Influence of atorvastatin therapy on biological markers and cardiovascular risk in patients with chronic lymphocytic leukemia in remission

Authors

  • B.B. Samura Zaporizhzhia State Medical University, Ukraine,

DOI:

https://doi.org/10.14739/2310-1210.2019.1.155793

Keywords:

biomarkers, chronic lymphocytic leukemia, cardiovascular diseases, atorvastatin

Abstract

Purpose – to assess the impact of atorvastatin on plasma biomarkers and cardiovascular risk in patients with chronic lymphocytic leukemia in remission.

Materials and methods. A total of 157 subjects with chronic lymphocytic leukemia in complete or partial remission were enrolled in the study. Atorvastatin at doses 20 mg/d and 40 mg/d were prescribed for patients with hypercholesterinemia, dyslipidemia and risk factors for coronary artery disease. Blood samples were collected for measurements of biomarkers such as galectin-3, VE-cadherin, VEGF-1, sCD40L, NT-proBNP and interleukin-6 by ELISA method at the time of inclusion into the study and after a 1-year follow-up. Cardiovascular events occurrence was assessed throughout a 3-year follow-up.

Results. There were 170 clinical events occurred in 68 patients (43.3 %) within the follow-up, with the following distribution: 12 cardiovascular deaths, 17 life-threatening arrhythmias, 36 cardiac ischemic events, 9 strokes, 38 cases of chronic heart failure decompensation, and 58 hospital admissions for cardiovascular reasons.

Patients were divided into two groups depending on the atorvastatin treatment. There were no differences in baseline levels of biomarkers between groups. Significant differences were observed in levels of galectin-3 (8.86 ± 5.62 ng/ml vs 16.74 ± 8.52 ng/ml; P = 0.035), VE-cadherin (0.76 ± 0.64 ng/ml vs 2.19 ± 1.66 ng/ml; P = 0.046) only in the group without atorvastatin treatment in the 1-year follow-up. Significant differences in levels of VEGF-1, IL-6, sCD40L, NT-proBNP were not revealed between groups during observation time.

Atorvastatin treatment was associated with decreased cumulative cardiovascular event incidence with early differences in their occurrence between groups during the 3-year follow-up (log-rank test, χ2 = 11.775, P = 0.001). Event-free survival were better in patients treated with atorvastatin 40 mg/d in comparison to patients treated with atorvastatin 20 mg/d (log-rank test, χ2 = 6.147, P = 0.013) during the first year of follow-up.

Conclusions. Among patients with chronic lymphocytic leukemia in remission, the key biomarkers of angiogenesis such as galectin-3 and VE-cadherin are associated with increased risk of cardiovascular events within 3-year follow up. Atorvastatin prevents an increase in angiogenesis biomarkers and reduces risk of cardiovascular events in this group of patients.

 

References

Vatutin, N. T., Sklyanaya, E. V., Shevelek, A. N., Smirnova, M. A., E'l'-Khatib, Yu. P., Gricenko, V. S., et al. (2017). Preparaty, vyzyvayushhie ili ukhudshayushchie techenie serdechnoj nedostatochnosti. Obzor rekomendacij Amerikanskoj associacii serdca [Drugs That May Cause or Exacerbate Heart Failure. A Scientific Statement From the American Heart Association]. Praktychna anhiolohiya, 1(76), 52–65. [in Russian].

Kriachok, I. A. (2013). Khronicheskij limfolejkoz: novoe v lechenii. Podhody k terapii pervoj linii i ikh e'volyuciya [Chronic lymphocytic leukemia: new in treatment Approaches to the first-line treatment and their evolution]. Klinicheskaya onkologiya, 3, 121–129. [in Russian].

Samura, B. B., Kolesnik, Y. M., & Syvolap, V. V. (2014). Znachimost' cirkuliruyushchego galektina-3 v prognozirovanii kardiovaskulyarnykh sobytij u pacientov s khronicheskoj limfocitarnoj lejkemiej v remissii [Value of circulating galectin-3 for prognosis of cardiovascular events in patients with chronic lymphocytic leukemia]. Zaporozhye medical journal, 6, 44–47. [in Russian]. doi: https://doi.org/10.14739/2310-1210.2014.6.35662

Tselujko, V. I., & Radchenko, O. V. (2018). Serdechno-sosudistye zabolevaniya u onkologicheskikh bol'nykh [Cardiovascular disease in oncological patients]. Liky Ukrainy, 3, 7–20. [in Russian].

Amin, H. Z., Amin, L. Z., & Wijaya, I. P. (2017). Galectin-3: a novel biomarker for the prognosis of heart failure. Clujul. Med., 90(2), 129–132. doi: 10.15386/cjmed-751

Siegel, R., DeSantis, C., Virgo, K., Stein, K., Mariotto, A., Smith, T., et al. (2012). Cancer treatment and survivorship statistics. Ca-a Cancer Journal for Clinicians, 62(4), 220–241. doi: 10.3322/caac.21149

Cavallaro, U., Liebner, S., & Dejana, E. (2006). Endothelial cadherins and tumor angiogenesis. Experimental Cell Research, 312(5), 659–667. doi: 10.1016/j.yexcr.2005.09.019

Chiorazzi, N., Rai, K. R., & Ferrarini, M. (2005). Mechanisms of disease: Chronic lymphocytic leukemia. New England Journal of Medicine, 352(8), 804–815. doi: 10.1056/NEJMra041720

Eissa, L. A., & Esmaeel, M. I. (2008). Relevance of some serum biomarkers (E Cadherin, GAGs & MDA in patients with diffuse large B-cell lymphoma. Pakistan Journal of Pharmaceutical Sciences, 21(1), 29–35.

Soeki, T., Tamura, Y., Shinohara, H., Sakabe, K., Onose, Y., & Fukuda, N. (2004). Elevated concentration of soluble vascular endothelial cadherin is associated with coronary atherosclerosis. Circulation Journal, 68(1), 1–5. doi: 10.1253/circj.68.1

Thijssen, V. L., Heusschen, R., Caers, J., & Griffioen, A. W. (2015). Galectin expression in cancer diagnosis and prognosis: A systematic review. Biochimica Et Biophysica Acta-Reviews on Cancer, 1855(2), 235–247. doi: 10.1016/j.bbcan.2015.03.003

Garshick, M., & Underberg, J. A. (2017). The Use of Primary Prevention Statin Therapy in Those Predisposed to Atherosclerosis. Current Atherosclerosis Reports, 19(12), 48. doi: 10.1007/s11883-017-0685-7

Hassan, G. S., Merhi, Y., & Mourad, W. (2012). CD40 Ligand: A neo-inflammatory molecule in vascular diseases. Immunobiology, 217(5), 521–532. doi: 10.1016/j.imbio.2011.03.010

Samura, B. B. (2016). Predictive value of circulating N-Terminal ProBrain Natriuretic Protein and VE-Catherin in patients with regression of multiple myeloma. Biological Markers and Guided Therapy, 1(3), 125–132. http://dx.doi.org/10.12988/bmgt.2016.6413.

Melincovici, C. S., Bosca, A. B., Susman, S., Marginean, M., Mihu, C., Istrate, M., et al. (2018). Vascular endothelial growth factor (VEGF) – key factor in normal and pathological angiogenesis. Romanian Journal of Morphology and Embryology, 59(2), 455–467.

How to Cite

1.
Samura B. Influence of atorvastatin therapy on biological markers and cardiovascular risk in patients with chronic lymphocytic leukemia in remission. Zaporozhye medical journal [Internet]. 2019Feb.8 [cited 2024Feb.24];(1). Available from: http://zmj.zsmu.edu.ua/article/view/155793

Issue

Section

Original research