambient air. In this prespecified analysis involving 5,010 patients with confirmed MI, 934 had known diabetes. Oxidative stress may be of particular importance in diabetes, and the primary objective was to study the effect of supplemental oxygen on the composite of all-cause death and rehospitalization with MI or heart failure (HF) at 1 year in patients with and without diabetes.RESULTS: = 0.81). There was no statistically significant difference for the individual components of the composite end point or the rate of cardiovascular death up to 1 year. Likewise, corresponding end points in patients without diabetes were similar between the treatment groups.CONCLUSIONS: Despite markedly higher event rates in patients with MI and diabetes, oxygen therapy did not significantly affect 1-year all-cause death, cardiovascular death, or rehospitalization with MI or HF, irrespective of underlying diabetes, in line with the results of the entire study.
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12. |
- Rautio, Aslak, et al.
(author)
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The effect of basal insulin glargine on the fibrinolytic system and von Willebrand factor in people with dysglycaemia and high risk for cardiovascular events : Swedish substudy of the Outcome Reduction with an Initial Glargine Intervention trial
- 2017
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In: Diabetes & Vascular Disease Research. - : Sage Publications. - 1479-1641 .- 1752-8984. ; 14:4, s. 345-352
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Journal article (peer-reviewed)abstract
- Introduction: Fibrinolytic factors, plasminogen activator inhibitor-1, tissue plasminogen activator, tissue plasminogen activator/plasminogen activator-complex and the haemostatic factor von Willebrand factor are known markers of cardiovascular disease. Their plasma levels are adversely affected in patients with dysglycaemia, and glucose normalization with insulin glargine might improve the levels of these factors. Methods: Prespecified Swedish substudy of the Outcome Reduction with an Initial Glargine Intervention trial (ClinicalTrials.gov number, NCT00069784). Tissue plasminogen activator activity, tissue plasminogen activator antigen, plasminogen activator inhibitor-1 antigen, tissue plasminogen activator/plasminogen activator inhibitor-1 complex and von Willebrand factor were analysed at study start, after 2 years and at the end of the study (median follow-up of 6.2 years). Results: Of 129 patients (mean age of 64 ± 7 years, females: 19%), 68 (53%) and 61 (47%) were randomized to the insulin glargine and standard care group, respectively. Allocation to insulin glargine did not significantly affect the studied fibrinolytic markers or von Willebrand factor compared to standard care. Likewise, there were no significant differences in plasminogen activator inhibitor-1, tissue plasminogen activator antigen and von Willebrand factor. During the whole study period, the within-group analysis revealed a curvilinear pattern and significant changes for tissue plasminogen activator/plasminogen activator inhibitor-1 complex, tissue plasminogen activator antigen and von Willebrand factor in the insulin glargine but not in the standard care group. Conclusion: In people with dysglycaemia and other cardiovascular risk factors, basal insulin does not improve the levels of markers of fibrinolysis or von Willebrand factor compared to standard glucose-lowering treatments.
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13. |
- Rautio, Elina, et al.
(author)
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Implantable cardioverter defibrillator and cardiac resynchronization treatment in people with type 2 diabetes: a comparison with age- and sex matched controls from the general population
- 2024
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In: CARDIOVASCULAR DIABETOLOGY. - 1475-2840. ; 23:1
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Journal article (peer-reviewed)abstract
- BackgroundIncreased risk of severe tachyarrhythmias is reported in patients with type 2 diabetes mellitus (T2DM). The aim of this study was to explore if treatment with cardiac implantable electronic device (CIED) such as implantable cardioverter defibrillator (ICD), cardiac resynchronization therapy- pacemaker and -defibrillator (CRT-P/CRT-D) differed in patients with vs. without T2DM. A secondary aim was to identify patient characteristics indicating an increased CIED treatment.Method416 162 adult patients with T2DM from the Swedish National Diabetes Registry and 2 081 087 controls from the Swedish population, matched for age, sex and living area, were included between 1/1/1998 and 31/12/2012 and followed until 31/12/2013. They were compared regarding prevalence of ventricular tachycardia (VT) at baseline and the risk of receiving a CIED during follow-up. Multivariable Cox regression analysis was performed to estimate the risk of CIED-treatment and factors identifying patients with such risk.ResultsVentricular fibrillation (VF) (0.1% vs 0.0004%) and (VT) (0.2% vs. 0.1%) were more frequent among patients with T2DM compared to controls. CIED-treatment was significantly increased in patients with T2DM both in unadjusted and adjusted analyses. HR and 95% CI, after adjustment for sex, age, marital status, income, education, country of birth, coronary artery disease and congestive heart failure, were 1.32 [1.21-1.45] for ICD, 1.74 [1.55-1.95] for CRT-P and 1.69 [1.43-1.99] for CRT-D. Blood-pressure and lipid lowering therapies were independent risk factors associated to receiving CIED, while female sex was protective.ConclusionsAlthough the proportion of VT/VF was low, patients with T2DM had a higher prevalence of these conditions and increased risk for treatment with CIED compared to controls. This underlines the importance of recognizing that T2DM patients have an increased need of CIED.
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14. |
- Riccio, Alessia, et al.
(author)
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Sex differences in the association between insulin resistance and non-fatal myocardial infarction across glycaemic states
- 2024
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In: Cardiovascular Diabetology. - : Springer Nature. - 1475-2840. ; 23:1
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Journal article (peer-reviewed)abstract
- 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 females (odds ratios and 95% confidence intervals: 1.7, 1.0-2.9, and 1.9, 1.1–3.4 respectively). Conclusions: These results support the assumption that IR indexes based on anthropometrics and lipid panel, i.e., VAI and TG/HDL-C, could be a better measure of IR and CV-predictor for non-fatal MI in females, even without glycaemic perturbations.
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15. |
- Rydén, Lars, et al.
(author)
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ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD
- 2013
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In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 34:39, s. 3035-3087
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Journal article (peer-reviewed)abstract
- This is the second iteration of the European Society of Cardiology (ESC) and European Association for the Study of Diabetes (EASD) joining forces to write guidelines on the management of diabetes mellitus (DM), pre-diabetes, and cardiovascular disease (CVD), designed to assist clinicians and other healthcare workers to make evidence-based management decisions. The growing awareness of the strong biological relationship between DM and CVD rightly prompted these two large organizations to collaborate to generate guidelines relevant to their joint interests, the first of which were published in 2007. Some assert that too many guidelines are being produced but, in this burgeoning field, five years in the development of both basic and clinical science is a long time and major trials have reported in this period, making it necessary to update the previous Guidelines.
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16. |
- Savarese, Gianluigi, et al.
(author)
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Comorbidities and cause-specific outcomes in heart failure across the ejection fraction spectrum : A blueprint for clinical trial design
- 2020
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In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 313, s. 76-82
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Journal article (peer-reviewed)abstract
- BackgroundComorbidities may differently affect treatment response and cause-specific outcomes in heart failure (HF) with preserved (HFpEF) vs. mid-range/mildly-reduced (HFmrEF) vs. reduced (HFrEF) ejection fraction (EF), complicating trial design. In patients with HF, we performed a comprehensive analysis of type 2 diabetes (T2DM), atrial fibrillation (AF) chronic kidney disease (CKD), and cause-specific outcomes.Methods and resultsOf 42,583 patients from the Swedish HF registry (23% HFpEF, 21% HFmrEF, 56% HFrEF), 24% had T2DM, 51% CKD, 56% AF, and 8% all three comorbidities. HFpEF had higher prevalence of CKD and AF, HFmrEF had intermediate prevalence of AF, and prevalence of T2DM was similar across the EF spectrum. Patients with T2DM, AF and/or CKD were more likely to have also other comorbidities and more severe HF. Risk of cardiovascular (CV) events was highest in HFrEF vs. HFpEF and HFmrEF; non-CV risk was highest in HFpEF vs. HFmrEF vs. HFrEF. T2DM increased CV and non-CV events similarly but less so in HFpEF. CKD increased CV events somewhat more than non-CV events and less so in HFpEF. AF increased CV events considerably more than non-CV events and more so in HFpEF and HFmrEF.ConclusionHFpEF is distinguished from HFmrEF and HFrEF by more comorbidities, non-CV events, but lower effect of T2DM and CKD on events. CV events are most frequent in HFrEF. To enrich for CV vs. non-CV events, trialists should not exclude patients with lower EF, AF and/or CKD, who report higher CV risk.
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17. |
- Sharad, Bashaaer, et al.
(author)
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Structured diabetes care routines in cardiac rehabilitation are associated with increased diabetes detection and improved treatment after myocardial infarction : a nationwide observational study
- 2024
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In: Cardiovascular Diabetology. - 1475-2840. ; 23:1, s. 330-330
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Journal article (peer-reviewed)abstract
- BACKGROUND: Despite the detrimental impact of abnormal glucose metabolism on cardiovascular prognosis after myocardial infarction (MI), diabetes is both underdiagnosed and undertreated. We investigated associations between structured diabetes care routines in cardiac rehabilitation (CR) and detection and treatment of diabetes at one-year post-MI.METHODS: Center-level data was derived from the Perfect-CR survey, which evaluated work routines applied at Swedish CR centers (n = 76). Work routines involving diabetes care included: (1) routine assessment of fasting glucose and/or HbA1c, (2) routine use of oral glucose tolerance test (OGTT), (3) having regular case rounds with diabetologists, and (4) whether glucose-lowering medication was adjusted by CR physicians. Patient-level data was obtained from the national MI registry SWEDEHEART (n = 7601, 76% male, mean age 62.6 years) and included all post-MI patients irrespective of diabetes diagnosis. Using mixed-effects regression we estimated differences between patients exposed versus. not exposed to the four above-mentioned diabetes care routines. Outcomes were newly detected diabetes and the proportion of patients receiving oral glucose-lowering medication at one-year post-MI.RESULTS: Routine assessment of fasting glucose/HbA1c was performed at 63.2% (n = 48) of the centers, while 38.2% (n = 29) reported using OGTT for detecting glucose abnormalities. Glucose-lowering medication adjusted by CR physicians (n = 13, 17.1%) or regular case rounds with diabetologists (n = 7, 9.2%) were less frequently reported. In total, 4.0% of all patients (n = 304) were diagnosed with diabetes during follow-up and 17.9% (n = 1361) were on oral glucose-lowering treatment one-year post-MI. Routine use of OGTT was associated with a higher rate of newly detected diabetes at one-year (risk ratio [95% confidence interval]: 1.62 [1.26, 1.98], p = 0.0007). At one-year a higher proportion of patients were receiving oral glucose-lowering medication at centers using OGTT (1.22 [1.07, 1.37], p = 0.0046) and where such medication was adjusted by CR physicians (1.31 [1.06, 1.56], p = 0.0155). Compared to having none of the structured diabetes care routines, the more routines implemented the higher the rate of newly detected diabetes (from 0 routines: 2.7% to 4 routines: 6.3%; p for trend = 0.0014).CONCLUSIONS: Having structured routines for diabetes care implemented within CR can improve detection and treatment of diabetes post-MI. A cluster-randomized trial is warranted to ascertain causality.
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18. |
- Thorvaldsen, Tonje, et al.
(author)
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Eligibility for Dapagliflozin and Empagliflozin in a Real-world Heart Failure Population
- 2022
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In: Journal of Cardiac Failure. - : Churchill Livingstone. - 1071-9164 .- 1532-8414. ; 28:7, s. 1050-1062
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Journal article (peer-reviewed)abstract
- 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 regulatory agencies, in a real-word heart failure population. Our results from the Swedish Heart Failure Registry show that a great number of patients with heart failure might be candidates for these therapies, which have been shown to significantly decrease morbidity and mortality; therefore, their use should be implemented in clinical practice. Lay summary: When strictly applying selection criteria used in clinical trials, only one-third of a real-world heart failure population is eligible for treatment with empagliflozin and dapagliflozin. Adopting approaches that consider the most meaningful criteria, that is, those most clinically relevant or those mandated by regulatory agencies, significantly broadened eligibility. These results might contribute to future trial design taking into consideration the characteristics of real-world populations, feasibility, and potential cost benefits. Conclusions: In a real-world HF setting, eligibility for sodium glucose co-transporter-2 inhibi-tors was similar whether selection criteria from DAPA-HF or EMPEROR-Reduced were applied in HFrEF, or EMPEROR-Preserved or DELIVER in HFpEF. These data might help stakeholders assessing the consequences of future trial eligibility. (J Cardiac Fail 2022;28:1050-1062)
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19. |
- Venetsanos, Dimitrios, et al.
(author)
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Prasugrel versus ticagrelor in patients with myocardial infarction undergoing percutaneous coronary intervention
- 2021
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In: Heart. - : BMJ Publishing Group Ltd. - 1355-6037 .- 1468-201X. ; 107:14, s. 1145-1151
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Journal article (peer-reviewed)abstract
- Objective: The comparative efficacy and safety of prasugrel and ticagrelor in patients with myocardial infarction (MI) treated with percutaneous coronary intervention (PCI) remain unclear. We aimed to investigate the association of treatment with clinical outcomes.Methods: In the SWEDEHEART (Swedish Web-system for enhancement and development of evidence-based care in heart disease evaluated according to recommended therapies) registry, all patients with MI treated with PCI and discharged on prasugrel or ticagrelor from 2010 to 2016 were included. Outcomes were 1-year major adverse cardiac and cerebrovascular events (MACCE, death, MI or stroke), individual components and bleeding. Multivariable adjustment, inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were used to adjust for confounders.Results: We included 37 990 patients, 2073 in the prasugrel group and 35 917 in the ticagrelor group. Patients in the prasugrel group were younger, more often admitted with ST elevation MI and more likely to have diabetes. Six to twelve months after discharge, 20% of patients in each group discontinued the P2Y12 receptor inhibitor they received at discharge. The risk for MACCE did not significantly differ between prasugrel-treated and ticagrelor-treated patients (adjusted HR 1.03, 95% CI 0.86 to 1.24). We found no significant difference in the adjusted risk for death, recurrent MI or stroke alone between the two treatments. There was no significant difference in the risk for bleeding with prasugrel versus ticagrelor (2.5% vs 3.2%, adjusted HR 0.92, 95% CI 0.69 to 1.22). IPTW and PSM analyses confirmed the results.Conclusion: In patients with MI treated with PCI, prasugrel and ticagrelor were associated with similar efficacy and safety during 1-year follow-up.
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20. |
- Wang, Anne, et al.
(author)
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Androgen receptor polymorphism, testosterone levels, and prognosis in patients with acute myocardial infarction
- 2021
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In: European Heart Journal Open. - : Oxford University Press (OUP). - 2752-4191. ; 1:2
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Journal article (peer-reviewed)abstract
- Aims Low testosterone has been associated with cardiovascular disease in men but with contradictory findings. Testosterone bind to the androgen receptor and polymorphisms of the receptor gene such as CAG repeat length may affect transcriptional activity, possibly mitigating testosterone effects. The aims were to study the CAG repeat length and testosterone levels at four time points following a myocardial infarction (MI) and to analyse possible relationships between CAG repeat length and cardiovascular prognosis. Methods and results Male patients admitted for acute MI (n = 122) from the Glucose in Acute Myocardial Infarction study were included. Blood samples were drawn at four time points (day after admission, at discharge, and at 3 and 12 months post-infarction) for assessment of testosterone levels. Patients were followed for a median of 11.6 years. Cox regression analyses were performed for CAG repeat length by one unit increment and by > vs. <_median for cardiovascular events and all-cause mortality. Median CAG repeat length was 20. There was no difference in testosterone levels at each time point when dividing the cohort into <_ vs. >CAG repeat median (=20). There was no association between CAG repeat length either as a continuous or categorical variable in unadjusted and age-adjusted Cox analyses for cardiovascular events. While CAG >20 was associated with all-cause mortality in unadjusted analyses (hazard ratio 2.19, 95% confidence interval 1.13–4.22; P = 0.02), it did not remain significant following adjustment for age. Conclusion CAG repeat length was not associated with testosterone levels or prognosis in men with acute MI.
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21. |
- Wang, Anne, et al.
(author)
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Dynamics of testosterone levels in patients with newly detected glucose abnormalities and acute myocardial infarction
- 2018
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In: Diabetes & Vascular Disease Research. - : Sage Publications. - 1479-1641 .- 1752-8984. ; 15:6, s. 511-518
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Journal article (peer-reviewed)abstract
- Objective: Low testosterone has been associated with increased cardiovascular risk and glucose abnormalities. This study explored the prevalence of low testosterone, dynamics over time and prognostic implications in acute myocardial infarction patients with or without glucose abnormalities. Methods: Male acute myocardial infarction patients (n = 123) and healthy controls (n = 124) were categorised as having normal or abnormal glucose tolerance (impaired glucose tolerance or diabetes) by oral glucose tolerance testing. Testosterone was measured at hospital admission, discharge, 3 and 12 months thereafter in patients. Patients and controls were followed for 11 years for major cardiovascular events (cardiovascular death/acute myocardial infarction/stroke/severe heart failure). Results: At hospital admission, more patients had low testosterone (<= 300 ng/dl) and lower median levels than controls (64 vs 28%; p < 0.001 and 243 vs 380 ng/dl; p < 0.01). At the subsequent time points, testosterone had increased to 311, 345 and 357 ng/dl. Patients with abnormal glucose tolerance had the highest prevalence (75%) of low levels. In adjusted Cox regression models, neither total nor free testosterone predicted major cardiovascular events. Conclusion: Low testosterone levels were common in male acute myocardial infarction patients in the acute phase, especially in the presence of abnormal glucose tolerance, but increased over time indicating that testosterone measured in close proximity to acute myocardial infarction should be interpreted with caution.
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22. |
- Wang, Anne, et al.
(author)
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Testosterone, sex hormone-binding globulin and risk of cardiovascular events : A report from the Outcome Reduction with an Initial Glargine Intervention trial
- 2019
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In: European Journal of Preventive Cardiology. - : Sage Publications. - 2047-4873 .- 2047-4881. ; 26:8, s. 847-854
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Journal article (peer-reviewed)abstract
- Aims: Testosterone and its binding protein sex hormone-binding globulin have been associated with cardiovascular disease and dysglycaemia. However, information on the prognostic implication in patients at high cardiovascular risk with dysglycaemia is inconsistent. The study objective was to determine whether testosterone and/or sex hormone-binding globulin predict cardiovascular events or death in dysglycaemic patients.Methods: Dysglycaemic males at high cardiovascular risk (n = 5553) who participated in the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial and provided baseline blood samples were studied. Testosterone and sex hormone-binding globulin were measured at baseline and used to estimate free testosterone. Low levels of total and free testosterone were defined as ≤300 ng/dl and ≤7 ng/dl, respectively. Patients were followed for six years for cardiovascular events (defined as the composite of cardiovascular death, non-fatal myocardial infarction or stroke) and all-cause mortality.Results: The mean total and free testosterone levels were 416.6 ng/dl and 8.4 ng/dl, and low levels were present in 13% and 37% of the patients. The median sex hormone-binding globulin level was 35 nmol/l. In Cox regression models adjusted for age, previous diseases and pharmacological treatment, neither total nor free testosterone predicted cardiovascular events. However, a one-standard-deviation increase in sex hormone-binding globulin predicted both cardiovascular events (hazard ratio 1.07; 95% confidence interval 1.00–1.14; p = 0.03) and all-cause mortality (hazard ratio 1.13; 95% confidence interval 1.06–1.21; p < 0.01).Conclusion: Sex hormone-binding globulin, but not total testosterone, predicts cardiovascular disease and all-cause mortality in dysglycaemic males at high cardiovascular risk.
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