Hindawi

International Journal of Hypertension

Volume 2020, Article ID 1347165, 10 pages
https://doi.org/10.1155/2020/1347165

Clinical Study
Association of Lactate Dehydrogenase with In-Hospital
Mortality in Patients with Acute Aortic Dissection: A Retrospective
Observational Study

Huaping He ,1,2 Xiangping Chai ,1,2 Yang Zhou ,1,2 Xiaogao Pan ,1,2
and Guifang Yang 1,2
1
Department of Emergency Medicine, The Second Xiangya Hospital, Central South University, Changsha, China
2
Emergency Medicine and Difficult Diseases Institute, Central South University, Changsha, China

Correspondence should be addressed to Guifang Yang; yangguifang@csu.edu.cn

Received 15 May 2019; Revised 3 December 2019; Accepted 9 December 2019; Published 7 January 2020

Academic Editor: Franco Veglio

Copyright © 2020 Huaping He et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background. Evidence regarding the relationship between serum lactate dehydrogenase (LDH) levels and in-hospital mortality in acute
aortic dissection (AAD) patients is extremely limited. We aimed to investigate the relationship between LDH and in-hospital mortality in
AAD patients. Methods. The present study was a retrospective observational study. A total of 1526 participants with acute aortic dissection
were involved in a hospital in China from January 2014 to December 2018. The target-independent variable was LDH measured at
baseline, and the dependent was all-cause mortality during hospitalization. Covariates involved in this study included age, gender, body
mass index (BMI), hypertension, diabetes, smoking, stroke, atherosclerosis, systolic blood pressure (SBP), diastolic blood pressure (DBP),
white blood cell (WBC), hemoglobin (Hb), alanine transaminase (ALT), aspartate aminotransferase (AST), albumin (ALB), creatinine
(Cr), symptom, type of AAD (Stanford), and management. Results. The average age of 1526 selected participants was 52.72 ± 11.94 years
old, and about 80.41% of them were male. The result of the fully adjusted model showed LDH was positively associated with in-hospital
mortality in AAD patients after adjusting confounders (OR � 1.09, 95% CI 1.05 to 1.13). A nonlinear relationship was detected between
LDH and in-hospital mortality in AAD patients after adjusting for potential confounders (age, gender, BMI, hypertension, diabetes, stroke,
atherosclerosis, smoking, symptom, SBP, DBP, WBC, Hb, ALT, AST, ALB, Cr, type of AAD (Stanford), and management), whose point
was 557. The effect sizes and the confidence intervals of the left and right sides of the inflection point were 0.90 (0.74–1.10) and 1.12
(1.06–1.19), respectively. Subgroup analysis in participants showed that the relationship between LDH and in-hospital mortality was stable,
and all of the P value for the interaction in different subgroup were more than 0.05. Conclusions. The relationship between LDH and in-
hospital mortality in AAD patients is nonlinear. LDH was positively related with in-hospital mortality when LDH is more than 557.

1. Introduction injury, hypoxia, necrosis, and hemolysis [6]. Studies have

shown that in the case of idiopathic pulmonary arterial
Acute aortic dissection (AAD) is a catastrophic aortic disease hypertension, patients with high levels of LDH had a low
with high mortality and morbidity that requires immediate cumulative survival rate [7]. In addition, Lu et al. [8] have
diagnosis and treatment [1, 2]. From 1% to 2% of patients demonstrated that in patients with sepsis, LDH levels in-
with AAD die per hour for the first 24∼48 hours [3]. Pre- creased during hospitalization also indicated a worse short-
vious studies have found that many noninvasive markers, term prognosis. Moreover, increased LDH levels are also
such as CRP and D-dimer, are considered to be associated associated with worse cardiovascular mortality in the ar-
with AAD severity [4, 5]. As a cytoplasmic enzyme, LDH is senic-endemic areas of southwestern Taiwan [9]. However,
widely expressed in tissues. Increased LDH levels can be there are little available data on the relationship between
caused in many conditions such as malignancies, tissue LDH and clinical outcomes in AAD patients.
2 International Journal of Hypertension

2. Participants and Methods aspartate aminotransferase (AST), albumin (ALB), creatinine

(Cr), symptom, and type of AAD (Stanford). Then, we col-
2.1. Study Design and Settings. This is a retrospective ob- lected the data of management in AAD patients. No multiple
servational study design. Medical records of AAD patients imputation was performed in this study because the missing
admitted to the Second Xiangya Hospital of Central South for the covariates was less than 5% [12].
University from January 2014 to December 2018 were in-
vestigated. The study was reviewed and approved by the
hospital ethics committee, and as a retrospective study, 2.4. Statistical Analysis. We followed the methods of Chen
informed consent was waived. et al. [13] in this study. R (http://www.R-project.org) and
The type of AAD was classified according to Stanford Empower States (http://www.empowerstates.com, X&Y So-
criteria, and the diagnosis of AAD was confirmed by lution, Inc, Boston, MA) software were used to carry out all
computed tomography angiography (CTA) or magnetic the statistical analyses. Statistical data were presented in
resonance angiography (MRA) [10]. AAD patients with a mean ± standard deviation for normal data while non-normal
time interval of ≤14 days from the onset of symptoms to data, interquartile range (IQR), and median were used. The
hospital admission were included in the present study. categorical variables were presented as percentages and
Exclusion criteria included (1) uncompleted LDH tests, (2) numbers. Wilcoxon Mann–Whitney tests for non-normally
prior history of a malignant tumor or liver cirrhosis, (3) distributed continuous variables and unpaired Student t-tests
diagnosis with pregnancy, and (4) presence of AAD for more for normally distributed continuous variables were used to
than 14 days. establish the correlations among the survivor and the non-
survivor groups. We used chi-squared test (categorical var-
iables), one-way ANOVA test (normal distribution), or one-
2.2. AAD Treatment. For AAD patients combined with way ANOVA test (skewed distribution) to test for differences
high blood pressure, urapidil, sodium nitroprusside, or among different LDH groups (Tertile). Three criteria were
nitroglycerin is administered intravenously to reduce used in the process of this data analysis. First, what is the
systolic blood pressure (SBP) to 100–120 mmHg. All pa- relationship between LDH and in-hospital mortality (linear or
tients were given beta-blockers except for contraindica- nonlinear)? Second,which factors interfere or modify the
tions. Acute type A aortic dissection patients and a small relationship between LDH and in-hospital mortality. Third,
portion of acute type B aortic dissection patients were what is the true relationship between LDH and in-hospital
surgically repaired under cardiopulmonary bypass. Under mortality while adjusting the interference factors or after the
general anesthesia, patients with acute type B aortic dis- stratified analysis? Therefore, univariate and multivariate
section were performed an endovascular repair using analyses were employed firstly. We constructed three models:
available grafts. The criteria for endovascular treatment of crude model, with no adjustment of covariates; model I,
type B AAD were based on the 2014 ESC guidelines. adjusted for sociodemographic data; and model II, model I
Thoracic endovascular aortic repair (TEVAR) is the including other covariates presented in Table 1. A sensitivity
treatment of choice in complicated acute type B AD. The analysis was carried out for robustness during data analysis.
term “complicated” means persistent or recurrent pain, LDH was converted to an absolute variable, and P value for
uncontrolled hypertension despite full medication, early tendency was determined. And then, to address for nonlin-
aortic expansion, malperfusion, and signs of rupture earity of LDH and in-hospital mortality, a generalized ad-
(haemothorax, increasing periaortic, and mediastinal ditive model and smooth curve fitting (penalized spline
hematoma). AAD patients who did not undergo surgery method) were conducted. If nonlinearity was detected, we
were given conservative medical treatment [11]. first calculated the inflection point using recursive algorithm
and then constructed a two-piecewise on both sides of the
2.3. Variables Included for Analysis. Serum LDH was mea- inflection point. How to determine which model is more
sured at baseline for all the AAD participants. A plasma LDH suitable for fitting the correlation between target independent
assay was performed on blood collected with a Roche Cobas variable, and the dependent variable was mainly based on the
automated platform, using a colorimetric pyruvate-lactate P value of the log-likelihood ratio test. Survival curves were
enzymatic assay technique. Sample collection always made constructed using the Kaplan–Meier method estimates and
before any surgical/endovascular treatment. The normal compared with the log-rank test. Finally, the subgroup an-
reference range is 109 to 245 μ/L at our hospital. All LDH alyses were performed using stratified models. For a con-
measures were performed at our hospitals’ clinical laboratory. tinuous variable, we first converted it to a categorical variable
The covariates used in this study can be classified as follows: according to the clinical cut point or tertile and then per-
(1) demographic data; (2) variables that can affect LDH or in- formed an interaction test. Tests for effect modification for
hospital mortality among AAD patients reported by previous those of subgroup indicators were followed by the likelihood
literature; and (3) based on our clinical experiences. The ratio test.
following clinical data were collected on admission: age,
gender, body mass index (BMI), hypertension, diabetes, 3. Results
smoking, stroke, atherosclerosis, systolic blood pressure
(SBP), diastolic blood pressure (DBP), white blood cell 3.1. Baseline Characteristics of Selected Participants. A total
(WBC), hemoglobin (Hb), alanine transaminase (ALT), of 1526 patients with AAD were enrolled in the present study
International Journal of Hypertension 3

Table 1: Baseline characteristics of the patients (N � 1526).

Lactate dehydrogenase (μ/L) (tertile)
Characteristic P value
Total T1 (54.6–209.3) T2 (209.7–274.7) T3 (274.8–4981.0)
No. of patients 1526 504 511 511
Age (years, mean ± sd) 52.72 ± 11.94 53.71 ± 11.87 52.52 ± 11.82 51.94 ± 12.09 0.055
BMI (kg/m2, mean ± sd) 25.03 ± 4.28 24.44 ± 3.94 25.20 ± 4.33 25.44 ± 4.49 <0.001
Gender 0.238
Male 1227 (80.41%) 397 (78.77%) 407 (79.65%) 423 (82.78%)
Female 299 (19.59%) 107 (21.23%) 104 (20.35%) 88 (17.22%)
Hypertension 0.362
No 469 (30.73%) 162 (32.14%) 162 (31.70%) 145 (28.38%)
Yes 1057 (69.27%) 342 (67.86%) 349 (68.30%) 366 (71.62%)
Diabetes 0.386
No 1468 (96.20%) 480 (95.24%) 494 (96.67%) 494 (96.67%)
Yes 58 (3.80%) 24 (4.76%) 17 (3.33%) 17 (3.33%)
Smoking 0.501
No 1044 (68.41%) 337 (66.87%) 359 (70.25%) 348 (68.10%)
Yes 482 (31.59%) 167 (33.13%) 152 (29.75%) 163 (31.90%)
Stroke 0.865
No 1465 (96.00%) 482 (95.63%) 491 (96.09%) 492 (96.28%)
Yes 61 (4.00%) 22 (4.37%) 20 (3.91%) 19 (3.72%)
Atherosclerosis 0.002
No 1393 (91.28%) 443 (87.90%) 470 (91.98%) 480 (93.93%)
Yes 133 (8.72%) 61 (12.10%) 41 (8.02%) 31 (6.07%)
Symptom 0.002
Chest pain 1166 (76.41%) 362 (71.83%) 401 (78.47%) 403 (78.86%)
Back pain 69 (4.52%) 27 (5.36%) 26 (5.09%) 16 (3.13%)
Abdominal pain 108 (7.08%) 37 (7.34%) 29 (5.68%) 42 (8.22%)
Syncope 19 (1.25%) 5 (0.99%) 3 (0.59%) 11 (2.15%)
Other 164 (10.75%) 73 (14.48%) 52 (10.18%) 39 (7.63%)
Type of AAD (Stanford) <0.001
A 703 (46.07%) 200 (39.68%) 221 (43.25%) 282 (55.19%)
B 823 (53.93%) 304 (60.32%) 290 (56.75%) 229 (44.81%)
SBP (mmHg, mean ± sd) 145.97 ± 29.23 144.38 ± 27.12 147.46 ± 28.13 146.05 ± 32.15 0.242
DBP (mmHg, mean ± sd) 81.79 ± 18.14 81.10 ± 16.21 82.98 ± 17.82 81.28 ± 20.14 0.189
WBC (×109/L, mean ± sd) 11.21 ± 4.15 9.79 ± 3.50 11.28 ± 3.81 12.55 ± 4.59 <0.001
Hb (g/L, mean ± sd) 124.96 ± 20.83 123.54 ± 20.72 125.94 ± 20.38 125.40 ± 21.34 0.158
ALT (μ/L, mean ± sd) 78.85 ± 422.73 22.44 ± 17.32 33.49 ± 41.04 179.85 ± 718.99 <0.001
AST (μ/L, mean ± sd) 100.92 ± 639.72 22.16 ± 16.13 28.49 ± 27.54 251.03 ± 1090.29 <0.001
ALB (g/L, mean ± sd) 35.61 ± 4.62 35.49 ± 4.48 35.81 ± 4.65 35.53 ± 4.72 0.483
Cr (μmol/L, mean ± sd) 116.16 ± 135.88 109.73 ± 146.47 101.39 ± 95.58 137.28 ± 155.59 <0.001
Management <0.001
Medical 412 (27.00%) 130 (25.79%) 118 (23.09%) 164 (32.09%)
Endovascular 647 (42.40%) 236 (46.83%) 230 (45.01%) 181 (35.42%)
Surgical 467 (30.60%) 138 (27.38%) 163 (31.90%) 166 (32.49%)
Mortality <0.001
Survivor 1229 (80.54%) 423 (83.93%) 429 (83.95%) 377 (73.78%)
Nonsurvivor 297 (19.46%) 81 (16.07%) 82 (16.05%) 134 (26.22%)
Length of stay in hospital (d) 16.06 ± 10.11 16.55 ± 9.72 16.36 ± 9.34 15.27 ± 11.15 0.097
Length of stay in ICU (d) 2.18 ± 5.08 1.78 ± 4.55 2.14 ± 5.20 2.56 ± 5.38 0.221
Abbreviations: BMI, body mass index; SBP, systolic blood pressure; DBP, diastole blood pressure; WBC, white blood cell; Hb, hemoglobin; ALT, alanine
transaminase; AST, aspartate aminotransferase; ALB, albumin; Cr, creatinine; AAD, acute aortic dissection.

based on the inclusion and exclusion criteria (see Figure 1 of AAD, and management of medical and surgical than
for a flow chart). Patient characteristics are shown in Table 1 those of other groups.
according to the tertile of LDH. There were no significant
differences in age, gender, hypertension, diabetes, smoking, 3.2. Univariate Analysis. We listed the results of univariate
and stroke among these groups and the level of SBP, DBP, analyses in Table 2. By univariate analysis, we found that age,
Hb, and ALB. Participants with the highest group of LDH BMI, gender, hypertension, diabetes, stroke, atherosclerosis,
(T3) had higher values in BMI, a symptom of chest pain, back pain, and other symptom were not associated with in-
abdominal pain, and syncope, WBC, ALT, AST, Cr, A type hospital mortality. We also found that SBP (0.99, 0.98-0.99),
4 International Journal of Hypertension

1699 patients with AAD were identified between

January 2014 and December 2018

173 patients excluded:

LDH data not completed, 113 patients
Prior history of malignant tumor, 5 patients
Prior history of liver cirrhosis, 13 patients
Pregnancy, 11 patients
>14 days after onset of symptoms, 31 patients

1526 patients included

Survivors Nonsurvivors
N = 1229 N = 297

Figure 1: Flow chart of patient enrollment.

Table 2: Univariate analysis for in-hospital mortality.

OR 95 CI P value
Age (years) 1.00 (0.99, 1.01) 0.898
BMI (kg/m2) 1.00 (0.97, 1.03) 0.825
SBP (mmHg) 0.99 (0.98, 0.99) <0.001
DBP (mmHg) 0.98 (0.97, 0.98) <0.001
WBC (×109/L) 1.07 (1.04, 1.11) <0.001
Hb (g/L) 0.99 (0.99, 1.00) 0.003
ALT (μ/L) 1.00 (1.00, 1.00) <0.001
AST (μ/L) 1.00 (1.00, 1.00) <0.001
ALB (g/L) 0.96 (0.94, 0.99) 0.005
Cr (μmol/L) 1.00 (1.00, 1.00) <0.001
Gender
Male Ref
Female 1.02 (0.74, 1.40) 0.896
Hypertension
No Ref
Yes 0.99 (0.75, 1.30) 0.920
Diabetes
No Ref
Yes 0.97 (0.50, 1.89) 0.922
Smoking
No Ref
Yes 0.74 (0.56, 0.99) 0.040
Stroke
No Ref
Yes 1.64 (0.92, 2.90) 0.094
Atherosclerosis
No Ref
Yes 1.17 (0.76, 1.80) 0.476
Symptom
Chest pain Ref
Back pain 1.09 (0.61, 1.97) 0.764
Abdominal pain 0.49 (0.27, 0.91) 0.025
Syncope 2.87 (1.14, 7.20) 0.025
International Journal of Hypertension 5

Table 2: Continued.
OR 95 CI P value
Other 0.74 (0.48, 1.16) 0.187
Type of AAD (Stanford)
A Ref
B 0.16 (0.12, 0.22) <0.001
Management
Medical Ref
Endovascular 0.02 (0.01, 0.03) <0.001
Surgical 0.08 (0.05, 0.11) <0.001
Lactate dehydrogenase (μ/L)
(per 100 increment) 1.10 (1.06, 1.14) <0.001
Abbreviations: CI, confidence interval; OR, odds ratio; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; WBC, white blood
cell; Hb, hemoglobin; ALT, alanine transaminase; AST, aspartate aminotransferase; ALB, albumin; Cr, creatinine; AAD, acute aortic dissection.

DBP (0.98, 0.97-0.98), Hb (0.99, 0.99-1.00), ALB (0.96, aspartate aminotransferase, albumin, creatinine, and
0.94–0.99), smoking (0.74, 0.56–0.99), abdominal pain (0.49, management. We used both linear regression model and
0.27–0.91), B type of AAD (Stanford) (0.16, 0.12–0.22), two-piecewise linear regression model to fit the association
endovascular (0.02, 0.01–0.03), and surgical (0.08, 0.05–0.11) and select the best-fit model based on P for log-likelihood
were negatively associated with in-hospital mortality. In ratio. Because the P for log-likelihood ratio test was less
contrast, univariate analysis showed that WBC (1.07, than 0.05, we chose a nonlinear regression model for fitting
1.04–1.11), ALT (1.00, 1.00-1.00), AST (1.00, 1.00-1.00), Cr the association between LDH and in-hospital mortality
(1.00, 1.00-1.00), smoking (0.74, 0.56–0.99), syncope (2.87, because it can accurately represent the relationship. By
1.14–7.20), and LDH (1.10, 1.06–1.14) (per 100 increment) two-piecewise linear regression model and recursive al-
were positively correlated with in-hospital mortality. gorithm, we calculated the inflection point was 557. On the
left side of inflection point, the effect size and 95% CI were
0.90, 0.74–1.10, respectively. On the right side of inflection
3.3. Results of Unadjusted and Adjusted. In this study, we point, the effect size and 95% CI were 1.12, 1.06–1.19,
constructed three models to analyze the independent effects of respectively (Table 4).
LDH on in-hospital mortality (univariate and multivariate).
The effect sizes (OR) and 95% confidence intervals were listed
in Table 3. In the unadjusted model (crude model). The model- 3.5. Survival Curve Analysis. Kaplan–Meier analysis showed
based effect size can be explained as the difference in 100 u/L of that the cumulative in-hospital survival rate was significantly
LDH associated with in-hospital mortality (1.10, 95% CI lower in high-level LDH group (P � 0.013) (Figure 3).
1.06–1.14). In the minimum-adjusted model (model I), the
LDH was increased by 100 μ/L, in-hospital mortality increased 3.6. Subgroup Analysis. We used age, BMI, SBP, DBP, WBC,
by 10% (1.10, 95% CI 1.06–1.14). In the fully adjusted model Hb, ALT, AST, ALB, Cr, gender, symptom, hypertension,
(model II) (adjusted all covariates presented in Table 1) for diabetes, smoking, stroke, atherosclerosis, type of AAD
each additional 100 μ/L of LDH, in-hospital mortality in- (Stanford), and management as the stratification variables to
creased by 9% (1.09, 95% CI 1.05–1.13). For the purpose of observe the trend of effect sizes in these variables (Table 5)
sensitivity analysis, we converted the LDH from continuous We noted that none interactions were observed based on our
variable to categorical variable (tertile of LDH); the P for trend a priori specification (all P values for interaction >0.05).
of LDH with categorical variables in the fully adjusted model
was not consistent with the result when LDH is a continuous 4. Discussion
variable. However, we found the trend of the effect size in
different LDH groups was consistent with the result when The major finding of this study was that LDH levels were
LDH is a continuous variable. positively associated with in-hospital mortality in AAD
patients after adjusting other covariates. Besides, we also
find the trend of the effect sizes on the left and right sides of
3.4. The Results of Nonlinearity of LDH and In-Hospital the inflection point is not consistent [left 0.90 (95% CI
Mortality. In the present study, we analyzed the nonlinear 0.74–1.10) and right 1.12 (95% CI 1.06–1.19)]. This result
relationship between LDH and in-hospital mortality suggests a threshold effect on the independent association
(Figure 2). Smooth curve and the result of generalized between LDH and in-hospital mortality in AAD patients.
additive model showed that the relationship between LDH Subgroup analysis will help us to better understand the
and in-hospital mortality was nonlinear after adjusting for trend of LDH and in-hospital mortality in different
age, gender, BMI, hypertension, diabetes, stroke, athero- populations. The results of this study find the association
sclerosis, smoking, symptom, systolic blood pressure, di- between LDH and in-hospital mortality was stable, and all
astolic blood pressure, type of AAD (Stanford), admission of the P value for the interaction in different subgroups
of white blood cell, hemoglobin, alanine transaminase, were more than 0.05.
6 International Journal of Hypertension

Table 3: Relationship between lactate dehydrogenase and in-hospital mortality in different models.
Exposure Crude model (OR, 95 CI, P) Model I (OR, 95 CI, P) Model II (OR, 95CI, P)
Lactate dehydrogenase (μ/L) (per 100 increment) 1.10 (1.06, 1.14) <0.001 1.10 (1.06, 1.14) <0.001 1.09 (1.05, 1.13) <0.001
Lactate dehydrogenase (μ/L) (tertile)
T1 Ref Ref Ref
T2 1.00 (0.71, 1.40) 0.992 1.00 (0.71, 1.40) 0.998 1.05 (0.65, 1.67) 0.853
T3 1.86 (1.36, 2.53) <0.001 1.86 (1.37, 2.54) <0.001 1.25 (0.79, 1.99) 0.346
P for trend <0.001 <0.001 0.337
Abbreviations: CI, confidence interval; OR, odds ratio. Model I adjusted for age, gender, and BMI. Model II adjusted for age, gender, BMI, hypertension,
diabetes, stroke, atherosclerosis, smoking, symptom, systolic blood pressure, diastolic blood pressure, type of AAD (Stanford), admission of white blood cell,
hemoglobin, alanine transaminase, aspartate aminotransferase, albumin, creatinine, and management.

1.0

0.8
Mortality

0.6

0.4

0.2

0.0
0 1000 2000 3000 4000 5000
Lactate dehydrogenase (µ/L)
Figure 2: Association between lactate dehydrogenase and in-hospital mortality. A nonlinear association between lactate dehydrogenase and
in-hospital mortality was found in a generalized additive model (GAM). The solid red line represents the smooth curve fit between variables.
Blue bands represent the 95% confidence interval from the fit. All adjusted for age, gender, BMI, hypertension, diabetes, stroke, ath-
erosclerosis, smoking, symptom, systolic blood pressure, diastolic blood pressure, type of AAD (Stanford), admission of white blood cell,
hemoglobin, alanine transaminase, aspartate aminotransferase, albumin, creatinine, and management.

Table 4: The results of two-piecewise linear model.

Mortality (OR, 95% CI) P value
Fitting model by standard linear regression (per 100
1.09 (1.05, 1.13) <0.001
increment)
Fitting model by two-piecewise linear regression (per
100 increments)
Inflection point of lactate dehydrogenase 557
≤557 0.90 (0.74, 1.10) 0.296
>557 1.12 (1.06, 1.19) <0.001
P for log-likelihood ratio test 0.048
Abbreviations: CI, confidence interval; OR, odds ratio. Adjusted: age, gender, BMI, hypertension, diabetes, stroke, atherosclerosis, smoking, symptom,
systolic blood pressure, diastolic blood pressure, type of AAD (Stanford), admission of white blood cell, hemoglobin, alanine transaminase, aspartate
aminotransferase, albumin, creatinine, and management.

Mortality prediction in AAD is clinically important. could predict mortality in acute aortic syndromes. However,
Previous studies have shown that organ malperfusion and in their research, they mainly discussed AAS and did not
hemodynamic statuses, such as hypotension, shock, cardiac focus on aortic dissection. We know that AAS includes
tamponade, pulse deficits, and kidney failure, confer an even classic acute aortic dissection (AAD), intramural hematoma,
higher mortality rate in AAD patients. Morello et al. [14] and penetrating atherosclerotic aortic ulcer. In addition,
demonstrated that plasma lactate dehydrogenase levels they did not discuss the nonlinear relationship between LDH
International Journal of Hypertension 7

Lactate dehydrogenase (μ/L)

1.00 +
+
++
++
+++
+++++
+ +++++
++++++
+++
+ ++
0.75 ++
++++++++++
+ +++
+ ++
+ +++++++++

Survival probability
++++++ +++ +++ ++
+
0.50 ++ + +
+ + ++

0.25 +
P < 0.0001

0.00

0 20 40 60
Length of stay in hospital (d)

<557
≥557
(a)
Number at risk
dehydrogenase (μ/L)

<557 1404 451 39 2

Lactate

≥557 95 28 6 0

0 20 40 60
Length of stay in hospital (d)

(b)

Figure 3: Survival curve analysis in the chronological trend in mortality after AAD.

Table 5: Results of subgroup analysis and interaction analysis.

Characteristic No. OR (95% CI) P for interaction
Age (years) 0.851
<70 1408 1.10 (1.06, 1.14)
≥70 118 1.12 (0.93, 1.35)
BMI (kg/m2) 0.476
<18.5 57 1.12 (0.97, 1.29)
≥18.5, <23 445 1.07 (1.02, 1.13)
≥23 1024 1.12 (1.07, 1.18)
SBP (mmHg) 0.291
Low (50.00–132.00) 493 1.12 (1.06, 1.19)
Middle (133.00–157.00) 510 1.10 (1.04, 1.17)
High (158.00–246.00) 523 1.05 (0.99, 1.11)
DBP (mmHg) 0.398
Low (26.00–73.00) 480 1.09 (1.04, 1.14)
Middle (74.00–88.00) 522 1.13 (1.05, 1.22)
High (89.00–157.00) 524 1.05 (0.98, 1.13)
WBC (×109/L) 0.593
Low (2.14–9.25) 509 1.07 (0.98, 1.17)
Middle (9.26–12.48) 508 1.12 (1.05, 1.21)
High (12.49–29.10) 509 1.08 (1.04, 1.13)
8 International Journal of Hypertension

Table 5: Continued.
Characteristic No. OR (95% CI) P for interaction
Hb (g/L) 0.496
Low (11.00–118.00) 508 1.07 (1.02, 1.11)
Middle (119.00–134.00) 497 1.23 (1.12, 1.35)
High (135.00–215.00) 521 1.09 (1.03, 1.14)
ALT (μ/L) 0.062
Low (3.00–15.50) 506 1.19 (0.99, 1.42)
Middle (15.60–28.70) 510 0.89 (0.72, 1.09)
High (28.80–6817.30) 510 1.11 (1.07, 1.15)
AST (μ/L) 0.969
Low (2.85–17.00) 503 1.09 (0.84, 1.43)
Middle (17.10–26.20) 512 1.11 (0.95, 1.29)
High (26.30–11216.00) 511 1.09 (1.05, 1.13)
ALB (g/L) 0.234
Low (16.10–33.50) 494 1.10 (1.05, 1.15)
Middle (33.60–37.80) 522 1.19 (1.06, 1.32)
High (37.90–53.80) 510 1.07 (1.02, 1.13)
Cr (μmol/L) 0.268
Low (5.00–71.10) 505 1.14 (1.02, 1.28)
Middle (71.20–97.90) 511 1.01 (0.90, 1.14)
High (98.00–1718.80) 510 1.08 (1.04, 1.13)
Gender 0.133
Male 1227 1.12 (1.07, 1.17)
Female 299 1.05 (0.98, 1.13)
Symptom 0.055
Chest pain 1166 1.08 (1.04, 1.12)
Back pain 69 1.11 (0.94, 1.30)
Abdominal pain 108 1.30 (1.05, 1.60)
Syncope 19 2.04 (0.79, 5.23)
Other 164 1.10 (0.98, 1.23)
Hypertension 0.308
No 469 1.13 (1.06, 1.19)
Yes 1057 1.08 (1.04, 1.13)
Diabetes 0.944
No 1468 1.10 (1.06, 1.14)
Yes 58 1.11 (0.90, 1.37)
Smoking 0.833
No 1044 1.10 (1.06, 1.14)
Yes 482 1.11 (1.03, 1.19)
Stroke 0.805
No 1465 1.10 (1.06, 1.14)
Yes 61 1.15 (0.85, 1.55)
Atherosclerosis 0.360
No 1393 1.10 (1.06, 1.14)
Yes 133 1.23 (0.94, 1.61)
Type of AAD (Stanford) 0.798
A 703 1.09 (1.04, 1.14)
B 823 1.08 (1.03, 1.13)
Management 0.284
Medical 412 1.19 (1.06, 1.34)
Endovascular 647 1.10 (1.03, 1.17)
Surgical 467 1.09 (1.03, 1.15)
Abbreviations: CI, confidence interval; OR, odds ratio; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; WBC, white blood cell;
Hb, hemoglobin; ALT, alanine transaminase; AST, aspartate aminotransferase; ALB, albumin; Cr, creatinine; AAD, acute aortic dissection.

and in-hospital mortality in AAD patients. Furthermore, myocardium, skeletal muscle, liver, red blood cells, and
there were only 166 AAD patients in their research, which intestinal tract are the most well-known tissue sources of
were far less than our study. LDH [15]. Therefore, these tissue damage or ischemia are
Increased LDH levels can be caused in many conditions potential sources of elevated plasma LDH levels in AAD
such as malignancies, tissue injury, hypoxia, necrosis, and patients. When the oxygen supply is insufficient, the en-
hemolysis [6]. Previous studies have demonstrated that zyme converts the final product of glycolysis, pyruvate, to
International Journal of Hypertension 9

lactic acid. It enables hypoxic cells to produce adenosine Data Availability

triphosphate and remain viable in a relatively low oxygen
environment [16]. The data sets used and/or analyzed during the present study
Elevated levels of LDH are not only associated with were availed by the corresponding author on reasonable
hypoxia but also a marker of inflammation and oxidative request.
stress, which indicated an increased risk of AAD and a poor
prognosis. In the pathogenesis and progression of AAD, the Ethical Approval
role of hypoxia and inflammation is well defined. The re-
search of Colgan et al. [17] showed that hypoxia can induce The study was approved by the Ethics Committee of the
lactate dehydrogenase expression. Moreover, Gaisl et al. [18] Second Xiangya Hospital, Central South University
have found that the relationship between hypoxia and aortic (Changsha, China), and informed consent was waived due to
dissection may be intermittent hypoxia associated with its retrospective nature.
autonomic nervous system activation and consequently
increased oxidative stress. In addition, Drent et al. [19] Conflicts of Interest
concluded that LDH is an indicator of pathological con-
ditions in the lungs, such as cell damage or inflammation. The authors declare that they have no conflicts of interest.
Furthermore, Duan et al. [20] deduced that inflammation is
related to preoperative hypoxemia in patients with acute Authors’ Contributions
Stanford type A aortic dissection. Overall, the mechanism of GY wrote the manuscript and collected the patient infor-
elevated lactate dehydrogenase in patients with AAD may be mation. HH, YZ, and XP helped in data collection. XC
due to hypoxia or inflammatory reactions. analyzed and interpreted the patients’ general indices. All
The clinical value of this study is as follows: (1) Elevated authors read and approved the final manuscript.
LDH may be used by physicians for counseling patients and
their families in helping them to understand their predicted
risk and to have realistic expectations in terms of outcomes,
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