Patients with CKD on hemodialysis exhibit increased cardiovascular risk. Fibrin clot structure and clot lysis are crucially involved in development of cardiovascular events, but little is known about the influence of clot density on outcome in patients on hemodialysis. We determined fibrin clot structure parameters and effect on mortality in a prospective cohort of 171 patients on chronic hemodialysis (mean±SD age =59±11 years old; 54% men) using a validated turbidimetric assay. Kaplan–Meier analysis revealed that patients on hemodialysis with a denser clot structure had increased all–cause and cardiovascular mortality risks (log rank P=0.004 and P=0.003, respectively). Multivariate Cox regression models (adjusted for age, diabetes, sex, and duration of dialysis or fibrinogen, C-reactive protein, and complement C3) confirmed that denser clots are independently related to mortality risk. We also purified fibrinogen from healthy controls and patients on hemodialysis using the calcium–dependent IF-1 mAb against fibrinogen for additional investigation using mass spectrometric analysis and electron microscopy. Whereas purified fibrinogen from healthy controls displayed no post-translational modifications, fibrinogen from patients on hemodialysis was glycosylated and guanidinylated. Clots made of purified fibrinogen from patients on hemodialysis exhibited significantly thinner fibers compared with clots from fibrinogen of control individuals (mean±SD =63±2 and 77±2 nm, respectively; P<0.001). In vitro guanidinylation of fibrinogen from healthy subjects increased the formation of thinner fibers, suggesting that difference in fiber thickness might be at least partially due to post-translational modifications. Thus, in patients on hemodialysis, a denser clot structure may be a potent independent risk factor for mortality.

Background: The clinical and prognostic implications of platelet reactivity (PR) testing in a P2Y₁₂-inhibitor naïve population are poorly understood. Objectives: This explorative study aims to assess the role of PR and explore factors that may modify elevated mortality risk in patients with altered PR. Methods: Platelet ADP-induced CD62P and CD63 expression were measured by flow-cytometry in 1520 patients who were referred for coronary angiography in the Ludwigshafen Risk and Cardiovascular Health Study (LURIC). Results: High- and Low-platelet reactivity to ADP were strong predictors of cardiovascular and all-cause mortality and risk equivalent to the presence of coronary artery disease. (High platelet reactivity 1.4 [95% CI 1.1–1.9]; Low platelet reactivity: 1.4 [95% CI 1.0–2.0]). Relative weight analysis indicated glucose control (HbA1c), renal function ([eGFR]), inflammation (high-sensitive C-reactive protein [hsCRP]) and antiplatelet therapy by Aspirin as consistent mortality risk modifiers in patients with Low- and High-platelet reactivity. Pre-specified stratification of patients by risk modifiers HbA1c (60 mL/min/1.73 m²) and CRP (<3 mg/L) was associated with a lower mortality risk, however irrespective of platelet reactivity. Aspirin treatment was associated with reduced mortality in patients with high platelet reactivity only (p for interaction: 0.02 for CV-death [<0.01 for all-cause mortality]. Conclusions: Cardiovascular mortality risk in patients with High- and Low platelet reactivity is equivalent to the presence of coronary artery disease. Targeted glucose control, improved kidney function and lower inflammation are associated with reduced mortality risk, however independent of platelet reactivity. In contrast, only in patients with High-platelet reactivity was Aspirin treatment associated with lower mortality.

Patients with diabetes mellitus (DM) have a significantly increased risk of developing cardiovascular diseases with their sequelae of acute myocardial infarction, stroke and cardiovascular death. For example, even today a 60-year-old diabetic man has 6 years less life expectancy compared to a non-diabetic man of the same age, and a 60-year-old with diabetes and a previous history of a heart attack has 12 years less [1]. These data highlight the need for targeted risk stratification of patients with diabetes and the consistent treatment of diabetes, associated risk factors and cardiovascular disease. Patients with diabetes mellitus should be categorized according to their cardiovascular risk into those with very high cardiovascular risk, high cardiovascular risk and moderate cardiovascular risk [2]. DM and existing cardiovascular disease, or end organ damage, or ≥ 3 risk factors or diabetes duration >20 years DM with a diabetes duration >10 years without end organ damage, but with an additional risk factor Young patients (type 1 diabetes <35 years; type 2 diabetes <50 years) with a diabetes duration <10 years without other risk factors In addition to diagnostics for the above-mentioned risk stratification, patients with diabetes and hypertension or clinical suspicion of cardiovascular disease should receive a resting ECG. At present, no convincing data exist to use additional imaging techniques such as echocardiography, stress echocardiography, scintigraphy or MRI in asymptomatic patients with diabetes mellitus. As part of clinical routines, no determination of circulating biomarkers should be carried out as part of risk stratification.

Diabetes mellitus (DM) stellt eine wichtige Komorbidität bei Patienten mit Herzinsuffizienz dar, die maßgeblich die Prognose der Patienten determiniert. Von entscheidender Bedeutung zur Verbesserung der Prognose dieser Hochrisiko-Patienten ist daher eine frühzeitige Diagnostik und differenzierte medikamentöse Therapie mit Ausschöpfung aller möglichen Therapieoptionen und Absetzen potenziell schädlicher Substanzen. Das gemeinsame Positionspapier der Deutschen Gesellschaft für Kardiologie (DGK) und der Deutschen Diabetes Gesellschaft (DDG) fasst die vorhandene wissenschaftliche Evidenz zusammen und gibt Empfehlungen, was bei der Diagnose und Therapie der Herzinsuffizienz und des DM zu beachten ist, um die Prognose zu verbessern. Diabetes is a very important and preventable risk factor for the development of heart failure and a frequent comorbidity observed in patients with heart failure with increased cardiovascular morbidity and mortality. Therefore, it is of clinical importance to treat both diseases as early as possible with an optimal therapy. This joint position paper of the DGK and DDG outlines the scientific evidence and provides recommendations about diagnosis and therapy of heart failure and diabetes to improve outcome. Received: 10 May 2022 Accepted: 17 May 2022 Article published online: 18 July 2022 © 2022. Deutsche Gesellschaft für Kardiologie – Herz- und Kreislaufforschung e.V. und Deutsche Diabetes Gesellschaft e.V. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Patients with diabetes mellitus (DM) have a significantly increased risk of developing cardiovascular diseases with their sequelae of acute myocardial infarction, stroke and cardiovascular death. For example, even today a 60-year-old male patient with diabetes has 6 years less life expectancy compared to a metabolically healthy male of the same age, and a 60-year-old patient with diabetes and a previous history of a heart attack has 12 years less [1]. These data highlight the need for targeted risk stratification of patients with diabetes and the consistent treatment of diabetes, associated risk factors and cardiovascular disease. Patients with diabetes mellitus should be categorized according to their cardiovascular risk into those with very high cardiovascular risk, high cardiovascular risk and moderate cardiovascular risk [2]. DM and existing cardiovascular disease, or end organ damage, or≥3 risk factors or diabetes duration>20 years. DM with a diabetes duration>10 years without end organ damage, but with an additional risk factor. Young patients (type 1 diabetes<35 years; type 2 diabetes<50 years) with a diabetes duration<10 years without other risk factors. In addition to diagnostics for the above-mentioned risk stratification, patients with diabetes and hypertension or clinical suspicion of cardiovascular disease should receive a resting ECG. At present, no convincing data exist to use additional imaging techniques such as echocardiography, stress echocardiography, scintigraphy or MRI in asymptomatic patients with diabetes mellitus. As part of clinical routines, no determination of circulating biomarkers should be carried out as part of risk stratification. Publication Date: 31 March 2022 (online) © 2022. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany