Journal: Circulation
This publication reviews the relationship between clonal hematopoiesis (CH) and cardiovascular disease (CVD), emphasizing CH as a biologically plausible, clinically relevant CVD risk factor.
Key points:
- Definition and genetics
- • CH is a benign clonal expansion of hematopoietic stem cells driven by somatic variants in genes classically linked to hematologic malignancies.
- • It is common with aging but also influenced by germline predisposition and environmental/clinical exposures.
- Association with cardiovascular disease
- • CH is linked to multiple CVDs: atherosclerotic disease, heart failure, atrial fibrillation, and thrombosis.
- • Cardiovascular risk is heterogeneous and depends on:
- • The specific mutated gene and variant
- • Clone size (variant allele fraction)
- • Extrinsic factors such as comorbidities and exposures.
- Mechanistic insights
- • CH appears to promote CVD via:
- • Gene-specific pathways
- • Heightened systemic inflammation, including:
- • Aberrant cytokine production
- • Inflammasome activation
- • Other proinflammatory mechanisms
- • These inflammatory effects can accelerate atherosclerosis, foster thrombosis, and impair vascular and myocardial function.
- • CH appears to promote CVD via:
- Risk modifiers and epidemiology
- • Although age-related, CH risk and clone fitness are modulated by:
- • Germline variants
- • Obesity
- • Chronic inflammatory states
- • Environmental toxins (e.g., tobacco, certain cancer therapies).
- • Understanding these influences is important for both individual and population-level risk assessment.
- • Although age-related, CH risk and clone fitness are modulated by:
- Clinical implications and future directions
- • Incorporating CH into CVD risk prediction models may enable more personalized prevention and treatment strategies.
- • At present, there are no CH-specific therapies proven to prevent or treat CVD.
- • Multiple molecularly targeted strategies based on CH biology are under active investigation.