Effect of Blood Pressure Level at Admission on In-Hospital Case-Fatality Rate in Patients with Aortic Dissection

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Effect of Blood Pressure Level at Admission on In-Hospital Case-Fatality Rate in Patients with Aortic Dissection

https://doi.org/10.21203/rs.3.rs-1628275/v1

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Objective: To observe the correlation between the blood pressure level at admission in patients with aortic dissection and the in-hospital case-fatality rate.

Methods: A retrospective analysis was carried out on the clinical data of 580 aortic dissection patients (198 cases of Stanford type A aortic dissection and 382 cases of Stanford type B aortic dissection) who were hospitalized in our hospital from 2011 to 2018. According to the level of blood pressure at admission, the patients were assigned into five groups: group A (90-119/60-79 mmHg, n=107), group B (120-139/80-90 mmHg, n=121), group C (140-159/90-99 mmHg, n=140), group D (160-179/100-109 mmHg, n=107) and group E (≥180 mmHg, n=105). The number of cases of different types of aortic dissections, treatment methods and number of deaths at discharge were recorded in each group.

Results: No statistically significant differences in the sex, and histories of smoking, drinking, hypertension and diabetes were observed among the five groups (p>0.05). Group A exhibited higher proportions of patients with Stanford type A aortic dissection and Marfan syndrome, a younger mean age of patients, a lower heart rate of patients at admission and more cases of surgical treatment than the other groups (p<0.01). The proportions of cases of pain at admission, Stanford type B aortic dissection and interventional therapy in groups D and E were higher than those in the other groups (p<0.01). Of 580 inpatients, there were 87 (15%) cases of death, and the in-hospital case-fatality rate in group A was higher than that in the other groups (p<0.01). Group E had a lower in-hospital case-fatality rate than groups A, B, C and D (p<0.05), and the differences among the latter three groups were statistically significant (p<0.05). Therefore, the in-hospital case-fatality rate declined with the increase in the level of blood pressure at admission.

Conclusion: A lower blood pressure level (<120/80 mmHg) and a higher blood pressure level (>160/100 mmHg) at admission in patients with aortic dissection can predict the classification of aortic dissection to a certain extent. The patients with a higher blood pressure level have obvious symptoms at admission and receive prompt treatments, and among them, more patients suffer from Stanford type B aortic dissection and undergo interventional therapy, so the overall case-fatality rate can be decreased.

aortic dissection

blood pressure

prognosis

Aortic dissection is the most devastating acute aortic syndrome ^[1] that is caused by many factors, such as hypertension, atherosclerosis, arteritis and trauma. In addition to trauma, the breakage and necrosis of aortic medial elastic fibers are the fundamental pathological changes of aortic dissection. The annual morbidity rate of aortic dissection is about 30/1,000,000 ^[2]. It was proposed in the study of Coady MA et al from Yale University (USA) ^[3] that if acute Stanford type A aortic dissection is not treated, its mortality rate will be increased by 1% per 1 h, and the 3-day and 2-week mortality rates will reach up to 50% and 80%, respectively. Evangelista A et al ^[4] pointed out in their study that acute Stanford type B aortic dissection has a slightly lower mortality rate, but its mortality rate can still reach up to 10% within 30 d, and remains as high as 70% and even above in patients with complications. Hypertension has long been considered as the leading risk factor for aortic dissection ^[5], which plays an important role in the development and progression of aortic dissection. The aim of the present study is to observe the effect of blood pressure level at admission in patients with aortic dissection on the in-hospital case-fatality rate and emphasize special attention to be paid to such a simple but non-negligible clinical indicator blood pressure in treating aortic dissection.

Enrollment of patients

A total of 580 aortic dissection patients hospitalized in our hospital from January 2012 to December 2018 were enrolled according to the criteria for the diagnosis of aortic dissection in the Guidelines for the Diagnosis and Management of Patients with Thoracic Aortic Disease formulated by ACCF/AHA in 2010 ^[6], and the aortic dissection was classified using the common Stanford classification. Blood pressure was measured at the right upper limb of patients upon admission. According to the level of blood pressure at admission, the patients were assigned into five groups: group A (90–119/60–79 mmHg), group B (120–139/80–90 mmHg), group C (140–159/90–99 mmHg), group D (160–179/100–109 mmHg), and group E (≥ 180 mmHg), and the total number of patients, number of in-hospital deaths and number of survivors in each group were recorded (Fig. 1).

Methods

A retrospective analysis was performed on the inpatients, and the sex, age, presence or absence of pain at admission, history of smoking, history of drinking, past medical history, diagnosis at admission, duration from admission to definite diagnosis of aortic dissection, total dose of intravenously administered beta (β)-blocker for controlling blood pressure at the target level from admission, blood pressure and heart rate at admission, treatment methods after admission, and number of in-hospital deaths were recorded in detail.

2. Statistical analysis

The data of patients eligible for hospitalization were pooled and statistically analyzed using SPSS 18.0 software. Measurement data were presented as (mean ± SD)and compared among groups using one-way analysis of variance. Besides, the influencing factors for the case-fatality rate were statistically analyzed via logistic regression analysis. The differences were considered to be statistically significant at p < 0.05.

Clinical data

Among 580 patients, there were 455 (78.4%) males and 125 (21.6%) females at a ratio of 4:1, and there were no statistically significant differences in the sex, and histories of smoking, drinking, hypertension and diabetes among the five groups (Table 1). Group A exhibited a higher proportion of cases of Marfan syndrome (p<0.05), a younger mean age of patients (p<0.05) and a lower heart rate of patients at admission (p<0.01) than the other groups. Groups D and E had a higher proportion of patients with pain than the other groups (p<0.01). The duration from admission to definite diagnosis of aortic dissection in group E [(5.5±2.7) h] was shorter than that in group A [(14.7±10.8) h], group B [(11.6±7.1) h], group C [(9.6±5.1) h] and group D [(8.0±3.7) h] (p<0.05) (Figure 2), and statistically significant differences were also observed among the latter four groups (p<0.05). Group E showed a larger dose of β-blocker for controlling blood pressure at the target level from admission than the other four groups (p<0.001) (Figure 3).

Classification of aortic dissection, treatment methods and case-fatality rate in patients with different blood pressure levels after admission

As shown in Table 2, the proportion of patients with Stanford type A aortic dissection in group A was higher than that in the other groups (p<0.01), and group D and group E had more cases of Stanford type B aortic dissection than the other groups (p<0.01). Groups A and B had more patients receiving surgical treatment than the other groups (p<0.01), whereas groups D and E had more cases of interventional therapy than the other groups (p<0.01). Additionally, 87 (15%) out of 580 inpatients died, and the case-fatality rate was the highest in group A (24.3%) (p<0.01), and the lowest in group E (9.52%) (p<0.05), with statistically significant differences among group B (15.7%), group C (14.3%) and group D (11.2%) (p<0.05). It can be inferred that the in-hospital case-fatality rate declines with the increase in the level of blood pressure at admission.

3. Logistic regression analysis of influencing factors for the in-hospital case-fatality rate

According to the univariate analysis results of factors influencing the in-hospital case-fatality rate, the histories of drinking and hypertension, blood pressure, heart rate and pain at admission, Marfan syndrome, Stanford classification of aortic dissection, treatment methods and dose of intravenously administered β-blockers for controlling blood pressure at the target level from admission obviously affected the in-hospital case-fatality rate (p<0.05). The above factors were assigned into the logistic regression formula. It was found that after correcting other factors, the history of hypertension at admission and Marfan syndrome were the independent risk factors for the in-hospital case-fatality rate, while Stanford type B aortic dissection, pain at admission and interventional therapy were the protective factors for the in-hospital case-fatality rate (Table 3).

Table 1: Clinical data of aortic dissection patients with different levels of blood pressure at admission [n (%),mean±SD]

Parameter

Group A

n=107

Group B

n=121

Group C

n=140

Group D

n=107

Group E

n=105

Male

Pain

Smoking

Drinking

Hypertension

Diabetes

Marfan syndrome

Age (year old)

Heart rate (beat/min)

Duration from admission to definite diagnosis (h)

Dose of intravenous β-blockers (mg)

84 (78.5)

42 (39.3)

48 (44.9)

36 (33.6)

65 (60.7)

3 (2.8)

15 (14.0)^b

51±13^c

78±17

14.7±10.8

34±279.52

91 (75.2)

56 (46.3)

67 (55.4)

50 (41.3)

70 (57.9)

4 (3.3)

15 (12.4)

56±13

79±18

11.6±7.1

134±102

104 (74.3)

72 (51.4)

71 (50.7)

44 (31.4)

81 (57.9)

4 (2.9)

14 (10.0)

56±12

83±14^d

9.6±5.1

308±133

89 (83.2)

76 (71.0)^a

56 (52.3)

43 (40.2)

71 (66.4)

4 (3.7)

11 (10.3)

54±12

81±17^d

8.0±3.7

448±143

87 (82.9)

78 (74.3)^a

66 (62.9)

53 (50.5)

71 (67.6)

3 (2.9)

12 (11.4)

53±11

84±19^d

5.5±2.7

661±245

Note: ^ap<0.01 vs. the other three groups, ^bp<0.05 and ^cp<0.05 vs. the other four groups, ^dp<0.01 vs. group A.

Table 2: Classification of aortic dissection, treatment methods and in-hospital death in patients with different levels of blood pressure [n (%)]

Group	Stanford classification		Treatment method			Death
Group	Type A (n=198)	Type B (n=382)	Conservative treatment (n=364)	Interventional therapy (n=138)	Surgery (n=78)	(n=96)
A	56(52.3%) ^a	51(47.7%)	64 (59.8%)	21 (19.6%)	22 (20.6%)^a	26 (24.3%)^a
B	42(34.7%)	79(65.3%)	74 (61.2%)	21 (17.4%)	26 (21.4%)^b	19 (15.7%)
C	53(37.9%)	87 (62.1%)	99 (70.7%)	34 (24.3%)	7 (5%)	20 (14.3%)
D	24 (22.4%)	83 (77.6%)^c	63 (58.9%)	34 (31.8%)^d	10 (9.3%)	12 (11.2%)
E	23 (21.9%)	82 (78.1%)^c	64 (61.0%)	28 (26.7%)^d	13 (12.3%)	10 (9.52%)

Note: ^ap<0.01 vs. the other four groups, ^bp<0.01 vs. groups C, D and E, ^cp<0.01 and ^dp<0.01 vs. groups A, B and C.

Table 3: Logistic regression analysis of influencing factors for in-hospital case-fatality rate

Factor

Odd ratio (OR)

95% confidential interval (CI)

History of hypertension

Marfan syndrome

Pain at admission

Stanford type B

Interventional therapy

Male

Drinking

1.832

2.805

0.526

0.435

0.000

2.306

1.189

1.048-3.202

1.209-6.507

0.319-0.867

0.261-0.726

0.181-0.516

1.542-1.983

1.362-1.674

0.034

0.016

0.012

0.001

0.000

0.670

0.730

Hypertension has long been regarded as an important risk factor for cardiovascular disease and the leading risk factor for aortic dissection, and it can induce atherosclerosis in the large arteries including the aorta. Hypertension has a very high prevalence rate in aortic dissection patients, which can reach 60-70%. In the present study, the prevalence rate of hypertension was 61.7% in aortic dissection patients, equal to that in literature reports. For patients with aortic dissection, blood pressure is a simple and very useful risk stratification index, and the severity of disease in patients needs to be deeply understood through this superficial vital sign, so the changes in the blood pressure of patients should be closely observed to guide clinical treatment.

According to the study report of Khan IA et al ^[7], although most aortic dissection patients have an increased level of blood pressure at onset, the systolic blood pressure is under 100 mmHg in about 25% of patients with Stanford type A aortic dissection at onset and hypotension is mainly induced by acute aortic regurgitation, aortic rupture and pericardial tamponade. Moreover, Stanford type A aortic dissection is the major risk factor for the death of patients. In the present study, the patients in group A had a lower level of blood pressure, with a higher in-hospital case-fatality rate, suggesting that blood pressure <120/80 mmHg at admission may have a certain predictive effect on the classification of aortic dissection. Besides, the patients in group A had a lower heart rate at admission than those in the other groups, especially those with the systolic blood pressure >140 mmHg. The possible reason is that there was a higher proportion of patients with Stanford type A aortic dissection in group A, and Stanford type A aortic dissection mostly involves only the ascending aorta, and less likely affects the blood supply to the thoracic and lumbar spines. There are 56 patients with ascending aortic dissection. In addition, the thoracic and lumbar nerves, dominated by sympathetic nerves, are sensitive to pain stimulation, and heart rate is a window representing sympathetic activation ^[8]. In this study, there were a higher proportion of patients with Stanford type B aortic dissection in groups C, D and E (systolic blood pressure >140 mmHg). Stanford type B aortic dissection mainly occurs in the descending thoracic aorta and tends to influence the blood supply to the thoracic and lumbar spines, so the risk of sympathetic activation is heightened, which accelerates the heart rate of patients.

Additionally, there was a strange finding in this study that the in-hospital case-fatality rate in the four groups except group A declined with the increase in blood pressure. Von Kodolitsch Y et al ^[9] concluded in their study that the patients with a higher level of blood pressure at admission have a higher in-hospital survival rate than those with a lower level of blood pressure at admission. After analyzing the results of this study and referring to published literature, it was found that the in-hospital case-fatality rate declined in the patients with a higher blood pressure level at admission due to the following three aspects of factors:

(1) The patients with a higher blood pressure level at admission have typical symptoms that easily arouse the vigilance and attention of clinicians and facilitate the diagnosis and treatment, while the symptoms are not obvious in those with a lower blood pressure level at admission. In the present study, group D and group E (blood pressure >160/100 mmHg) had a higher proportion of patients with pain than the other groups. The study of Toru Suzuki et al ^[10] revealed for the first time that the risk of in-hospital death rises in the aortic dissection patients with no such typical symptom as chest or back pain at admission, probably because the typical symptoms such as intense chest and back pain enable clinicians to promptly diagnose aortic dissection and accelerate the treatment, thereby raising the survival rate. Conversely, the duration from admission to diagnosis of patients will be extended for lack of typical symptoms. The patients with no such manifestations as chest and back pain have more severe aortic dissection than those with obvious symptoms. In other words, the disease is so severe that some patients cannot complain of pain. Therefore, lack of typical symptoms at admission delays the diagnosis and aggravates the disease condition of patients. According to the study of Toru Suzuki et al, 77% and 51% of patients with no typical symptoms at admission have not been definitely diagnosed until 6 h and 2 d after admission, respectively, whereas the patients definitely diagnosed at 6 h and 2 d after admission account for 49% and 27% of those with typical symptoms, respectively. The incidence rates of disturbance of consciousness, poor organ perfusion, and aortic diameter ≥6 cm in the patients with atypical symptoms at admission are obviously higher than those in patients with typical symptoms at admission^[11]. It is noteworthy that a higher blood pressure level itself is a symptom that tends to attract the attention from clinicians. In the present study, the logistic regression analysis results of influencing factors for in-hospital case-fatality rate revealed that pain was a protective factor for the in-hospital case-fatality rate in aortic dissection patients (OR: 0.526, 95% CI: 0.319-0.867, p=0.012). Group E had more patients with typical symptoms at admission. Besides, the duration from admission to definite diagnosis [(5.5±2.7) h] in group E was shorter than that in the other four groups showing statistically significant differences, and it was gradually shortened with the increases in blood pressure level and pain severity. As described above, the mortality rate of Stanford type A aortic dissection rises by 1% per 1 h and the mortality rate is also increasing with time in patients with Stanford type B aortic dissection, so shortening the duration from admission to definite diagnosis will contribute to standardized and timely treatments, thereby decreasing the in-hospital case-fatality rate in patients.

(2) A larger dose of β-blockers is used for patients with higher blood pressure at admission. Pharmacologically, β-blockers mainly reduce drivers for the progression of aortic dissection, dp/dt and blood pressure, and beta-blockers prevented excessive inflammation and LOI after distal type AAD, suggesting a pleiotropic effect of beta-blockers on the inflammatory response after AAD^[12]. It has been confirmed through both animal experiments and studies of hypertension patients that β-blockers can lower dp/dt. Besides, β-blockers can decrease sympathetic tone and enhance parasympathetic tone, thereby improving autonomic dysfunction. Some studies have demonstrated that administration of β-blockers in the early stage of aortic dissection can reduce leukocytes and C-reactive protein to prevent excessive inflammatory responses and oxidative damage in the lung. The above results indicate that β-blockers have pluripotent anti-inflammatory effects. It has been well recognized that sympathetic activation is closely associated with the enhancement of both inflammatory responses and the activity of renin-aldosterone system. When aortic dissection occurs, sympathetic nerves are greatly activated in the body, with the primary manifestations of increased heart rate and blood pressure, so β-blockers are undoubtedly the preferred medications if there are no contraindications. Several studies have reported that β-blockers can produce favorable efficacy in patients with aortic dissection. For example, the study of Michele Genoni et al suggested that treatment with β-blockers at admission can reduce the risk of increase in aortic diameter, admission rate, and incidence of later relevant complications in patients with Stanford type B aortic dissection. Therefore, β-blockers play an important role in the treatment of aortic dissection. In the present study, the patients in group E were intravenously administered with an obviously larger dose of β-blockers at admission than those in the other groups, which effectively reduced dp/dt and prevented inflammatory responses, oxidative stress and oxidative damage in the lung, thereby helping improve the prognosis of patients.

(3) Among patients with higher blood pressure at admission, there were more cases of Stanford type B aortic dissection and interventional therapy, but fewer cases of surgical treatment, suggesting that the blood pressure >160/100 mmHg at admission has a certain predictive effect on the classification of aortic dissection. Compared with surgical treatment, interventional therapy can decline the in-hospital case-fatality rate in aortic dissection patients. According to the study of Evangelista A et al, acute Stanford type B aortic dissection has a slightly lower mortality rate than acute Stanford type A aortic dissection, but the 30-day mortality rate can still reach up to 10% and remains as high as 70% and even higher in patients with complications. Based on the natural disease course, the mortality rate of Stanford A aortic dissection is higher than that of Stanford type B aortic dissection. In the present study, it was discovered through the logistic regression analysis of influencing factors for in-hospital case-fatality rate that Stanford type A aortic dissection was a protective factor for the in-hospital case-fatality rate in aortic dissection patients (OR: 0.435, 95% CI: 0.261-0.726, p=0.001). In Table3, type B dissection is a protective factor. Interventional therapy for aortic dissection, an emerging treatment, has been rapidly accepted by the majority of clinicians since the paper as a milestone published in the New England Journal of Medicine in 1999 reported the clinical experience of endovascular stent-graft placement for acute aortic dissection ^[13-14]. In the retrospective and observational research, Pasquale Mastroroberto1 et al ^[15] compared interventional therapy and surgical treatment in treating Stanford type B aortic dissection and found that interventional therapy can substantially lower the early mortality rate and incidence rate of postoperative complications in patients with Stanford type B aortic dissection. Besides, Michael E. Brunt et al^[16] applied surgical treatment and interventional therapy to the treatment of Stanford type B aortic dissection and discovered that there is a statistically significant difference in the in-hospital case-fatality rate for Stanford type B aortic dissection between surgical treatment and interventional therapy (17.5% vs. 10.8%). These findings imply that interventional therapy can reduce the in-hospital case-fatality rate of Stanford type B aortic dissection. In the present study, it was found through the logistic regression analysis of influencing factors for in-hospital case-fatality rate that interventional therapy was a protective factor for the in-hospital case-fatality rate (OR: 0.306, 95% CI: 0.181-0.516, p=0.000). Hence, the prognosis of aortic dissection patients can be improved to the largest extent by making full use of the advantages of interventional therapy.

Summary

This study was retrospective research that only reflected the influencing factors for the in-hospital case-fatality rate in patients, but failed to involve the affecting factors for the mid-term and long-term survival rates after discharge. Therefore, the subsequent study will focus on the effects of controlled blood pressure level in patients treated with endovascular stent-graft exclusion on the mid-term and long-term survival rates.

Declarations

Note

^a p<0.01 vs. the other three groups, ^bp<0.05 and ^cp < 0.05 vs. the other four groups, ^dp<0.01 vs. group A.

Declarations

Note

^a p<0.01 vs. the other four groups, ^bp<0.01 vs. groups C, D and E, ^cp < 0.01 and ^dp < 0.01 vs. groups A, B and C.

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No competing interests reported.

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Effect of Blood Pressure Level at Admission on In-Hospital Case-Fatality Rate in Patients with Aortic Dissection

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Abstract

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Introduction

Materials And Methods

2. Statistical analysis

Results

Discussion

Declarations

Declarations

Declarations

References

Additional Declarations

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