Clonal Hematopoiesis and Acute Ischemic Stroke Outcomes

Area of Science:

• Hematology
• Neurology
• Genetics

Background:

• Clonal hematopoiesis of indeterminate potential (CHIP) involves somatic mutations in hematopoietic stem cells, increasing with age.
• The impact of CHIP on acute ischemic stroke (AIS) manifestation and clinical outcomes remains incompletely understood.

Purpose of the Study:

• To investigate the association between CHIP and the incidence and clinical outcomes of AIS.
• To identify specific genetic mutations within CHIP that may serve as prognostic indicators for AIS.

Main Methods:

• Prospective registry and DNA repository data from 380 AIS patients and 446 age-matched controls were analyzed.
• Targeted next-generation sequencing was performed on 25 genes commonly mutated in hematologic neoplasms.
• Multivariate regression models assessed the relationship between CHIP and stroke severity, hemorrhagic transformation, and 90-day functional outcomes.

Main Results:

• CHIP prevalence was significantly higher in AIS patients (29.0%) compared to controls (22.0%, p=0.024).
• CHIP was associated with increased stroke severity (NIHSS score, β=1.67, p=0.022) and higher rates of hemorrhagic transformation (aOR=5.63, p<0.001).
• CHIP independently predicted worse functional outcomes at 90 days (aOR=2.15, p=0.011) and was strongly linked to PPM1D mutations (aOR=7.85, p=0.006).

Conclusions:

• CHIP is significantly associated with an increased risk of AIS.
• Specific CHIP-related gene mutations, particularly in PPM1D, TET2, and DNMT3A, represent novel prognostic factors for AIS.
• These findings highlight CHIP as a potential risk factor and therapeutic target in AIS management.