Causes and mechanisms of an adverse outcome in patients with glucose abnormalities and cardiovascular disease : epidemiological and biochemical analyses

Background: Diabetes and previously undetected glucose abnormalities are common in patients with acute myocardial infarction (AMI). It is well established that patients with diabetes have a higher mortality rate after coronary events than patients without diabetes but the complication pattern in a contemporary perspective, the impact of glucose control and whether unknown glucose abnormalities affect the longterm prognosis is less well studied. Data on the prognostic implications of adipokines in patients with prevalent coronary heart disease are contradictory and long-term outcome studies are lacking. Aims: To identify high-risk individuals and study long-term prognosis by 1. Investigating the lasting effect of intensified, insulin-based glucose control on mortality after AMI in patients with diabetes. 2. Analysing mortality and morbidity patterns after AMI in patients with newly discovered glucose abnormalities. 3. Investigating complication patterns after a first percutaneous coronary intervention. 4. Analysing the significance of adiponectin and leptin as biomarkers of cardiovascular complications. Glucose control and mortality after AMI: 306 patients with AMI and diabetes were randomised to intensified insulin-based glycaemic control while 314 served as controls in the DIGAMI-study. During a mean follow-up of 7.3 years 90% of the study population died. The median survival was 2.3 years longer in patients receiving intensified insulin-based glycaemic control after AMI (7.0 years) compared to patients in the control group (4.7 years). Impact of undetected glucose abnormalities on long-term outcome after AMI: Patients (n=167) with AMI and healthy controls (n=184) without previously known diabetes (included in the GAMI study) were investigated with an oral glucose tolerance test (OGTT) at the time of hospital discharge (patients) or at inclusion (controls). Cardiovascular events (cardiovascular mortality, AMI, heart failure and stroke) during 10 years of follow-up were more frequent in patients with abnormal glucose tolerance than in patients with normal glucose tolerance and in controls. Abnormal glucose tolerance at the OGTT was independently associated with future cardiovascular events after an AMI (HR 2.30; 95% CI 1.24-4.25, p=0.008) in contrast to HbA1c (p=0.81) and fasting blood glucose (p=0.52). Long-term outcome after coronary artery disease and revascularisation: High event rates of mortality, heart failure, myocardial infarction and stroke were demonstrated after a first percutaneous coronary intervention in patients with diabetes followed up to five years after inclusion in the Swedish Coronary Angiography Angioplasty Registry (SCAAR) between 2006-2010 (n=58891, 19% with diabetes). Diabetes was an independent predictor for mortality and cardiovascular events. Insulin-treated patients were at a particularly high risk. Adiponectin and leptin as biomarkers for identifying high risk patients: In 180 patients with AMI and without diabetes (the GAMI cohort) elevated levels of adiponectin at discharge independently predicted mortality (HR 1.79; 95% CI 1.07-3.00, p=0.027) but not cardiovascular events the coming decade. High levels of leptin at day 2 were associated with cardiovascular events during the first seven years but did not predict mortality. Conclusion: Diabetes and previously undetected glucose abnormalities are common in patients with coronary events and their presence has a negative influence on the prognosis. Despite improved longevity patients with diabetes are still at increased risk for mortality and cardiovascular complications. An OGTT, but not HbA1c, identifies patients with previously undetected glucose abnormalities at increased cardiovascular risk the next coming 10 years. These findings support that an OGTT should be considered as an important screening tool after AMI. High levels of adiponectin and leptin identifies patients with compromised outcome after AMI. Future studies are warranted to confirm their role as suitable biomarkers. Finally a close follow-up of patients with glucose abnormalities is advocated where multifactorial treatment is important to improve long-term survival after AMI. The present studies do also underline that new treatment strategies are highly warranted

Admission Glucose Levels and Associated Risk for Heart Failure After Myocardial Infarction in Patients Without Diabetes.

Background Dysglycemia at acute myocardial infarction (AMI) is common and is associated with mortality. Information on other outcomes is less well explored in patients without diabetes in a long-term perspective. We aimed to explore the relationship between admission glucose level and long-term outcomes in patients with AMI without diabetes in a nationwide setting. Methods and Results Patients without diabetes (n=45 468) with AMI registered in SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) and admission glucose ≤11 mmol/L (≤198 mg/dL) were followed for outcomes (AMI, heart failure, stroke, renal failure, and death) between 2012 and 2017 (mean follow-up time 3.3±1.7 years). The association between categorized glucose levels and outcomes was assessed in adjusted Cox proportional hazards regression analyses (glucose levels 4.0-6.0 mmol/L [72-109 mg/dL] as reference). Further nonfatal complications and their associated mortality were explored (patients without events served as a reference). A glucose level of 7.8-11.0 mmol/L (140-198 mg/dL) was associated with hospitalization for heart failure (hazard ratio [HR] 1.40 [95% CI, 1.30-1.51], P<0.001), renal failure (1.17; 1.04-1.33, P=0.009), and death (1.31; 1.20-1.43, P<0.001), but not with recurrent myocardial infarction (0.99; 0.92-1.07, P=0.849) or stroke (1.03; 0.88-1.19, P=0.742). Renal failure had the strongest association with future mortality (age-adjusted HR 4.93 [95% CI, 4.34-5.60], P<0.001), followed by heart failure (3.71; 3.41-4.04, P<0.001), stroke (3.39; 2.94-3.91, P<0.001), and myocardial infarction (2.08; 1.88-2.30, P<0.001). Conclusions Elevated glucose levels at AMI admission identifies patients without diabetes at increased risk of long-term complications: in particular, hospitalization for heart and renal failure. These results emphasize that glucose levels at admission could be useful in risk assessment after myocardial infarction

Diabetes, metformin and glucose lowering therapies after myocardial infarction : Insights from the SWEDEHEART registry

OBJECTIVE: To explore real-life use of glucose lowering drugs and prognosis after acute myocardial infarction (AMI) with a special focus on metformin. METHODS: Patients (n = 70270) admitted for AMI 2012-2017 were stratified by diabetes status and glucose lowering treatment and followed for mortality and MACE+ (AMI, heart failure (HF), stroke, mortality) until end of 2017 (mean follow-up time 3.4 ± 1.4 years) through linkage with national registries and SWEDEHEART. Hazard ratios (HR) were calculated in adjusted Cox proportional hazard regression models. RESULTS: Mean age was 68 ± 11 years and 70% were male. Of patients with diabetes (n = 16356; 23%), a majority had at least one glucose lowering drug (81%) of whom 51% had metformin (24% monotherapy), 43% insulin and a minority any SGLT2i/GLP-1 RA (5%). Adjusted HR for patients with versus without diabetes was 1.31 (95% CI 1.27-1.36) for MACE+ and 1.48 (1.41-1.56) for mortality. Adjusted HR for MACE+ for diabetes patients on metformin was 0.92 (0.85-0.997), p = 0.042 compared to diet treated diabetes. CONCLUSION: Diabetes still implies a high complication risk after AMI. Metformin and insulin were the most common treatment used in almost half of the diabetes population. Furthermore, patients treated with metformin had a lower cardiovascular risk after AMI and needs to be confirmed in prospective controlled trials

History of heart failure and chronic kidney disease and risk of all-cause death after COVID-19 during the first three waves of the pandemic in comparison with influenza outbreaks in Sweden: a registry-based, retrospective, case–control study

Objectives To explore how cardiorenal disease (CRD; heart failure and/or chronic kidney disease) impacted mortality in men and women hospitalised for COVID-19 during the first three waves of the pandemic in Sweden in comparison to previous influenza outbreaks.Design A registry-based, retrospective, case–control study.Setting Hospital care in Sweden.Participants All patients in Sweden with a main hospital diagnosis of COVID‐19 (January 2020–September 2021) or influenza (January 2015–December 2019) with previous CRD were identified in registries and compared with a reference group free from CRD but with COVID-19 or influenza.Primary outcome measure Associated risk of all-cause death during the first year was analysed using adjusted Cox proportional hazards models.Results In COVID-19 patients with and without prior history of CRD (n=44 866), mean age was 79.8 years (SD 11.8) and 43% were women. In influenza patients (n=8897), mean age was 80.6 years (SD 11.5) and 45% were women. COVID-19 versus influenza was associated with higher mortality risk during the first two COVID-19 waves (HR 1.53; 95% CI 1.45 to 1.62, p<0.001 and HR 1.52; 95% CI 1.44 to 1.61, p<0.001), but not in the third wave (HR 1.07; 95% CI 0.99 to 1.14, p=0.072). CRD was an independent risk factor for all-cause death after COVID-19 in men and women (men: 1.37; 95% CI 1.31 to 1.44, p<0.001; women: 1.46; 95% CI 1.38 to 1.54, p<0.001). At ages <70 years, women with CRD had a similar mortality rate to men with CRD, while at ages ≥70 years, the mortality rate was higher in men.Conclusions Outcome after COVID-19 is worse if CRD is present. In women at ages <70 years, the presence of CRD attenuates the protective effect of female sex. COVID-19 was associated with higher mortality risk than influenza during the first two pandemic waves

Patients with type 1 and type 2 diabetes hospitalized with COVID-19 in comparison with influenza : mortality and cardiorenal complications assessed by nationwide Swedish registry data

Background The risk of severe coronavirus disease 2019 (COVID-19) is increased in people with diabetes, but effects of diabetes type and other risk factors remain incompletely characterized. We studied this in a Swedish cohort of hospitalized patients with type 1 and type 2 diabetes (T1D and T2D), also including comparisons with influenza epidemics of recent years. Methods Nationwide healthcare registries were used to identify patients. A total of 11,005 adult patients with diabetes (T1D, n = 373; T2D, n = 10,632) were hospitalized due to COVID-19 from January 1, 2020 to September 1, 2021. Moreover, 5111 patients with diabetes (304 T1D, 4807 T2D) were hospitalized due to influenza from January 1, 2015 to December 31, 2019. Main outcomes were death within 28 days after admission and new hospitalizations for heart failure (HF), chronic kidney disease (CKD), cardiorenal disease (CRD; composite of HF and CKD), myocardial infarction (MI) and stroke during 1 year of follow-up. Results Number of deaths and CRD events were 2025 and 442 with COVID-19 and 259 and 525 with influenza, respectively. Age- and sex-adjusted Cox regression models in COVID-19 showed higher risk of death and HF in T1D vs. T2D, hazard ratio (HR) 1.77 (95% confidence interval 1.41–2.22) and 2.57 (1.31–5.05). With influenza, T1D was associated with higher risk of death compared with T2D, HR 1.80 (1.26–2.57). Older age and previous CRD were associated with higher risks of death and hospitalization for CRD. After adjustment for prior comorbidities, mortality differences were still significant, but there were no significant differences in cardiovascular and renal outcomes. COVID-19 relative to influenza was associated with higher risk of death in both T1D and T2D, HR 2.44 (1.60–3.72) and 2.81 (2.59–3.06), respectively. Conclusions In Sweden, patients with T1D as compared to T2D had a higher age- and sex-adjusted risk of death within 28 days and HF within one year after COVID-19 hospitalization, whereas the risks of other non-fatal cardiovascular and renal disease events were similar. Patients with T1D as well as T2D have a greater mortality rate when hospitalized due to COVID-19 compared to influenza, underscoring the importance of vaccination and other preventive measures against COVID-19 for diabetes patients

dvdres-dec-2017-00190-Supplementary_File – Supplemental material for Elevated levels of insulin-like growth factor-binding protein 1 predict outcome after acute myocardial infarction: A long-term follow-up of the glucose tolerance in patients with acute myocardial infarction (GAMI) cohort

<p>Supplemental material, dvdres-dec-2017-00190-Supplementary_File for Elevated levels of insulin-like growth factor-binding protein 1 predict outcome after acute myocardial infarction: A long-term follow-up of the glucose tolerance in patients with acute myocardial infarction (GAMI) cohort by Viveca Ritsinger, Kerstin Brismar, Linda Mellbin, Per Näsman, Lars Rydén, Stefan Söderberg and Anna Norhammar in Diabetes & Vascular Disease Research</p

Design and rationale of the myocardial infarction and new treatment with metformin study (MIMET) - Study protocol for a registry-based randomised clinical trial

Aims: To investigate if addition of metformin to standard care (life-style advice) reduces the occurrence of cardiovascular events and death after myocardial infarction (MI) in patients with newly detected prediabetes. Methods: The Myocardial Infarction and new treatment with Metformin study (MIMET) is a large multicentre registry-based randomised clinical trial (R-RCT) within the SWEDEHEART registry platform expected to include 5160 patients with MI and newly detected prediabetes (identified with fasting blood glucose, HbA1c or 2-h glucose on oral glucose tolerance test) at similar to 20 study sites in Sweden. Patients 18-80 years, without known diabetes and naive to glucose lowering therapy, will be randomised 1:1 to open-label metformin therapy plus standard care or standard care alone. Outcomes: Patients will be followed for 2 years for the primary outcome new cardiovascular event (first of death, non-fatal MI, hospitalisation for heart failure or non-fatal stroke). Secondary endpoints include individual components of the primary endpoint, diabetes diagnosis, initiation of any glucose lowering therapy, cancer, and treatment safety. Events will be collected from national healthcare registries. Conclusions: The MIMET study will investigate if metformin is superior to standard care after myocardial infarction in preventing cardiovascular events in patients with prediabetes (Clinicaltrials.gov identifier: NCT05182970; EudraCT No: 2019-001487-30)