Biomedical Research

Abstract

Objective: Our objective is to explore the clinical value of combined detection of N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP), blood lipid, coagulation, and fibrinolytic function in Pregnancy Induced Hypertension (PIH).

Methods: 172 PIH patients admitted in our hospital during February, 2014-Auguest, 2016 were included in the observation group, which were divided into mild (n=81), moderate (n=52) and severe (n=39) groups according to PIH severity. Meanwhile, 140 healthy pregnant women were included in the control group. NT-proBNP, blood lipid, coagulation, and fibrinolytic function in both groups were detected and the differences were compared. The correlation analysis was used to analyze the correlation of the above indexes with Mean Arterial Pressure (MAP).

Results: The MAP, NT-proBNP, TC, HDL-C, LDL-C, FIB, D-D and FDP in the observation group were higher than those in the control group, and the PT, APTT and TT of the observation group were lower than those of the control group, the differences were statistically significant (P<0.05). With the aggravation of PIH, the MAP, NT-proBNP, TG, HDL-C, TC, LDL-C, FIB, D-D and FDP were gradually increased, and the PT, APTT and TT were gradually decreased, the differences were statistically significant (P<0.05). Pearson correlation analysis showed that NT-proBNP, TC, TG, FIBG, D-D and FDP were positively correlated with MAP in PIH and PT, APTT and TT were negatively correlated with MAP in pregnant women with PIH (P<0.05).

Conclusion: The combined detection of NT-proBNP, blood lipid, blood coagulation and fibrinolytic function can reflect the severity of PIH patients, and provide a reference for the early diagnosis, treatment and prognosis evaluation of PIH.

Keywords

N-terminal pro-brain natriuretic peptide (NT-proBNP), Blood lipid, Coagulation and fibrinolysis, Pregnancy induced hypertension syndrome (PIH)

Introduction

Pregnancy Induced Hypertension (PIH) is a specific obstetric disease of pregnant women. It usually appears after 20 weeks of pregnancy, which is the common reason of poor prognosis or even death of perinatal infants [1-3]. In the developed countries, the morbidity of PIH is 6%-8%, and in China it’s even up to 9.4% [4-6]. Thus, how to diagnose and evaluate the severity of PIH is always the key point of clinical research, which is also the key to direct the proper intervention and guarantee the outcome of mothers and infants. The previous studies have shown that in the development of PIH, N-terminal pro-brain natriuretic peptide (NT-proBNP), blood lipid, coagulation and fibrinolytic function play important roles [1,7-11]. However, there is no study related to the exploration of the comprehensive influence of the above indexes. In this study, 172 PIH patients and 140 healthy pregnant women were selected, and the correlation of the above indexes and the PIH severity were analyzed.

Materials and Methods

General data

172 PIH patients admitted in our hospital during February, 2014-August, 2016 were included in the observation group, which were divided into mild (n=81), moderate (n=52) and severe (n=39) groups according to PIH criteria. Meanwhile, 140 healthy pregnant women were included in the control group. In the observation group, the age was 22-37 y old and the average age was 26.29 ± 5.32 y old, the body weight was 46-72 kg and the average weight was 54.26 ± 9.11 kg, the gestational week was 20-37 and the average gestational week was 27.66 ± 5.82. In the observation group, the age was 21-39 y old and the average age was 27.11 ± 5.58 y old, the body weight was 43-75 kg and the average body weight was 53.59 ± 10.63 kg, the gestational week was 20-38 and the average gestational weeks was 27.51 ± 5.90. The age, body weight, and gestational week between two groups were not statistically different (P>0.05), which were comparable. This study was approved by the Ethics Committee in our hospital, the pregnant women and the surrogates all signed the informed consent.

Inclusion criteria and exclusion criteria

The inclusion data of the observation group: the patients were conformed to the diagnostic criteria of PIH and the PIH degree was confirmed [6,12]. The inclusion data of control group: the patients received comprehensive physical examination, laboratory examination and image logical examination to confirm that they were in a good condition. Exclusion data: the patients had drug history that affects NT-proBNP, blood lipid, coagulation, or fibrinolytic function; the patients were complicated with the diseases that affect NT-proBNP, blood lipid, coagulation, or fibrinolytic function; the patients were complicated with thyroid dysfunction, heart, liver or kidney dysfunction, eclampsia, placental abruption, severe infection or malignant tumor; the patients were complicated with primary hypertension.

Detection methods

The detection of serum and plasmic indexes: 4 ml fasting venous blood on the second day was collected and kept in EDTA anti-coagulative tube. Then the tube was centrifuged at 3000 r/min for 10 min (the centrifugal radius was 13.5 cm). The serum was separated for NT-proBNP and blood lipid detection, and the plasma was separated for coagulation and fibrinolysis detection. Roche Diagnostics Elecsys 2010 Immunoassay Analyzer (F. Hoffmann-La Roche Ltd., Basel, Switzerland) was used to detect NT-proBNP by electro-chemiluminescence immunoassay, the kit was purchased from F. Hoffmann-La Roche Ltd., Basel, Switzerland; Hitachi 7180 Automatic Biochemical Analyzer (Hitachi, Ltd., Tokyo, Japan) was used to detect blood lipid indexes, including Total Cholesterol (TC), Triacylglycerol (TG), High Density Lipoprotein Cholesterol (HDL-C) and Low Density Lipoprotein Cholesterol (LDL-C); Sysmex CS-5100 Automated Coagulation Analyzer (Simens Co., Munich, Germany) was used to detect coagulation and fibrinolytic function by coagulation method and immunoturbidimetry, including Prothrombin time (PT), Activated Partial Thromboplastin Time (APTT), Thrombin Time (TT), Fibrinogen (FIB), D-Dimer (D-D) and Fibrin Degradation Product (FDP), all the kits were purchased from Simens Co., Munich, Germany.

Detection of Mean Arterial Pressure (MAP): 24 h dynamic blood pressure values of pregnant women were monitored by dynamic blood pressure analyzer. The blood pressure values at 6:00-8:00, 16:00-18:00 (peak time) and 2:00-3:00 (off-peak time) were recorded and MAP was calculated based on those values.

Statistical analysis

All the data in this clinical research were analyzed by SPSS 18.0 (International Business Machines Corp., New York, USA), the enumeration data were presented by (n/%) and analyzed by χ², and the measurement data were presented by (͞x ± s) and analyzed by t-test. The correlation was analyzed by Pearson correlation analysis and P<0.05 was considered as statistically significant.

Results

Comparison of indexes between the observation group and control group

The MAP, NT-proBNP, TC, HDL-C, LDL-C, FIB, D-D, FDP in the observation group were higher than those in the control group, and the PT, APTT and TT of the observation group were lower than those of the control group, the differences were statistically significant (P<0.05), as shown in Table 1.

Table 1: Comparison of NT-proBNP, blood lipid, coagulation and fibrinolytic function and MAP between the observation and control group (͞x ± s).

Comparison of NT-proBNP, blood lipid, coagulation, fibrinolytic function and MAP between the pregnant women with different PIH severity

With the aggravation of PIH, the MAP, NT-proBNP, TG, HDL-C, TC, LDL-C, FIB, D-D and FDP were gradually increased, and the PT, APTT and TT were gradually decreased, and the differences were statistically significant (P<0.05), as shown in Table 2.

Table 2: Comparison of different indexes between the pregnant women with different PIH severity (͞x ± s).

Correlation analysis

Pearson correlation analysis showed that NT-proBNP, TC, TG, FIBG, D-D and FDP were positively correlated with MAP in PIH, and PT, APTT and TT were negatively correlated with MAP in pregnant women with PIH (P<0.05), as shown in Table 3.

Table 3: The correlation analysis of NT-proBNP, blood lipid, coagulation and fibrinolytic function with MAP.

Discussion

During the pregnancy, the physical volume load is significantly increased, manifesting as the increase of the preload volume and left ventricle muscle mass, which is the main reason of the abnormity of hemodynamics and even the development of PIH [13-18]. As a disease that significantly affects the health of pregnant women and perinatal infants, PIH can cause the spasm of arteriole and increase of peripheral arterial resistance, and further increase the afterload of left ventricle. As the continuous development of PIH, the myocardial fiber remodelling is more and more obvious, which further causes concentric hypertrophy and left ventricle function change [19-21]. Thus, some scholars consider that due to that NT-proBNP can reflect the ventricular filling pressure increase and cardiocyte traction and the level is related to the cardiac function, serum NT-proBNP is expected to indicate the PIH severity [22].

In this study, NT-proBNP was combined with blood lipid, coagulation and fibrinolytic function to indicate the PIH severity. The results showed that except HDL-C and LDL-C, the other indexes were all related to PIH security, the mechanism may be the following: NT-proBNP is a biomarker that resists the increase of blood pressure, as the increase of the blood pressure the serum concentration is usually obviously increased to have diuretic, natriuretic and blood vessel dilating functions, and antagonize the volume load increase in PIH [23-26]. As the progress of PIH, MAP of the pregnant women is significantly increased, NT-proBNP concentration is also increased, which is considered as a sensitive index of PIH; the results also showed that as the progress of PIH, the hyperlipemia manifestation was more obvious, which is considered to be related to the decreased colloid osmotic pressure and increased urinary albumin excretion caused by PIH. These pathological changes can cause vascular endothelial injury and aggravated arteriosclerosis, and then further affect the development of the foetus [12,27-29]. In the severe cases, there is even hypoxia, organ failure and even death due to the decrease of anti-vascular disease ability; compared with the healthy pregnant women, PIH women are in coagulation and fibrinolysis unbalanced status manifesting as decreased PT, APTT, TT and increased FIB, D-D, FDP. Decreased PT indicates that some serum coagulation factors such as I, II, V, VI and X are activated, at that time the blood is at a hypercoagulation status and the thrombus formation risk is very high [30]. APTT can not only reflect the status of coagulation factor activation, but is also closely related to the prekallikrein activation, and shortened APTT is related to the endogenous blood coagulation [31]. Shortened TT indicates that the plasma heparinoids and fibrin degradation product are increased [32]. The fibrinmonomer produced from fibrin by the thrombin mainly participate in the hemostatic process. Thus, the change of TT and FIB indicate that the body of PIH women is in a prethrombotic state [33]. As the increase of severity, the risk of thrombus is increased and is more reliable to have eclampsia. The increase of D-D and FDP indicates that the body is at a coagulation and fibrinolysis activated state, in this case there are primary and secondary hyperfibrinolysis and the coagulation factors are significantly consumed. Thus there is high risk of thrombus formation and postpartum haemorrhage, and the risk of kidney failure is also increased [34,35].

In clinical practice, the evaluation of PIH is always a difficult point, and the early prediction of PIH is also a big difficulty in medical field. In this study, NT-proBNP, blood lipid, coagulation, and fibrinolytic function were all different between the PIH and non-PIH patients, or different PIH degree. The above indexes are correlated to the MAP of pregnant women. Thus, the combined detection of the above indexes can provide a reference for the early diagnosis, disease evaluation, treatment decision and prognosis judgment, which is worthy of further attention.

The limitation of this is that the diagnostic criteria are a relatively older version, which may cause the screening omission of some patients. Besides, the sample volume in this study is only 172, which cannot fully reflect the whole PIH population in China. In the further study, a larger size prospective analysis will be conducted to further clarify the effects of the NT pro-BP, blood lipid, coagulation and fibrinolytic function on the diagnosis and treatment of PIH.

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