Correlation between serum laminin level and prognosis of acute heart failure

Abstract Objective To investigate the correlation between serum laminin (LN) level and the prognosis of acute heart failure (AHF). Methods A total of 199 patients with AHF treated in Nantong First People's Hospital from March 2019 to November 2021 were included in this study. The patients were divided into the event group and the non‐event group according to whether major adverse cardiovascular events (MACEs) occurred during hospitalization. We collected the baseline data of all patients and their LN levels were measured. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of LN for the occurrence of MACE in AHF patients during hospitalization. Multivariate Logistic regression analysis was used to screen the independent factors associated with the occurrence of MACE in patients with AHF. Results Among 199 patients with AHF, 43 were in the event group and 156 were in the non‐event group. The area under ROC curve of LN to predict MACE in AHF patients during hospitalization was 0.8144, 95% confidence interval (CI): 0.7433–0.8855, p < .0001, cutoff point = 77.9, specificity 58.33%, and sensitivity 88.37%. Multivariate logistic regression analysis showed that the independent factors associated with the occurrence of MACE in AHF patients were the increase of LN level (odds ratio [OR]: 1.020, 95% CI: 1.012–1.028), the decrease of ejection fraction (OR: 0.007, 95% CI: 0.000–0.362) and diastolic blood pressure (OR: 0.946, 95% CI: 0.913–0.981; p < .05). Conclusion The increase of LN level is independently correlated with the occurrence of MACE in AHF patients during hospitalization, which has the potential to be a serological indicator for poor prognosis in patients with AHF.

Compared with chronic heart failure, acute heart failure (AHF) is a group of clinical syndromes with rapid onset or deterioration of symptoms and signs, 1 and patients are often complicated with organic cardiovascular diseases before onset. This disease can be broadly defined as a "malignant disease" because its high mortality rate exceeds that reported for most cancer diseases. 2,3 Although the etiology of heart failure is complex, the activation of neurohormones and the increase of inflammatory mediators can be said to be the key factors in the development of ventricular remodeling and heart failure. 4 Myocardial fibrosis caused by excessive deposition of myocardial extracellular matrix is the main pathological manifestation of ventricular remodeling. 5 Extracellular matrix is a complex network structure with both strength and plasticity, which is composed of structural proteins and nonstructural proteins, and laminin (LN) is the main component. 6 However, the current studies on LN and heart failure mostly focus on basic research, and there are few clinical studies on the correlation between serum LN level and the prognosis of AHF. Therefore, the aim of this study was to investigate the correlation between LN and prognosis in patients with AHF.

| Research objects
A total of 210 patients with AHF treated in Nantong First People's Hospital from March 2019 to November 2021 were included in this study. Eleven patients were censored from the analysis due to the following reasons: patients regretting being included in the study, poor patient compliance and withdrawal from the study, and patients lost to follow-up without access to relevant data. In the end, only 199 people were included in the study. The flow chart is shown in Figure 1

| Collection of baseline data
The basic information of all patients at admission was obtained from medical records, including gender, age, history of diabetes and hypertension, blood pressure, heart rate, liver and kidney function, NT-proBNP, C-reactive protein, electrocardiogram, echocardiogram, and so forth.

| LN detection
In the morning of the next day after admission, 4 mL of fasting venous blood was collected from all enrolled patients, centrifuged for 10 min at a | 819 rate of 2500 r/min. Serum LN levels were determined by chemiluminescence immunoassay (MAGLUMI2000). The kit is provided by Fosun Diagnostic Company. The normal reference range of LN kit in this study is 0.51-50 ng/mL.

| Major adverse cardiovascular events
Major adverse cardiovascular events (MACEs) are the most commonly used complex endpoints in cardiovascular studies, including a combination of clinical events: death, nonfatal cardiac events, nonfatal cerebrovascular events, and so forth. 8

| Statistical processing
SPSS25.0 statistical software was used for data analysis. T test was used to evaluate continuous variables with normal distribution, expressed as mean ± standard deviation; Chi-square test was used to evaluate categorical variables; Mann-Whitney U test was used to evaluate measurement data with skewed distribution, expressed as median (25%-75%). p < .05 was considered statistically significant.
Multivariate Logistic regression analysis was used to screen the independent factors associated with MACE in AHF patients during hospitalization. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of LN for MACE in patients with AHF during hospitalization. GraphPad Prism8 was used for plotting. Table 1 summarizes the baseline characteristics of the AHF event group and the non-event group. Compared with the non-event group, the levels of NT-proBNP, LN, urea nitrogen, creatinine, and C-reactive protein in the event group were significantly increased (p < .05). The EF, systolic blood pressure, and diastolic blood pressure levels of patients in the event group were significantly lower than those in the non-event group (p < .05). There were no significant differences in cardiac troponin I (CTNI), gender, age, hypertension, diabetes, heart rate, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, direct bilirubin and indirect bilirubin between the two groups (p > .05). which is the cutoff point. In this experiment, the maximum value of the Youden index is 0.467, the corresponding cutoff point is 77.9 ng/mL, the specificity is 58.33%, and the sensitivity is 88.37%. This means that when LN is higher than 77.9 mmol/L, it has a good predictive value for MACE in patients with AHF during hospitalization (see Figure 2).

| Multivariate logistic regression analysis
To explore the independent factors associated with MACE in patients with AHF during hospitalization, LN, NT-proBNP, EF, CTNI, gender, age, presence or absence of hypertension, presence or absence of diabetes, systolic blood pressure, diastolic blood pressure, heart rate, collagen IV, ALT, AST, total bilirubin, direct bilirubin, indirect bilirubin, creatinine, urea T A B L E 1 Comparison of baseline data between the two groups. Although great progress has been made in medical equipment and treatment, the prognosis of patients with AHF is still poor. Its high morbidity and mortality make this disease a major public health problem and a major challenge for current cardiovascular research.
LN was first discovered and named by Timple et al. in 1979. It is a family of heterodimeric trimer glycoproteins composed of one heavy chain and two light chains. 9 As one of the components of interstitial cells, it is mainly secreted in the hyaline layer of basement membrane, plays the role of adhesion to epithelial cells and matrix, and jointly maintains the network structure of basement membrane with type Ⅲ collagen, thus participating in the process of fibrosis. 10 In the past, it was common in the study of fibrosis in liver, lung, and other organs. There are few clinical studies on the relationship between LN and heart failure, especially AHF. These studies confirm that LN is involved in myocardial fibrosis, and we speculate that the increase of LN reflects a more severe degree of myocardial fibrosis and predicts more adverse cardiovascular events. If this index is included in the existing risk stratification of heart failure, it may be able to predict the adverse outcome of patients early and can be intervened as soon as possible, which can improve the prognosis of patients to some extent. In addition, LN may be used as a therapeutic target for heart failure, changing cardiomyocytes and improving the prognosis of heart failure. 10 Of course, this study also has some limitations, such as the overall sample size is small, and this study is a cross-sectional study, although it has been confirmed that there is an independent correlation between LN and poor prognosis of AHF, but large-scale prospective studies are still needed to further confirm this conclusion.