Increase of Arterial Stiffness in Patients with Polycythemia Vera

Introduction: Preventing thrombotic adverse events (TAEs) is crucial in Polycythemia Vera (PV), as it is the leading cause of death. A targeted approach is required to achieve this, aiming to lower hematocrit (HCT) blood levels and manage thrombocytosis through cytoreductive therapy and anti-platelet treatments. The reasons behind the higher incidence of TAEs in PV are partially known. A novel perspective considers that increased blood vessel content may result in a stiffer aorta, which is clinically measurable with the Pulse Wave Velocity (PWV). The stiffer aorta, a proxy of arterial aging, has been recognized as a significant independent contributor to TAEs.

Objectives: This study aimed to investigate the impact of hematological parameters on arterial stiffness in PV patients

Methods: Clinical and laboratory information was collected for each patient. Aorta PWV (PWV) was estimated using the SphygmoCor System (AtCor Medical Pty Ltd., Head Office, West Ryde, Australia). The patients were observed and measured twice with a minimum interval of six months between sessions.

Results: We evaluated patients with a diagnosis of PV according to WHO 2016 classification, attending from November 2021 to March 2023, the Hematology Unit of the Businco Hospital in Cagliari, Italy. The study involved 26 patients aged 27 to 77 years old. Among them, 58% were female. The median follow-up between diagnosis and PWV evaluation was 7±3 years. The median Hemoglobin (Hb) level was 13.9±1.7 g/dl, with an HCT level of 44.1±4.6 %. Leucocytes and platelets at evaluation time were 9.1±4.2×10 ³/μL and 395±227 ×10 ³/μL, respectively. Fourteen (53.8%) patients reported a high-risk thrombotic score at diagnosis, and 65.3% had at least one comorbidity. Two (7.7%) patients had diabetes. Moreover, 15.4% showed dyslipidemia, while 38.5% had arterial hypertension. The median body mass index (BMI) was 24.8 ± 3.6 Kg/m2, and the median waist circumference was 94.4 ±13.4 cm. Characteristics of patients were resumed in Table 1. A significant correlation with a high level of PWV was found with age (r:0.54, p=0.004), systolic and diastolic blood pressure (r:0.55, p=0.004 and r:0.44, p=0.025 respectively), heart rate (r:0.47, p=0.02), Hb (r:0.50, p=0.009), and use of hydroxycarbamide (r:0.42, p=0.03). Even after adjusting for age, waist circumference, BMI, and hypertension, the hemoglobin level still significantly correlated with PWV (β0.64 ± 0.27, p<0.05). No associations were found with hematocrit levels (β0.09 ± 0.12, p=0.42). When comparing patients treated only with phlebotomy versus those treated with hydroxycarbamide, PWV was significantly higher (stiffer artery) in the second group (8.9 ± 1.8 vs 11.2 ± 3.2, p< 0.05, respectively). Still, the difference lost significance when accounting for age and blood pressure levels.

Conclusion: In PV, Hb levels showed a significant positive correlation with arterial stiffness, indexed as PWV, regardless of PV-specific treatment. The stiffer artery may contribute to the higher TAEs in PV patients. Reducing Hb levels in PV patients also seems beneficial for arterial aging. Further studies are necessary to determine the possible role of PWV in defining and preventing thrombotic events.