Determination of the temporary disability duration in patients with acute myocardial infarction depending on the body mass index

Prolonged temporary disability in patients with acute myocardial infarction (AMI) is more common in the presence of concomitant abnormalities. Adipokine C1q/TNF-related protein 3 (CTRP-3) is produced by adipose tissue and exhibits anti-inflammatory and cardioprotective properties. The course and prognosis of AMI depend on the presence of comorbid disorders and hence are objects of scientific interest.

Acute myocardial infarction (AMI) with comorbidity is a topical issue in practical medicine today. Complicated course of AMI is observed more often in the presence of concomitant abnormalities. One of these concomitant abnormalities is obesity, which is associated with the development of AMI [1]. According to G. Velazquez et al. [2], obese patients were more likely to develop inpatient mortality than those with normal body mass index (BMI), and the use of percutaneous coronary intervention improved the course of AMI in obese patients. According to E. Joyce et al. studies [3], adverse left ventricular (LV) and impaired LV deformation were found in patients with ST-segment elevation myocardial infarction (STEMI) and obesity compared with AMI patients and normal BMI. In our opinion, the length of hospital stay is an important indicator of the hospital resource effectiveness, and AMI-related complications in patients are the reasons for longer hospital stays.
Adipokine C1q/TNF-related protein 3 (CTRP-3 or cartonectin) has been shown to be involved in carbohydrate and lipid metabolism in obesity [4,5]. CTRP-3 exhibits anti-inflammatory and cardioprotective properties through signaling pathways, attenuates pathological remodeling of the heart after AMI, reduces cardiac dimensions and cardiomyocyte apoptosis, decreases interstitial fibrosis, improves survival rate, and restores the heart function [6].
Zhang C. L. et al. [7] found that CTRP-3 can inhibit cardiac fibrosis and promote mitochondrial biogenesis and bioenergetics in cardiomyocytes. However, the use of CTRP-3 as a factor influencing the length of hospital stay in AMI patients depending on BMI has not been studied to date and therefore is an object of scientific interest.
In our view, the proper use of hospital resources is important for controlling economic costs. According to S. Rehman et al. [8], patients with cardiogenic shock, higher lipid levels, and thyroid disease were more likely to be correlated with longer hospital stays. Improved funding for the diagnosis and treatment of patients might be determined by a decrease in the length of hospital stay. It is essential to identify a complex of risk factors associated with prolonged hospital stays among AMI patients of working age depending on BMI.

Aim
The aim of the study was to identify predisposing factors affecting the temporary disability duration in AMI patients depending on BMI.

Materials and methods
In this study we examined 189 subjects with ST-segment elevation AMI depending on BMI, admitted to the SI "L. T. Ma laya National Institute of Therapy of the National Academy of Medical Sciences of Ukraine" and Kharkiv Clinical Hospital on Railway Transport No. 1, a branch of the Health Care Center of the Ukrainian Railways Public Joint-Stock Company. The study was conducted from 01 September 2018 to 31 December 2020.
Patients with ST-segment elevation AMI were divided into 3 groups depending on BMI. Group 1 included 60 AMI patients with normal BMI, Group 2 involved 68 AMI patients with excess body weight (EBW) and Group 3 was composed of 61 AMI patients with obesity.
Exclusion criteria were diabetes mellitus type 1 and 2, autoimmune diseases, connective tissue diseases, SARS-CoV-2, pituitary and hypothalamic diseases, thyroid disease, the presence of symptomatic hypertension, cancer, chronic obstructive pulmonary disease, heart valve diseases, congestive heart failure IV FC AMI, severe liver and kidney dysfunction, severe anemia.
The author followed all the European Society of Cardiology 2017 guidelines for the diagnosis and management of patients with ST-segment elevation AMI [9]. The diagnosis of permanent atrial fibrillation (it is considered that there is no possibility to restore sinus rhythm for a long time period) was determined according to European recommendations [10]. Early complications included at least one of the parameters: acute LV failure (ALVF) according to Killip classes 1, 2, 3, 4 within 1-14 days, 2 nd -3 rd degree atrioventricular (AV) block within 1-14 days, recurrent AMI within 1-14 days. All the patients underwent stenting of the affected coronary artery and subsequently were given standard therapeutic agents. Laboratory parameters were measured in the Biochemical Central Research Laboratory of Kharkiv National Medical University. Serum was collected in 1-2 days following admission.
Serum concentration of CTRP-3 was identified by enzyme-linked immunosorbent assay using Labline-90 analyzer (Austria, No. 2910-2037) and commercial test systems "Human CTRP3" manufactured by Aviscera Bioscience Inc, Santa Clara, USA according to the instructions supplied with a kit. The mean value and reference range for CTRP-3 were set at 325.97 (274.59-399.96) ng/ml. Fasting blood glucose level was measured using glucose oxidase method. Total cholesterol (TC) and high-density lipoprotein cholesterol (HDLC) were determined by peroxidase method using a Human Cholesterol LiquiColor test kit (Germany). The level of triglycerides (TG) was determined by enzymatic colorimetric method using a set of reagents "Triglycerides GPO" produced by "Human" company (Germany). The atherogenic factor (AF) was calculated by the standard The optimal weight was defined using BMI (Quetelet index), calculated by dividing weight (in kilograms) by the square of the body height measured in meters. An individual was considered to be normal weight if the BMI was 18.5 kg/m 2 to 24.9 kg/m 2 , overweight if the BMI was 25 kg/m 2 to 29.9 kg/m 2 , and obese if it was 30 kg/m 2 or greater. The type of adipose tissue distribution was calculated by the waist circumference to thigh circumference (WC/TC) ratio. Abdominal obesity was diagnosed by the WC/TC ratio ≥0.90 for men and ≥0.85 for women [11]. Doppler echocardiographic examination was performed according to the generally accepted manner on an ultrasound scanner Radmir ULTIMA Pro30 [12]. All the patients underwent standard 12-lead electrocardiography using a three-channel electrocardiograph "Fukuda" FX˗326U (Japan).
The study was performed according to the World Medical Association Declaration of Helsinki "Ethical principles for medical research involving human subjects". Prior to the study, the patients were informed about the study purpose and possible results. The informed consent was signed by all participants. The study design was approved by the Ethics Commission of Kharkiv National Medical University (Minutes No. 2 dated 2 April 2018).
Statistical analysis. Statistical data were processed with the help of the licensed software package IBM SPPS Statistics (version 27.0) (IBM Inc., USA, license No. L-CZAA-BKKMKE). All quantitative indicators were checked for normal distribution with the Kolmogorov-Smirnov test. The results of descriptive statistics included indicators for normally distributed quantitative characteristic: mean (M) and standard deviation (SD). Nominal variables were expressed as number and percentage. t-Test for variables with normal distribution were used for paired comparison. The χ 2 test with Yates's correction was used to compare nominal variables depending on the group size. Significance of differences between normally distributed mean values of quantitative variables was assessed by ANOVA with Bonferroni correction for multiple comparisons. Logistic regression method was used to determine the temporary disability period. The difference was considered statistically significant at a value of P ˂ 0.05.

Results
BMI-dependent characteristics of AMI patients, including demographics and laboratory parameters, are shown in Table 1.
The data obtained from 189 AMI patients depending on BMI were included to build the model. The method was as follows: a patient was diagnosed with early complications (ALVF according to Killip classes 1, 2, 3, 4 within 1-14 days, 2 nd -3 rd degree AV block within 1-14 days, recurrent AMI where D is the number of disability days; X 1 -blood glucose on day 1, mmol/l; X 2 -permanent atrial fibrillation (1 -absent; 2 -present); X 3 -early complications of AMI (1 -absent; 2 -present); X 4 -cartonectin on day 1, ng/ml. The probability of the disability period duration was determined by the method of logistic regression and by the conversion log using the formula: -15.5) where Р -the probability of prolonged disability; е -the basis of the natural logarithm (е = 2.718); D -the number of disability days. The mean disability period in hospital patients was 15.5 days and if values ranged from 0.5 to 0.8, the probability was estimated as average, if more than 0.8 -as high, if less than 0.5 -as low.
All variables and the constants of the proposed model met the considered statistical significance at the level of P < 0.05. The mean relative error in calculating the number of work disability days was only 1.1 %.
Clinical example 1. A 57-year-old patient was hospitalized to the cardiology department with coronary heart disease (CHD). The patient was diagnosed with ST-segment elevation AMI (05.12.2019). According to medical history, the patient's risk profile included obesity. In the course of the treatment, the patient was not found to have recurrent chest pain, dizziness, resting or exertional breathlessness, arrhythmia and conduction disorders. On examination, his BMI was 25.7 kg/m 2 . Based on laboratory data, the glucose level on day 1 was 5.11 mmol/l, the content of cartonectin on day 1 was 301.2 ng/ml. The patient showed no signs of atrial fibrillation on electrocardiography (ECG). Calculation according to the proposed formula was as follows: D = 0.144 × 5.11 -3.056 × 1 + 5.288 × 1 --0.006 × 301.2 + 12.212 =13.37 and the probable duration of the patient's disability was determined as: = 0.11. 1 + e - (13.37 -15.5) Thus, the length of stay probability for the patient was defined as insignificant, the determined disability period in the hospital was 13 days. Therefore, the patient was discharged on day 12.
Clinical example 2. A 63-year-old patient was hospitalized to the cardiology department with CHD. The patient was diagnosed with ST-segment elevation (23.05.2019). The patient had a history of obesity over the last 5 years. In the treatment course, the patient presented with resting or exertional breathlessness. He was diagnosed with ALVF: pulmonary edema. BMI of 30.8 kg/m 2 was determined on examination, and grade 1 obesity was diagnosed. Based on the laboratory data, the glucose level on day 1 was 11.6 mmol/l, the cartonectin content on day 1 was 187.58 ng/ml. The patient showed no signs of atrial fibrillation on ECG. Calculation according to the proposed formula was as follows: Therefore, the probability of the hospital length of stay for the patient was defined as very high, the estimated disability period in the hospital was 20 days. Therefore, the patient was discharged on day 20.

Discussion
In our study, the risk factors for long-term temporary disability in AMI patients depending on BMI were the content of cartonectin on day 1, the presence of permanent atrial fibrillation, glucose level on day 1, at least one detected case of early complications of AMI. The use of glucose in the model can be explained by the fact that CTRP-3 was associated with carbohydrate metabolism. According to our study, cartonectin was associated with TC, LDLC, and TG in AMI patients with obesity.
Chen L. et al. [13] identified that CTRP-3 rates were significantly decreased in subjects with persistent atrial fibrillation compared with paroxysmal atrial fibrillation. In our opinion, a decrease in the concentration of cartonectin leads to a deterioration in the ability to protect the heart and thus may affect the process of LV myocardial remodeling in AMI patients with different BMI values. According to studies  [14], decreased CTRP-3 levels were associated with the presence of ventricular tachycardia in patients with heart failure and low ejection fraction. Jang S. et al. [15] determined that a longer stay was an independent prognostic factor for the increase in overall costs for both patients with non-ST elevation myocardial infarction and STEMI. Wasfy J. H. et al. [16] identified that the predictors of prolonged hospital stay were as follows: older age, heart failure on hospital admission, higher heart rate on admission, systolic blood pressure <150 mm Hg, cardiogenic shock, diabetes, decreased glomerular filtration rate and hemoglobin. Scientists S. Vallabhajosyula et al. [17] found that longer hospital stays, higher hospital costs, and fewer home discharges were associated with the development of LV aneurysms in patients with AMI.
According to C. Baechlia et al. [18], not only older age prolonged hospital stays compared to younger age, but hospital stays also depended on the presence of comorbid abnormalities.

Conclusions
1. The study showed the low CTRP-3 content in AMI patients depending on BMI indicating an imbalance in the adipokine system and the lesser impact of CTRP-3 on the inflammatory process in AMI.
2. Patients with AMI were found to have positive correlations between TC, LDLC, TG, AF. In contrast, AMI patients with obesity were shown to have inverse correlations between CTRP-3 and lipid metabolism, namely TC, LDLC, TG.
3. The study provided a possibility to elaborate the mathematical model for determining the temporary disability duration in AMI patients depending on BMI, which included the following indicators: glucose, cartonectin on day 1 day, the presence of a permanent atrial fibrillation and early complications of AMI.
Perspectives for further research. It is planned to study the effect of СTRP-3 on the condition of coronary arteries in AMI patients depending on BMI. We plan to determine the dynamics of the cartonectin level in AMI patients depending on BMI throughout a 1-year-follow-up.