Endothelial function in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors is not related to cardiovascular risk assessed by the Systematic Coronary Risk Estimation 2 algorithm.

ABSTRACT

INTRODUCTION: Tyrosine kinase inhibitors (TKIs) revolutionized treatment of chronic myeloid leukemia (CML), but are endowed with negative effects on endothelial function. OBJECTIVES: We aimed to characterize endothelial function in patients with CML treated with various TKIs. PATIENTS AND METHODS: A total of 48 patients diagnosed with chronic­phase CML treated with TKIs, such as imatinib, bosutinib, nilotinib, ponatinib, and asciminib were included. Endothelial function was assessed in the brachial artery and microcirculation based on flow­mediated dilation (FMD), reactive hyperemia peripheral arterial tonometry (RH­PAT) and flow­mediated skin fluorescence (FMSF). RESULTS: Reactive hyperemia index, FMD, reactive hyperemia response (RHR), normoxia oscillatory index, and hyperemic response index did not differentiate between the group of patients with low / moderate risk in the Systematic Coronary Risk Estimation 2 (SCORE2), SCORE2­Older Persons (SCORE2­OP), and those with high / very high risk scores. Among the patients with low / intermediate risk based on the SCORE2 algorithm, some had lower (below the first quartile) values of the endothelial parameters, reflecting impaired endothelial function, as compared with the high / very high risk patient population. Lower values of the endothelial function parameters were associated with overall long­term treatment with TKIs or ponatinib. Importantly, endothelial function assessed by FMSF (RHR) negatively correlated with total duration of TKI treatment, also after adjustment for age. CONCLUSIONS: Endothelial function in CML patients treated with TKIs was not related to cardiovascular risk based on SCORE2/SCORE2­OP algorithms but correlated with CML­specific factors, including duration of TKI treatment. FMSF­based assessment of skin microcirculation was a sensitive method for detecting the vascular effects of TKIs.