Risk of Pulmonary Hypertension in High-Risk Polycythemia Vera: A Retrospective Cohort Study

Introduction/Background/Significance: Polycythemia vera (PV) is a chronic myeloproliferative neoplasm associated with thrombotic complications and progressive end-organ dysfunction. Pulmonary hypertension (PH), though increasingly recognized in PV, remains poorly studied especially in high-risk patients. Existing reports have described PH in small PV cohorts, but its long-term risk and clinical burden are not well understood. This study aimed to determine the long-term risk of developing PH using a large real-world dataset, and to better characterize its clinical burden over time.

Materials and Methods/Case Presentation/Objective: We conducted a retrospective cohort study using the TriNetX global federated health research network, which aggregates electronic health records from over 130 healthcare organizations. Adult patients (≥18 years) with a diagnosis of PV between January 2005 and January 2020 were included if they met high-risk criteria per NCCN guidelines: age ≥60 years and/or history of thrombotic events. Thromboses was defined using ICD-coded diagnoses, including myocardial infarction, stroke, transient ischemic attack, deep vein thrombosis, pulmonary embolism, and other arterial or venous events. Patients with a prior diagnosis of PH were excluded. Risk of PH development was assessed at 5, 7, 10, and 15 years following diagnosis. Kaplan-Meier analysis was used to estimate PH-free survival. PH-related healthcare burden was quantified by the number of PH-coded clinical encounters during the observation period.

Results/Description/Main Outcome Measures: Among the 29,794 high-risk PV patients, the risk of developing PH increased steadily over time. At 5 years, 6.1% of patients (1,697/27,889) developed PH, increasing to 7.5% (2,100/27,889) by 7 years, 8.9% (2,506/28,156) by 10 years, and 9.5% (2,660/27,889) by 15 years. Kaplan-Meier survival analysis showed PH-free survival rates of 92.5% at 5 years, 89.9% at 7 years, 85.6% at 10 years, and 78.8% at 15 years. The clinical burden of PH was reflected in rising healthcare utilization. Among patients who developed PH, the mean number of PH-related encounters increased over time: 4.8 (5 years), 5.4 (7 years), 6.0 (10 years), and 6.5 (15 years).

Conclusions: In this large, retrospective analysis of patients with high-risk PV, we found a steady and clinically meaningful increase in the risk of developing PH, rising from 6.1% at 5 years to 9.5% at 15 years. Beyond incident diagnosis, the mean number of PH-related encounters also increased over time, further emphasizing the chronic disease burden. These findings highlight PH as an under-recognized but significant long-term complication in PV, particularly in those with a prior thrombotic event or older age at diagnosis. These findings underscore the need for increased clinical vigilance and consideration of targeted screening for PH in high-risk PV patients, particularly in those with symptoms suggestive of cardiopulmonary complications.