Clonal haematopoiesis of indeterminate potential and atrial fibrillation: an east Asian cohort study

European Heart Journal, Journal Year: 2024, Volume and Issue: 45(10), P. 778 - 790

Published: Jan. 17, 2024

Abstract Background and Aims Both clonal haematopoiesis of indeterminate potential (CHIP) atrial fibrillation (AF) are age-related conditions. This study investigated the role CHIP in development progression AF. Methods Deep-targeted sequencing 24 mutations (a mean depth coverage = 1000×) was performed 1004 patients with AF 3341 non-AF healthy subjects. Variant allele fraction ≥ 2.0% indicated presence mutations. The association between evaluated by comparison (i) prevalence subjects (ii) clinical characteristics discriminated within patients. Furthermore, risk outcomes—the composite heart failure, ischaemic stroke, or death—according to from UK Biobank cohort. Results age 67.6 ± 6.9 vs. 58.5 6.5 years (paroxysmal, 39.0%; persistent, 61.0%) cohorts, respectively. a variant ≥2.0% were found 237 (23.6%) (DNMT3A, 13.5%; TET2, 6.6%; ASXL1, 1.5%) more prevalent than [356 (10.7%); P < .001] across age. After multivariable adjustment (age, sex, smoking, body mass index, diabetes, hypertension), 1.4-fold higher [adjusted odds ratio (OR) 1.38; 95% confidence interval 1.10–1.74, .01]. ORs highest long-standing persistent (adjusted OR 1.50; 1.14–1.99, .004) followed 1.44) paroxysmal 1.33) In gene-specific analyses, TET2 somatic mutation presented 1.65; 1.05–2.60, .030). older had longer duration, E/E′, severely enlarged left atrium those without (all .05). analysis 21 286 (1297 19 989 CHIP), is associated 1.32-fold event (heart death). Conclusions mutations, primarily DNMT3A whilst their progressive nature unfavourable outcomes.

Language: Английский

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Chronic kidney disease promotes atrial fibrillation via inflammasome pathway activation

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(19)

Published: Aug. 15, 2023

Chronic kidney disease (CKD) is associated with a higher risk of atrial fibrillation (AF). The mechanistic link between CKD and AF remains elusive. Interleukin (IL)-1β, main effector 'NLR-family pyrin domain-containing 3' (NLRP3) inflammasome activation, key modulator conditions inflammation, such as CKD. Circulating IL-1β levels were elevated in CKD-patients vs sinus rhythm. Moreover, NLRP3-activity was enhanced atria CKD-patients. To elucidate the role NLRP3/IL-1β signaling pathogenesis CKD-induced AF, wildtype (WT) Nlrp3-/- mice subjected to two-stage subtotal nephrectomy protocol induce 4-weeks post-surgery, serum tissue increased WT-CKD (vs WT-sham) mice. susceptibility pacing-induced longer AF-duration electrical remodeling, enlarged atria, fibrosis. Genetic inhibition NLRP3 or neutralizing anti-IL-1β antibodies effectively reduced IL-1β-levels, normalized left dimensions, fibrosis AF-incidence. These data suggest that creates substrate for development by activating which structural remodeling. Neutralizing may be beneficial prevention AF.

Language: Английский

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Clonal hematopoiesis of indeterminate potential and type 2 diabetes mellitus among patients with STEMI: from a prospective cohort study combing bidirectional Mendelian randomization

Cardiovascular Diabetology, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 22, 2025

Both clonal hematopoiesis of indeterminate potential (CHIP) and type 2 diabetes mellitus (T2DM) are conditions closely associated with advancing age. This study delves into the possible implications prognostic significance CHIP T2DM in patients diagnosed ST-segment elevation myocardial infarction (STEMI). Deep-targeted sequencing employing a unique molecular identifier (UMI) for analysis 42 mutations—achieving an impressive mean depth coverage at 1000 × —was conducted on cohort 1430 acute (473 930 non-DM subjects). Variant allele fraction ≥ 2.0% indicated presence mutations. The association between was evaluated by comparison (i) prevalence mutations among individuals versus those without, (ii) clinical characteristics delineated within diabetic (iii) correlation mortality rates subjects. Furthermore, two-sample bidirectional Mendelian randomization performed using genetic instruments from genome-wide TET2 mutation CH UK Biobank (UKB) (2041 cases,173,918 controls) to investigate causal relationship FinnGen consortium (65,085 cases 335,112 controls), vice versa. Most commonly exhibiting variant were identified 50/473 (10.6%) T2DM, demonstrating greater compared subjects [69/930 (7.4%); P < 0.05] across various age groups. After multivariable adjustment, any 2.03-fold higher DM [adjusted hazard ratio (HR) 2.03; 95% confidence interval (CI) 1.07–3.84, 0.05]. In gene-specific analyses, somatic presented highest (adjusted HR 5.24; CI 2.02–13.61, = 0.001). ASXL1 which displayed striking cardiac death (HR: 3.14; 1.24–7.93; 0.05) consistent associations observed subgroup 4.51; 1.30–15.6; 0.05). (iv) PCSK9 Tet2-CHIP both (correlation 0.1215, 0.011) overall enrolled 0.0578, 0.0382). (v) Bidirectional studies that development increases propensity CHIP. However, does not subsequently accelerate onset T2DM. mutations, particularly TET2, more prevalent without diabetes. these is adverse outcomes, notably increased rates. Moreover, analyses provide supporting evidence TET2-related Central Illustration: (T2DM): as demonstrated prospective Asian (AMI). predictive value marker poor prognosis has been assessed this study. suggest may increase CHIP, findings consortium. mellitus; haematopoiesis potential.

Language: Английский

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Inflammaging: mechanisms and role in the cardiac and vasculature

Trends in Endocrinology and Metabolism, Journal Year: 2023, Volume and Issue: 34(6), P. 373 - 387

Published: April 17, 2023

Language: Английский

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Association between red blood cell distribution width‐to‐albumin ratio and prognosis in non‐ischaemic heart failure

ESC Heart Failure, Journal Year: 2024, Volume and Issue: 11(2), P. 1110 - 1120

Published: Jan. 24, 2024

Abstract Aims Red blood cell distribution width‐to‐albumin ratio (RAR), an innovate biomarker of inflammation, can independently predict adverse cardiovascular outcomes. However, the association between RAR and prognosis in patients with non‐ischaemic heart failure (NIHF) remains unclear. Methods results A total 2077 NIHF admitted to Heart Failure Care Unit, Fuwai Hospital, were consecutively enrolled from December 2006 October 2017 this retrospective study. The primary endpoint was a composite outcome all‐cause mortality transplantation. correlation assessed by Kaplan–Meier survival analysis Cox regression analysis. Incremental predictive values clinical performance for or transplantation also based on 12‐variable traditional risk model. median follow‐up time study 1433 (1341, 1525) days. As gender no longer satisfied proportional assumption after 1150 days, we set 1095 days as 500 reached outcome. Multivariable showed that per log 2 increase significantly associated 132.9% [hazard 2.329, 95% confidence interval (CI) 1.677–3.237, P < 0.001] increased Better model discrimination [concordance index: 0.766 (95% CI 0.754–0.778) vs. 0.758 0.746–0.770), 0.001], calibration (Akaike information criterion: 1487.3 1495.74; Bayesian 1566.25 1569.43; Brier score: 1569.43 likelihood test 0.001), reclassification (integrated improvement: 1.35%, 0.63–2.07%, 0.001; net 13.73%, 2.05–27.18%, = 0.034) improved adding ( 0.001 all). higher overall benefit obtained threshold probability 20–55%. Conclusions High level independent factor poor NIHF.

Language: Английский

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Advances in the study of S100A9 in cardiovascular diseases

Cell Proliferation, Journal Year: 2024, Volume and Issue: 57(8)

Published: March 19, 2024

Abstract Cardiovascular disease (CVD) is a group of diseases that primarily affect the heart or blood vessels, with high disability and mortality rates, posing serious threat to human health. The causative factors, pathogenesis, characteristics common CVD differ, but they all involve pathological processes such as inflammation, oxidative stress, fibrosis. S100A9 belongs S100 family calcium‐binding proteins, which are mainly secreted by myeloid cells bind Toll‐like receptor 4 for advanced glycation end products involved in regulating inflammatory response, fibrosis, vascular calcification, endothelial barrier function CVD. latest research has found key biomarker diagnosing predicting various Therefore, this article reviews progress on diagnostic predictive, therapeutic value inflammatory‐related atherosclerosis, myocardial infarction, arterial aneurysm summarizes its molecular mechanisms progression CVD, aiming explore new predictive methods identify potential intervention targets clinical practice.

Language: Английский

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An inflammation resolution–promoting intervention prevents atrial fibrillation caused by left ventricular dysfunction

Cardiovascular Research, Journal Year: 2023, Volume and Issue: 120(4), P. 345 - 359

Published: Dec. 13, 2023

Abstract Aims Recent studies suggest that bioactive mediators called resolvins promote an active resolution of inflammation. Inflammatory signalling is involved in the development substrate for atrial fibrillation (AF). The aim this study to evaluate effects resolvin-D1 on arrhythmogenic remodelling resulting from left ventricular (LV) dysfunction induced by myocardial infarction (MI) rats. Methods and results MI was produced anterior descending coronary artery ligation. Intervention groups received daily intraperitoneal resolvin-D1, beginning before surgery (early-RvD1) or Day 7 post-MI (late-RvD1) continued until 21 post-MI. AF vulnerability evaluated performing electrophysiological study. Atrial conduction analysed using optical mapping. Fibrosis quantified Masson’s trichrome staining gene expression quantitative polymerase chain reaction RNA sequencing. Investigators were blinded group identity. Early-RvD1 significantly reduced size (17 ± 6%, vs. 39 6% vehicle-MI) preserved LV ejection fraction; these unaffected late-RvD1. Transoesophageal pacing tachyarrhythmia 2/18 (11%) sham-operated rats, 18/18 (100%) MI-only 5/18 (28%, P &lt; 0.001 MI) early-RvD1 7/12 (58%, 0.01) late-RvD1 velocity decreased post-MI, effect suppressed RvD1 treatment. Both limited MI-induced fibrosis prevented increases inflammation-related fibrosis-related biomarkers pathways. Conclusions MI-related remodelling. had sparing suppressant effects, whereas attenuated promotion without protection, revealing atrial-protective actions unrelated function changes. These point inflammation resolution–promoting compounds as novel cardio-protective interventions with a particular interest attenuating development.

Language: Английский

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Risk of death, thrombotic and hemorrhagic events in anticoagulated patients with atrial fibrillation and systemic autoimmune diseases: an analysis from a global federated dataset

Clinical Research in Cardiology, Journal Year: 2024, Volume and Issue: 113(6), P. 942 - 950

Published: March 6, 2024

Abstract Background Growing evidence showing that systemic autoimmune diseases (SADs) are associated with a high risk of atrial fibrillation (AF). However, the impact SAD on clinical course AF patients is largely unknown. Methods Retrospective cohort study within federated healthcare network (TriNetX). Using ICD codes, anticoagulant therapy were categorized according to presence (M32: Systemic Lupus Erythematosus (SLE); M33: Dermato-polymyositis (DMP); M34: Sclerosis (SSc); M35: Sjogren syndrome). The primary outcomes 5-year risks (1) all-cause death, (2) thrombotic events (ischemic stroke, acute myocardial infarction, deep vein thrombosis, and pulmonary embolism), (3) bleeding (intracranial (ICH) gastrointestinal (GI)). Secondary each component outcomes. Cox regression analysis after propensity score matching (PSM) was used estimate hazard ratio (HR) 95% confidence interval (95%CI). Results We identified 16,098 (68.2 ± 13.4 years; 71.0% female) 828,772 controls (70.7 12.9 years, 41.1% females). After PSM, higher death (HR 1.13, 95%CI 1.09–1.71), 1.37, 1.32–1.43), hemorrhagic 1.41, 1.33–1.50) compared without SAD. highest GI SSc, while ICH SLE. Conclusion thrombotic, events. These merit careful follow-up integrated care management improve their prognosis. Graphical

Language: Английский

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Antidiabetic agents and risk of atrial fibrillation/flutter: A comparative critical analysis with a focus on differences between SGLT2 inhibitors and GLP-1 receptor agonists

Diabetes & Metabolism, Journal Year: 2022, Volume and Issue: 48(6), P. 101390 - 101390

Published: Sept. 25, 2022

Language: Английский

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Inhibition of the pyroptosis-associated inflammasome pathway: The important potential mechanism of ginsenosides in ameliorating diabetes and its complications

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 253, P. 115336 - 115336

Published: April 5, 2023

Language: Английский

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