Myeloperoxidase activity affects the high-density lipoprotein cholesterol level and the course of chronic coronary heart disease in patients with arterial hypertension

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Abstract

BACKGROUND: Coronary heart disease is one of the leading causes of death and disability worldwide. Myeloperoxidase plays the key role in its pathogenesis. Oxidative modification of high-density lipoprotein particles by myeloperoxidase followed by impaired reverse cholesterol transport and the decrease of high-density lipoprotein cholesterol level results in atherosclerosis progression. We studied the effect of myeloperoxidase on reverse cholesterol transport among patients with arterial hypertension and different clinical forms of chronic coronary heart disease, judging by findings in blood plasma.

AIM: The ultimate goal was to establish whether that effect is associated with the total amount of myeloperoxidase or its activity.

METHODS: 93 patients were recruited (65.4 ± 10.1 years old in average; men — 30 (32%)) with arterial hypertension and different clinical forms of chronic coronary heart disease. Depending on the diagnosis established, all participants were divided into 3 groups. Group I (control) contained patients with arterial hypertension, but without chronic coronary heart disease (n = 46). Group II (n = 26) included patients with initially stable coronary syndromes of chronic coronary heart disease (stable angina and/or scheduled surgical interventions for stable coronary heart disease), who never experienced acute adverse cardiac events. Group III (n = 21) contained patients with acute coronary syndrome (acute myocardial infarction) in the past 6 months or earlier. The total myeloperoxidase content (MPO-T) was assayed by enzyme-linked immunosorbent assay (ELISA). Home-modified specific immune-extraction followed by enzymatic detection (SIEFED) test was used to measure the active myeloperoxidase (MPO-A). Then, the coefficient of myeloperoxidase activity (MPO-CA) and the ratio of coefficient of myeloperoxidase activity to high-density lipoprotein cholesterol (MPO-CA/HDL-C) were calculated.

RESULTS: The level of MPO-A was higher in patients from group III with complicated form of chronic coronary heart disease, as compared with group II (p < 0.05). MPO-CA in patients of group III also was higher in comparison with group II (p = 0.001). Weak positive correlation was found between MPO-T and MPO-A in the whole cohort under investigation (r = 0.26; p < 0.05), and the relationship was stronger in the group III (r = 0.59; p < 0.05). In addition, negative correlation between MPO-A and HDL-C was found in group III (r = –0.46; p < 0.05). The MPO-CA/HDL-C ratio was higher in patients with anamnestic acute coronary syndrome, as compared with patients manifesting non-complicated stable coronary heart disease (p < 0.001) and with patients of group I who had no coronary heart disease (p < 0.001). To determine diagnostic value of the MPO-CA/HDL-C the receiver operating characteristic curve (ROC-curve) was plotted. The calculated area under curve (AUC) was 0.8 which indicates a high predictive value of the MPO-CA/HDL-C ratio for different forms of chronic coronary heart disease.

CONCLUSION: The results of our study demonstrate that in patients with preceding history of acute coronary syndrome, as compared with those having a stable course of chronic coronary heart disease, the effect of myeloperoxidase on reverse cholesterol transport depends on its activity rather than concentration. MPO-CA/HDL-C ratio mirrors the complicated chronic coronary heart disease and might serve as an additional indicator of residual risk.

About the authors

Irina A. Churashova

Institute of Experimental Medicine

Email: asyl@list.ru
ORCID iD: 0000-0001-8064-6861
SPIN-code: 5916-3140

Researcher at the Department of Molecular Genetics

Russian Federation, Saint Petersburg

Alexey V. Sokolov

Institute of Experimental Medicine

Email: biochemsokolov@gmail.com
ORCID iD: 0000-0001-9033-0537
SPIN-code: 7427-7395

Dr. Sci. (Biology), Professor, Head of the Laboratory of Biochemical Genetics of the Department of Molecular Genetics

Russian Federation, Saint Petersburg

Valeria A. Kostevich

Institute of Experimental Medicine

Email: hfa-2005@yandex.ru
ORCID iD: 0000-0002-1405-1322
SPIN-code: 2726-2921

Cand. Sci. (Biology), Senior Researcher of the Department of Molecular Genetics

Russian Federation, Saint Petersburg

Nikolay P. Gorbunov

Institute of Experimental Medicine

Email: niko_laygo@mail.ru
ORCID iD: 0000-0003-4636-0565
SPIN-code: 6289-7281

Researcher of the Department of Molecular Genetics

Russian Federation, Saint Petersburg

Tatyana V. Baranova

Institute of Experimental Medicine

Email: tanjabaranova@mail.ru
ORCID iD: 0000-0002-8269-8881
SPIN-code: 1356-1402

Cand. Sci. (Biology), Junior Researcher of the Department of Molecular Genetics

Russian Federation, Saint Petersburg

Elvira M. Firova

Institute of Experimental Medicine

Email: Firova@yandex.ru

MD, Cand. Sci. (Medicine), Head of the Department of Cardiology, Cardiologist at the Clinic

Russian Federation, Saint Petersburg

Mikhail Yu. Mandelstam

Institute of Experimental Medicine

Email: amitinus@mail.ru
ORCID iD: 0000-0002-7135-3239
SPIN-code: 1893-9417

Dr. Sci. (Biology), Leading Researcher at the Department of Molecular Genetics

Russian Federation, Saint Petersburg

Vadim B. Vasilyev

Institute of Experimental Medicine

Author for correspondence.
Email: vadim@biokemis.ru
ORCID iD: 0000-0002-9707-262X
SPIN-code: 6699-6350

MD, Dr. Sci. (Medicine), Professor, Head of the Department of Molecular Genetics

Russian Federation, Saint Petersburg

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2. Fig. 1. Relationships between MPO-T, MPO-A and HDL-C. a, Scatter plot of correlation between MPO-T and MPO-A in all groups. b, Scatter plot of correlation between MPO-T and MPO-A in group III. c, Scatter plot of correlation between MPO-T/HDL-C ratio and MPO-A/HDL-C ratio in all groups. d, Scatter plot of correlation between MPO-T/HDL-C ratio and MPO-A/HDL-C ratio in group III. MPO-T, total myeloperoxidase; MPO-A, active myeloperoxidase; MPO-T/HDL-C, the ratio of total myeloperoxidase to high-density lipoprotein cholesterol; MPO-A/HDL-C, the ratio of active myeloperoxidase to high-density lipoprotein cholesterol.

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3. Fig. 2. Box plot of MPO-CA/HDL-C ratio comparison among the groups. The data are represented as median, interquartile range, minimum and maximum values. Statistical significance of the Kruskal–Wallis H test for multiple comparison, p < 0.001. MPO-CA/HDL-C, the ratio of coefficient of myeloperoxidase activity to high-density lipoprotein cholesterol.

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4. Fig. 3. The results of ROC analysis of the MPO-CA/HDL-C ratio among the patients with different clinical forms of chronic coronary heart disease. ROC, receiver operating characteristic; AUC, area under curve; MPO-CA/HDL-C, the ratio of coefficient of myeloperoxidase activity to high-density lipoprotein cholesterol.

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