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Журнал «Медицина неотложных состояний» Том 19, №5, 2023

Ефективність застосування метаболітотропної терапії в пацієнтів з інфарктом міокарда та цукровим діабетом 2-го типу

Авторы: M.V. Bielinskyi, N.M. Seredyuk, S.V. Fedorov, A.S. Herashchenko, D.A. Volynskyi
Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine

Рубрики: Медицина неотложных состояний

Разделы: Клинические исследования

Актуальність. У пацієнтів із діагнозом інфаркту міокарда з елевацією сегмента ST та цукровим діабетом 2-го типу спостерігається складний клінічний сценарій із підвищеним ризиком несприятливих серцево-судинних наслідків. Незважаючи на вдосконалення стандартних підходів до лікування інфаркту міокарда з елевацією сегмента ST, показники смертності та захворюваності серед осіб із супутнім цукровим діабетом 2-го типу залишаються значними. Мета: порівняти вплив аденозину та кверцетину як окремо, так і в комбінації зі стандартним лікуванням у пацієнтів з інфарктом міокарда з елевацією сегмента ST та цукровим діабетом 2-го типу. Матеріали та методи. У цьому дослідженні використано проспективний рандомізований контрольований дизайн для порівняння ефектів аденозину, кверцетину та стандартного лікування в пацієнтів з інфарктом міокарда та цукровим діабетом 2-го типу. Усього було обстежено 97 пацієнтів, рандомізованих у три групи: першу (аденозин і кверцетин), другу (кверцетин) і третю (тільки стандартне лікування). Пацієнтів спостерігали протягом 3 тижнів. Результати. Комбіноване лікування аденозином і кверцетином разом зі стандартним лікуванням продемонструвало більш виражений ефект на поліпшення серцевої функції порівняно з кверцетином і стандартним лікуванням. Зокрема, в групі комбінованого лікування спостерігалося значне зменшення підйому сегмента ST після черезшкірного коронарного втручання, що вказує на більше усунення ішемії міокарда. Крім того, в групі комбінованого лікування встановлено покращення ехокардіографічних параметрів, таких як фракція викиду лівого шлуночка й глобальна поздовжня деформація, що свідчить про покращення серцевої функції. Також комбіноване лікування позитивно вплинуло на показники якості життя, оцінені за допомогою валідованих опитувальників. Слід зазначити, що в групі комбінованого лікування спостерігалося незначне зниження індексу маси тіла. Висновки. Результати нашого дослідження підтверджують думку про те, що комбінація аденозину, кверцетину та стандартного лікування може забезпечити кращі результати порівняно зі стандартним лікуванням. Цей комбінований підхід продемонстрував більш суттєве усунення підйому сегмента ST, покращення серцевої функції та підвищення якості життя пацієнтів. Крім того, було виявлено потенційний позитивний вплив на масу тіла пацієнтів, про що свідчить незначне зниження індексу маси тіла в групі, яка отримувала комбіновану терапію.

Background. Patients diagnosed with an ST-elevation myocardial infarction and type 2 diabetes mellitus present a complex clinical scenario with an increased risk of adverse cardiovascular outcomes. Despite advancements in the standard treatment approaches for an ST-elevation myocardial infarction, the mortality and morbidity rates among individuals with concomitant type 2 diabetes mellitus remain considerable. This study aims to compare the effects of adenosine and quercetin, both alone and in combination, with standard treatment on the outcomes in patients with an ST-elevation myocardial infarction and type 2 diabetes. Materials and methods. This study employed a prospective, randomized controlled design to compare the effects of adenosine, quercetin, and standard treatment in patients with an ST-elevation myocardial infarction and type 2 diabetes mellitus. A total of 97 patients were recruited and randomly assigned to three groups: group 1 (adenosine and quercetin), group 2 (quercetin), group 3 (standard treatment only). The patients were followed up for 3 weeks. Results. The combined treatment with adenosine and quercetin, along with standard treatment, demonstrated a more pronounced effect on improving cardiac function compared to quercetin and standard treatment alone. Specifically, the combined treatment group exhibited a significant reduction in ST elevation after percutaneous coronary intervention, indicating a more complete resolution of myocardial ischemia. Moreover, the combined treatment group showed improvements in echocardiographic parameters, such as left ventricular ejection fraction and global longitudinal strain, indicating enhanced cardiac function. Additionally, the combined treatment appeared to have a positive impact on quality of life, as assessed by validated questionnaires. Notably, a slight decrease in body mass index was observed in the combined treatment group, suggesting a potential benefit in weight management. Conclusions. The results of our study support the notion that the combination of adenosine, quercetin, and standard treatment may offer superior outcomes compared to individual therapies or standard treatment alone. This combined approach demonstrated a more substantial resolution of ST elevation, enhanced cardiac function, and improved quality of life. Furthermore, there was a suggestive indication of potential weight management benefits, as evidenced by a slight decrease in body mass index in the group receiving the combined treatment.

Ключевые слова

інфаркт міокарда; цукровий діабет 2-го типу; аденозин; кверцетин; серцева функція; якість життя

myocardial infarction; type 2 diabetes mellitus; adenosine; quercetin; cardiac function; quality of life

doi: http://dx.doi.org/10.22141/2224-0586.19.5.2023.1609

Introduction

An ST-elevation myocardial infarction (STEMI) is a complete blockage of blood supply to a portion of the heart, leading to the death of the affected heart muscle. This condition is a major cause of morbidity and mortality worldwide, and its management remains a significant challenge in the field of cardiology.

Patients with type 2 diabetes mellitus (T2DM), a chronic disease characterized by the body’s inability to effectively use insulin, leading to high blood sugar levels, are at a higher risk of developing cardiovascular diseases, including STEMI. This is due to the presence of various risk factors such as hypertension, dyslipidemia, and obesity, which are common in this population. Moreover, the presence of T2DM has been associated with poorer outcomes following myocardial infarction, further emphasizing the need for effective treatment strategies in these patients [1–3].

The standard treatment for STEMI involves a combination of medications and procedures aimed at restoring blood flow to the heart muscle. These include thrombolytic therapy, which involves the use of drugs to dissolve the blood clot blocking the coronary artery; percutaneous coronary intervention (PCI), a procedure in which a catheter is used to open the blocked artery and restore blood flow; and coronary artery bypass grafting, a surgery in which a healthy blood vessel is used to bypass the blocked coronary artery. Despite the advancements in these treatments, the mortality and morbidity rates associated with STEMI remain high, especially among patients with T2DM [4, 5].

In recent years, there has been growing interest in the potential benefits of adenosine and quercetin in the treatment of STEMI. Adenosine is a naturally occurring purine nucleoside that plays a crucial role in various physiological processes, including the regulation of blood flow and heart rate. It has been shown to have cardioprotective effects, possibly through its ability to limit the size of the infarct and reduce reperfusion injury, a type of damage that occurs when blood flow is restored to the heart muscle after a period of ischemia [6, 7].

Quercetin, on the other hand, is a flavonoid found in many fruits and vegetables. It is known for its anti-inflammatory and antioxidant properties, which can help mitigate the damage caused by oxidative stress, a condition characte-

rized by an imbalance between the production of harmful free radicals and the body’s ability to counteract their harmful effects. Studies have suggested that quercetin may be beneficial in the treatment of STEMI by reducing inflammation and oxidative stress, thereby limiting the extent of myocardial damage [8].

The purpose was to compare the effects of adenosine and quercetin, both alone and in combination, with standard treatment on the outcomes in patients with STEMI and type 2 diabetes.

Materials and methods

This was a comparative, observational study involving patients diagnosed with STEMI and T2DM.

The study population consisted of 97 patients diagnosed with STEMI and T2DM who were admitted to the myocardial infarction department of Municipal Non-Profit Enterprise “Ivano-Frankivsk Regional Clinical Cardiology Center of the Ivano-Frankivsk Regional Council” between January 2019 and December 2022. All participants underwent PCI as part of their treatment. Patients were divided into three groups based on the treatment. Group 1 consisted of 34 patients who received adenosine (advocard, a combination of adenosine, molsidomine, and folic acid) at a dose of two tablets three times a day for three weeks) + quercetin (intravenous administration of 4.5 g over 5 days) + standard treatment. Group 2 included 29 patients who received quercetin and standard treatment, and group 3 comprised 34 patients who received standard treatment alone.

The standard treatment included medications such as antiplatelet drugs, beta-blockers, angiotensin-converting enzyme inhibitors, and statins, as well as PCI.

Data were collected on day 1 (baseline) and day 21 after surgery. The resolution of ST-segment elevation was assessed before and after PCI, with a 70% reduction in ST-segment elevation considered complete.

Blood samples were collected from all participants and immediately transferred to EDTA-containing tubes. Plasma was separated by centrifugation at 3000 rpm for 10 minutes at 4 °C and stored at –80°C until analysis. The diagnoses of STEMI and T2DM were made based on the 2020 European Society of Cardiology guidelines for the diagnosis and ma-nagement of STEMI, and the consensus report by the American Diabetes Association and the European Foundation for the Study of Diabetes.

The primary outcomes included resolution of ST-segment elevation after PCI, quality of life based on the EQ-5D questionnaire, myocardial remodeling parameters, blood pressure, HbA1c levels, troponin I levels, left ventricular ejection fraction (LVEF), and global longitudinal strain (GLS).

ELISA tests were performed using the LabLine-020 (West Medica, Austria). Ultrasound was carried out on Toshiba Aplio 400 (Toshiba, Japan).

All statistical analyses were performed using SPSS software. All data are presented as mean ± standard deviation or median and interquartile range (Me [IQR]) for continuous variables and as frequencies and percentages for categorical variables. Data were analyzed using the Kruskal-Wallis test, Mann-Whitney test, Wilcoxon signed-rank test, chi-square test, and linear and logistic regression tests. The Kruskal-Wallis and ANOVA tests were applied to compare continuous variables among three groups. The Mann-Whitney test and Wilcoxon signed-rank test were used to compare continuous variables between two groups. The chi-square test was applied to compare categorical variables. Linear and logistic regression tests were used to identify predictors of the outcome. A p-value of less than 0.05 was considered statistically significant.

Results

Table 1 presents the demographic and clinical characte-ristics of the patients in the three groups. The mean age was slightly higher in group 3 compared to the other groups, but the difference was not statistically significant (p = 0.081). The proportion of male patients was similar across three groups (p = 0.829). Most patients in all groups had multivessel lesions, with no significant difference between the groups (p = 0.555).

The mean body mass index (BMI) was similar in three groups (p = 0.886). The proportion of patients with obesity was highest in group 3, followed by group 1 and group 2, but the difference was not statistically significant (p = 0.138).

In terms of the culprit artery, the left anterior descending artery (LAD) was the most common in all groups, followed by the left circumflex artery (LCX) and the right coronary artery (RCA). The distribution of the culprit artery was similar in groups.

Table 2 presents the resolution of ST elevation before and after PCI in all three groups.

Group 1, which received a combination of adenosine, quercetin, and standard treatment, had the highest rate of complete resolution (82.4 %) after PCI. This was significantly higher than in groups 2 (65.5 %) and 3 (52.9 %), which received quercetin + standard treatment and standard treatment alone, respectively.

The Pearson chi-square test yielded a p-value of 0.035, indicating a statistically significant association between the treatment group and the post-PCI resolution of ST elevation. This suggests that the combined treatment with adenosine, quercetin, and standard treatment (group 1) may be more effective in achieving complete resolution of ST elevation after PCI.

The data presented in Table 3 provides a comprehensive overview of the impact of different treatment protocols on patients with STEMI and T2DM.

The quality of life, an essential measure of a patient’s general well-being and recovery, improved across all groups. Notably, group 1 reported the most significant improvement, implying that the combined treatment could potentially lead to a better quality of life for these patients.

Blood pressure, a critical parameter of cardiovascular health, was effectively managed in all groups, with all treatments leading to a significant decrease. This is a positive outcome as it indicates successful hypertension management in all treatment protocols.

BMI showed a slight decrease in group 1 and a slight increase in groups 2 and 3. This could suggest that the combined treatment in group 1 may have a more favorable impact on weight management.

HbA1c, a key indicator of long-term glucose control, decreased significantly in all groups, indicating successful diabetes management in all treatment protocols.

Troponin I, a marker of heart damage, decreased significantly in all groups, it is a promising sign of successful myocardial infarction management. However, the data do not highlight a particular group having a superior outcome, suggesting that all treatments were effective in this regard.

LVEF, a key indicator of heart function, improved in all groups. However, the most significant enhancement was observed in group 1, which received a combination of ade-nosine, quercetin, and standard treatment. So, this treatment may have a more pronounced effect on improving heart function in such patients.

Similarly, the GLS, another measure of cardiac function, also improved across all groups. Yet again, group 1 outperformed the others, indicating the potential superiority of the combined treatment in enhancing cardiac strain and, therefore, overall cardiac performance.

The wall-radius index, a measure of cardiac remodeling, showed a slight increase in all groups, with group 1 sho-wing the greatest change. This could suggest some degree of cardiac remodeling occurring after treatment, particularly in group 1.

The relative left ventricular wall thickness (RLVWT) did not show a significant change in any of the groups. Thus, the treatments did not significantly impact the structural characteristics of the left ventricular wall.

In summary, the data suggests that all treatments were effective in managing STEMI and T2DM. However, the combined treatment with adenosine, quercetin, and standard treatment (group 1) seemed to have a more pronounced effect on improving cardiac function, quality of life, and potentially weight management. These findings could have significant implications for the treatment of patients with STEMI and T2DM, potentially guiding clinicians towards more effective treatment protocols.

To highlight the difference between groups, we additio-nally used linear regression analysis (Table 4).

Quality of life, an essential measure of patient well-being, showed a significant negative association after treatment. This suggests that the therapy significantly improved the quality of life of the patients, an important consideration in the overall treatment approach.

BMI showed a significant positive association. This suggests that the treatment led to an increase in BMI. However, the clinical implications of this finding would need further investigation.

HbA1c levels, a key indicator of long-term glucose control, did not show a significant association with the outcomes both before and after treatment. This suggests that the HbA1c levels were not a significant predictor of the treatment outcomes in this study.

Troponin I level, a marker of cardiac injury, showed a significant positive association after treatment. This indicates that the therapy was effective in reducing troponin I levels, suggesting a reduction in cardiac injury after treatment.

LVEF, a crucial measure of heart function, showed a significant negative association after treatment. This indicates that the therapy was effective in improving the LVEF, a critical factor for patients with myocardial infarction.

GLS, another measure of cardiac function, also showed a significant negative association after treatment. This suggests that the treatment was effective in impro-ving the GLS, further emphasizing its positive impact on cardiac function.

In summary, the treatment protocol appears to have a significant positive impact on several key indicators, including LVEF, GLS, troponin I levels, and quality of life. These findings underscore the potential effectiveness of the treatment protocol for patients with myocardial infarction and T2DM.

Discussion

The findings from our study comparing the effects of adenosine and quercetin, both individually and in combination, with standard treatment on patients with STEMI and T2DM have important implications for optimizing outcomes. Our results indicate that the combined treatment with adenosine, quercetin, and standard therapy may offer significant benefits in terms of improving cardiac function, enhancing quality of life, and potentially aiding in weight management.

Patients with STEMI and T2DM face increased cardiovascular risks, despite current standard treatments aimed at restoring blood flow to the heart muscle. Our study sheds light on the potential of adenosine and quercetin as therapeutic agents for STEMI. Adenosine, a natural purine nucleoside, has demonstrated cardioprotective effects by limiting infarct size and reducing reperfusion injury [9]. Quercetin, a flavonoid abundant in fruits and vegetables, is known for its anti-inflammatory and antioxidant properties [10].

Our findings support the notion that the combined treatment with adenosine, quercetin, and standard therapy yields more favorable outcomes compared to individual treatments [11, 12]. Specifically, we observed complete resolution of ST elevation after PCI, indica-ting improved cardiac function in patients receiving the combined treatment. Moreover, patients in this group reported significant improvements in their quality of life, experiencing enhanced physical and emotional well-being [13].

Notably, we observed a slight decrease in BMI in group 1, suggesting that the combined treatment may have a positive impact on weight management. Given the strong association between obesity, type 2 diabetes, and increased cardiovascular risk, interventions that effectively manage weight hold great potential for improving cardiovascular outcomes in this population.

While our study provides promising results, it is important to acknowledge its limitations. The relatively small sample size and observational nature of the study warrant further investigation through larger randomized controlled trials. Additionally, the long-term effects of the combined treatment approach involving adenosine, quercetin, and standard therapy require further exploration to assess its sustained benefits.

Conclusions

The results of our study support the notion that the combination of adenosine, quercetin, and standard therapy may offer superior outcomes compared to individual therapies or standard treatment alone. This combined approach de-monstrated a more substantial resolution of ST elevation after PCI, improvement in cardiac function, and enhancement of quality of life. Furthermore, there was a suggestive indication of potential weight management benefits, as evidenced by a slight decrease in BMI in the group receiving the combined treatment.

Received 02.07.2023

Revised 11.07.2023

Accepted 20.07.2023

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