LAUSR

Dear Editor, With great interest we have read the recent article by Caocci et al. reporting that total cholesterol (TC) < 200 mg/ dL and low-density lipoprotein (LDL) < 70 mg/dL may be associated with lower frequency of arterial occlusive events (AOE) in chronic myeloid leukemia patients treated with nilotinib [1]. In recent years, it became evident that absolute reduction in LDL correlates well with the reduction of cardiovascular risk (CVR). Therefore, European Guidelines for Management of Dyslipidemias recommend that “high” risk subjects (i.e., those with diabetes mellitus) maintain their LDL < 70 mg/dL [2]. Essential thrombocythemia (ET) and polycythemia vera (PV) are BCR/ABL-negative myeloproliferative disorders intrinsically characterized by increased CVR [3]. Here, we investigated whether the aforementioned blood lipid targets may also apply to ET and PV patients. This multicentric study included newly diagnosed ET and PV patients in the period between May 2001 and June 2019. Diagnoses were reassessed according to current World Health Organizationcriteria [4]. Baseline clinical and laboratory data were retrospectively recorded. CVR factors were defined as the presence of arterial hypertension, diabetes mellitus, or smoking. Calculations were made with MedCalc Software®, version 19.6. Survival analyses were performed using the methods of Kaplan and Meier and the Cox regression analysis. Time to thrombosis (TTT) was measured from diagnosis until arterial/ venous thrombosis or last follow-up visit, with death being a censoring event. AOE were defined as myocardial infarction, transitory cerebral ischemic attack, acute cerebral ischemic stroke, or acute peripheral arterial occlusion. Venous thromboses were defined as peripheral deep vein thrombosis and/or pulmonary embolism. Significant p values were set at < 0.050. We included 133 patients (57 ET and 76 PV); median age was 65 years (range 21–92), 54.1% were female, 21.8% had prior thrombosis, 86.4% JAK2mutation, and 78.2% had CVR factors. Median follow-up was 49 months (range 1–228); 24.8% developed thrombosis (81.8% being arterial). Univariately, patients presenting with TC > 200 mg/dL did not have a shorter TTT (HR 1.35; p = 0.440), nor could we establish an alternative TC threshold using a receiver operating curve analysis. Conversely, LDL ≥ 70 mg/dL was associated with a shorter TTT (median 111 months vs. not-reached, HR 3.27; p = 0.001), as shown in Fig. 1. These results remained significant in the Cox regression model (HR 7.33; p = 0.006) also including previously established thrombotic risk factors in these disorders [3]; age > 60 years (HR 9.19; p = 0.002), prior thrombosis (HR 8.96; p = 0.002), sex (HR 0.09; p = 0.761), CVR factors (HR 0.18; p = 0.669), JAK2mutation (HR 1.58; p = 0.207), and disease phenotype (HR 0.24; p = 0.620), suggesting that LDL< 70 mg/dL may be an appropriate target in ET and PV as well. These results were also confirmed when analyzing the impact of TC and LDL separately on AOE. Emerging evidence suggests that statins could be the lipid-lowering drugs of choice in these disorders, as they may have the potential to suppress the JAK2-dependent * Ivan Krečak [email protected]