High Sensitivity C-Reactive Protein and Circulating Biomarkers of Endothelial Dysfunction in Patients with Chronic Myeloid Leukemia Receiving Tyrosine Kinase Inhibitors

Tyrosine kinase inhibitors (TKIs) have revolutionized the management of patients with chronic myelogenous leukemia (CML); however, reports of cardiovascular (CV) toxicities caused by these drugs are concerning. While the role of CV risk factors and high sensitivity C-reactive protein (hsCRP) in the pathogenesis of CV events is known, limited data exist in CML patients. In this study, we investigated the relationship between hsCRP, CV risk factors, CML disease activity, and exposure to TKIs in 262 CML patients enrolled in a cross-sectional study. Additionally, we explored whether novel markers of vascular dysfunction were associated with exposure to specific TKIs. In multivariable analyses only body mass index (BMI) (OR: 1.15, 95% I: 1.108–1.246; P < 0.001) and CML duration (OR: 1.004, 95% CI: 1.001–1.008; P = 0.024) were independently associated with higher hsCRP. HsCRP level was not associated with CML disease activity or a specific TKI. In exploratory analyses, novel endothelial-centric markers (e.g., ET-1 and VCAM-1) were differential across the various TKIs, particularly amongst nilotinib- and ponatinib-treated patients. Using hsCRP to risk stratify CML patients may be a potential strategy for implementing aggressive CV risk factor modification in these patients while circulating markers of vascular dysfunction should be explored as potential markers of TKI-associated CV risk.