Effect of Combination Therapy with Alpha-Lipoic Acid on the Fractalkine Level in Patients with Coronary Artery Disease and Type 2 Diabetes Mellitus

L.V. Zhuravlyova, N.A. Lopina


Background. The aim of research — to assess the fractalkine levels in patients with coronary artery disease (CAD), depending on the presence of type 2 diabetes mellitus (DM) and the nature of coronary artery lesions before treatment and during the standard and combination therapy with the addition of alpha-lipoic acid. Materials and methods. We have examined 131 patients with CAD (89 men and 42 women), mean age of them was 59.60 ± 9.11 years. The control group consisted of 20 apparently healthy volunteers of the same age and sex. Depending on the presence of type 2 DM, patients with CAD were divided into 2 groups: the first group (n = 70) — patients with concomitant type 2 DM, the second group (n = 61) — patients with CAD and without concomitant type 2 DM. All patients were performed coronary angiography to verify the diagnosis of CAD. All patients, depending on the nature of coronary artery lesions and therapy, were divided into 2 subgroups — subgroup IA (standard therapy) and the subgroup IB (combination therapy). All patients were evaluated fractalkine levels before therapy and after 3 months of treatment. Results. The study found that patients with CAD, both with concomitant type 2 DM or without it, had significantly increased levels of fractalkine compared with the control group (p < 0.05). When comparing treatment regimens, it was found that in the subgroup of standard therapy, fractalkine ave­rage level before treatment was 485.07 ± 106.55 pg/ml, and after 3 months of therapy — 444.08 ± 99.86 pg/ml, while there was no significant difference between baseline value and the value reached after 3 months (p = 0.08), although there was a trend to reduce the level of this indicator. Patients from IB subgroup (n = 105), who received combination therapy, had a significant trend to reduce the fractalkine level in 3 months as compared to the initial value before therapy (510.49 ± 103.95 pg/ml vs 575.56 ± 123.86 pg/ml; p = 0.00001). The relative reduction in fractalkine level in the subgroup IA was 8.45 %, in the subgroup IB — 11.3 %. Conclusions. The study results demonstrate the impact of endothelial dysfunction on the development and progression of atherosclerosis, especially in patients with concomitant type 2 DM. Applying alpha-lipoic acid in combination therapy schemes contributes to a significant reduction in fractalkine levels, and, thus, leads to a decrease in endothelial dysfunction and, as a result, to the possible improvement of prognosis in this group of patients.


fractalkine; coronary atherosclerosis; coronary artery disease; type 2 diabetes mellitus; marker of endothelial dysfunction; alpha-lipoic acid


Biduchak АS, Shkrobanets ID, Leonets SI. . Epidemiology features of cardio-vascolar diseases in Ukraine and Chernivtsi district. Bukovynskyi medychnyi visnyk. 2013;3(67):100-103. (Ukrainian)

Моskalenko VF, Gulchiy OP, Golubchikov MV, Liedoshchuk BO, Liekhan VM, Оgnev VA, Litvinova LO, Маksimenko OP, Тоnkovyd OB. Ed. VF. Moskalenko. Biostatistics. – Кyiv: Кnyga plus, 2009. 184 s. (Ukrainian)

Guidelines on diabetes, prediabetes and cardiovascular diseases. EASD/ESC. Rossiyskyi kardiologicheskiy zhurnal. – 2014; 3(107):6-70. (Russian)

Stable ischemic heart disease: clinical guidelines. Kyiv, 2016. 177 s. (Ukrainian)

Compatible clinical protocol of primary and secondary (specialized) medicare: Stable ischemic heart disease. Nakaz MOZ Ukrainy 02.03.2016 № 152. 61 s. (Ukrainian)

Compatible clinical protocol of primary and secondary (specialized) medicare: type 2 diabetes mellitus. Nakaz MOZ Ukrainy №1118 21.12.2012. 115 s. (Ukrainian)

Holme I, Faergeman O, Fayyad R, Wun CC, Kastelein J, Olsson A, Tikkanen M. Prognostic model of residual risk for major cardiovascular events in statin-treated coronary patients: a combined analysis of the IDEAL and TNT trials. Journal of the American College of Cardiology. 2012;59(13):1495-1495.

Huang Y, Cai X, Chen P, Mai W. et al. Associations of prediabetes with all-cause and cardiovascular mortality: A meta-analysis. Annals of Medicine. 2014;46:684–692.

Ikejima H, Imanishi T, Tsujioka H. et al. Upregulation of fractalkine and its receptor, CX3CR1, is associated with coronary plaque rupture in patients with unstable angina pectoris. Circulation Journal. 2010;74:337–345.

Kim KW, Vallon-Eberhard A, Zigmond E, Farache J, Shezen E, Shakhar G, Ludwig A, Lira SA, Jung S. In vivo structure/function and expression analysis of the CX3C chemokine fractalkine. Blood. 2011;118:156–167.

Liu H, Jiang D, Zhang S, Ou B. Aspirin inhibits fractalkine expression in atherosclerotic plaques and reduces atherosclerosis in ApoE gene knockout mice. Cardiovascular Drugs and Therapy. 2010;24:17–24.

Maas R, Quitzau K, Schwedhel E. et al. Asymmetrical dimethylarginine (ADMA) and coronary endothelial function in patients with coronary artery disease and mild hypercholesterolemia. Atherosclerosis. 2007;191:211–219.

Maegdefessel L, Schlitt A, Pippig S. et al. Patients with insulin-dependent diabetes or coronary heart disease following rehabilitation express serum fractalkine levels similar to those in healthy control subjects. Vascular Health and Risk Management. 2009;5:849–857.

Matsue Y, Yoshida K, Nagahori W, Ohno M, Suzuki M, Matsumura A, Hashimoto Y, Yoshida M. Peripheral microvascular dysfunction predicts residual risk in coronary artery disease patients on statin therapy. Atherosclerosis. 2014;20(1):186–190.

Poupel L, Boissonnas A, Hermand P, Dorgham K. et al. Pharmacological inhibition of the chemokine receptor, CX3CR1, reduces atherosclerosis in mice. Arteriosclerosis, Thrombosis, and Vascular Biology. 2013;33:2297–2305.

Sadeghi R, Adnani N, Erfanifar A, Gachkar L, Maghsoomi Z. Premature Coronary Heart Disease and Traditional Risk Factors-Can We Do Better? International Cardiovascular Research Journal. 2013;7(2):46–50.

Shah R, Hinkle CC, Ferguson JF. et al. Fractalkine is a novel human adipochemokine associated with type 2 diabetes. Diabetes. 2011;60:1512–1518.

Standards of medical care in diabetes – 2016. American Diabetes Association. Diabetes Care. 2016;39(1):1-109.

White GE, Tan TC, John AE, Whatling C, McPheat WL, Greaves DR. Fractalkine has anti-apoptotic and proliferative effects on human vascular smooth muscle cells via epidermal growth factor receptor signaling. Cardiovascular Research. 2010;85:825–835.

Yi X, Xu L, Hiller S. et al. Reduced alpha-lipoic acid synthase gene expression exacerbates atherosclerosis in diabetic apolipoprotein E-deficient mice. Atherosclerosis. 2012;223:137-143.

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