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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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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Proteomic signatures of type 2 diabetes predict the incidence of coronary heart disease

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

Published: March 14, 2025

Emerging evidence reveals a complex association between type 2 diabetes (T2D) and coronary heart disease (CHD), which share common risk factors biological pathways. This study aims to identify the shared proteomic signatures of T2D CHD, as well whether proteins predict incident CHD in patients, develop predictive models. Utilizing data from 53,014 UK Biobank participants 2923 plasma proteins, we identified 488 associated with T2D, 125 were also CHD. Among determine nine showing causal associations including PCSK9, NRP1, CD27. Mediation analyses suggest that mediate By integrating these into our model, achieved desirable prediction (AUC = 0.819) for future onset patients. Additionally, druggability evaluation show 32 potential therapeutic agents, established antihypertensives novel compounds, suggesting avenues dual-targeted treatment strategies. Collectively, findings unveil both providing implications screening predicting

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 and Thrombosis

American Journal of Hematology, Journal Year: 2025, Volume and Issue: unknown

Published: April 7, 2025

ABSTRACT Clonal hematopoiesis (CH) has been the focus of many research efforts in last years and emerged as a risk modifier for cardiovascular disease morbidity mortality. While substantial evidence accumulated regarding its impact on arterial system diseases, connection with venous thrombosis only recently explored. Both clinical preclinical suggest that magnitude mechanism underlying association CH events vary depending specific mutated gene involved, indicating causal link between development, not system, particularly context atherosclerosis, but also thrombosis. Although this growing body knowledge driven translational provided insights improving management, several questions remain unanswered. This review aims to summarize available thrombosis, while highlighting gaps need be addressed future research.

Language: Английский

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Clonal Hematopoiesis of Indeterminate Potential in Chronic Coronary Disease: A Report From the ISCHEMIA Trials Biorepository

Circulation Genomic and Precision Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

Language: Английский

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Impact of Frailty and Clonal Hematopoiesis on Cardiovascular Outcomes in Elderly Patients with Renal Artery Stenosis Undergoing Stenting

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 19, 2024

Background: Frailty and clonal hematopoiesis of indeterminate potential (CHIP) have emerged as crucial predictors adverse cardiovascular outcomes in older adults. However, their combined impact on major events (MACE) patients with severe atherosclerotic renal artery stenosis (ARAS) remains unclear. Methods: We conducted a prospective cohort study involving 175 aged 60 years ARAS (luminal ≥ 70%) who underwent stenting at Beijing Hospital between January 2019 December 2022. was assessed using the Fried phenotype, categorizing into robust, prefrail, frail subgroups. CHIP status determined through targeted gene sequencing peripheral blood, stratifying No (VAF < 2%), Small 2%-<10%), Large 10%) All were systematically followed up until June 30, 2024. The primary outcome incidence MACE, which composite function deterioration (RFD), initiation replacement therapy, revascularization, nonfatal myocardial infarction, hospitalization for heart failure, stroke, cardiorenovascular death. employed Cox proportional hazards models, Kaplan-Meier survival analysis, heatmaps to explore frailty MACE risk. Results: mean age 68.3 years. Of cohort, 64.6% had no CHIP, 26.8% 8.6% CHIP. Frail showed higher prevalence particularly (34.7%) (10.2%) categories. During median follow-up 32 months, 54 occurred. curve revealed that associated (35.7% vs. 29.5% prefrail 24.6% P = 0.045) RFD (16.3% 11.5% 7.7% 0.034). Patients experienced significantly rates (60.0% 36.2% 24.8% 0.004) (26.7% 14.9% 8.0% 0.019). Findings appeared be consistent those MACE. independent contribution overall greatest spread risk obtained models incorporated Conclusion: independently jointly, contribute elderly undergoing stenting. These findings highlight necessity integrated stratification management strategies this high-risk population.

Language: Английский

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Tet2-mediated clonal hematopoiesis modestly improves neurological deficits and is associated with inflammation resolution in the subacute phase of experimental stroke

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Dec. 17, 2024

Recent work has revealed that clonal hematopoiesis (CH) is associated with a higher risk of numerous age-related diseases, including ischemic stroke, however little known about whether it influences stroke outcome independent its widespread effects on cardiovascular disease. Studies suggest leukocytes carrying CH driver mutations have an enhanced inflammatory profile, which could conceivably exacerbate brain injury after stroke.

Language: Английский

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