Clonal Hematopoiesis Associates with Prevalent and Incident Cardiometabolic Disease in High-Risk Individuals

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Abstract Background Clonal hematopoiesis of indeterminate potential (CHIP) is the age-related presence expanded somatic clones secondary to leukemogenic driver mutations and associated with cardiovascular (CV) disease mortality. We sought evaluate relationships between CHIP cardiometabolic diseases incident outcomes in high-risk individuals. Methods genotyping was performed 8469 individuals referred for cardiac catheterization at Duke University (CATHGEN study) identify variants present a variant allele fraction (VAF) ≥2%. Associations were tested among any variant, large (VAF ≥10%) individual genes prevalent traits. Cox proportional hazard models associations time-to-overall mortality Fine-Gray analyses outcomes. Results identified 463 427 (5.0%) which 268 (3.2%) harbored clones. lower odds obesity (OR 0.79 [95% CI 0.65-0.98], p=0.03; OR 0.76 0.57-0.99], p=0.04, respectively). HF 1.25 1.01 - 1.55], p=0.04; especially non- DNMT3A 1.38 1.04-1.82], p=0.02). also events: Non- increased risk time-to-HF hospitalization (HR 1.29 1.02-1.63], p=0.03). Conclusions In catheterization, DNTM3A obesity, HF, CV events. These findings strengthen importance as biomarker highlight contributing variants. Condensed CHIP, myeloid hematopoietic cells, an emerging CVD biomarker. Using whole exome sequencing peripheral blood derived DNA from participants CATHGEN cohort, we significant mortality, AF after adjusting established clinical factors. add strength growing literature biomarker, emphasizing driving risk. Future studies should aim further elucidate gene-specific inflammatory metabolic mechanisms possibly mediating these relationships. Clinical Perspective What Is New? cohort high prevalence CAD, inversely higher subsequent even adjustment relevant comorbidities. Risk events driven by (VAF≥10%) other than . are Implications? Though more research needed, evidence around specific continues grow, clinicians be prepared provide gene- counseling

Language: Английский

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Association of Hematopoietic Loss of Y Chromosome With Atrial Fibrillation Incidence and Sex Disparity

JACC Basic to Translational Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Clonal haematopoiesis of indeterminate potential and risk of atrial fibrillation

Acta Cardiologica, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 2

Published: Feb. 25, 2025

Language: Английский

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Clonal hematopoiesis, cardiovascular disease and cancer treatment-induced cardiotoxicity

Seminars in Cancer Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Interleukin-6: Molecular Mechanisms and Therapeutic Perspectives in Atrial Fibrillation

Current Medical Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Language: Английский

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Clonal hematopoiesis of indeterminate potential and the risk of autoimmune diseases

Journal of Internal Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Clonal hematopoiesis of indeterminate potential (CHIP), characterized by the age-related expansion blood cells carrying preleukemic mutations, is associated with immune aging. This study aimed to investigate association between CHIP and established autoimmune diseases. We analyzed baseline data from 456,692 UK Biobank participants available whole-exome sequences. The primary outcome was 19 disorders. Associations among any (variant allele fraction ≥2%), large clones ≥10%), gene-specific subtypes incidence diseases were assessed using Cox regression. Mediation analysis performed explore role inflammation in link identified 17,433 11,970 at baseline. Participants 44% 43% higher risk for Crohn's disease, 25% 33% psoriasis, 13% 14% rheumatoid arthritis, 35% 55% vasculitis, respectively. status increased levels inflammatory markers, including white cell, platelets, neutrophils, neutrophil-to-lymphocyte ratio, overall mediation ratios 16.3% 7.1% 23.2% 7.2% vasculitis. an incident multiple diseases, potentially mediated elevated levels. Future research needed clarify mechanisms underlying these associations interventions reduce risk.

Language: Английский

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Clonal Hematopoiesis of Indeterminate Potential and Atrial Fibrillation: Insights into Pathophysiology and Clinical Implications

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2739 - 2739

Published: March 18, 2025

Clonal hematopoiesis of indeterminate potential (CHIP) has emerged as a novel risk factor for cardiovascular diseases. CHIP is characterized by the expansion hematopoietic stem cell clones harboring somatic mutations in genes such TET2, DNMT3A, and ASXL1, which are implicated inflammation, atrial remodeling, hypercoagulability. These foster pro-inflammatory pro-thrombotic environment conducive to arrhythmogenesis, thereby linking development progression fibrillation (AF). Mechanistic insights indicate that contributes fibrosis, disrupts calcium signaling, exacerbates oxidative stress, all heighten susceptibility AF. Clinical studies, including epidemiological Mendelian randomization analyses, further support association between an increased both incident progressive AF, with specific TET2 ASXL1 identified significant contributors. Additionally, been linked adverse outcomes elevated rates heart failure, thromboembolism, mortality. Understanding CHIP’s role AF pathophysiology offers opportunities precision medicine approaches, providing avenues early intervention targeted treatment. This review synthesizes current mechanistic clinical evidence on emphasizes its biomarker stratification, explores emerging therapeutic strategies targeting CHIP-associated pathways.

Language: Английский

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Clonal haematopoiesis in cardiovascular disease: prognostic role and novel therapeutic target

Nature Reviews Cardiology, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Language: Английский

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Clonal hematopoiesis of indeterminate potential (CHIP) in cerebromicrovascular aging: implications for vascular contributions to cognitive impairment and dementia (VCID)

GeroScience, Journal Year: 2025, Volume and Issue: unknown

Published: April 11, 2025

Language: Английский

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Implications of Clonal Hematopoiesis in Hematological and Non-Hematological Disorders

Cancers, Journal Year: 2024, Volume and Issue: 16(23), P. 4118 - 4118

Published: Dec. 9, 2024

Clonal hematopoiesis (CH) is associated with an increased risk of developing myeloid neoplasms (MNs) such as myelodysplastic neoplasm (MDS) and acute leukemia (AML). In general, CH comprises clonal indeterminate potential (CHIP) cytopenia undetermined significance (CCUS). It age-related phenomenon characterized by the presence somatic mutations in hematopoietic stem cells (HSCs) progenitor (HSPCs) that acquire a fitness advantage under selection pressure. Individuals CHIP have absolute 0.5-1.0% per year for progressing to MDS or AML. Inflammation, smoking, cytotoxic therapy, radiation can promote process expansion leukemic transformation. Of note, exposure chemotherapy patients solid tumors lymphomas increase therapy-related MN. Beyond hematological malignancies, also serves independent factor heart disease, stroke, chronic obstructive pulmonary kidney disease. Prognostic models score MN-prediction provide framework stratification clinical management CHIP/CCUS identify high-risk individuals who may benefit from close surveillance. For related disorders, therapeutic strategies targeting specific CH-associated pressure role future.

Language: Английский

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