Abstract

Objective:

This study aims to evaluate the predictive value of the albumin-bilirubin (ALBI) score for mortality risk in patients with non-ST-segment elevation myocardial infarction (NSTEMI).

Methods:

A retrospective analysis was conducted on 982 patients with NSTEMI. A multivariate Cox proportional hazards model was established to analyze the predictive value of ALBI for mortality after hospital discharge in NSTEMI patients. Additionally, restricted cubic spline (RCS) plots were used to analyze the relationship between ALBI and post-discharge mortality. Operating characteristic (ROC) curves were generated to assess the predictive accuracy of ALBI, and nomograms were constructed to facilitate clinical application in predicting mortality after hospital discharge in patients with NSTEMI.

Results:

Among the 982 participants, 62 (6.3%) developed death during the follow-up. In unadjusted Cox regression models, the ALBI index had a hazard ratio (HR) of 5.07 (95% confidence interval CI: 3.13–8.20, P < 0.001). In the adjusted models, the relationship still persisted. Furthmore, a non-linear and dose–response relationship between the ALBI index and the primary endpoint was observed (non-linear P = 0.050, P overall < 0.001). ROC curve analysis revealed good predictive performance for ALBI. The nomogram model correctly separates patients with and without death risk, with an AUC of 0.835. Our model showed improved prediction of death compared to GRACE, or NT-proBNP (all P < 0.05).

Conclusion:

ALBI was significantly associated with the risk of out-of-hospital death in NSTEMI patients. The novel nomogram based on ALBI, NT-proBNP, and GRACE scores showed an improvement in predicting mortality.

Background

Acute myocardial infarction (AMI) was a life-threatening condition caused by acute coronary artery occlusion, leading to insufficient blood supply to the corresponding myocardial region and resulting in myocardial necrosis (1). Despite standardized reperfusion therapy and pharmacological treatments significantly improving the prognosis of AMI patients over the past few decades (2, 3), the mortality rate, particularly among elderly patients, remains high (4). Therefore, continuous risk assessment was crucial for identifying high-risk patients and establishing optimal treatment strategies to improve outcomes.

Inflammation (5), nutrition (6) were related to the prognosis of AMI. ALBI, as an emerging indicator, reflects inflammation, oxidative stress and nutrition (7). Since the 2015 study on the association between the ALBI score and liver function assessment and prognosis in hepatocellular carcinoma patients (8), the ALBI score had gradually expanded to research on its correlation with other liver diseases and systemic conditions. Similar reports had also been made in cardiovascular diseases for example, Su et al. (9) conducted a study on 9,749 patients with heart failure,The results showed that the ALBI score could effectively predict the in-hospital mortality rate of patients with heart failure. The ALBI score had been extensively studied in relation to heart failure and cardiomyopathy. A study with an average follow-up of 8.9 years in 4,923 cardiovascular disease (CVD) patients found that higher ALBI scores were associated with increased prevalence of CVD and mortality (10).

The GRACE score was commonly used to assess the risk of non-ST-segment elevation acute coronary syndrome, providing critical decision-making support for clinical diagnosis and treatment (11). However, the GRACE score, which includes factors such as age, blood pressure, heart rate, and creatinine, no longer meets the higher clinical demands for AMI prognosis evaluation. Many researchers had attempted to improve accuracy by combining brain natriuretic peptide (BNP) with GRACE. For instance, Yang et al. (12) demonstrated that combining BNP with the traditional GRACE scoring system yielded higher predictive value for AMI patients than the GRACE score alone. In recent years, the roles of immune, inflammatory and nutritional factors in AMI prognosis have garnered increasing attention. Some scholars (13) had found that inflammation and malnutrition worsen the prognosis of acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI), while Other scholars have found that an S-shaped correlation between albumin changes and mortality in elderly AMI patients (14).

However, no studies, domestic or international, have yet reported on the association between the ALBI score and NSTEMI. Therefore, this study aims to retrospectively analyze cases of NSTEMI patients to explore the correlation between ALBI and NSTEMI prognosis. Additionally, it will evaluate the potential improvement of the GRACE score by combining ALBI with NT-proBNP.

Materials and methodsStudy population

This study was a single-center, retrospective cohort study. A total of 1,137 hospitalized patients diagnosed with NSTEMI upon discharge from the Cardiac Center of Sinopharm Dongfeng General Hospital affiliated with Hubei University of Medicine between January 2021 and December 2023 were included. These patients were re-evaluated by experienced cardiologists according to inclusion and exclusion criteria, resulting in a final cohort of 982 adult patients (Figure 1).

Inclusion of research objects and flow chart.

The inclusion criteria for the study were as follows: (1) Age ≥ 18 years; (2) The diagnosis of AMI was based on the “Fourth Universal Definition of Myocardial Infarction (2018)" (15), The following conditions are considered as acute myocardial infarction: at least one value above the 99th percentile URL and at least one of the following: symptoms of myocardial ischaemia; new ischaemic ECG changes; development of pathological Q waves; imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischaemic aetiology; identification of a coronary thrombus by angiography or autopsy. And the exclusion criteria were: (1) Incomplete clinical or coronary angiography data; (2) Post-coronary artery bypass grafting or procedure-related myocardial infarction; (3) Organic heart disease (congenital heart disease, rheumatic heart disease, aortic dissection, severe valvular disease, heart failure); (4) Severe liver or kidney dysfunction (Severe renal insufficiency was defined as eGFR < 30 mL/min. Severe hepatic insufficiency is defined as ALT or AST exceeding the upper limit of normal by a factor of 5, specifically AST > 180 U/L; ALT > 260 U/L), acute infection, malignant tumors, or autoimmune diseases.

Study methodsData collection

We collected patient demographic data using the hospital's electronic medical record system. We had collected clinical data including basic patient information. electrocardiography, left ventricular ejection fraction (LVEF), laboratory examination results and the use of medications.

Indicator definition

The ALBI score was calculated using the following formula (8): ALBI score = (log10 bilirubin × 0.66) + [albumin × (−0.085)], where bilirubin is in μmol/L and albumin in g/L.

The GRACE Score (11, 16) was a risk stratification model for acute coronary syndrome (ACS) developed based on the Global Registry of Acute Coronary Events. It includes eight indicators: age, systolic blood pressure, heart rate, cardiac arrest at admission, Killip class, ST-segment changes, serum creatinine level, and cardiac enzyme changes.

Hypertension (17): Systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg measured on three different occasions without antihypertensive medication. SBP ≥140 mmHg with DBP <90 mmHg was defined as isolated systolic hypertension. Patients with a history of hypertension currently using antihypertensive medication, even with blood pressure below 140/90 mmHg, were still diagnosed with hypertension. Type 2 diabetes (18) was defined as the use of diabetes medication or self-reported diabetes. Newly diagnosed diabetes was based on diagnostic criteria: diabetes symptoms + random blood glucose ≥11.1 mmol/L or fasting blood glucose ≥7.0 mmol/L or 2 h postprandial blood glucose ≥11.1 mmol/L during an oral glucose tolerance test. Smoking: Continuous or cumulative smoking for more than 6 months, with regular or occasional smoking prior to admission. Alcohol consumption: Drinking alcohol at least once a week before admission.

Endpoint events and follow-up

Enrolled patients were followed up after discharge. Follow-up information was collected through outpatient visits, telephone contact (obtained from patients or their family members), and review of electronic medical records pertaining to re-hospitalizations. The primary endpoint of this study was all-cause mortality post-discharge; meanwhile, all patients were followed for at least one year or until an endpoint event occurred.

Statistical methods

Continuous, normally distributed variables were described as mean ± standard deviation and compared with the t-test; non-normally distributed variables were summarized as median (P25,P75) and compared with the Mann–Whitney U-test. Categorical variables were expressed as frequency (percentage) and compared using the Chi-square test or Fisher's exact test, as appropriate.

Kaplan–Meier method was applied to construct cumulative survival curves, and differences between groups were compared using the Log-Rank test. Univariate and multivariate Cox proportional hazards models were used to examine the correlation between ALBI and mortality incidence. Restricted cubic splines (RCS) were employed to reflect the dose-response relationship between ALBI and major endpoint events. Receiver operating characteristic (ROC) curves were plotted to indicate the predictive value of ALBI score for mortality.The variance inflation factor (VIF) is calculated to assess multicollinearity among model variables, with variables exhibiting a VIF greater than 5 being excluded. And evaluate the overall model performance using the likelihood ratio test and report the concordance index (C-index) to quantify the model's discriminatory ability.

This study employed the Statistical software used includes SPSS 26.0 and R language 4.1. All tests were twosided, and a significance level of P < 0.05 was considered statistically significant.

ResultsBaseline characteristics

During the follow-up period (median, 27 months), the incidence of death among 982 participants was 62 (6.31%). As shown in Table 1, the study population was stratified into a survival group (n = 920) and a death group (n = 62).Compared with the survival group, the death group had older age, higher proportion of males, higher GRACE Risk Score and higher proportion of combined diabetes history, and lower body mass index (BMI). Comparisons of pulse rate, LVEF, white blood cell count (WBC), hemoglobin (Hb), K+, Na+, Urea, creatinine(Crea), glucose (GLU), albumin (ALB), aspartate aminotransferase (AST) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) between the two groups revealed statistically significant differences(P < 0.05). Notably, the death group exhibited a lower proportion of patients using aspirin,stains, P2Y12 receptor blockers, angiotensin converting enzyme inhibitor(ACEI) and β-blockers (P < 0.05). Moreover, the comparison of ALBI scores between the survival group and the death group showed a statistically significant difference (−2.38 vs. −2.12, P < 0.001).

VariablesTotal (n = 982)Survival (n = 920)Death (n = 62)PAge, (years)68.00 (57.00, 75.75)67.00 (57.00, 75.00)75.50 (67.50, 83.00)<0.001Male, [n(%)]683 (69.55)647 (70.33)36 (58.06)0.042Smoking, [n(%)]444 (45.21)423 (45.98)21 (33.87)0.064Drinking, [n(%)]444 (45.21)423 (45.98)21 (33.87)0.083Hypertension, [n(%)]582 (59.27)544 (59.13)38 (61.29)0.738Diabetes, [n(%)]235 (23.93)208 (22.61)27 (43.55)<0.001Stroke, [n(%)]53 (5.40)49 (5.33)4 (6.45)0.929BMI, (kg/m2)23.44 (21.20, 24.61)23.44 (21.20, 24.61)21.89 (21.11, 23.89)0.005SBP, (mmHg)132.00 (116.00, 148.00)132.00 (117.00, 148.00)128.00 (107.00, 144.75)0.135DBP, (mmHg)77.00 (69.00, 88.75)77.00 (69.75, 89.00)75.50 (66.00, 85.75)0.098P, (times/minutes)78.00 (69.00, 90.00)78.00 (68.00, 90.00)86.00 (76.00, 102.75)<0.001LVEF, (%)58.00 (48.00, 62.00)58.00 (50.00, 63.00)44.00 (37.25, 57.50)<0.001WBC, (109/L)7.86 (6.19, 10.02)7.80 (6.19, 9.91)9.19 (6.45, 11.86)0.036Hb, (g/L)134.00 (119.00, 147.00)136.00 (120.00, 148.00)116.50 (91.00, 129.50)<0.001K+, (mmol/L)3.80 (3.50, 4.10)3.70 (3.50, 4.05)4.10 (3.73, 4.38)<0.001Na+, (mmol/L)139.00 (137.00, 141.00)139.00 (137.00, 141.00)138.00 (135.00, 141.00)0.043Urea, (mmol/L)5.66 (4.47, 7.44)5.58 (4.41, 7.16)9.46 (6.38, 13.21)<0.001Crea, (umol/L)73.00 (62.00, 98.75)73.00 (62.00, 93.00)119.50 (77.00, 171.00)<0.001Glu, (mmol/L)7.30 (5.90, 9.60)7.20 (5.90, 9.40)8.85 (6.57, 11.94)0.002ALB, (g/L)39.00 (36.00, 42.00)39.00 (36.00, 42.00)35.00 (32.25, 38.00)<0.001ALT, (U/L)23.50 (16.00, 36.00)24.00 (16.00, 36.00)23.00 (15.00, 48.00)0.500AST, (U/L)39.00 (28.00, 65.75)38.00 (28.00, 62.00)52.00 (34.25, 121.00)0.001TBIL, (umol/L)13.60 (10.50, 17.90)13.60 (10.60, 17.80)12.55 (8.83, 18.93)0.178TC, (mmol/L)4.03 (3.24, 4.90)4.03 (3.23, 4.87)3.99 (3.27, 5.35)0.347TG, (mmol/L)1.38 (0.94, 2.09)1.37 (0.93, 2.10)1.45 (1.06, 2.06)0.553HDL-C, (mmol/L)0.94 (0.78, 1.12)0.94 (0.78, 1.13)0.85 (0.76, 1.04)0.054LDL-C, (mmol/L)2.24 (1.65, 2.98)2.23 (1.66, 2.96)2.32 (1.63, 3.35)0.295Hs-TnI, (pg/mL)3,442.15 (634.55, 30,383.05)3,326.20 (623.00, 30,585.92)6,295.35 (889.98, 24,194.30)0.377NT-proBNP, (pg/mL)1,097.50 (305.75, 3,444.75)962.60 (279.00, 2,892.50)7,035.50 (2,953.50, 11,669.00)<0.001GRACE119.00 (97.00, 150.75)117.00 (95.00, 146.00)177.00 (145.50, 196.75)<0.001ALBI−2.36 (−2.60, −2.09)−2.38 (−2.62, −2.11)−2.12 (−2.29, −1.84)<0.001P2Y12receptor, [n(%)]865 (88.09)832 (90.43)33 (53.23)<0.001Aspirin, [n(%)]838 (85.34)807 (87.72)31 (50.00)<0.001Statins, [n(%)]897 (91.34)859 (93.37)38 (61.29)<0.001ACEI, [n(%)]597 (60.79)575 (62.50)22 (35.48)<0.001β-blockers, [n(%)]630 (64.15)610 (66.30)20 (32.26)<0.001Diuretics, [n(%)]308 (31.36)287 (31.20)21 (33.87)0.660

Baseline characteristics of different prognostic groups.

BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; P, pulse; LVEF, left ventricular ejection fraction; WBC, white blood cell; Hb, hemoglobin; K, potassium; Na, sodium; Urea, blood urea nitrogen; Crea, creatinine; NA, blood sodium; K, blood urea nitrogen; Scr serum creatinine; GLU, blood glucose; ALB, albumin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; TBIL, total bilirubin; TC, total cholesterol; TG, triglyceride; HDLC, high-density lipoprotein cholesterol; LDLC, low-density lipoprotein cholesterol; Hs-TnI, high-sensitivity troponin I; NT-pro-BNP, N-terminal pro-B-type natriuretic peptide; ALBI, albumin-bilirubin sore; ACEI, angiotensin-converting enzyme inhibitor;.

Baseline characteristics of groups with different ALBI score levels

Patients with acute myocardial infarction were divided into four groups based on the quartile range of serum ALBI score: (I) Q1 (ALBI score from <−2.6); (II) Q2 (ALBI score from −2.6 to −2.36); (III) Q3 (ALBI score from −2.36 to −2.08); and (IV) Q4 (ALBI score > −2.08).The high ALBI score group showed statistically significant differences compared to the low ALBI score group in terms of age, smoking, BMI, SBP, DBP, GRACE score, LVEF, WBC, hemoglobin (Hb) level, platelet count (PLT), glycated hemoglobin, CRP, serum sodium level, serum calcium level, Crea, Urea, indirect bilirubin(IBIL), ALB, ALT, AST, total bilirubin (TBIL), direct bilirubin (DBIL), cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and NT-proBNP levels. Moreover, the high ALBI score group exhibited higher usage of aspirin and diuretics compared to the low ALBI score group. Furthermore, the difference between the high and low ALBI score groups was statistically significant with P < 0.001. Table 2 shows the patient characteristics according to the ALBI score quartiles.

VariablesTotal (n = 982)Q1 (n = 245) (≤−2.60)Q2 (n = 246) (−2.60 to −2.36)Q3 (n = 245) (−2.36 to −2.08)Q4 (n = 246) (>−2.08)χ²PAge, (years)68.00 (57.00, 75.75)58.00 (51.00,70.00)66.00 (58.00,75.00)70.00 (61.00,76.00)72.00 (62.00,78.00)86.397<0.001Male, n(%)683 (69.55)156 (63.42)176 (71.84)171 (69.51)180 (73.47)6.7550.080Smoking, n(%)444 (45.21)94 (38.21)109 (44.49)112 (45.53)129 (52.65)10.4050.015Drinking, n(%)175 (17.82)37 (15.04)44 (17.96)49 (19.92)45 (18.37)2.0910.554Hypertension, n(%)582 (59.27)135 (54.88)153 (62.45)156 (63.42)138 (56.33)5.6210.132Diabetes, n(%)235 (23.93)64 (26.02)64 (26.12)50 (20.33)57 (23.27)3.0510.384Stroke, n(%)53 (5.40)13 (5.29)17 (6.94)10 (4.07)13 (5.31)2.0050.571BMI, (kg/m2)23.44 (21.20, 24.61)23.44 (21.20,24.61)23.44 (21.58,24.61)22.89 (21.20,24.04)23.25 (21.20,24.04)12.9800.005SBP, (mmHg)132.00 (116.00, 148.00)136.00 (121.00,151.00)132.00 (118.00,148.00)130.00 (116.000,146.00)130.00 (110.25,144.75)13.2180.004DBP, (mmHg)77.00 (69.00, 88.75)79.00 (72.00,92.00)78.00 (71.00,90.00)76.00 (70.00,86.00)75.00 (66.00,85.00)19.881<0.001P, (times/minutes)78.00 (69.00, 90.00)79.00 (70.00,92.00)77.00 (69.00,88.00)77.00 (66.000,89.00)80.00 (69.000,92.00)3.0400.386LVEF, (%)58.00 (48.00, 62.00)60.00 (53.00,65.00)58.00 (50.00,62.75)57.00 (48.00,62.00)54.00 (45.00,60.00)34.919<0.001WBC, (109/L)7.86 (6.19, 10.02)8.55 (6.60,10.91)7.45 (6.15,9.47)7.38 (5.94,9.62)7.88 (6.08,9.84)17.199<0.001Hb, (g/L)134.00 (119.00, 147.00)142.00 (128.00,152.00)138.00 (123.25,149.00)130.00 (118.00,142.00)125.00 (108.25,140.00)66.631<0.001PLT, (g/L)200.00 (161.00, 242.75)214.00 (174.00,262.00)205.00 (164.50,243.75)194.00 (163.00,234.00)181.00 (138.25,240.00)30.272<.001HbA1c, (%)5.90 (5.50, 6.70)6.20 (5.58,7.00)5.90 (5.50,6.43)6.00 (5.60,6.90)5.85 (5.50,6.60)8.2230.042CRP, (mg/L)5.01 (1.31, 18.31)2.52 (0.96,10.77)3.64 (1.172,11.85)5.16 (1.22,19.55)13.69 (3.22,43.07)81.085<0.001K+, (mmol/L)3.80 (3.50, 4.10)3.80 (3.50,4.10)3.80 (3.50,4.00)3.80 (3.50,4.10)3.70 (3.50,4.20)2.1400.544Na+, (mmol/L)139.00 (137.00, 141.00)140.00 (138.00,141.00)139.00 (137.00,141.00)139.00 (136.00,141.00)138.00 (136.00,140.00)20.094<0.001Cl−, (mmol/L)107.00 (104.00, 109.00)107.00 (105.00,109.00)107.00 (104.00,109.75)107.00 (105.00,109.00)107.00 (104.00,109.00)3.6220.305Ca2+, (mmol/L)2.20 (2.12, 2.28)2.27 (2.20,2.35)2.22 (2.15,2.29)2.17 (2.10,2.24)2.14 (2.07,2.22)139.394<0.001Urea, (mmol/L)5.66 (4.47, 7.44)5.25 (4.32,6.79)5.54 (4.55,7.03)5.93 (4.71,7.73)6.11 (4.50,9.21)19.028<0.001Crea, (umol/L)73.00 (62.00, 98.75)70.00 (61.00,85.00)75.00 (62.25,99.00)74.00 (63.00,101.00)75.00 (62.00,110.00)8.1580.043Glu, (mmol/L)7.30 (5.90, 9.60)7.40 (6.20,9.80)7.10 (5.90,9.00)7.50 (6.00,10.60)7.10 (5.90,9.78)3.4460.328IBIL, (umol/L)9.00 (6.70, 12.00)7.80 (5.80,10.30)8.90 (6.90,11.48)9.40 (6.60,13.50)10.75 (7.80,14.98)66.100<0.001ALB, (g/L)39.00 (36.00, 42.00)43.00 (42.00,44.00)40.00 (39.00,41.00)38.00 (36.00,39.00)34.00 (33.00,36.00)700.551<0.001ALT (U/L)23.50 (16.00, 36.00)26.00 (18.00,36.00)22.00 (15.25,32.00)21.00 (16.00,36.00)27.00 (17.00,43.75)19.246<0.001AST, (U/L)39.00 (28.00, 65.75)36.00 (28.00,55.00)37.00 (28.00,56.00)38.00 (26.00,68.00)47.00 (31.00,105.00)28.870<0.001TBIL, (umol/L)13.60 (10.50, 17.90)11.40 (8.90,14.50)13.15 (10.50,16.48)14.30 (10.70,18.90)16.50 (12.30,24.00)112.312<0.001DBIL, (umol/L)4.30 (3.40, 5.70)3.60 (2.90,4.50)4.10 (3.30,5.20)4.70 (3.60,5.90)5.60 (4.10,7.58)157.585<0.001TC, (mmol/L)4.03 (3.24, 4.90)4.37 (3.47,5.24)4.22 (3.32,5.06)3.91 (3.29,4.61)3.63 (3.05,4.42)41.289<0.001TG, (mmol/L)1.38 (0.94, 2.09)1.72 (1.07,2.78)1.46 (0.99,2.16)1.27 (0.93,1.82)1.12 (0.82,1.66)54.504<0.001HDLC, (mmol/L)0.94 (0.78, 1.12)0.96 (0.79,1.13)0.92 (0.78,1.10)0.94 (0.77,1.14)0.92 (0.77,1.14)2.6050.457LDLC, (mmol/L)2.24 (1.65, 2.98)