Risk Factors for Cardiovascular Events in Myeloproliferative Syndromes.
Authors: Vincelli Iolanda , Oliva Esther N. , Latagliata Roberto , Specchia Giorgina , Alimena Giuliana , Breccia Massimo , Alati Caterina , Carmosino Ida , Iaria Grazia , Marino Antonio , Ranieri Natale , Liso Vincenzo , Ronco Francesca , Martino Bruno , Nobile Francesco 
Published: October 2019

Abstract
There is a high prevalence of thromboembolic events in myeloproliferative syndromes (MPS) ranging from 20% to 40% as compared to the general elderly Italian population (males 2.4–3.6%, females 1.1–1.9%, data from Progetto Cuore). In particular, in Polycythemia Vera (PV), cardiovascular events (CVE) represent a major cause of mortality. In MPS, in addition to common cardiovascular (CV) risk factors (RF), the role of disease-related hemostatic abnormalities are far from being elucidated. A retrospective chart review in 463 patients in 3 Italian hematology centers was performed to evaluate the prevalence of CVE and to identify RF in patients with MPS diagnosed between 1977 and 2006. Mean age was 59 (range 17–89) years, 237 M/ 226 F. CVE were recorded in 164 patients.One hundred (21.6%) patients had a CVE before diagnosis: Essential Thrombocytemia (ET) 41/173 (24%); Myelofibrosis (MF) 13/43 (30%); PV 36/142 (25%); other MPS 2/12; Hypereosinophilic Syndrome 1/6; Hypoplasia 1/7; Myelodysplastic Syndromes (MDS) 4/28 (14%); CML 1/51 (2%) and the only patient with CMMoL. Comparing to CML, the risk (OR) of CVE in patients with ET was 12.1 (p=0.001, 95% CI: 1.7–85.7), with PV 12.8 (p=0.006, 95% CI: 1.8–91.3), and with MF 15.4 (p=0.004, 95% CI: 2.1–113.1). However, after adjusting for age, sex, dyslipidemia, diabetes, arterial hypertension, chronic renal failure, and tobacco use, there was no significant difference in CV risk between these MPD. In a logistic regression analysis, the overall independent factors associated with a history of CVE were hypertension (p<0.0001), age (p=0.001), and diabetes (p=0.021); in TE age (p=0.005); in PV hypertension (p=0.020); in MF hypertension (p=0.016). Ninety-five patients had at least one CVE after diagnosis, 12 of which were mortal: TE 22%, PV 22%, CML 20%, MF 16%, MDS 29% (8 cardiac events, 5 of which mortal). A CVE prior to diagnosis was associated with a repeated CVE in 31 patients (OR 2.1, 95% CI: 1.3–3.5, p=0.004). On multivariate analysis, only age (OR for each 10 year increase 1.4, 95% CI 1.1–1.7, p=0.002) and hypertension (OR 1.8, 95% CI: 1.0–3.3, p = 0.046) predicted a CVE after diagnosis. Noteworthy, 75 patients (80%) were on antiplatelet therapy when the CVE occurred. Independent RF in TE were age (p=0.001) and chronic renal failure (p=0.006), in MF age (p=0.007) and hypertension (p=0.021) while in PV no disease-related nor conventional RF were identified.
CONCLUSION: Contrary to conventional belief, we do not conclude that erythrocytosis, thrombocytosis or leukocytosis be independent RF for CVE in patients with MPS. Conventional RF, mainly arterial hypertension and increasing age, play a major role. Future clinical research should primarily aim to assess the risk/benefit ratio of antiplatelet therapy and to better characterize other disease-related risk factors for thromboembolic events in MPS.