Polycythemia Vera as a Predisposing Factor for Aortic Stenosis: Prevalence and Correlation with Blood Cells Count and Mutational Status
Authors: Barone Ri ta , Caracciolo Clementina , di Maggio Rosario , Fazio Giovanni , d’Angelo Luciana , Montana Maria , Novo Salvatore , Coco Lucio lo , Caramazza Domenica , Abbadessa Vincenzo , Siragusa Sergio 
Published: October 2019

Abstract
The association between Polycythemia Vera (PV) and thrombosis is multi-factorial involving the complex interaction between activated leukocytes, platelets and endothelium. Recent reports have postulated that PV patients may over express adhesive molecules on red cell surface, likely by JAK2 mutation (Wautier M et al. Blood.2007;110(3):894–901). This process activates endothelium with production of vascular growth factors and other mechanisms leading to atherosclerosis. Aortic Stenosis (AS) is the commonest valvular heart disease in western countries; its pathogenesis is mainly related to a degenerative process sharing many characteristics with atherosclerosis. At the present is not known whether patients with PV are at high risk of developing AS.
Objective of the study. We perform a case-control study for evaluating rate of AS and its correlation with blood cells count and mutational status in patients with PV.
Materials and methods. Prevalence of AS among PV patients have been compared with control patients matched for age, cardiovascular risk factors (hypertension, hyperlipidemia, diabetes, smoke and alcohol abuse) and coexisting cardiac diseases (i.e. heart failure). Diagnosis of PV has been posted accordingly to PVSG criteria. Diagnosis and severity of AS has been posted by echocardiography: stenosis with a valve area <1.0 cm2 has been considered severe.
Results. Over a period of 18 months we recruited 43 PV patients (28 males and 15 females) and 74 controls. No differences were found in regard of the above cited characteristics; median age was 66.7 among PV patients and 68.2 among controls. The average duration of PV was 5.7 years with an average follow-up of 2.5 years. Most of the PV patients were on antiplatelet/anticoagulant therapy (27/43, 62.7%) and have been treated with cytoreductive therapy. Twelve (27.9%) had a thrombotic event before PV diagnosis; 4 (9.3%) developed thrombosis during the follow-up (median 1.3 years). A moderate/severe AS was found in 11 PV patients (25.6%) in comparison to 4 (5.4%) in control group (P= 0.023), thus giving a Relative Risk of 4.7. Among PV patients, the multivariate analysis did not show any correlation regarding JAK2 V617F mutational status, duration of disease, previous thrombosis, cytoreductive therapy and other common cardiovascular factors. Comparison of laboratory findings is reported in Table 1; a not significant trend was demonstrated in favor of patients with elevated hematocrit (>55%).
Conclusions. Our study clearly shows that PV patients carry a fourfold risk of developing AS, without a clear association with blood cell alterations or previous thrombosis. Whether high prevalence of AS may be related to expression of adhesive molecules on red cells or altered share stress is currently under investigation.
Table 1. Comparison of laboratory findings between PV patients with and without AS
Laboratory parameter* PV patients with AS (11) PV patients without AS (32) Relative Risk P value *At diagnosis Legend: PV (Polycythemia Vera), AS (Aortic Stenosis) White blood cell×109/L (mean± SD) 9520 ± 1230 12.900 ± 2120 0.73 .078 Hemoglobin, g/dL (mean ± SD) 17.5 ± 1.3 17.1 ± 1.2 1.02 .088 Hematocrit, % (mean ± SD) 56.2 ± 0.6 51.1 ± 0.8 1.1 0.06 Platelets × 109/L(mean ± SD) 415.9 ± 43 353 ± 55 1.1 0.76 JAK2 V617F, n/N (%) 11/11 (100%) 31/32 (97%) - -