Trends in prognosis and use of SGLT2i and GLP-1 RA in patients with diabetes and coronary artery disease.

OBJECTIVE: To explore trends in prognosis and use of glucose-lowering drugs (GLD) in patients with diabetes and coronary artery disease (CAD). RESEARCH DESIGN AND METHODS: All patients with diabetes and CAD undergoing a coronary angiography between 2010 and 2021 according to the Swedish Angiography and Angioplasty Registry were included. Information on GLD (dispended 6 months before or after coronary angiography) was collected from the Swedish Prescribed Drug Registry. Data on major cardiovascular events (MACE; mortality, myocardial infarction, stroke, heart failure) through December 2021 were obtained from national registries. Cox proportional survival analysis was used to assess outcomes where cardioprotective GLD (any of Sodium Glucose Lowering Transport 2 receptor inhibitors [SGLT2i] and Glucagon Like Peptide Receptor Agonists [GLP-1 RA]) served as a reference. RESULTS: Among all patients (n = 38,671), 31% had stable CAD, and 69% suffered an acute myocardial infarction. Mean age was 69 years, 67% were male, and 81% were on GLD. The use of cardioprotective GLD increased rapidly in recent years (2016-2021; 7-47%) and was more common in younger patients (66 vs. 68 years) and men (72.9% vs. 67.1%) than other GLD. Furthermore, compared with other GLD, the use of cardioprotective GLD was more common in patients with a less frequent history of heart failure (5.0% vs. 6.8%), myocardial infarction (7.7% vs. 10.5%) and chronic kidney disease (3.7% vs. 5.2%). The adjusted hazard ratio (HR) (95% CI) for MACE was greater in patients on other GLD than in those on cardioprotective GLD (1.10; 1.03-1.17, p = 0.004). Trend analyses for the years 2010-2019 revealed improved one-year MACE in patients with diabetes and CAD (year 2019 vs. 2010; 0.90; 0.81-1.00, p = 0.045), while 1-year mortality was unchanged. CONCLUSIONS: The prescription pattern of diabetes medication is changing quickly in patients with diabetes and CAD; however, there are worrying signals of inefficient use prioritizing cardioprotective GLD to younger and healthier individuals at lower cardiovascular risk. Despite this, there are improving trends in 1-year morbidity.

Glycemic Control and Coronary Stent Failure in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: The impact of glycemic control in the risk of stent failure in subjects with type 2 diabetes (T2D) is currently unknown. OBJECTIVES: This study sought to study whether poor glycemic control is associated with a higher risk of stent failure in subjects with T2D. METHODS: This observational study included all patients in Sweden with T2D who underwent implantation of second-generation drug-eluting stents (DES) during 2010 to 2020. The exposure variable was the updated mean of glycated hemoglobin (HbA1c). Individuals were stratified by glycemic control, with HbA1c 6.1% to 7.0% (43-53 mmol/mol) as the reference group. The primary endpoint was the occurrence of stent failure (in-stent restenosis and stent thrombosis). The main result was analyzed in a complete cases model. Sensitivity analyses were performed for missing data and a model with death as a competing risk. RESULTS: The study population consisted of 52,457 individuals (70,453 DES). The number of complete cases was 24,411 (29,029 DES). The median follow-up was 6.4 years. The fully adjusted HR was 1.10 (95% CI: 0.80-1.52) for HbA1c of ≤5.5% (≤37 mmol/mol), 1.02 (95% CI: 0.85-1.23) for HbA1c of 5.6% to 6.0% (38-42 mmol/mol), 1.25 (95% CI: 1.11-1.41) for HbA1c of 7.1% to 8.0% (54-64 mmol/mol), 1.30 (95% CI: 1.13-1.51) for HbA1c of 8.1% to 9.0% (65-75 mmol/mol), 1.46 (95% CI: 1.21-1.76) for HbA1c of 9.1% to 10.0% (76-86 mmol/mol), and 1.33 (95% CI: 1.06-1.66) for HbA1c of ≥10.1% (≥87 mmol/mol). Sensitivity analyses did not change the main result. CONCLUSIONS: We found a significant association between poor glycemic control and a higher risk of stent failure driven by in-stent restenosis.

Endodontic Inflammatory Disease and Future Cardiovascular Events and Mortality: A Report from the PAROKRANK Study.

INTRODUCTION: Prospective studies assessing the relation between endodontic inflammatory disease and subsequent cardiovascular events are few. The present aim was to explore associations between endodontic variables and future cardiovascular events in patients with myocardial infarction and matched controls participating in the PAROKRANK (Periodontitis and Its Relation to Coronary Artery Disease) study. METHODS: Eight-hundred five patients hospitalized for a first myocardial infarction and 805 controls were recruited between 2010 and 2014. Signs of endodontic inflammatory disease were assessed in panoramic radiographs taken at baseline. Mortality and morbidity data during the approximately 8 years of follow up were obtained from national registries. The risk for future cardiovascular events (first of mortality and nonfatal myocardial infarction, stroke, or hospitalization for heart failure) was analyzed with the log-rank test and Cox proportional hazards regression adjusted for the following confounders: sex, age, smoking, myocardial infarction, diabetes, education, marital status, family history of cardiovascular disease, and marginal periodontitis. RESULTS: In total, 285 future events were observed during the follow-up period. Unadjusted analyses revealed that ≥1 root-filled tooth increased the risk of a future event. After adjustment, the number of remaining teeth and non-root-filled teeth decreased the risk of future events, whereas a higher Decayed, Missing and Filled Teeth score increased the risk and ≥1 primary apical periodontitis decreased the risk of suffering cardiovascular events. A higher Decayed, Missing and Filled Teeth score and decayed teeth increased the risk of all-cause mortality. CONCLUSIONS: Tooth loss is a strong indicator of an increased risk for future cardiovascular events. Root-filled teeth seem of limited value as a risk indicator when accounting for other risk factors. The potential effect of dental interventions on future events should be assessed in future research.

Are there lost opportunities in chronic kidney disease? A region-wide cohort study.

OBJECTIVES: Identify the windows of opportunity for the diagnosis of chronic kidney disease (CKD) and the prevention of its adverse outcomes and quantify the potential population gains of such prevention. DESIGN AND SETTING: Observational, population-wide study of residents in the Stockholm and Skåne regions of Sweden between 1 January 2015 and 31 December 2020. PARTICIPANTS: All patients who did not yet have a diagnosis of CKD in healthcare but had CKD according to laboratory measurements of CKD biomarkers available in electronic health records. OUTCOME MEASURES: We assessed the proportions of the patient population that received a subsequent diagnosis of CKD in healthcare, that used guideline-directed pharmacological therapy (statins, renin-angiotensin aldosterone system inhibitors (RAASi) and/or sodium-glucose cotransporter-2 inhibitors (SGLT2i)) and that experienced adverse outcomes (all-cause mortality, cardiovascular mortality or major adverse cardiovascular events (MACE)). The potential to prevent adverse outcomes in CKD was assessed using simulations of guideline-directed pharmacological therapy in untreated subsets of the study population. RESULTS: We identified 99 382 patients with undiagnosed CKD during the study period. Only 33% of those received a subsequent diagnosis of CKD in healthcare after 5 years. The proportion that used statins or RAASi was of similar size to the proportion that didn't, regardless of how advanced their CKD was. The use of SGLT2i was negligible. In simulations of optimal treatment, 22% of the 21 870 deaths, 27% of the 14 310 cardiovascular deaths and 39% of the 22 224 MACE could have been avoided if every patient who did not use an indicated medication for their laboratory-confirmed CKD was treated with guideline-directed pharmacological therapy for CKD. CONCLUSIONS: While we noted underdiagnosis and undertreatment of CKD in this large contemporary population, we also identified a substantial realisable potential to improve CKD outcomes and reduce its burden by treating patients early with guideline-directed pharmacological therapy.

[Periodontitis - an often neglected risk factor for several other diseases]. / Parodontit ­ en ofta förbisedd riskfaktor för en rad sjukdomar.

Periodontitis is a chronic inflammatory disease that degrades dental supporting tissues, including the alveolar bone. The global prevalence is 19%, in Sweden it is 11%. Left untreated, periodontitis can cause loss of teeth. The initial clinical manifestations of periodontitis usually start between 35 and 45 years of age. The underlying pathological mechanism is an aberrant inflammatory response to the bacteria colonizing the gingival crevice. Periodontitis has been associated with several other diseases, most prominently diabetes. The relation between periodontitis and diabetes is bidirectional in the sense that diabetes increases the risk for periodontitis and vice versa. Periodontitis also increases the risk for cardiovascular disease and cancer.

[Diabetes and periodontitis - common, important but often neglected]. / Diabetes och parodontit ­ viktig aspekt av diabetesvården.

Diabetes and periodontitis are two global epidemics. There is a two-way relationship between diabetes and periodontitis. Diabetes increases the risk of periodontitis and periodontitis increases the risk for deteriorating glucose levels, having undetected diabetes, and for future diabetes. A recent Cochrane report summarized that there is moderate-certainty evidence that periodontal treatment improves glycaemic control in people with both periodontitis and diabetes. The recent PAROKRANK study found that undetected dysglycaemia was independently associated to both myocardial infarction and to periodontitis. To increase awareness of oral health in people with diabetes this article summarizes recent evidence.

Heart failure outcomes by left ventricular ejection fraction in a contemporary region-wide patient cohort.

AIMS: This study aimed to characterize a contemporary population with subtypes of incident or prevalent heart failure (HF) based on reduced (HFrEF), mildly reduced, or preserved (HFpEF) left ventricular ejection fraction (LVEF) and to assess how outcomes, healthcare, treatments, and healthcare costs vary between each subtype of incident HF. METHODS AND RESULTS: Using Swedish data from the CardioRenal and Metabolic disease Heart Failure (CaReMe HF) study, updated to cover a more recent time period, this population-based study characterized patients from Stockholm County, Sweden, with incident HF (patients with a first HF diagnosis between 1 January 2015 and 31 December 2019) or prevalent HF (patients with a first HF diagnosis before 1 January 2020). Patients with incident HF had LVEF measured by echocardiography within ±90 days of their first HF diagnosis, and patients with prevalent HF within 5 years prior to the index date. The 13 375 patients with prevalent HF (39.2% women, mean age 73.9 years) had multiple comorbidities (cardiovascular diseases, chronic kidney disease, diabetes, and cancer). These were already highly prevalent at the time of the first HF diagnosis in the 8042 patients with incident HF (40.5% women, mean age 72.3 years). Patients with incident HFpEF received less specialist HF care at outpatient secondary care facilities following their first HF diagnosis than those with incident HFrEF. Patients with HFrEF had higher risks of complications and exerted a higher burden, in terms of care for and costs of HF, on the healthcare system. CONCLUSIONS: This study of contemporary patients with incident HF demonstrates that those with HFpEF and HFrEF differ considerably in terms of clinical presentation, prognosis, and care, highlighting a potential to improve HF outcomes.

Primary apical periodontitis correlates to elevated levels of interleukin-8 in a Swedish population: A report from the PAROKRANK study.

AIM: To explore associations between root filled teeth, primary and secondary apical periodontitis, and levels of inflammatory markers in blood from patients with a first myocardial infarction and matched controls. METHODOLOGY: Between May 2010 and February 2014, 805 patients with a first myocardial infarction and 805 controls, matched for sex, age, and postal code area, were recruited to the multicentre case-control study PAROKRANK (periodontitis and its relation to coronary artery disease). All participants underwent a physical and oral examination, as well as blood sampling. Using panoramic radiography, root filled teeth, primary apical periodontitis, and secondary apical periodontitis were assessed by three independent observers. Blood samples were analysed with enzyme-linked immunosorbent assay method for the following inflammatory markers: interleukin-1ß (IL-1ß), IL-2, IL-6, IL-8, IL-12p70, tumour necrosis factor-α, and high-sensitivity C-reactive protein (hsCRP). Additionally, white blood cell count and plasma-fibrinogen were analysed. Associations between endodontic variables and the levels of inflammatory markers were statistically analysed with Mann-Whitney U-test and Spearman correlation, adjusted for confounding effects of baseline factors (sex, age, myocardial infarction, current smoking, diabetes, family history of cardiovascular disease, education, marital status, and periodontal disease). RESULTS: Mean age of the cohort was 62 years, and 81% were males. Root fillings were present in 8.4% of the 39 978 examined teeth and were associated with higher levels of hsCRP, fibrinogen, and leukocyte count, but lower levels of IL-2 and IL-12p70. After adjusting for confounders, root filled teeth remained associated with higher levels of fibrinogen, but lower levels of IL-1ß, IL-2, IL-6, and IL-12p70. Primary apical periodontitis was found in 1.2% of non-root filled teeth and associated with higher levels of IL-8 (correlation 0.06, p = .025). Secondary apical periodontitis was found in 29.6% of root filled teeth but did not relate to the levels of any of the inflammatory markers. CONCLUSIONS: This study supports the notion that inflammation at the periapex is more than a local process and that systemic influences cannot be disregarded. Whether the observed alterations in plasma levels of inflammatory markers have any dismal effects on systemic health is presently unknown but, considering the present results, in demand of further investigation.

Sex differences in the association between insulin resistance and non-fatal myocardial infarction across glycaemic states.

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.

High Mannose Correlates With Surrogate Indexes of Insulin Resistance and Is Associated With an Increased Risk of Cardiovascular Events Independently of Glycemic Status and Traditional Risk Factors.

OBJECTIVE: To explore the associations among mannose, indexes of insulin resistance (IR) and secretion, and long-term cardiovascular outcomes. RESEARCH DESIGN AND METHODS: Fasting mannose was assayed in 1,403 participants, one-half of which had a first myocardial infarction (MI) with either normal glucose tolerance (n = 1,045) or newly detected dysglycemia (i.e., impaired glucose tolerance or type 2 diabetes; n = 358). Regression models were used to explore mannose associations with surrogate indexes of IR/insulin secretion. Multivariate Cox models were used to investigate the independent association between high (higher quartile) versus low (lower three quartiles) mannose and major adverse cardiac events (MACE) (n = 163) during the 10-year follow-up. RESULTS: Mannose was independently associated with IR indexes (all P ≤ 0.001). High versus low mannose was independently associated with MACE (hazard ratio 1.54, 95% CI 1.07-2.20) in the overall population. CONCLUSIONS: Mannose might represent a new biomarker able to track early, potentially detrimental glucometabolic alterations independently of glycemic state.

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 ∼20 study sites in Sweden. Patients 18-80 years, without known diabetes and naïve 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).

Empagliflozin improves insulin sensitivity in patients with recent acute coronary syndrome and newly detected dysglycaemia : Experiences from the randomized, controlled SOCOGAMI trial.

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 ß-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 ß-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 ß-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.

Temporal trends in cardiovascular risk factors, lifestyle and secondary preventive medication for patients with myocardial infarction attending cardiac rehabilitation in Sweden 2006-2019: a registry-based cohort study.

OBJECTIVES: Registries have been highlighted as means to improve quality of care. Here, we describe temporal trends in risk factors, lifestyle and preventive medication for patients after myocardial infarction (MI) registered in the quality registry Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART). DESIGN: A registry-based cohort study. SETTING: All coronary care units and cardiac rehabilitation (CR) centres in Sweden. PARTICIPANTS: Patients attending a CR visit at 1-year post-MI 2006-2019 were included (n=81 363, 18-74 years, 74.7% men). OUTCOME MEASURES: Outcome measures at 1-year follow-up included blood pressure (BP) <140/90 mm Hg, low-density lipoprotein-cholesterol (LDL-C)<1.8 mmol/L, persistent smoking, overweight/obesity, central obesity, diabetes prevalence, inadequate physical activity, and prescription of secondary preventive medication. Descriptive statistics and testing for trends were applied. RESULTS: The proportion of patients attaining the targets for BP<140/90 mmHg increased from 65.2% (2006) to 86.0% (2019), and LDL-C<1.8 mmol/L from 29.8% (2006) to 66.9% (2019, p<0.0001 both). While smoking at the time of MI decreased (32.0% to 26.5%, p<0.0001), persistent smoking at 1 year was unchanged (42.8% to 43.2%, p=0.672) as was the prevalence of overweight/obesity (71.9% to 72.9%, p=0.559). Central obesity (50.5% to 57.0%), diabetes (18.2% to 27.2%) and patients reporting inadequate levels of physical activity (57.0% to 61.5%) increased (p<0.0001 for all). From 2007, >90.0% of patients were prescribed statins and approximately 98% antiplatelet and/or anticoagulant therapy. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker prescription increased from 68.7% (2006) to 80.2% (2019, p<0.0001). CONCLUSIONS: While little change was observed for persistent smoking and overweight/obesity, large improvements were observed for LDL-C and BP target achievements and prescription of preventive medication for Swedish patients after MI 2006-2019. Compared with published results from patients with coronary artery disease in Europe during the same period, these improvements were considerably larger. Continuous auditing and open comparisons of CR outcomes might possibly explain some of the observed improvements and differences.

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.

Prevalence, outcomes and costs of a contemporary, multinational population with heart failure.

OBJECTIVE: Digital healthcare systems could provide insights into the global prevalence of heart failure (HF). We designed the CardioRenal and Metabolic disease (CaReMe) HF study to estimate the prevalence, key clinical adverse outcomes and costs of HF across 11 countries. METHODS: Individual level data from a contemporary cohort of 6 29 624 patients with diagnosed HF was obtained from digital healthcare systems in participating countries using a prespecified, common study plan, and summarised using a random effects meta-analysis. A broad definition of HF (any registered HF diagnosis) and a strict definition (history of hospitalisation for HF) were used. Event rates were reported per 100 patient years. Cumulative hospital care costs per patient were calculated for a period of up to 5 years. RESULTS: The prevalence of HF was 2.01% (95% CI 1.65 to 2.36) and 1.05% (0.85 to 1.25) according to the broad and strict definitions, respectively. In patients with HF (broad definition), mean age was 75.2 years (95% CI 74.0 to 76.4), 48.8% (40.9-56.8%) had ischaemic heart disease and 34.5% (29.4-39.6%) had diabetes. In 51 442 patients with a recorded ejection fraction (EF), 39.1% (30.3-47.8%) had a reduced, 18.8% (13.5-24.0%) had a mildly reduced and 42.1% (31.5-52.8%) had a preserved left ventricular EF. In 1 69 518 patients with recorded estimated glomerular filtration rate, 49% had chronic kidney disease (CKD) stages III-V. Event rates were highest for cardiorenal disease (HF or CKD) and all cause mortality (19.3 (95% CI 11.3 to 27.1) and 13.1 (11.1 to 15.1), respectively), and lower for myocardial infarction, stroke and peripheral artery disease. Hospital care costs were highest for cardiorenal diseases. CONCLUSIONS: We estimate that 1-2% of the contemporary adult population has HF. These individuals are at significant risk of adverse outcomes and associated costs, predominantly driven by hospitalisations for HF or CKD. There is considerable public health potential in understanding the contemporary burden of HF and the importance of optimising its management.

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.

SOdium-glucose CO-transporter inhibition in patients with newly detected Glucose Abnormalities and a recent Myocardial Infarction (SOCOGAMI).

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 variables expressing LV function, coronary flow reserve and ECV. An explanation may be that the LV function of the patients was within the normal range.

Plasma mannose as a novel marker of myocardial infarction across different glycaemic states: a case control study.

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.