Disparities in prevalence and treatment of diabetes, cardiovascular and chronic kidney diseases - Recommendations from the taskforce of the guideline workshop.

There is a mounting clinical, psychosocial, and socioeconomic burden worldwide as the prevalence of diabetes, cardiovascular disease (CVD), and chronic kidney disease (CKD) continues to rise. Despite the introduction of therapeutic interventions with demonstrated efficacy to prevent the development or progression of these common chronic diseases, many individuals have limited access to these innovations due to their race/ethnicity, and/or socioeconomic status (SES). However, practical guidance to providers and healthcare systems for addressing these disparities is often lacking. In this article, we review the prevalence and impact of healthcare disparities derived from the above-mentioned chronic conditions and present broad-based recommendations for improving access to quality care and health outcomes within the most vulnerable populations.

CVOT Summit Report 2023: new cardiovascular, kidney, and metabolic outcomes.

The 9th Cardiovascular Outcome Trial (CVOT) Summit: Congress on Cardiovascular, Kidney, and Metabolic Outcomes was held virtually on November 30-December 1, 2023. This reference congress served as a platform for in-depth discussions and exchange on recently completed outcomes trials including dapagliflozin (DAPA-MI), semaglutide (SELECT and STEP-HFpEF) and bempedoic acid (CLEAR Outcomes), and the advances they represent in reducing the risk of major adverse cardiovascular events (MACE), improving metabolic outcomes, and treating obesity-related heart failure with preserved ejection fraction (HFpEF). A broad audience of endocrinologists, diabetologists, cardiologists, nephrologists and primary care physicians participated in online discussions on guideline updates for the management of cardiovascular disease (CVD) in diabetes, heart failure (HF) and chronic kidney disease (CKD); advances in the management of type 1 diabetes (T1D) and its comorbidities; advances in the management of CKD with SGLT2 inhibitors and non-steroidal mineralocorticoid receptor antagonists (nsMRAs); and advances in the treatment of obesity with GLP-1 and dual GIP/GLP-1 receptor agonists. The association of diabetes and obesity with nonalcoholic steatohepatitis (NASH; metabolic dysfunction-associated steatohepatitis, MASH) and cancer and possible treatments for these complications were also explored. It is generally assumed that treatment of chronic diseases is equally effective for all patients. However, as discussed at the Summit, this assumption may not be true. Therefore, it is important to enroll patients from diverse racial and ethnic groups in clinical trials and to analyze patient-reported outcomes to assess treatment efficacy, and to develop innovative approaches to tailor medications to those who benefit most with minimal side effects. Other keys to a successful management of diabetes and comorbidities, including dementia, entail the use of continuous glucose monitoring (CGM) technology and the implementation of appropriate patient-physician communication strategies. The 10th Cardiovascular Outcome Trial Summit will be held virtually on December 5-6, 2024 ( http://www.cvot.org ).

Increased levels of a mycophenolic acid metabolite in patients with kidney failure negatively affect cardiomyocyte health.

Chronic kidney disease (CKD) significantly increases cardiovascular risk and mortality, and the accumulation of uremic toxins in the circulation upon kidney failure contributes to this increased risk. We thus performed a screening for potential novel mediators of reduced cardiovascular health starting from dialysate obtained after hemodialysis of patients with CKD. The dialysate was gradually fractionated to increased purity using orthogonal chromatography steps, with each fraction screened for a potential negative impact on the metabolic activity of cardiomyocytes using a high-throughput MTT-assay, until ultimately a highly purified fraction with strong effects on cardiomyocyte health was retained. Mass spectrometry and nuclear magnetic resonance identified the metabolite mycophenolic acid-ß-glucuronide (MPA-G) as a responsible substance. MPA-G is the main metabolite from the immunosuppressive agent MPA that is supplied in the form of mycophenolate mofetil (MMF) to patients in preparation for and after transplantation or for treatment of autoimmune and non-transplant kidney diseases. The adverse effect of MPA-G on cardiomyocytes was confirmed in vitro, reducing the overall metabolic activity and cellular respiration while increasing mitochondrial reactive oxygen species production in cardiomyocytes at concentrations detected in MMF-treated patients with failing kidney function. This study draws attention to the potential adverse effects of long-term high MMF dosing, specifically in patients with severely reduced kidney function already displaying a highly increased cardiovascular risk.

Application of wearables for remote monitoring of oncology patients: A scoping review.

Objective: This review aims to systematically map and categorize the current state of wearable applications among oncology patients and to identify determinants impeding clinical implementation. Methods: A Medline, Embase and clinicaltrials.gov search identified journal articles, conference abstracts, letters, reports, dissertations and registered studies on the use of wearables in patients with malignancies published up to 10 November 2021. Results: Of 2509 records identified, 112 met the eligibility criteria. Of these, 9.8% (11/112) were RCTs and 47.3% (53/112) of publications were observational. Wearables were investigated pre-treatment (2.7%; 3/112), during treatment (34.8%; 39/112), post-treatment (17.9%; 20/112), in survivors (27.7%; 31/112) and in non-specified or multiple treatment phases (17.0%; 19/112). Medical-grade wearables were applied in 22.3% (25/112) of publications. Primary objectives ranged from technical feasibility (8.0%; 9/112), user feasibility (42.9%; 48/112) and correlational analysis (40.2%; 45/112) to outcome change analysis (8.9%; 10/112). Outcome change was mostly investigated regarding physical activity improvement (80.0%; 8/10). Most publications (42.9%; 48/112) and registered studies (39.3%; 24/61) featured multiple cancer types, with breast cancer as the most prevalent specific type (22.3% in publications, 16.4% in registered studies). Conclusions: Most studies among oncology patients using wearables are focused on assessing the user feasibility of consumer-grade wearables, whereas rates of RCTs assessing clinical efficacy are low. Substantial improvements in clinically relevant endpoints by the use of wearables, such as morbidity and mortality are yet to be demonstrated.

Platelets from patients with chronic inflammation have a phenotype of chronic IL-1ß release.

Background: Chronic inflammation is a cardiovascular risk factor, and interleukin-1ß (IL-1ß) is central to the inflammatory host response. Platelets contain the NLRP3 inflammasome and are able to translate IL-1ß messenger RNA (mRNA) and secrete mature IL-1ß upon activation. However, the role of a chronic inflammatory environment in platelet IL-1ß mRNA and protein content remains unclear. Objectives: The aim of the current study was to investigate intracellular platelet IL-1ß and IL-1ß mRNA in a chronic inflammatory state. Methods: Sixty-five patients with stable inflammation (ie, high-sensitivity C-reactive protein within predefined margins in 2 separate measurements) were stratified according to high-sensitivity C-reactive protein levels in low (0.0-0.9 mg/L), medium (1.0-2.9 mg/L), and high (3.0-9.9 mg/L) risk groups. Platelet reactivity as well as platelet IL-1ß protein synthesis were studied. Results: The highest risk group was characterized by a distinct cardiovascular risk profile and approximately 20% higher platelet counts. While platelet reactivity was not different, a reduction in intracellular platelet IL-1ß mRNA and IL-1ß protein levels was observed in the highest risk group and was linked to decreased platelet size and granularity. This signature suggests a phenotype of chronic IL-1ß secretion and could be experimentally phenocopied by stimulation of platelets from healthy volunteers with either TRAP-6 or collagen related peptide (CRP-XL). Conclusion: Our data suggest a phenotype of chronic IL-1ß secretion by platelets in patients with chronic sterile inflammation.

Diabetes mellitus and presentation, care and outcomes of patients with NSTEMI: the Association for Acute Cardiovascular Care-European Association of Percutaneous Cardiovascular Interventions EURObservational Research Programme NSTEMI Registry of the European Society of Cardiology.

AIM: Diabetes mellitus (diabetes) is common amongst patients with NSTEMI. We describe presentation, care and outcomes of patients admitted with NSTEMI by diabetes status. METHODS: Prospective cohort study including 2928 patients (1104 with prior diabetes, 1824 without) admitted to hospital with NSTEMI from 287 centres in 59 countries. Quality of care was evaluated based on 12 guideline-recommended care interventions. Outcomes included in-hospital acute heart failure, cardiogenic shock, repeat myocardial infarction, stroke/transient ischaemic attack (TIA), BARC Type ≥ 3 bleeding and death, as well as 30-day mortality. RESULTS: Patients with diabetes had higher comorbidity burden and more frequently presented with Killip Class II-IV heart failure (10.2% vs 3.7%, P < 0.001), haemodynamic instability (7.1% vs 3.7%, P < 0.001) and ongoing chest pain (43.1% vs 37.0%, P < 0.001), than those without diabetes. Overall, care quality received was similar by diabetes status (60.0% vs 60.5% received ≥ 80% of eligible care interventions, P = 0.786), but patients with diabetes experienced higher rates of in-hospital acute heart failure (15.3% vs 6.8% P < 0.001), cardiogenic shock (4.5% vs 2.5%, P = 0.002), stroke/TIA (2.0% vs 0.8%, P = 0.006) and death (2.5% vs 1.4%, P = 0.022), and higher 30-day mortality (3.3% vs 2.0%, P = 0.025). Of NSTEMI with diabetes, only 1.9% and 9.0% received prescription for GLP-1 RAs and SGLT2 inhibitors, respectively, on discharge, and only 45.9% were referred for cardiac rehabilitation. CONCLUSION: NSTEMI patients with diabetes, compared to those without, present more clinically unwell and have worse outcomes despite receiving equal quality of care. Prescription of cardiovascular-protective glycaemic agents is an actionable target to reduce risk of further events.

GLP-1 in patients with myocardial infarction complicated by cardiogenic shock-an IABP-SHOCK II-substudy.

BACKGROUND: Glucagon-like peptide-1 (GLP-1) is a gut-derived peptide secreted in response to nutritional and inflammatory stimuli. Elevated GLP-1 levels predict adverse outcome in patients with acute myocardial infarction or sepsis. GLP-1 holds cardioprotective effects and GLP-1 receptor agonists reduce cardiovascular events in high-risk patients with diabetes. In this study, we aimed to investigate the capacity of GLP-1 to predict outcome in patients with cardiogenic shock (CS) complicating myocardial infarction. METHODS: Circulating GLP-1 levels were serially assessed in 172 individuals during index PCI and day 2 in a prospectively planned biomarker substudy of the IABP-SHOCK II trial. All-cause mortality at short- (30 days), intermediate- (1 year), and long-term (6 years) follow-up was used for outcome assessment. RESULTS: Patients with fatal short-term outcome (n = 70) exhibited higher GLP-1 levels [86 (interquartile range 45-130) pM] at ICU admission in comparison to patients with 30-day survival [48 (interquartile range 33-78) pM; p < 0.001] (n = 102). Repeated measures ANOVA revealed a significant interaction of GLP-1 dynamics from baseline to day 2 between survivors and non-survivors (p = 0.04). GLP-1 levels above vs. below the median proved to be predictive for short- [hazard ratio (HR) 2.43; 95% confidence interval (CI) 1.50-3.94; p < 0.001], intermediate- [HR 2.46; 95% CI 1.62-3.76; p < 0.001] and long-term [HR 2.12; 95% CI 1.44-3.11; p < 0.001] outcome by multivariate Cox-regression analysis. CONCLUSION: Elevated plasma levels of GLP-1 are an independent predictor for impaired prognosis in patients with myocardial infarction complicated by CS. The functional relevance of GLP-1 in this context is currently unknown and needs further investigations. TRIAL REGISTRATION: www. CLINICALTRIALS: gov Identifier: NCT00491036.

Hypoglycemia and Cardiovascular Outcomes in the CARMELINA and CAROLINA Trials of Linagliptin: A Secondary Analysis of Randomized Clinical Trials.

Importance: Previous studies have reported an association between hypoglycemia and cardiovascular (CV) events in people with type 2 diabetes (T2D), but it is unclear if this association is causal or identifies a high-risk patient phenotype. Objective: To evaluate the associations between hypoglycemia and CV outcomes. Design, Setting, and Participants: This secondary analysis was a post hoc assessment of the multinational, double-blind CARMELINA (Cardiovascular and Renal Microvascular Outcome Study With Linagliptin; 2013-2016) and CAROLINA (Cardiovascular Outcome Trial of Linagliptin vs Glimepiride in Type 2 Diabetes; 2010-2018) randomized clinical trials of the antihyperglycemic drug, linagliptin, a dipeptidyl peptidase 4 inhibitor. Participants were adults with T2D at high CV risk with or without high kidney risk. By design, participants in the CARMELINA trial had longer duration of T2D and had a higher CV risk than participants in the CAROLINA trial. Data analyses were conducted between June 2021 and June 2023. Intervention: Linagliptin or placebo in the CARMELINA trial, and linagliptin or glimepiride in the CAROLINA trial. Main Outcomes and Measures: The primary outcome for both trials was CV death, myocardial infarction (MI), or stroke (3-point major adverse CV events [3P-MACE]). For the present analyses, hospitalization for heart failure (HF) was added. Hypoglycemia was defined as plasma glucose less than 54 mg/dL or severe hypoglycemia (episodes requiring the assistance of another person). Associations between the first hypoglycemic episode and subsequent CV events and between nonfatal CV events (MI, stroke, hospitalization for HF) and subsequent hypoglycemic episodes were assessed using multivariable Cox proportional hazards regression models. Sensitivity analyses explored the risk of CV events within 60 days after each hypoglycemic episode. Results: In the CARMELINA trial (6979 patients; 4390 males [62.9%]; mean [SD] age, 65.9 [9.1] years), there was an association between hypoglycemia and subsequent 3P-MACE plus hospitalization for HF (hazard ratio [HR], 1.23; 95% CI, 1.04-1.46) as well as between nonfatal CV events and subsequent hypoglycemia (HR, 1.39; 95% CI, 1.06-1.83). In the CAROLINA trial (6033 patients; 3619 males (60.0%); mean [SD] age, 64.0 [9.5] years), there was no association between hypoglycemia and subsequent 3P-MACE plus hospitalization for HF (HR, 1.00; 95% CI, 0.76-1.32) and between nonfatal CV events and subsequent hypoglycemia (HR, 1.44; 95% CI, 0.96-2.16). In analyses of CV events occurring within 60 days after hypoglycemia, there was either no association or too few events to analyze. Conclusions and Relevance: This study found bidirectional associations between hypoglycemia and CV outcomes in the CARMELINA trial but no associations in either direction in the CAROLINA trial, challenging the notion that hypoglycemia causes adverse CV events. The findings from the CARMELINA trial suggest that both hypoglycemia and CV events more likely identify patients at high risk for both. Trial Registration: ClinicalTrials.gov Identifier: NCT01897532 (CARMELINA) and NCT01243424 (CAROLINA).

Effect of oral melatonin treatment on insulin resistance and diurnal blood pressure variability in night shift workers. A double-blind, randomized, placebo-controlled study.

BACKGROUND: Night shift work is associated with sleep disturbances, obesity, and cardiometabolic diseases. Disruption of the circadian clock system has been suggested to be an independent cause of type 2 diabetes and cardiovascular disease in shift workers. We aimed to improve alignment of circadian timing with social and environmental factors with administration of melatonin. METHODS: In a randomized, placebo-controlled, prospective study, we analysed the effects of 2 mg of sustained-release melatonin versus placebo on glucose tolerance, insulin resistance indices, sleep quality, circadian profiles of plasma melatonin and cortisol, and diurnal blood pressure profiles in 24 rotating night shift workers during 12 weeks of treatment, followed by 12 weeks of wash-out. In a novel design, the time of melatonin administration (at night or in the morning) depended upon the shift schedule. We also compared the baseline profiles of the night shift (NS) workers with 12 healthy non-night shift (NNS)-working controls. RESULTS: We found significantly impaired indices of insulin resistance at baseline in NS versus NNS (p < 0.05), but no differences in oral glucose tolerance tests nor in the diurnal profiles of melatonin, cortisol, or blood pressure. Twelve weeks of melatonin treatment did not significantly improve insulin resistance, nor did it significantly affect diurnal blood pressure or melatonin and cortisol profiles. Melatonin administration, however, caused a significant improvement in sleep quality which was significantly impaired in NS versus NNS at baseline (p < 0.001). CONCLUSIONS: Rotating night shift work causes mild-to-moderate impairment of sleep quality and insulin resistance. Melatonin treatment at bedtime improves sleep quality, but does not significantly affect insulin resistance in rotating night shift workers after 12 weeks of administration.

[Management of cardiovascular diseases in patients with diabetes : ESC guidelines 2023]. / Management kardiovaskulärer Erkrankungen bei Patienten mit Diabetes : ESC-Leitlinie 2023.

Patients with diabetes mellitus have an increased risk for the development of cardiovascular diseases. The presence of both comorbidities has a major impact not only on the prognosis of the patients but is also decisive for the implementation of evidence-based treatment strategies for reduction of the cardiovascular risk. The new guidelines of the European Society of Cardiology (ESC) were published in 2023 and provide clear recommendations for the management of cardiovascular diseases in patients with diabetes. The most relevant aspects of these guidelines are summarized in the following overview article.

Chronic kidney disease is related to impaired left ventricular strain as assessed by cardiac magnetic resonance imaging in patients with ischemic cardiomyopathy.

INTRODUCTION: Chronic kidney disease (CKD) is an important cardiovascular risk factor. However, the relationship between CKD and myocardial strain as a parameter of myocardial function is still incompletely understood, particularly in patients with ischemic cardiomyopathy (ICM). Cardiac magnetic resonance imaging (CMR) feature tracking allows to analyze myocardial strain with high reproducibility. Therefore, the aim of the present study was to assess the relationship between CKD and myocardial strain as described by CMR in patients with ICM. METHODS: We retrospectively performed CMR-based myocardial strain analysis in 89 patients with ICM and different stages of CKD, classified according to the KDIGO stages. In all patients, global longitudinal strain (GLS), global circumferential strain (GCS) and global radial strain (GRS) analysis of left ventricular myocardium were performed. Furthermore, segmental longitudinal (SLS), circumferential (SCS) and radial strain (SRS) according to the AHA 16/17-segment model was determined. RESULTS: Creatinine levels (GLS: r = 0.46, p < 0.001; GCS: r = 0.34, p = 0.001; GRS: r = - 0.4, p < 0.001), urea levels (GLS: r = 0.34, p = 0.001; GCS: r = 0.30, p = 0.005; GRS: r = - 0.31, p = 0.003) as well as estimated glomerular filtration rate (GLS: r = -0.40, p < 0.001; GCS: r = - 0.27, p = 0.012; GRS r = 0.34, p < 0.001) were significantly associated with global strains as determined by CMR. To further investigate the relationship between CKD and myocardial dysfunction, segmental strain analysis was performed: SLS was progressively impaired with increasing severity of CKD (KDIGO-1: - 11.93 ± 0.34; KDIGO-5: - 7.99 ± 0.38; p < 0.001 for KDIGO-5 vs. KDIGO-1; similar data for SCS and SRS). Interestingly, myocardial strain was impaired with CKD in both segments with and without scarring. Furthermore, in a multivariable analysis, eGFR was independently associated with GLS following adjustment for LV-EF, scar burden, diabetes, hypertension, age, gender, LV mass or LV mass index. CONCLUSION: CKD is related to impaired LV strain as assessed by CMR in patients with ICM. In our cohort, this relationship is independent of LV-EF, the extent of myocardial scarring, diabetes, hypertension, age, gender, LV mass or LV mass index.

Data from network meta-analyses can inform clinical practice guidelines and decision-making in diabetes management: perspectives of the taskforce of the guideline workshop.

In recent years, several novel agents have become available to treat individuals with type 2 diabetes (T2D), such as sodium-glucose cotransporter-2 inhibitors (SGLT-2i), tirzepatide, which is a dual glucose-dependent insulinotropic polypeptide receptor agonist (GIP RA)/glucagon-like peptide-1 receptor agonist (GLP-1 RA), and finerenone, a non-steroidal mineralocorticoid receptor antagonist (MRA) that confers significant renal and cardiovascular benefits in individuals with (CKD). New medications have the potential to improve the lives of individuals with diabetes. However, clinicians are challenged to understand the benefits and potential risks associated with these new and emerging treatment options. In this article, we discuss how use of network meta-analyses (NMA) can fill this need.

Recurrent cardiovascular events in patients with type 2 diabetes and haemodialysis: analysis from the 4D Study.

Background: In the 'Die Deutsche Diabetes Dialyse Studie' (4D Study), treatment of patients with type 2 diabetes mellitus (T2DM) on haemodialysis (HD) with atorvastatin compared with placebo had no significant effect on the first composite primary major adverse cardiovascular event (MACE) endpoint of death from cardiac causes, fatal stroke, non-fatal myocardial infarction or non-fatal stroke. In this study we analysed first and recurrent events in 1255 patients from the 4D Study. Methods: We conducted an event history analysis to investigate the effects of previous clinical events on the risk of different endpoints in the total patient group and after stratification by randomization group. Results: During a median follow-up of 4 years, a total of 548 MACEs occurred, with 469 first and 79 recurrent events. The most frequent event was sudden cardiac death, followed by death due to infection/sepsis. Of the 548 total MACEs, 260 occurred in the atorvastatin group and 288 in the placebo group [hazard ratio 0.91 (95% confidence interval 0.76-1.07), P = .266]. Interestingly, analyses of the baseline hazard functions for first and recurrent events as a function of time after randomization demonstrated that the risks of the composite primary endpoint continually increased in the placebo group with increasing time in the study, whereas the risk in the atorvastatin group remained constant after ≈1.5 years. Conclusion: This recurrent and total event analysis from the 4D Study underscores the high risk of sudden cardiac death and death due to infection/sepsis in patients with T2DM receiving HD and raises the hypothesis that atorvastatin may stabilize cardiovascular risk only after 1-2 years in this high-risk population.