PF391 INFLUENCE OF ATORVASTATIN THERAPY ON GALECTIN‐3, VE‐CADHERIN, AND CARDIOVASCULAR RISK IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA
Authors: Samura B. , Kolestik Y. , Syvolap V. 
Published: June 2019

Background:

The vast majority of chronic lymphocytic leukemia survivors experience late effect of treatment including cardiovascular events. These effects contribute most of the substantial effects excess mortality in patients with full or partial response to CLL treatment.

Aims:

We aimed to evaluate the impact of atorvastatin on galectin‐3 and VE‐cadherin, and cardiovascular risk in patients with chronic lymphocytic leukemia in remission.

Methods:

One hundred fifty seven out subjects with chronic lymphocytic leukemia in full or partial remission were enrolled in the study. Atorvastatin at doses 20 mg/d and 40 mg/d was prescribed for patients with hypercholesterinemia, dyslipidemia, coronary artery disease risk factors. Blood samples for biomarkers measurements were collected at the visit of inclusion into the study. Plasma levels of galectin‐3, and VE‐cadherin were measured by ELISA method at baseline and after 1 year of observation period.

Results:

Two hundred seventy cumulative clinical events occurred in 68 patients (43.3%) within the follow‐up, with their distribution being as follows: 12 deaths for cardiovascular reasons, 17 life‐threatening arrhythmias, 36 cardiac ischemic events, 9 strokes, 38 decompensated chronic heart failures, and 58 hospital admissions for cardiovascular reasons. Patients were divided to two groups depending on the atorvastatin treatment. At baseline there were no difference in levels of biomarkers between groups. In one year there were significant differences in levels of galectin‐3 (8,86 ± 5,62 ng/ml vs 16,74 ± 8,52 ng/ml; р = 0,035), VE‐cadherin (0,76 ± 0,64 ng/ml vs 2,19 ± 1,66 ng/ml; р = 0,046) in the group without atorvastatin treatment. The optimal cut‐off point of galectin‐3 level for distinguishing high cardiovascular risk patients from low risk ones was 11.75 ng/ml, with a sensitivity of 70.4% and a specificity of 96.8%; for VE‐cadherin – 0.53 ng/ml, with a sensitivity of 72.6% and a specificity of 95.2%. Combination of galectin‐3 and VE‐cadherin had high negative prognostic value (93.4%) for evaluation of cardiovascular events.

Atorvastatin treatment were associated with decreasing of cumulative cardiovascular events with appearance of early differences between groups during 3 year observation time (long‐rank test, χ2 = 11,775, р = 0,001). During first year of observation event‐free survival were better for patients treated with atorvastatin 40 mg/d in comparing to patients treated with atorvastatin 20 mg/d (long‐rank test, χ2 = 6,147, р = 0,013).

Summary/Conclusion:

Among patients with chronic lymphocytic leukemia in remission galectin‐3 and VE‐cadherin are associated with increased risk of cardiovascular events within 3 year observation period. Atorvastatin prevents increasing of galectin‐3 and VE‐cadherin and reduces risk of cardiovascular events in this group of patients. It was proposed to prescribe atorvastatin to patients with level of galectin‐3 11.75 ng/ml or higher, and/or level of VE‐cadherin 0.53 mg/ml or higher for prevention of cardiovascular events during 3 year period.