Serum Albumin-to-Creatinine Ratio Predicts One-Year Mortality in Elderly Patients with Non-ST-Elevation Acute Coronary Syndrome After Percutaneous Coronary Intervention: A Prospective Cohort Analysis

Introduction

Acute coronary syndrome (ACS), a critical subtype of cardiovascular disease, is a leading cause of morbidity and mortality worldwide [1]. Despite rapid progress in optimal medical treatment, advanced interventional techniques, and well-controlled cardiovascular risk factors, the prognosis of ACS remains unsatisfactory in some cases [2]. As one of the most important risk factors for ACS, aging has been suggested to be associated with poor prognosis in non-ST elevated ACS (NSTE-ACS) [3]. Previous studies have discovered that one-third of hospitalized patients with ACS and two-thirds of patients who died from ACS were over 75 years of age [4,5]. In contrast to younger patients, elderly patients tend to have more complicated comorbidities, more severe coronary lesions, a higher incidence of frailty, and an increased risk of major adverse cardiovascular and cerebrovascular events (MACCEs) [3]. Moreover, patients with NSTE-ACS have a higher incidence of mortality than do patients with ST-elevated myocardial infarction (STEMI), which is attributed to the increased incidence of multivessel disease, more complicated lesion characteristics, and delayed revascularization therapy [6,7]. Therefore, identification of other potential risk factors and their prognostic value is important for the management of these individuals.

A previous study suggested that elderly patients with ACS tend to have a higher incidence of poor renal function [8,9]. Poor renal function is associated with less optimal medical treatment, less frequent selection for PCI, and poor cardiovascular risk management [10]. Moreover, poorer renal function has been associated with an elevated incidence of multivessel and complex lesions [11]. Similar to previous cardiovascular factors, poor renal function has been suggested as an independent predictor of MACCEs, including short- and long-term mortality in elderly patients with ACS [8,9,12]. Serum albumin, the most abundant protein, has been shown to relate to the role of anti-inflammatory and antiplatelet aggregation [13,14]. A lower serum albumin level is associated with an increased risk of mortality in patients [15]. Combining serum albumin with creatinine, the albumin-to-creatinine ratio (ACR) has been shown to be a reliable indicator of poor prognosis in STEMI after primary PCI [16]. However, to date, no studies have focused on the effect of ACR on mortality in elderly patients with NSTE-ACS. More importantly, ACR can be affected by various indicators, including age, sex, and other comorbidities. Therefore, we aimed to explore the relationship between ACR and all-cause mortality in very elderly patients with NSTE-ACS to improve risk stratification and management of these patients.

Material and Methods

STUDY POPULATION:

This was a prospective, observational study. A total of 424 very elderly patients (≥80 years) with NSTE-ACS who underwent PCI between March 2018 and November 2022 were included. A flowchart including the inclusion and exclusion criteria is presented in Figure 1. All patients received follow-up every month after discharge via a telephone call, outpatient visit, re-admission, or WeChat. A total of 40 patients met the exclusion criteria, and 30 were lost to follow-up. Ultimately, 354 elderly patients with NSTE-ACS were included in this study. Since ACR was not normally distributed, the enrolled patients were divided into 3 groups according to the ACR tertiles. Clinical indicators and MACCEs, including all-cause mortality, were recorded for all individuals. This study was performed in accordance with the principles of the Declaration of Helsinki. All patients provided informed consent before participating in the study.

CLINICAL, LABORATORY, AND PROCEDURAL DATA ASSESSMENTS AND DEFINITIONS:

Clinical and procedural characteristics were acquired from the hospital information system and the central imaging laboratory. The ACR was calculated and used as an indicator for the assessment of 1-year prognosis. All the laboratory parameters were acquired from the core laboratory of our hospital. All the angiography and PCI were performed by experienced physicians with relatively high PCI volumes, following the latest guidelines [17]. All the patients received complete revascularization in the hospital or on their next readmission. The coronary lesion characteristics were recorded in detail. The infarct-related artery was identified by interventional cardiologists. If there was a dispute, a second expert was consulted for determination. Totally and subtotally occluded vessels or thrombolysis in myocardial infarction (MI) flow ≤2 grade are usually considered infarct-related arteries [18]. In some cases, intravascular ultrasound, optical coherence tomography, or fractional flow reserve was performed to determine the real infarct-related artery.

FOLLOW-UP AND ENDPOINTS:

The primary endpoint was the all-cause mortality rate. The second endpoint was MACCEs, defined as a composite of all-cause death, target vessel revascularization (TVR), acute myocardial infarction (AMI), and ischemic stroke. The fourth universal definition of AMI was used for diagnosis [19]. TVR was defined as the revascularization of any previous infarct-related artery or its main branches [20]. Monthly follow-up was conducted via WeChat, telephone calls, re-admission, or outpatient visits.

STATISTICAL ANALYSIS:

SPSS version 20.0 (IBM Corp, Armonk, NY, USA) was used for statistical analysis. The patients were divided into 3 groups according to ACR: tertile 1 (n=118, ACR ≤38.5), tertile 2 (n=118, ACR 38.5–49.4), and tertile 3 (n=118, ACR ≥49.4). Categorical variables are shown as rates or percentages and were analyzed using the chi-squared test or Fisher exact test. Normally distributed continuous variables are presented as mean±standard deviation; otherwise, they are presented as median (interquartile range) for a non-normal distribution. Data were analyzed using one-way ANOVA and the Kruskal-Wallis test. The factors associated with all-cause mortality or MACCE in very elderly patients undergoing PCI for NSTE-ACS were explored using univariate analysis. Related factors were included in the logistic regression analysis to investigate the independent predictors of all-cause mortality or MACCEs in very elderly patients with NSTE-ACS after PCI. Receiver operating characteristic (ROC) curves were used to explore the prognostic value of ACR for all-cause mortality and MACCEs. Kaplan-Meier curves and log-rank tests were used to compare survival rates free of mortality or MACCEs among the 3 groups. All tests were 2-sided, and statistical significance was set at P<0.05.

Results

BASELINE AND CLINICAL CHARACTERISTICS:

A total of 354 patients with NSTE-ACS who underwent PCI between March 2018 and November 2022 in our hospital were consecutively included. The flowchart of the study is presented in Figure 1. Clinical parameters, laboratory characteristics, and procedural presentations are shown in Table 1. The included patients were divided into 3 groups according to ACR: tertile 1 (n=118, ACR ≤38.5), tertile 2 (n=118, ACR 38.5–49.4), and tertile 3 (n=118, ACR ≥49.4). The following factors were similar among the 3 groups: cardiovascular risk factors (smoking, diabetes mellitus, and hypertension), medical history (previous heart failure, stroke, MI, and PCI), proportions of non-ST-elevation myocardial infarction and unstable angina, target lesion, lesion characteristics, and medications (all P>0.05). Other indicators, including sex, fasting blood glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), NT-proBNP, and left ventricular ejection fraction, were also comparable among the 3 groups (P>0.05). However, patients with a lower ACR had an advanced age, decreased albumin level, and increased uric acid and creatinine levels (P<0.05; Table 1).

INCIDENCE OF CLINICAL OUTCOMES IN THE OVERALL POPULATION DURING 1-YEAR FOLLOW-UP:

The incidence rates of all-cause mortality and MACCE are presented in Table 2. A total of 62 patients died during the 1-year follow-up, and MACCEs developed in 41.5% (49/118) of the tertile 1 group, 34.7% (41/118) of the tertile 2 group, and 20.3% (24/118) of the tertile 3 group. The incidences of TVR, AMI, and stroke were comparable among the 3 groups. However, compared with those with higher ACR, patients with lower ACR showed an elevated incidence of all-cause mortality (22.9% vs 17.8% vs 8.5%, respectively; P=0.010) and MACCEs (41.5% vs 34.7% vs 20.3%, respectively; P=0.002; Table 2). Kaplan-Meier analysis showed that patients with a lower ACR tended to have a poor clinical outcome, defined as survival free of mortality and MACCEs, which was statistically significant (Figure 2A, 2B).

FACTORS ASSOCIATED WITH MORTALITY:

Univariate analysis showed that age, LDL-C level, uric acid level, and ACR were associated with all-cause mortality in very elderly patients with NSTE-ACS after PCI. The logistic regression model revealed that ACR was an independent predictor of all-cause mortality in the elderly patients with NSTE-ACS after PCI (Table 3). ROC analysis showed that when ACR was ≤42.8, the sensitivity and specificity were 75.2% and 80.2%, respectively, and the area under the ROC curve (AUC) was 0.802 (95% CI: 0.745–0.859; P<0.001; Figure 3). By combining creatinine and albumin values, ACR provided a better predictive value for all-cause mortality in the very elderly patients with NSTE-ACS after PCI than creatinine or albumin values alone (P<0.001; Figure 3).

Discussion

LIMITATIONS:

This study had some limitations. First, we measured ACR only on admission; we did not collect data on ACR continuously and dynamically in the hospital and during follow-up. Second, although we tried to include all the potential indicators in the statistical analysis, some of the factors can still be missing. Third, we included only very elderly patients with low serum creatinine levels; therefore, the results could not be extended to other populations. Fourth, 7.8% of the patients were lost during the follow-up, which was a relatively high percentage. It is estimated that the incidence of outcomes and adverse events can be even higher in patients lost to follow-up; therefore, this introduces a significant study bias. Finally, this was an observational study with a relatively small sample size, especially in the subgroup analysis. Further studies are required to confirm these results.

Conclusions

In the present study, we discovered that a lower ACR was an independent predictor for all-cause mortality in very elderly individuals with NSTE-ACS after PCI. Moreover, ROC analysis showed that ACR provided a better prognostic value than albumin or creatinine levels alone. As an easy acquired indicator in clinical practice, the ACR can serve as a promising indicator for risk stratification and prognostic assessment in these patients. Further investigation is needed to determine whether the ACR could improve the predictive value of established indicators, such as the Global Registry of Acute Coronary Events score.