Association between the De Ritis ratio and 28-day mortality in patients with cerebrovascular accident: A MIMIC-Ⅳ database analysis

doi:10.3969/j.issn.1004-583X.2025.11.003

Abstract

Abstract:

Objective To evaluate the association between the aspartate transaminase (AST)/alanine transaminase (ALT) (De Ritis) ratio and 28-day mortality in patients with cerebrovascular accident (stroke) and to assess its predictive value across clinical subgroups. Methods We performed a retrospective cohort study using the MIMICIV database (2008-2019). From 6, 165 stroke admissions identified by ICD codes I60, I63, and I69, 1, 674 patients were retained after excluding cases with excessive missing data. Missing values were imputed by mean substitution; variables with >20% missingness were excluded. Candidate predictors were selected using LASSO regression. A multivariable Cox proportional hazards model-including restricted cubic splines to evaluate nonlinearity-was used to estimate the association between the De Ritis ratio and 28-day mortality, adjusting for potential confounders such as Sequential Organ Failure Assessment (SOFA)/Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) scores, organ support measures, and relevant biomarkers. Model discrimination and calibration were assessed using ROC-AUC and calibration plots. Preplanned subgroup analyses explored effect modification by comorbidities. Results The De Ritis ratio was an independent predictor of 28-day mortality. KaplanMeier analysis showed significantly lower survival in the highest quartile (Q4) compared with lower quartiles (P<0.01). In univariate Cox models, mortality risk increased with higher De Ritis quartiles (Q3: HR=2.073, 95%CI: 1.477-2.91; Q4: HR=2.066, 95%CI: 1.452-2.939; both P<0.01). The multivariable model retained the De Ritis ratio as an independent predictor and achieved an AUC of 0.764. Restricted cubic spline analysis identified an inflection point at a De Ritis ratio of approximately 2: Risk increased with rising ratio up to 2, while the relationship beyond 2 was less consistent. Decision curve analysis demonstrated clinical net benefit across a wide range of threshold probabilities. Subgroup analyses indicated stronger predictive value in older patients and in those without acute kidney injury, cirrhosis, or coronary artery disease. Conclusion The De Ritis (AST/ALT) ratio is a promising prognostic biomarker for stroke. It may help clinicians better estimate shortterm mortality risk, inform treatment decisions, and ultimately improve patient outcomes.

Key words: stroke, De Ritis ratio, MIMIC-Ⅳ database

CLC Number:

R743

Ren Dezhi, Xu Siyao, Wang Shuai, Duan Jun. Association between the De Ritis ratio and 28-day mortality in patients with cerebrovascular accident: A MIMIC-Ⅳ database analysis[J]. Clinical Focus, 2025, 40(11): 978-987.

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URL: https://www.lchc.cn/EN/10.3969/j.issn.1004-583X.2025.11.003

https://www.lchc.cn/EN/Y2025/V40/I11/978

Figures/Tables 9

Fig.1 Flowchart of inclusion and exclusion procedures and quantitative grouping

Tab.1 Baseline characteristics between groups

项目	总体	Q1:0.791(0~1.037)	Q2:1.219(1.038~1.426)	Q3:1.675(1.429~2.000)	Q4: 2.462(2.000~3.429)	$P$ 值
例数	1 674	432	421	454	367
年龄(岁)	72(22~104)	69(22~104)	73(27~93)	74(24~104)	73(26~97)	<0.01
BMI(kg/m²)	27.257(12.24~95.84)	28.439(14.06~61.592)	27.218(14.985~95.84)	26.607(16.005~50.529)	26.91(12.24~54.444)	0.013
性别[例(%)]
女性男性	700(41.82) 974(58.18)	157(36.34) 275(63.66)	179(42.52) 242(57.48)	188(41.41) 266(58.59)	176(47.96) 191(52.04)	0.011
CRRT天数(d)	0(0~33)	0(0~17)	0(0~32)	0(0~24)	0(0~33)	0.034
生命体征
HR(次/min)	85(28~166)	85(28~148)	85(41~150)	85.5(39~154)	86(37~166)	0.581
平均动脉压(mmHg)	85.667(33.333~210.667)	91.333(40.667~149.667)	85.5(33.333~210.667)	84.667(37~198.667)	80.833(33.667~175.333)	<0.01
RR(次/min)	18(0~73)	19(0~50)	18(0~48)	18(0~40)	18(0~73)	0.828
温度(°F)	98.1(34.9~106)	98.2(92.4~103.1)	98.1(34.9~104.3)	98.2(93~103.9)	98.1(85.4~106)	0.105
评分系统(分)
OASIS	34(10~72)	32(15~72)	34(10~60)	36(15~64)	36(15~58)	<0.01
SAPSⅡ	40(9~98)	36(9~98)	39(13~88)	41(13~93)	42(15~90)	<0.01
CHARLSON	6(0~17)	6(0~14)	6(0~15)	7(0~17)	6(0~16)	0.001
SOFA	5(0~20)	4(0~17)	5(0~17)	6(0~18)	6(0~20)	<0.01
GCS	15(3~15)	15(3~15)	15(3~15)	15(3~15)	15(3~15)	0.651
APACHEⅡ	19(2~49)	17(2~49)	18(5~45)	19.5(4~48)	21(7~48)	<0.01
合并症
心肌梗死[例(%)]
否是	1 497(89.43) 177(10.57)	393(90.97) 39(9.03)	384(91.21) 37(8.79)	404(88.99) 50(11.01)	316(86.10) 51(13.90)	0.076
高血压[例(%)]
否是	913(54.54) 761(45.46)	229(53.01) 203(46.99)	214(50.83) 207(49.17)	261(57.49) 193(42.51)	209(56.95) 158(43.05)	0.158
肝硬化[例(%)]
否是	1 587(94.80) 87(5.20)	427(98.84) 5(1.16)	408(96.91) 13(3.09)	427(94.05) 27(5.95)	325(88.56) 42(11.44)	<0.001
2型糖尿病[例(%)]
否是	1 056(63.08) 618(36.92)	271(62.73) 161(37.27)	258(61.28) 163(38.72)	305(67.18) 149(32.82)	222(60.49) 145(39.51)	0.176
COPD[例(%)]
否是	1 350(80.65) 324(19.35)	356(82.41) 76(17.59)	331(78.62) 90(21.38)	369(81.28) 85(18.72)	294(80.11) 73(19.89)	0.542
心力衰竭[例(%)]
否是	1 012(60.45) 662(39.55)	277(64.12) 155(35.88)	269(63.90) 152(36.10)	255(56.17) 199(43.83)	211(57.49) 156(42.51)	0.025
实验室参数
血红蛋白(g/dl)	10.5(4.6~20)	11(5~16.3)	10.8(4.6~18.6)	10.2(4.8~20)	9.9(4.7~17.2)	<0.01
RBC(×10¹²/L)	3.53(1.15~7.25)	3.77(1.52~6.17)	3.635(1.54~6.2)	3.42(1.45~5.82)	3.32(1.15~7.25)	<0.01
WBC(×10⁹/L)	11.3(0.1~59.7)	10.8(0.1~59.7)	11.65(0.3~52.3)	11(0.6~56.3)	11.9(0.6~47)	0.317
白蛋白(g/dl)	3.1(1.1~4.9)	3.2(1.2~4.9)	3.1(1.5~4.7)	3.1(1.1~4.9)	3(1.4~4.9)	<0.01
pH值	7.38(6.89~7.65)	7.39(6.95~7.59)	7.38(6.98~7.61)	7.39(6.97~7.56)	7.37(6.89~7.65)	0.004
凝血酶原时间(s)	14.4(8.9~150)	13.7(9.3~124.6)	14(10.4~92.2)	14.9(10.1~150)	15.1(8.9~84.5)	0.015
总胆红素(mg/dl)	0.6(0.1~31.3)	0.5(0.1~22)	0.5(0.1~14)	0.6(0.1~20.5)	0.6(0.1~31.3)	0.003
BUN(mg/dl)	22(3~212)	23(6~212)	21(5~139)	23(5~200)	22(3~159)	0.236
血小板计数(×10⁹/L)	193(5~1647)	200(31~796)	204(16~855)	189(5~1592)	165(17~1647)	<0.01
SIRS[例(%)]
0	18(1.08)	6(1.39)	3(0.71)	7(1.54)	2(0.54)
1	168(10.04)	55(12.73)	45(10.69)	45(9.91)	23(6.27)
2	495(29.57)	134(31.02)	126(29.93)	140(30.84)	95(25.89)	0.029
3	677(40.44)	169(39.12)	174(41.33)	175(38.55)	159(43.32)
4	316(18.88)	68(15.74)	73(17.34)	87(19.16)	88(23.98)

Tab.1 Baseline characteristics between groups

项目	总体	Q1:0.791(0~1.037)	Q2:1.219(1.038~1.426)	Q3:1.675(1.429~2.000)	Q4: 2.462(2.000~3.429)	$P$ 值
例数	1 674	432	421	454	367
年龄(岁)	72(22~104)	69(22~104)	73(27~93)	74(24~104)	73(26~97)	<0.01
BMI(kg/m²)	27.257(12.24~95.84)	28.439(14.06~61.592)	27.218(14.985~95.84)	26.607(16.005~50.529)	26.91(12.24~54.444)	0.013
性别[例(%)]
女性男性	700(41.82) 974(58.18)	157(36.34) 275(63.66)	179(42.52) 242(57.48)	188(41.41) 266(58.59)	176(47.96) 191(52.04)	0.011
CRRT天数(d)	0(0~33)	0(0~17)	0(0~32)	0(0~24)	0(0~33)	0.034
生命体征
HR(次/min)	85(28~166)	85(28~148)	85(41~150)	85.5(39~154)	86(37~166)	0.581
平均动脉压(mmHg)	85.667(33.333~210.667)	91.333(40.667~149.667)	85.5(33.333~210.667)	84.667(37~198.667)	80.833(33.667~175.333)	<0.01
RR(次/min)	18(0~73)	19(0~50)	18(0~48)	18(0~40)	18(0~73)	0.828
温度(°F)	98.1(34.9~106)	98.2(92.4~103.1)	98.1(34.9~104.3)	98.2(93~103.9)	98.1(85.4~106)	0.105
评分系统(分)
OASIS	34(10~72)	32(15~72)	34(10~60)	36(15~64)	36(15~58)	<0.01
SAPSⅡ	40(9~98)	36(9~98)	39(13~88)	41(13~93)	42(15~90)	<0.01
CHARLSON	6(0~17)	6(0~14)	6(0~15)	7(0~17)	6(0~16)	0.001
SOFA	5(0~20)	4(0~17)	5(0~17)	6(0~18)	6(0~20)	<0.01
GCS	15(3~15)	15(3~15)	15(3~15)	15(3~15)	15(3~15)	0.651
APACHEⅡ	19(2~49)	17(2~49)	18(5~45)	19.5(4~48)	21(7~48)	<0.01
合并症
心肌梗死[例(%)]
否是	1 497(89.43) 177(10.57)	393(90.97) 39(9.03)	384(91.21) 37(8.79)	404(88.99) 50(11.01)	316(86.10) 51(13.90)	0.076
高血压[例(%)]
否是	913(54.54) 761(45.46)	229(53.01) 203(46.99)	214(50.83) 207(49.17)	261(57.49) 193(42.51)	209(56.95) 158(43.05)	0.158
肝硬化[例(%)]
否是	1 587(94.80) 87(5.20)	427(98.84) 5(1.16)	408(96.91) 13(3.09)	427(94.05) 27(5.95)	325(88.56) 42(11.44)	<0.001
2型糖尿病[例(%)]
否是	1 056(63.08) 618(36.92)	271(62.73) 161(37.27)	258(61.28) 163(38.72)	305(67.18) 149(32.82)	222(60.49) 145(39.51)	0.176
COPD[例(%)]
否是	1 350(80.65) 324(19.35)	356(82.41) 76(17.59)	331(78.62) 90(21.38)	369(81.28) 85(18.72)	294(80.11) 73(19.89)	0.542
心力衰竭[例(%)]
否是	1 012(60.45) 662(39.55)	277(64.12) 155(35.88)	269(63.90) 152(36.10)	255(56.17) 199(43.83)	211(57.49) 156(42.51)	0.025
实验室参数
血红蛋白(g/dl)	10.5(4.6~20)	11(5~16.3)	10.8(4.6~18.6)	10.2(4.8~20)	9.9(4.7~17.2)	<0.01
RBC(×10¹²/L)	3.53(1.15~7.25)	3.77(1.52~6.17)	3.635(1.54~6.2)	3.42(1.45~5.82)	3.32(1.15~7.25)	<0.01
WBC(×10⁹/L)	11.3(0.1~59.7)	10.8(0.1~59.7)	11.65(0.3~52.3)	11(0.6~56.3)	11.9(0.6~47)	0.317
白蛋白(g/dl)	3.1(1.1~4.9)	3.2(1.2~4.9)	3.1(1.5~4.7)	3.1(1.1~4.9)	3(1.4~4.9)	<0.01
pH值	7.38(6.89~7.65)	7.39(6.95~7.59)	7.38(6.98~7.61)	7.39(6.97~7.56)	7.37(6.89~7.65)	0.004
凝血酶原时间(s)	14.4(8.9~150)	13.7(9.3~124.6)	14(10.4~92.2)	14.9(10.1~150)	15.1(8.9~84.5)	0.015
总胆红素(mg/dl)	0.6(0.1~31.3)	0.5(0.1~22)	0.5(0.1~14)	0.6(0.1~20.5)	0.6(0.1~31.3)	0.003
BUN(mg/dl)	22(3~212)	23(6~212)	21(5~139)	23(5~200)	22(3~159)	0.236
血小板计数(×10⁹/L)	193(5~1647)	200(31~796)	204(16~855)	189(5~1592)	165(17~1647)	<0.01
SIRS[例(%)]
0	18(1.08)	6(1.39)	3(0.71)	7(1.54)	2(0.54)
1	168(10.04)	55(12.73)	45(10.69)	45(9.91)	23(6.27)
2	495(29.57)	134(31.02)	126(29.93)	140(30.84)	95(25.89)	0.029
3	677(40.44)	169(39.12)	174(41.33)	175(38.55)	159(43.32)
4	316(18.88)	68(15.74)	73(17.34)	87(19.16)	88(23.98)

Fig.2 The Kaplan-Meier survival curve

Fig.3 Cox proportional H R for 28-day mortality

Fig.4 LASSO regression analysis, lambda 1se=-4.508, lambda min=-7.113 a.Lasso regression coefficients trajectory plot b.Lasso regression cross-validation plot

Tab.2 Multivariable Cox regression analysis for 28-day mortality in CVA patients

项目	数值	$H R$	95% $C I$		$P$ 值
项目	数值	$H R$	下限	上限	$P$ 值
年龄(岁)	70.87±13.71	1.03	1.018	1.043	0
BMI(kg/m²)	28.32±7.02	0.985	0.967	1.004	0.118
Na⁺	138.83±5.34	0.984	0.963	1.004	0.122
MAP(mmHg)	87.89±20.11	1.003	0.998	1.009	0.275
血红蛋白(mmol/L)	10.62±2.27	1.007	0.892	1.136	0.916
pH	7.36±0.09	0.381	0.12	1.213	0.102
血小板计数(×10⁹/L)	210.97±116.40	1	0.999	1.001	0.991
总胆红素	0.96±1.67	1.042	0.993	1.094	0.096
凝血酶原时间(s)	17.73±10.78	1.004	0.994	1.014	0.44
OASIS	34.69±8.60	1.023	1.003	1.043	0.023
APACHE Ⅱ	41.04±13.83	0.994	0.978	1.009	0.435
APS Ⅲ	50.21±21.74	1.009	1	1.018	0.044
Charlson	6.32±2.73	1.077	1.021	1.136	0.006
冠心病(例)
否是	911 763	0.9	0.703	1.152	0.402
急性肾衰竭(例)
否是	948 726	1	0.775	1.29	0.999
CRRT天数(d)	0.40±2.15	0.929	0.868	0.994	0.032
CRRT(例)
否是	1 549 125	3.443	2.201	5.387	0
SIRS(例)
0	18
1	168	0.334	0.121	0.917	0.033
2	495	0.37	0.147	0.929	0.034
3	677	0.367	0.147	0.914	0.031
4	316	0.723	0.288	1.816	0.49
机械通气(例)
否是	690 984	2.095	1.536	2.857	0

Tab.2 Multivariable Cox regression analysis for 28-day mortality in CVA patients

项目	数值	$H R$	95% $C I$		$P$ 值
项目	数值	$H R$	下限	上限	$P$ 值
年龄(岁)	70.87±13.71	1.03	1.018	1.043	0
BMI(kg/m²)	28.32±7.02	0.985	0.967	1.004	0.118
Na⁺	138.83±5.34	0.984	0.963	1.004	0.122
MAP(mmHg)	87.89±20.11	1.003	0.998	1.009	0.275
血红蛋白(mmol/L)	10.62±2.27	1.007	0.892	1.136	0.916
pH	7.36±0.09	0.381	0.12	1.213	0.102
血小板计数(×10⁹/L)	210.97±116.40	1	0.999	1.001	0.991
总胆红素	0.96±1.67	1.042	0.993	1.094	0.096
凝血酶原时间(s)	17.73±10.78	1.004	0.994	1.014	0.44
OASIS	34.69±8.60	1.023	1.003	1.043	0.023
APACHE Ⅱ	41.04±13.83	0.994	0.978	1.009	0.435
APS Ⅲ	50.21±21.74	1.009	1	1.018	0.044
Charlson	6.32±2.73	1.077	1.021	1.136	0.006
冠心病(例)
否是	911 763	0.9	0.703	1.152	0.402
急性肾衰竭(例)
否是	948 726	1	0.775	1.29	0.999
CRRT天数(d)	0.40±2.15	0.929	0.868	0.994	0.032
CRRT(例)
否是	1 549 125	3.443	2.201	5.387	0
SIRS(例)
0	18
1	168	0.334	0.121	0.917	0.033
2	495	0.37	0.147	0.929	0.034
3	677	0.367	0.147	0.914	0.031
4	316	0.723	0.288	1.816	0.49
机械通气(例)
否是	690 984	2.095	1.536	2.857	0

Fig.5 Multivariate logistic regression analysis curve a. ROC curves of De Ritis for predicting 28-day mortality; b. DCA for evaluating De Ritis effectiveness

Fig.6 Restricted cubic splines regression model for De Ritis a. Model 1 represents the unadjusted analysis; b. Model 2 involves adjustments for sex, age, and BMI; c. Model 3 includes the variables from Model 2 and further adjusts for additional factors such as race, RR, MAP, HR, SOFA score, SIRS score, APSⅢ score, SAPSⅡ score, WHC, RBC, BUN, Scr, PCO2, potassium, sodium, pH, and PO2.

Tab.3 Subgroup analysis for De Ritis

项目	例数	百分比(%)	死亡风险	95% $C I$		$P$ 值	交互作用 $P$ 值
项目	例数	百分比(%)	死亡风险	下限	上限	$P$ 值	交互作用 $P$ 值
总数	1 674	100	1.15	1.08	1.22	<0.01
年龄(岁)
<65 ≥65	493 1 181	29.5 70.5	1.34 1.3	0.91 1.1	1.97 1.55	0.133 0.003	0.888
肝硬化
否是	1 587 87	94.8 5.2	1.34 1.58	1.14 0.8	1.58 3.12	<0.01 0.191	0.633
急性肾衰竭
否是	948 726	56.6 43.4	1.45 1.22	1.14 0.99	1.83 1.51	0.002 0.057	0.291
心力衰竭
否是	1 012 662	60.5 39.5	1.36 1.32	1.1 1.05	1.68 1.65	0.005 0.019	0.842
冠心病
否是	911 763	54.4 45.6	1.51 1.21	1.2 0.97	1.89 1.51	<0.01 0.09	0.17
SOFA
0	1 040	62.1	1.29	1.02	1.65	0.036
1	552	33	1.16	0.9	1.49	0.245	0.775
2	82	4.9	1.12	0.74	1.69	0.599
Charlson
0	127	7.6	1.62	0.69	3.79	0.266
1	311	18.6	1.64	1	2.69	0.051	0.531
2	1 236	73.8	1.25	1.05	1.48	0.01
APACHE Ⅱ
0	161	9.6	1.61	0.63	4.07	0.319
1	813	48.6	1.28	0.97	1.69	0.077	0.739
2	564	33.7	1.22	0.96	1.54	0.103
3	136	8.1	1.02	0.7	1.48	0.913
机械通气
否是	690 984	41.2 58.8	1.64 1.16	1.17 0.97	2.29 1.38	0.004 0.112	0.071

Tab.3 Subgroup analysis for De Ritis

项目	例数	百分比(%)	死亡风险	95% $C I$		$P$ 值	交互作用 $P$ 值
项目	例数	百分比(%)	死亡风险	下限	上限	$P$ 值	交互作用 $P$ 值
总数	1 674	100	1.15	1.08	1.22	<0.01
年龄(岁)
<65 ≥65	493 1 181	29.5 70.5	1.34 1.3	0.91 1.1	1.97 1.55	0.133 0.003	0.888
肝硬化
否是	1 587 87	94.8 5.2	1.34 1.58	1.14 0.8	1.58 3.12	<0.01 0.191	0.633
急性肾衰竭
否是	948 726	56.6 43.4	1.45 1.22	1.14 0.99	1.83 1.51	0.002 0.057	0.291
心力衰竭
否是	1 012 662	60.5 39.5	1.36 1.32	1.1 1.05	1.68 1.65	0.005 0.019	0.842
冠心病
否是	911 763	54.4 45.6	1.51 1.21	1.2 0.97	1.89 1.51	<0.01 0.09	0.17
SOFA
0	1 040	62.1	1.29	1.02	1.65	0.036
1	552	33	1.16	0.9	1.49	0.245	0.775
2	82	4.9	1.12	0.74	1.69	0.599
Charlson
0	127	7.6	1.62	0.69	3.79	0.266
1	311	18.6	1.64	1	2.69	0.051	0.531
2	1 236	73.8	1.25	1.05	1.48	0.01
APACHE Ⅱ
0	161	9.6	1.61	0.63	4.07	0.319
1	813	48.6	1.28	0.97	1.69	0.077	0.739
2	564	33.7	1.22	0.96	1.54	0.103
3	136	8.1	1.02	0.7	1.48	0.913
机械通气
否是	690 984	41.2 58.8	1.64 1.16	1.17 0.97	2.29 1.38	0.004 0.112	0.071

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