Myeloproliferative Neoplasms Are Associated with Increased Risk of Major Adverse Limb Events Among Patients Hospitalized for Peripheral Arterial Disease
Authors: Leiva Orly , Brunner Andrew M. , How Joan , Hobbs Gabriela S. , Berger Jeffrey S 
Published: December 2023

Background: Myeloproliferative neoplasms (MPN), including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), are at high risk of cardiovascular (CV) disease, including atherosclerosis and peripheral arterial disease (PAD). Major adverse limb events (MALE), including major amputation, are dreaded complications of PAD that portend poor prognosis. Among patients with MPN, arterial thrombotic events are common and prior studies suggest that PAD is a risk factor for arterial thrombosis in this patient population. However, there are limited data on outcomes of patients with MPN and PAD. Therefore, the effect of MPN status on MALE, in-hospital death and unplanned readmissions among patients hospitalized for PAD.

Methods: This was a retrospective cohort analysis of the National Readmission Database (NRD) of adult patients with a primary diagnosis of PAD from 2017 and 2018 with or without a history of MPN, as identified by ICD-10 codes. Primary outcome was MALE which was a composite of index hospitalization death, major amputation, 30-day readmission for PAD, lower extremity ulceration, gangrene, rest pain, major amputation or arterial thromboembolism. Secondary outcomes were bleeding complications at index hospitalization (including gastrointestinal, intracranial, post-procedure, and retroperitoneal bleeding), 90-day readmissions for any-cause, PAD, CV reason (including PAD, myocardial infarction, stroke, or heart failure), and bleeding. Propensity scores (PS) for estimating probability of MPN were calculated using non-parsimonious multivariable logistic regression that included all baseline patient characteristics examined. PS matching (PSM) 1 MPN case to 5 non-MPN controls was performed. Patients between groups were compared and standardized mean difference (SMD) was calculated for variables before and after PSM. Imbalances between groups were insignificant if SMD for a given co-variable was &lt; 0.10. Odds ratio (OR) for MALE and in-hospital outcomes were calculated using logistic regression. For 90-day readmission analyses, patients who died during index hospitalization were excluded and hazard ratios (HR) were estimated using Cox proportional hazards regression. Risk factors for MALE among patients with MPN were assessed using backward stepwise logistic regression.

Results: After PSM, 1702 patients with MPN (1338 ET, 273 PV, 91 PMF) were matched with 8510 non-MPN patients. After PSM, variables were well-balanced between patients with and without MPN, Table. MPN was associated with increased risk of MALE (40.3% vs 27.9%, OR 1.75, 95% CI 1.57 - 1.95) and major amputation at index hospitalization (34.6% vs 23.5%, OR 1.72, 95% CI 1.54 - 1.92) but not in-hospital death (1.8% vs 2.0%, OR 0.92, 95% CI 0.63 - 1.36) or bleeding (17.5% vs 19.5%, OR 0.90, 95% CI 0.79 - 1.03). MPN was associated with increased risk of 90-day readmission for any-cause (HR 1.21, 95% CI 1.10 - 1.33), PAD (HR 1.22, 95% CI 1.11 - 1.35), and CV reason (HR 1.32, 95% CI 1.17 - 1.49) but not for bleeding (HR 1.33, 95% CI 0.90 - 1.97), Figure. Among patients with MPN, ET (OR 2.08, 95% CI 1.44 - 3.01), end-stage renal disease (OR 1.59, 95% CI 1.12 - 3.11), anemia (OR 1.75, 95% CI 1.39 - 2.21), gangrene (HR 1.95, 95% CI 1.38 - 2.75), and sepsis (OR 1.90, 95% CI 1.36 - 2.66) were associated with increased risk of MALE while compared surgical bypass (OR 0.46, 95% CI 0.31 - 0.68) and endovascular revascularization (OR 0.71, 95% CI 0.54 - 0.94) during index hospitalization were associated with decreased risk of MALE.

Conclusions: Among patients hospitalized for PAD, MPN was associated with increased risk of MALE and 90-day readmission for any-cause, PAD, and CV reasons. Among patients with MPN, ET was associated with increased risk of MALE while revascularization during index hospitalization was associated with decreased risk. Further studies are needed to further elucidate risk of MALE and adverse CV events among patients with MPN in order to improve clinical outcomes in this high-risk patient population.