Introduction

Cardiovascular disease (CVD) is the most common cause of mortality and morbidity worldwide, in which acute coronary syndrome (ACS) is a primary clinical manifestation of CVD1. ACS is a serious cardiac condition caused by unstable rupture or erosion of atherosclerotic plaques within the coronary arteries, followed by the formation of fresh blood clots leading to acute ischaemia of the myocardium. ACS includes ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), and unstable angina (UA)1,2. Percutaneous coronary intervention (PCI) uses balloons and stents to dilate stenotic or obstructive sites in the coronary arteries, thereby restoring blood flow, alleviating myocardial ischemia, and improving patient clinical prognosis. No substitute for PCI exists in the treatment of ACS, especially in the management of STEMI1,2,3.

Serum albumin is the most abundant protein in human plasma and reflects not only nutritional status4,5but also plays important roles, such as in inflammation6,7, platelet aggregation8,9, and antioxidant regulation10,11. Albumin, as a negative acute phase protein, decreases in levels during inflammation. It possesses antioxidant properties, enabling it to scavenge free radicals and inhibit the expression of inflammatory mediators, thereby mitigating inflammatory damage. Additionally, it regulates the inflammatory response by binding and transporting these mediators12.Inflammation plays a crucial role in the pathogenesis of acute coronary syndrome (ACS). It not only promotes the development of atherosclerosis but also plays a key role in plaque rupture and thrombosis, which are the main pathological bases of ACS. In particular, the activation of inflammatory cells and mediators contributes to plaque instability and rupture, leading to acute occlusion of the coronary arteries13. The relative risks of coronary heart disease (CHD) morbidity and mortality14, cardiovascular disease mortality15, and all-cause mortality16,17are elevated in individuals with low serum albumin levels compared with those with high serum albumin levels. Hypoalbuminemia is also associated with poor reperfusion at the epicardial and tissue level after PCI18. Moreover, a decrease in albumin levels is associated with the occurrence of atrial fibrillation and the risk of mortality, especially in elderly patients with dual-chamber permanent pacemaker implantation19. In patients with ST-segment elevation myocardial infarction, newly developed atrial fibrillation is a common and serious complication closely linked to long-term mortality20. The uric acid/albumin ratio has been shown to have independent predictive value as a biomarker for predicting new-onset atrial fibrillation21. These findings further emphasize the important role of albumin in cardiovascular diseases and suggest its potential application value in disease management, risk assessment, and treatment. As low serum albumin levels increase coronary morbidity and mortality, poor reperfusion after PCI, and postoperative cardiovascular risk, we hypothesized that low serum albumin may be associated with a longer hospital stay in patients undergoing PCI for ACS. Therefore, the present study investigated this relationship.

Methods

This retrospective cohort study included non-selective consecutive patients diagnosed with ACS, including UA, STEMI, and NSTEMI, who underwent PCI in the Department of Cardiovascular Medicine of the Second People’s Hospital of Shenzhen, China. To protect patient privacy, these data did not include identifiable participants. The data were obtained from the hospital’s electronic medical record system. The Ethics Committee of the Affiliated Hospital of Shenzhen University approved this study (ethics number: 2024-021-02PJ), which was conducted in accordance with the principles of the Declaration of Helsinki. All patients participating in the study provided written informed consent.

Data were collected on a total of 2490 patients undergoing catheterization laboratory procedures between 1 January 2021 and 31 December 2023. The inclusion criteria were patients diagnosed with ACS who underwent PCI. The exclusion criteria were no baseline serum albumin data, postoperative request for transfer or abandonment of treatment to home, and intraoperative or preoperative death of patients who did not complete the procedure. Based on the inclusion/exclusion criteria, 1,493 patients without ACS, 586 patients who did not undergo PCI, and 66 patients without pre-count serum albumin data were excluded. Finally, this study included 345 cases.

Data collection

The primary study outcome was the patient’s length of stay, which was calculated as the number of days between the date of discharge and the date of admission. The clinical and demographic characteristics of patients were obtained from hospital files and computerized records. The covariates included demographic data, variables affecting the severity of coronary artery disease and length of hospital stay reported in previous studies22,23,24, and clinical data. A fully adjusted model was constructed using continuous variables (age, white blood cell [WBC] count, platelet count [PLT], hemoglobin (HGB) level, ultrasensitive C-reactive protein [Hs-CRP] level, potassium ion (K+) level, cardiac troponin I [cTnI] level, high-density lipoprotein cholesterol [HDL-C] level, low-density lipoprotein cholesterol [LDL-C] level, and ejection fraction [EF] obtained at baseline); and categorical variables (sex, chronic heart failure [CHF], chronic renal insufficiency [CRF], history of PCI, old myocardial infarction [OMI], stroke, hypertension, diabetes mellitus, smoking, intravascular ultrasound [IVUS], and aortic balloon counterpulsation pump [IABP]).

Statistical methods

Patients were categorized into four groups (Q1–4) based on the quartiles of their serum albumin levels measured prior to percutaneous coronary intervention (PCI). The specific ranges of serum albumin levels for each group were determined by the distribution of data collected from all participants, which were as follows: ≤32.9 g/L, 32.9–37.9 g/L, 37.9–42.9 g/L, and > 42.9 g/L. Normally distributed continuous variables are expressed as means ± standard deviation (SD). Continuous variables with a skewed distribution are expressed as medians [interquartile range]. Categorical variables are expressed as numbers (n) and percentages (%). The characteristics of the study population were compared according to serum albumin levels.

We assessed the relationship between serum albumin levels and the length of hospital stay. One-way analyses were first performed to compare the differences between different albumin quartiles using the chi-squared test (for categorical variables), one-way analysis of variance (ANOVA) (for normal distribution), or the Kruskal–Wallis H test (for skewed distribution). Multivariate linear regression analyses were performed to control for potential confounding factors. Model 1 was unadjusted, while Models 2 and 3 were adjusted. In addition, segmented linear regression was used to explore the threshold effect of serum albumin levels on the length of hospital stay according to the smoothing plots.

P < 0.05 was considered to be statistically significant. Data analyses were performed using the Empower Stats statistical package (http://www.empowerstats.com; X&Y Solutions, Inc., Boston, MA, USA).

Results

Baseline participant characteristics

Among 2490 patients initially assessed, 345 were finally included in this study after applying the inclusion and exclusion criteria. Table 1 demonstrates the baseline characteristics of the patients who participated in the study. Participants with lower serum albumin levels had older ages, lower platelet and haemoglobin levels, more right coronary artery lesions, and more frequent use of IABP during surgery, while anterior descending branch lesions were more likely to be observed in participants with higher serum albumin levels.

Table 1 Characteristics of the study participants.
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Univariate and multivariate analyses

The results of the univariate analysis showed that WBC count, Hr-CRP, BG, LVEF, IVUS, and IABP were strongly associated with the length of hospital stay (Table 2). The results of the multivariate analysis indicated that lower serum albumin levels were significantly associated with longer hospital stays (Table 3). In Model 1 (unadjusted), the length of stay first decreased and then increased with increasing serum albumin levels (Q2 vs. Q1, odds ratio [OR] -1.00, 95% confidence interval [CI] -1.80, -0.20, P = 0.015; Q3 vs. Q1, OR -1.56, 95%CI -2.35, -0.76, P < 0.001; Q4 vs. Q1, OR -1.26, 95%CI -2.06, -0.46, P < 0.001). In Model 2 after adjusting for sex, age, hypertension, diabetes mellitus, hyperlipidaemia, smoking, OMI, PCI, shock, CKD, CHF, HGB, Hs-CRP, BG, LVEF, IVUS, IABP, PLT, K+, cTnI, LDL-C, and HDL-C. The relationship between serum albumin levels and length of stay remained consistent with Model 1 (categorical variables: Q2 vs. Q1, OR -0.99, 95%CI -1.89, -0.09, P = 0.032; Q3 vs. Q1, OR -1.02, 95%CI -1.97, -0.07, P = 0.036; Q4 vs. Q1, OR -0.62, 95%CI-1.66, 0.43, P = 0.248). After further smoothing for age, HGB, Hs-CRP, BG, LVEF, PLT, K+, cTnI, LDL-C, and HDL-C in Model 3, the relationship between serum albumin levels and length of hospital stay remained significant (categorical variables: Q2 vs. Q1, OR -0.92, 95%CI -1.79, -0.05, P = 0.040; Q3 vs. Q1, OR -1.08, 95%CI -2.00, -0.16, P = 0.022; Q4 vs. Q1, OR -0.70, 95%CI -1.71, 0.30, P = 0.173).

Table 2 Univariate analysis.
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Table 3 Relationship between serum albumin level and length of hospital stay.
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Non-linear regression of serum albumin and length of hospital stay

Analysis of the relationship between serum albumin levels and length of hospital stay, after adjusting for sex, leukocytes, HBG, Hs-CRP, BG, LVEF, IVUS, and offender vascularity, showed a U-shaped relationship between serum albumin level and length of hospital stay (Fig. 1).

Figure 1
figure 1

Curvilinear relationship between serum albumin and length of hospital stay. (A) Scatter density indicates the number of patients. (B) Plot of the fitted curve with an infection point of 39.9 g/L. dashed lines: 95% confidence interval.

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We also performed a threshold effect analysis and calculated an inflection point of 39.9. When serum albumin levels were < 39.9 g/L, the length of hospital stay decreased with increasing serum albumin level (OR -0.29, 95% CI -0.43, -0.16 P < 0.001). When serum albumin levels were > 39.9, the length of hospital stay increased with increased serum albumin level (OR 0.09, 95% CI -0.09, -0.36 P = 0.331).

Discussion

This retrospective study analysed the relationship between serum albumin levels and length of hospital stay in 345 patients with ACS treated with PCI. We observed a U-shaped relationship between serum albumin level and length of hospital stay. The inflection point in threshold effect analysis was 39.9; thus, among patients with serum albumin levels < 39.9 g/L, the length of hospital stay decreased with increasing serum albumin (OR -0.29, 95% CI -0.43, -0.16 P < 0.001). In contrast, the effect of serum albumin > 39.9 g/L on the length of hospital stay was not significant (P = 0.331).

Our study findings are consistent those of Hideki Wada et al. and Oduncu et al. who demonstrated that low serum albumin concentrations are linked to poor outcome in patients with CAD and PCI16,25,26. The present study confirmed the association between serum albumin levels and hospital length of stay in patients diagnosed with ACS who underwent PCI. After adjusting for several potential confounders, we found that patients with serum albumin levels < 39.9 g/L experienced decreasing length of stay with increasing serum albumin levels, suggesting that, below a certain threshold, improved clinical recovery and shorter hospital stays are achieved by increasing serum albumin levels.

The mechanism underlying the U-shaped relationship between serum albumin and length of hospital stay is unclear. Low serum albumin levels are associated with higher SYNTAX score27, which is an independent predictor of freedom from regurgitation and in-stent restenosis after primary PCI28, as well as increased risks of several PCI complications, including contrast-induced acute renal failure29and new-onset cardiac insufficiency25,30. Serum albumin is not only a biomarker of nutritional status but is also involved in a variety of physiological processes, including the maintenance of colloid osmotic pressure, transport of a variety of compounds, modulation of inflammatory responses, and antioxidant activity4,5,6,7,8,9,10,11,31. The possible mechanisms linking low serum albumin levels to longer hospital stays include reduced albumin levels leading to a weakening of its antioxidant effect, causing increased oxidative stress, vascular endothelial cell damage32, and atherosclerosis promotion, thereby increasing the risk of cardiovascular events. Albumin helps prevent endothelial dysfunction by maintaining the integrity and function of the vascular endothelium. In an inflammatory state, the synthesis of acute phase proteins such as C-reactive protein and fibrinogen is increased in the liver, whereas albumin synthesis may be inhibited33, leading to a decrease in serum albumin levels, while the ACS counters the hyperinflammatory state34. Inflammation induces increased vascular permeability and impaired endothelium-dependent vasodilatation, which exacerbates cardiac insufficiency and may also directly impair cardiac function, leading to heart failure35. Finally, albumin has anticoagulant properties and is a potent inhibitor of platelet aggregation. As a result, platelets are activated when albumin levels decrease, leading to an increased risk of cardiovascular events36,37,38,39.

Serum albumin level has long been considered the primary indicator of malnutrition. However, the role of nutritional support in patients undergoing PCI for ACS is unclear: the results of the PICNIC study showed that nutritional intervention improved the prognosis of malnourished patients with acute heart failure40, while in patients with acute heart failure, the effect of nutritional intervention was consistent in hypoalbuminemic and normoalbuminemic patients compared with conventional treatment41. The significant protective effect of serum albumin observed in the present study further confirms its role in nutritional support. However, empirical support for the role of nutritional support such as albumin supplementation in patients with ACS is lacking; therefore. further research and evaluation are required.

This study has several limitations. First, as a retrospective observational study, this study has design limitations. Second, the study was performed in a single centre, and the population studied was mainly post-PCI patients with ACSs; hence, the findings are not applicable to the entire population. The research findings should take into account the potential impact of conditions such as acute infections and chronic inflammation on serum albumin levels, which were not excluded from our patient cohort. Although we aimed to include a representative sample of ACS patients without excluding these conditions, we acknowledge that this approach may introduce variability in the data. Finally, although we adjusted for confounders that may have been associated with the results, some unrecorded confounders may have affected the results. Therefore, a larger population and higher-level clinical trials are required.

Conclusions

Low serum albumin level was an independent predictor of longer hospital stays in patients undergoing PCI for ACS. Serum albumin levels showed a U-shaped relationship with the length of hospital stay, with an inflection point of 39.9 g/L. Low serum albumin may be used as a tool to identify patients who require longer hospitalization and may need additional nutritional support or interventions to improve their prognosis. Further evaluation and higher-level clinical trials are necessary to confirm and extend our findings.