IMPACT OF METABOLIC SYNDROME ON COVID-19 AND CORONARY ARTERY DISEASE: CLINICAL AND PATHOGENETIC INSIGHTS Текст научной статьи по специальности «Клиническая медицина»

IMPACT OF METABOLIC SYNDROME ON COVID-19 AND CORONARY ARTERY DISEASE: CLINICAL AND PATHOGENETIC INSIGHTS

1 2 3

Abdieva Gulnora , Annaev Muzaffar , Kumaravelayutham Atithi , Ankita Shreenivas

Deshpande3

1PhD, assistant professor of the Department of Internal medicine No 2 and cardiology,

Samarkand State Medical University, Samarkand, Uzbekistan MSc, assistant professor of the Department of Internal medicine No 2 and cardiology,

Samarkand State Medical University; Samarkand branch of Republican Specialized Scientific and Practical medical center of

Cardiology, Samarkand, Uzbekistan Student of Samarkand State Medical University, Samarkand, Uzbekistan Corresponding author: Annaev Muzaffar ([email protected]), ORCID: https://orcid.org/0000-0002-8034-4561. Address: 3 Olmazor street, Samarkand region,

Uzbekistan. Tel.: +99899143929

https://doi.org/10.5281/zenodo.8359219

Abstract. The emergence of SARS-CoV-2, causing Covid-19, posed a global threat at the end of 2019, with far-reaching consequences for humanity. Despite extensive efforts to combat the disease, Covid-19 continues to spread, accompanied by the emergence of new, unfavorable variants, and an overburdened healthcare system. This study delves into the intricate interplay between Covid-19 and individuals with pre-existing chronic organ and systemic disorders, shedding light on the patterns of adverse outcomes and prognosis.

Comorbidities, notably arterial hypertension, obesity, chronic lung disease, diabetes mellitus, and other cardiovascular conditions, have been strongly associated with severe Covid-19 cases and complications. These conditions often align with the concept of metabolic syndrome, a cluster of disorders encompassing arterial hypertension, obesity, and hyperglycemia. Metabolic syndrome's influence on Covid-19 outcomes is further compounded by concurrent chronic kidney, respiratory, and cardiovascular diseases.

The study emphasizes the role of adipose tissue in exacerbating the impact of metabolic syndrome. Visceral fat accumulation, a hallmark of obesity, intensifies the systemic effects of angiotensin II, culminating in microcirculatory disruptions and vascular elasticity loss, potentially leading to cardiovascular complications.

SARS-CoV-2 enters the body through ACE2 receptors, found in various tissues, including the respiratory tract, lungs, heart, central nervous system, kidneys, and adipose tissue. The presence of ACE2 receptors in adipose tissue facilitates viral entry, making the study of metabolic syndrome even more crucial for Covid-19 patients.

This research involved 147 individuals over 18 years of age, classified into three groups: Covid-19 patients with coronary artery disease (CAD) and metabolic syndrome, Covid-19 patients with CAD but without metabolic syndrome, and healthy individuals without clinical signs of CAD or metabolic syndrome. The study utilized clinical, instrumental, and laboratory data to establish correlations.

Among the findings, women with CAD and Covid-19, combined with metabolic syndrome, exhibited a higher prevalence of painless coronary artery disease, often linked to latent type 2 diabetes mellitus and diabetic neuropathy. Male patients in this group were more likely to be

smokers and had earlier CAD onset. Notably, Covid-19 prompted the first diagnosis of type 2 diabetes mellitus in 24% of cases among patients with CAD and metabolic syndrome.

Furthermore, Covid-19 exacerbated lipid profile parameters, resulting in a higher atherogenic index and increased triglyceride levels. Patients with metabolic syndrome demonstrated a higher prevalence of hyperlipidemia and dyslipidemia, characterized by elevated triglycerides, decreased HDL, and increased LDL. Echocardiological examinations revealed significant differences in left ventricular geometry, with a higher prevalence of concentric LV myocardial hypertrophy in patients with CAD and metabolic syndrome.

In summary, this study underscores the critical role of metabolic syndrome in shaping the clinical outcomes of Covid-19 patients with pre-existing coronary artery disease. It highlights the importance of managing comorbidities, particularly obesity and hyperglycemia, in mitigating the progression of Covid-19 and associated complications.

Keywords: Covid-19, SARS-CoV-2, metabolic syndrome, coronary artery disease, obesity, hyperglycemia, lipid metabolism, ACE2 receptors, cardiovascular complications.

Аннотация. Появление SARS-CoV-2, вызывающего COVID-19, представляло глобальную угрозу в конце 2019 года, с глубокими последствиями для человечества. Несмотря на обширные усилия по борьбе с этим заболеванием, COVID-19 продолжает распространяться, с появлением новых неблагоприятных вариантов и перегруженной системой здравоохранения. В данном исследовании рассматривается сложное взаимодействие между COVID-19 и лицами с хроническими поражениями органов и систем до начала инфекции, что позволяет более глубоко понять паттерны неблагоприятных результатов и прогноза.

Серьезные осложнения COVID-19 и острые формы заболевания часто ассоциируются с сопутствующими состояниями, такими как артериальная гипертензия, ожирение, хронические заболевания легких, сахарный диабет и другие сердечнососудистые заболевания. Эти состояния часто совпадают с концепцией метаболического синдрома, включающей артериальную гипертензию, ожирение и гипергликемию. Влияние метаболического синдрома на исходы COVID-19 усиливается наличием сопутствующих хронических заболеваний почек, дыхательных путей и сердечно-сосудистой системы.

Исследование подчеркивает роль жировой ткани в ухудшении последствий метаболического синдрома. Накопление висцерального жира, характерного для ожирения, усиливает системные эффекты ангиотензина II, что может привести к нарушению микроциркуляции и ухудшению упругости сосудистой стенки, с возможными сердечно-сосудистыми осложнениями.

SARS-CoV-2 попадает в организм через рецепторы ACE2, присутствующие в различных тканях, включая дыхательные пути, легкие, сердце, центральную нервную систему, почки и жировую ткань. Наличие рецепторов ACE2 в жировой ткани облегчает вирусу вход в клетки, что делает изучение метаболического синдрома еще более важным для пациентов с COVID-19.

В данном исследовании было изучено 147 лиц старше 18 лет, разделенных на три группы: пациенты с Covid-19 и коронарными артериальными заболеваниями (КАЗ) и метаболическим синдромом, пациенты с Covid-19 и КАЗ без метаболического синдрома и здоровые лица без клинических признаков КАЗ или метаболического синдрома. В

исследовании использовались клинические, инструментальные и лабораторные данные для выявления корреляций.

Среди результатов женщины с КАЗ и Covid-19, сочетающимися с метаболическим синдромом, чаще страдали бессимптомными формами коронарных артериальных заболеваний, что часто связывается с латентным сахарным диабетом 2-го типа и диабетической нейропатией. У мужчин в этой группе чаще наблюдалось курение и более раннее начало КАЗ. Интересно, что Covid-19 у 24% пациентов этой группы стал причиной первичного выявления сахарного диабета 2-го типа.

Кроме того, Covid-19 усугубил параметры липидного профиля, что привело к повышению атерогенного индекса и увеличению уровня триглицеридов. Пациенты с метаболическим синдромом продемонстрировали более высокую распространенность гиперлипидемии и дислипидемии, характеризующейся повышенными уровнями триглицеридов, снижением HDL и повышением LDL.

Эхокардиологические исследования выявили значительные различия в геометрии левого желудочка, с более высокой распространенностью концентрической гипертрофии миокарда левого желудочка у пациентов с КАЗ и метаболическим синдромом.

В заключении исследования подчеркивается важная роль метаболического синдрома в формировании клинических исходов пациентов с Covid-19 и сопутствующей коронарной болезнью. Исследование подчеркивает необходимость управления сопутствующими заболеваниями, особенно ожирением и гипергликемией, для смягчения последствий Covid-19 и сопутствующих осложнений.

Ключевые слова: Covid-19, SARS-CoV-2, метаболический синдром, коронарная болезнь, ожирение, гипергликемия, липидный обмен, рецепторы ACE2, сердечнососудистые осложнения.

At the end of 2019, with the appearance in the world of a new coronavirus called SARS-CoV-2, which causes Covid-19, a global threat with severe consequences loomed over humanity [6]. Today, despite the worldwide unified search for methods and countermeasures, the disease is still spreading, new unfavorable variants of the course are observed against the backdrop of an overloaded healthcare system [7].

A larger and deeper study of the etiopathogenetic and clinical manifestations of Covid-19 in individuals with chronic lesions of various organs and systems confirms the pattern of adverse outcomes and prognosis [6; 7]. The emerging complications in patients infected with SARS-CoV-2, both with overt clinical manifestations and asymptomatic carriage, are of interest to the scientific community.

The most common comorbidities giving severe course and complications of Covid-19 were arterial hypertension (49.7%), obesity (48.3%), chronic lung disease (34.6%), diabetes mellitus (28.3%) and other cardiovascular diseases (27.8%) [9]. Arterial hypertension (AH), obesity, hyperglycemia, which are currently socially significant diseases that have the nature of an epidemic, fit into the concept of metabolic syndrome (MS). [1-3; 13].

It is known that MS is strongly associated with adipose tissue dysfunction in obesity, while the presence of concomitant diseases such as chronic kidney disease, chronic respiratory and cardiovascular diseases worsen the prognosis of Covid-19 [13]. The literature highlights the phenomenon of "metabolically healthy obesity", however, all authors are unanimous in their

opinion that the compensatory mechanism of the body lasts a relatively short period of time. It is the duration of the presence of a large array of visceral fat in the human body that plays a key role in the development of associated complications, primarily carbohydrate and lipid metabolism disorders, as well as cardiac disorders.

With excess body weight in certain places in the body, a depot of adipose tissue is formed, mainly in subcutaneous adipose tissue, visceral adipose tissue, yellow bone marrow, mammary glands, and omentum. An increase in the mass of adipose tissue potentiates the systemic action of tissue angiotensin II, which ultimately disrupts microcirculation, the elasticity of the vascular wall and leads to different complications of cardiovascular system [10-12].

It has been reliably studied that the causative agent of a new coronavirus infection enters the human body through the entrance gate, which is the epithelium of the upper respiratory tract and the epithelial cells of the stomach and intestines. Penetration of SARS-CoV-2 RNA into target cells with type II angiotensin-converting enzyme (ACE2) receptors is the initial stage of infection. ACE2 receptors are present on the cells of the respiratory tract, especially alveolar cells of type II (AT2) of the lungs, heart, central nervous system, kidneys, bladder, esophagus, ileum, pancreatic parenchyma. Adipose tissue has a high concentration of ACE2 receptors, which facilitates penetration into the cells of the SARSCoV-2 coronavirus [4; 5; 8].

In view of the number of complications with which patients with MS infected with SARS-CoV-2 needed not only hospitalization, but also resuscitation, the problem of MS is even more acute than in the "favorable" period, before the spread of a new coronavirus infection.

Materials and research methods. During the study, 147 people over 18 years of age were examined with a virus infection and all patients were distributed as follows: the main group, which included 59 patients with COVID-19 and CAD on the background of metabolic syndrome; the comparison group, which included 58 patients with COVID-19 and CAD without MS, the control group consisted of 30 healthy individuals without clinical signs of coronary heart disease and metabolic syndrome.

Coronary artery disease (CAD) was diagnosed at the prehospital stage by collecting an anamnesis of clinical instrumental laboratory data.

The determination of the interdependence of the considered parameters of the samples using the Student's test and the Pearson chi test (x2) was carried out using the test of its significance.

Results. We examined 147 patients hospitalized in the COVID Specialized Center and the Samarkand Regional Infectious Diseases Hospital with a verified diagnosis of COVID-19. Of these, patients with CAD and MS were 59 (30 men and 29 women) and 58 patients with CAD without MS (26 men and 32 women). Table 1 presents the complaints of hospitalized patients, anamnesis indicating the presence of bad habits (smoking), physical and ECG data.

As the results of the study showed, in women with coronary heart disease and COVID-19 against the background of MS, painless forms of coronary artery disease were 26.4% more common than women without MS. Most likely, this is due to the pre-manifest period, that is, latent type 2 diabetes mellitus and the development of diabetic neuropathy in 54% of cases in patients with coronary artery disease against the background of MS. Among men, more than 50% were smokers and anamnesis showed an earlier onset of CAD.

Table 1

Clinical characteristics of patients with CAD and COVID-19

Women with CAD without MS (n=32) Women with CAD and MS (n=29) Men with CAD without MS (n=26) Men with CAD and MS (n=30)

Retrosternal pain 27 (93,1%)* 20 (66,67%)* ** 25 (89,28%) 26 (86,67%)**

Dyspnea 7 (24,1%) 9 (30%) 7 (25%) 10 (33,33%)

Interruptions in work of the heart 5 (17,24%) 7 (23,3%) 5 (17,87%) 7 (24,1%)

Nausea 4 (13,79%) 7 (23,3%) 7 (25%) 5 (17,24%)

Oppression of consciousness 2 (6,9%) 3 (10%) 4 (14,28%) 4 (13,79%)

Weakness 25 (86,2%) 27 (90%) 25 (89,28%) 28 (93,33%)

Smoking 2 (6,9%) 2 (6,67%) 15 (53,57%) 4 (13,79%)

Wheezing in the lungs 7 (24,1%) 11 (36,67%) 7 (25%) 11 (39,28%)

Complaints about palpitations 6 (20,68%) 9 (30%) 6 (21,43%) 8 (28,57%)

ECG changes:

ST segment elevation 17 (58,62%) 22 (73,33%) 21 (75%) 21 (75%)

ST segment depression 12 (41,38%) 8 (26,67%) 6 (21,43%) 9 (32,14%)

* X2=7,276, p=0,003493 **x2=3,8, p=0,02496

Among hospitalized patients, type 2 diabetes mellitus was first detected in 24% of cases among patients with CAD with MS, which developed against the background of COVID-19.

During hospitalization, the glucose level: in women with coronary artery disease without MS, on average, was 7.7±2.8 mmol/l; in women with MS - 9.8±5 mmol/l; while in men without MS this indicator was 7.7±2.4 mmol/l; in men with MS - 12 ± 4.9 mmol/l, which indicates an increased glucose level among men with CAD and MS with COVID-19. The results of the study showed that a quarter of the observed patients had persistent hyperglycemia, in whom type 2 diabetes mellitus was subsequently diagnosed for the first time. (Table 2).

Table 2

The frequency of newly diagnosed type 2 diabetes mellitus among patients with coronary artery disease and COVID-19

Women with CAD without MS (n=32) Women with CAD and MS (n=29) Men with CAD without MS (n=26) Men with CAD and MS (n=30)

Absolute number of patients with DM 3* 18** 1* 11**

% ratio of patients 12,5 60 1,7 37,5

Type 2 DM compensation phase:

Compensated 1 (25%) 4 (22,2%) 0 (0%) 4 (33,3%)

Subcompensated 2 (75%) 12 (66,7%) 1 (100%) 3 (25%)

Decompensated 0 (0%) 2 (11,1%) *** 0 (0%) 4 (33,3%) ***

* x2= 4,665, p=0,01539 ** X2=3,139, p=0,03823 *** X2=3,578, p=0,02628

Among patients without MS, diabetes mellitus was detected in women in 12.5% of cases, while in women with MS, type 2 diabetes developed due to COVID-19 in 60%. Moreover, it should be noted that in patients with decompensated DM among those with severe hyperglycemia, it was observed in patients with CAD with MS, which, apparently, is since severe forms of diabetes are combined with other components of MS.

Thus, coronavirus infection was a pathogenetic impetus for the progression of MS and destabilization of coronary artery disease, resulting in the manifestation of decompensated type 2 diabetes.

The analysis of lipid profile parameters in patients with COVID-19 and coronary heart disease with metabolic syndrome revealed an increase in the atherogenic index by 2.66 higher compared to patients without MS. The average level of TG was higher by 1.37 mmol compared to the comparison group. VLDL was also comparable higher in patients with CAD and MS. The values of serum concentrations of TC and LDL in patients with CAD were higher than the optimal values, but the intergroup differences were not significant. The average level of HDL was decreased in patients with metabolic syndrome relative to those of patients with CAD (Table

3).

A significant increase in the prevalence of hyperlipidemia and dyslipidemia was found in the main study group. The most common variant of lipid metabolism disorders in the metabolic syndrome was a combination of hypertriglycerinemia, low HDL levels and an increase in the LDL fraction (Table 4).

Table 3

Indicators of blood lipid spectrum in patients with CAD

Study Group

Index (M ± m)

CAD+MS (n = 59) CAD (n = 58)

Total cholesterol, mmol/l 6,49 ± 1,93 6,38 ± 2,04

Triglycerides, mmol/l 3,89 ± 0.67* 1,52 ± 0,49

LDL, mmol/l 5,61 ± 1,72 4,50 ± 1,05

HDL, mmol/l 0,67 ± 0,09* 2,26 ± 0,54

Atherogenic index 5,34 ± 1,23* 2,68 ± 0,21

* - significance of differences in indicators when compared wit i the CHD group at p <

0.05, • - at p < 0.01 Table 4

Lipid metabolism disorders among patients with COVID-19 and coronary artery disease

Index (M ± m) CAD+MS (n = 59) CAD (n = 58)

Number of patients % Number of patients %

Triglycerides, mmol/l 38 64* 25 43

LDL > 2,6 mmol/l 39 66 37 64

TC > 5,0 mmol/l 35 59 42 72

HDL < 1,0 mmol/l (male), < 1.3 mmol/l (female) 40 68* 21 36

* - significance of differences in indicators when comparec with the group of coronary

artery disease without MS at p < 0.05, • - at p < 0.01

In patients with CAD with MS in 38 patients of the main group, the level of TG> 1.7 mmol/l, the level of HDL < 1.0 mmol/l (male), <1.3 mmol/l (female) was observed in 40 patients which amounted to 68%.

When conducting an echocardiological study, the average values of the ejection fraction and stroke volume, calculated by the disk method, were found in the main group to be 50.93 ± 3.63 and 26.56 ± 2.48 ml/m2, in the comparison group -56.52 ± 2.29 and 30.18 ± 1.34 ml/m2, respectively.

The normal geometry of the left ventricle among patients with COVID-19 and coronary artery disease against the background of MS, when compared with the comparison group, was significantly lower (31% vs. 12%). In the structure of left ventricular remodeling in patients with COVID-19 and CAD without MS, the concentric type prevailed (55.5% vs. 25%, p<0.005). In patients with COVID-19 and CAD with MS, compared with patients with CAD without MS, concentric LV myocardial hypertrophy was more common (59% versus 10%).

Thus, a significant increase in the prevalence of hyperlipidemia, dyslipidemia in patients with CAD with metabolic syndrome was revealed. In such patients, an increase in the atherogenic index, the average level of triglycerides, a decrease in the average values of the serum concentration of HDL compared with the optimal parameters and values in the group of COVID-19 and coronary artery disease.

REFERENCES

1. Абдиева Г.А., Ташкенбаева Э.Н. Влияние метаболических и сердечно-сосудистых заболеваний на течение COVID-19 // Journal of cardiorespiratory research 2022. Volume 3, Issue 2, 33-37.

2. Абдиева Г. А., Ташкенбаева Э.Н. Влияние SARS-CoV-2 на течение ишемической болезни сердца на фоне метаболического синдрома // Journal of cardiorespiratory research 2022. SI 1.1, 8-15.

3. Ташкенбаева Э.Н., Абдиева Г.А., Хайдарова Д.Д., Саидов М.А., Юсупова М.Ф. Распространенность метаболического синдрома у пациентов с ишемической болезнью сердца // Journal of cardiorespiratory research 2021. Volume 2, Issue 1., 85-88.

4. Ташкенбаева, Э., Ражабова, Н., Кадирова, Ф., & Абдиева, Г. (2022). АССОЦИИРОВАННЫЕ ФАКТОРЫ РИСКА КАРДИОВАСКУЛЯРНЫХ СОБЫТИЙ У ЖЕНЩИН В ПОСТМЕНОПАУЗАЛЬНОМ ПЕРИОДЕ. Журнал кардиореспираторных

исследований, 1(3), 33-39. https://doi.org/10.26739.2181 -0974-2020-3-6

5. Тогаева Б. и др. COVID-19 YURAK QON TOMIR KASALLIKLARI BOR BEMORLARDA KECHISHI //Журнал кардиореспираторных исследований. - 2021. - Т. 2. - №. 2. - С. 47-50.

6. Cucinotta D., Vanelli M. Who Declares COVID-19 a pandemic. Acta Biomed. 2020;91(1):157-160. doi:10.23750/abm.v91i1.9397.

7. Dyer O. Covid-19: delta infections threaten herd immunity vaccine strategy. BMJ 2021;374. doi: 10.1136/bmj.n1933.

8. Sattar N., McInnes I. B., McMurray J. J. V. Obesity is a risk factor for severe COVID-19 infection: multiple potential mechanisms. Circulation 2020;142:4-6. doi: 10.1161/ circulationaha. 120.047659.

9. Sawadogo W., Tsegaye M., Gizaw A., Adera T. Overweight and obesity as risk factors for COVID-19 - associated hospitalisations and death: systematic review and meta-analysis. BMJ Nutrition, Prevention & Health 2022;0:e000375. doi:10.1136/ bmjnph-2021-000375.

10. Chen X, Chen Y, Wu C, Wei M, Xu J, Chao Y-C, Song J, Hou D, Zhang Y, Du C, Li X, Song Y. 2020. Coagulopathy is a major extrapulmonary risk factor for mortality in hospitalized patients with COVID-19 with type 2 diabetes. BMJ Open Diabetes Research & Care 8:e001851. DOI: https://doi.org/10.1136/bmjdrc-2020-001851, PMID: 33214191

11. UK Health Security Agency. 2022. The effectiveness of vaccination against long COVID A rapid evidence briefing. https://www.gov.uk [Accessed February 15, 2022].

12. Vimercati L, De Maria L, Quarato M, Caputi A, Gesualdo L, Migliore G, Cavone D, Sponselli S, Pipoli A, Inchingolo F, Scarano A, Lorusso F, Stefanizzi P, Tafuri S. 2021. Association between Long COVID and Overweight/Obesity. Journal of Clinical Medicine 10:4143. DOI: https://doi.org/10.3390/jcm10184143, PMID: 34575251

13. Worldometer. Available: https://www. worldometers.info/coronavirus Accessed 29 May 2022.