Prevalence and risk of aortic aneurysms in JAK2-positive myeloproliferative neoplasms: A multi-study review

Abstract Background: Myeloproliferative neoplasms (MPNs) harboring JAK2 mutations, particularly V617F, have been increasingly linked with vascular complications, including aortic aneurysms (AAs). This systematic analysis investigates the prevalence and anatomical distribution of thoracic and abdominal AAs in JAK2-positive patients with MPNs, comparing them to JAK2-negative individuals. Methods: We analyzed seven observational studies (retrospective, prospective, cross-sectional, and case-control), encompassing 446,839 total participants screened for aortic aneurysm, of whom at least 745 were JAK2-positive. The studies provided subgroup data on thoracic and abdominal aneurysm incidence by JAK2 mutation status. Hazard ratios (HRs) for thoracic aneurysm were extracted when available. Results: Across the included studies, a clear trend emerged indicating a higher frequency of thoracic aortic aneurysms among JAK2-positive individuals compared to JAK2-negative controls. In total, 176 thoracic aneurysms were reported among JAK2-positive patients, while at least 1,935 thoracic aneurysms were recorded in JAK2-negative individuals. Abdominal aneurysm data were more limited, with at least 3 cases reported in JAK2-positive patients and 2,432 cases in JAK2-negative patients. The largest retrospective cohort (n = 417,759) demonstrated a significantly elevated risk of thoracic aneurysm in JAK2-positive MPN patients, with a hazard ratio of 12.8 (95% CI: 4.8–34; P = 3.6 × 10⁻⁷). Similarly, a large cross-sectional study (n = 8,056) revealed that JAK2 variant allele frequency (VAF) greater than 1% was associated with a hazard ratio of 2.7 (95% CI: 1.5–5.1), while a lower VAF (<1%) was associated with a weaker but still notable risk (HR = 1.4; 95% CI: 1.01–2.0). Smaller studies consistently confirmed thoracic involvement, but none provided strong evidence of an association with abdominal aneurysms. Conclusion: JAK2-mutated MPNs are associated with a markedly increased risk of thoracic aortic aneurysms, supported by evidence from both large population cohorts and smaller observational studies. The risk for abdominal aortic aneurysms remains unclear due to limited data. These findings highlight the need for vigilant cardiovascular screening, particularly in patients with high JAK2 VAF, and underscore the importance of further prospective studies to validate the association and assess the progression of aneurysms in this high-risk population. Keywords: JAK2, myeloproliferative neoplasms, aortic aneurysm, thoracic aneurysm, abdominal aneurysm.