Clinical study of a new nutritional index for predicting long-term prognosis in patients with coronary atherosclerotic heart disease following percutaneous coronary intervention

1 Introduction

According to mortality data from the Global Burden of Disease Study, coronary heart disease (CHD) remains the leading cause of death worldwide, contributing to high morbidity and mortality^[1]. Especially in frigid zone, percutaneous coronary intervention (PCI) is an established procedure to restore blood flow by opening stenotic or obstructed vessels, alleviating patient’s symptoms. However, some patients continue to experience recurrent myocardial infarction, cardiac death, stroke, and other major adverse cardiovascular and cerebrovascular events (MACCE) after PCI. Therefore, early identification of CHD patients at risk for poor prognosis post-PCI, coupled with timely intervention is crucial.

Numerous studies have demonstrated that malnutrition is prevalent among CHD patients and is closely linked to poor prognosis. Objective nutritional indicators, such as the prognostic nutritional index (PNI)^[2-3], Geriatric Nutritional Risk Index (GNRI)^{[4, 5, 6]}, Con trolling Nutritional Status (CONUT)^[7-8], and Triglycerides × Total Cholesterol × Body Weight Index (TCBI)^[9-10] have proven to be significant in assessing cardiovascular prognosis. Of these, the CONUT score Of these predict all-cause mortality and major cardiovascular events within one year more effectively than PNI and GNRI^[11-12], although it is not yet widely adopted in clinical practice.

In addition to malnutrition, inflammation plays an important role in the progression of coronary atherosclerosis. The neutrophil/lymphocyte ratio (NLR), an emerging inflammatory marker, is strongly associated with prognosis in various cardiovascular diseases^[13-14]. Given that both nutritional and inflammatory factors influence long-term prognosis in CHD patients after PCI, a new index—albumin/NLR—was developed. This index combines conventional nutritional indicators, such as body mass index (BMI), total cholesterol, albumin, and total lymphocyte counts, with the inflammatory marker NLR. The purpose of this study is to determine whether the albumin/NLR index correlates with the prognosis of CHD patients post- PCI and whether it offers superior prognostic value and clinical relevance compared to traditional markers.

2 Methods

3 Results

3.1 Determining the cut-off value using the ROC curve

The albumin/NLR ratio, treated as a continuous variable, was used as the test variable, with all-cause death and MACCE as the outcome variables. Based on the results of the ROC curve, the Youden index (sensitivity + specificity - 1) was calculated. The point corresponding to the maximum Youden index was identified as the optimal cut-off value. The best cut-off value was determined to be 17.9509, with an area under the curve (AUC) of 0.655, sensitivity of 0.661, and specificity of 0.578. Fig. 1 illustrates the division of patients into low- and high-index groups based on this cut-off value.

Fig. 1

Receiver operating characteristic (ROC) curve of the new nutritional index

3.4 Kaplan-Meier survival curve and Log-rank analysis

During the five-year follow-up, 45 patients experienced all-cause mortality and major adverse cardiovascular and cerebrovascular events (MACCE). The incidence of endpoint events was significantly higher in the low-index group (12%) compared to the high-index group (4.9%). Kaplan–Meier analysis further demonstrated that the incidence of endpoint events following PCI was significantly greater in the low-index group than in the high-index group (P = 0.001) (Fig. 2).

Fig. 2

Kaplan–Meier and cumulative hazard curves.

(A) The Kaplan–Meier curve displays survival time (in months) on the horizontal axis and the cumulative survival rate on the vertical axis. (B) The cumulative risk curve shows time to event (in months) on the horizontal axis and the cumulative incidence of all-cause mortality and major adverse cardiovascular and cerebrovascular events (MACCE) on the vertical axis. Log-rank analysis indicates a significant difference (P = 0.001).

4 Discussion

Coronary artery disease (CAD) is a major global health concern, representing the leading cause of death and disability associated with cardiovascular diseases especially in frigid zone. Its primary pathogenesis is linked to atherosclerosis of the coronary arteries. Atherosclerosis is characterized by a specific inflammatory state, where inflammation can both indirectly and directly promote its development through mechanisms such as endothelial dysfunction, lipid metabolism disorders, and oxidative stress^[17]. Previous studies have shown that inflammation is associated with decreased albumin levels, and lower serum albumin is linked to a higher risk of mortality^[18]. Low albumin levels may also indicate malnutrition. Given the relationship between inflammation and nutrition, inflammatory-protein indicators could serve as valuable predictors of prognosis in cardiovascular disease.

Malnutrition is associated with a poor prognosis in CHD patients following PCI through various mechanisms. Albumin, the most abundant circulating protein in the plasma, plays a crucial role in antioxidant activity due to its numerous binding sites and free radical trapping properties^[19]. Lapenna et al.^[20] found that reduced serum albumin levels correlate with oxidative damage to atherosclerotic plaques and the severity of atherosclerosis. Albumin levels not only reflect nutritional status but also indicate acute-phase reactions. It serves as a serological marker of malnutrition associated with inflammation and exerts pro-inflammatory effects on vascular endothelium and lipoprotein structures^[21]. Studies have reported that low serum albumin levels are linked to an increased risk of atherosclerosis^[22], cardiovascular death^[23], and all-cause death^[24]. The pathological decrease in albumin levels in CAD may be related to the diminished antioxidant, anti-inflammatory, and antiplatelet aggregation activities, resulting in impaired endothelial function, increased blood viscosity, oxidative stress, and elevated levels of key platelet mediators of s, which contribute to coronary artery stenosis^[25]. Consequently, improving albumin levels may mitigate the risk of cardiovascular disease and inflammatory status of patients, potentially lowering mortality rates^[26].

Inflammation and oxidative stress are pivotal in the pathogenesis of cardiovascular diseases, prompting numerous studies on inflammatory markers. Currently, several inflammatory indices, including C-reactive protein (CRP) and the neutrophil-tolymphocyte ratio (NLR), have emerged as prognostic markers for patients with CAD. CRP, a classical downstream effector of various inflammatory pathways, promotes inflammation by stimulating the secretion of pro-inflammatory cytokines^[27]. Research confirms a correlation between elevated CRP levels and the severity of coronary heart disease, as well as an increased likelihood of future cardiovascular events^[28]. Eldrup, et al.^[29] demonstrated that high CRP levels are associated with an elevated risk of unstable angina, myocardial infarction, and mortality in patients with stable CAD. Additionally, a study by Li et al. highlighted that baseline CRP levels remain an independent predictor of long-term MACCE in patients undergoing coronary revascularization, even with comprehensive statin and anti-platelet therapy^[30]. Similarly, a meta-analysis involving 18,715 individuals found a significant association between elevated CRP levels and an increase in multiple adverse outcomes, including all-cause and cardiovascular mortality, in patients with acute myocardial infarction undergoing PCI^[31]. Atherosclerosis is characterized as a unique inflammatory state, with neutrophils reflecting this inflammatory status and lymphocyte counts indicating immune capacity. Low lymphocyte percentages have been significantly associated with CAD and serve as predictors of poor prognosis^[32]. Previous studies have shown that elevated white blood cell counts predict an increased risk of death or myocardial infarction in CAD patients; however, an increase in neutrophils coupled with a decrease in lymphocytes is more strongly correlated with poorer long-term outcomes than white blood cell count alone, suggesting that specific white blood cell components provide better prognostic value^[33]. The NLR, which combines neutrophil and lymphocyte counts, offers enhanced prognostic predictive capability for CAD. A meta-analysis of over 16,000 patients with acute coronary syndrome found that a high NLR at admission was associated with an increased risk of MACCE, hospitalization, and long-term mortality^[13]. Studies indicate that a pre-PCI NLR is significantly associated with long-term outcomes in patients with stable coronary heart disease, with higher NLR values correlating with increased all-cause and cardiovascular mortality^[14]. Therefore, the NLR demonstrates significant predictive value for CAD prognosis, with higher values indicating a poorer outlook. Additionally, previous research has shown that lipid-lowering therapies (such as statin and ezetimibe combinations) can influence CD4+ lymphocytes, thereby interfering with the body’s immune-inflammatory system and potentially delaying the progression of atherosclerosis^[34].

The new nutritional index developed in this study, which integrates both nutritional and inflammatory factors, demonstrated superior predictive value for the prognosis of patients with CAD following PCI, consistent with the study’s objectives. Malnutrition is a complex condition characterized by protein reserve depletion, inadequate caloric intake, and diminished immune defense^[35], and it serves as an independent risk factor affecting CAD prognosis. Previous studies have shown that cardiac rehabilitation in CAD patients after PCI can significantly reduce hospitalization and mortality rates^[36]. Nutritional prescription, one of the five major components of cardiac rehabilitation, is vital for improving outcomes in these patients. This highlights the importance of addressing not only traditional inflammatory markers but also the nutritional status of patients with CAD post-PCI. In the present study, the implementation of this new nutritional index for assessing comprehensive nutritional and inflammatory status enabled the identification of patients at risk for poor outcomes. This facilitated early intensifications in anti-inflammatory therapy and cardiac rehabilitation, particularly through targeted nutritional interventions, which are crucial for enhancing patient prognosis. In clinical practice, intensive anti-inflammatory therapies, such as statins, ezetimibe, and PCSK9 inhibitors, combined with nutritional interventions, can be utilized to lower inflammation levels and improve the nutritional status of patients.

In this study, the use of calcium channel blockers (CCBs) in the low-index group was significantly lower than that in the high-index group (P < 0. 05). While several trials have demonstrated the effectiveness of CCBs in treating patients with coronary heart disease, they have not shown a mortality benefit^[37]. This difference in medication usage does not impact the anticipated results of this study. Although only baseline information collected at the time of patient admission was utilized, many large studies^[38-39] have similarly relied on single test indices without tracking changes in these indices during the follow-up period. Despite not capturing changes in patient status over time, these studies have still yielded valuable results.

This study has several limitations. First, it was a small-scale, single-center, retrospective observational study. Future research should involve large-scale, multicenter, prospective cohort studies to further investigate the impact of improved nutritional and inflammatory status on the prognosis of patients with CHD after PCI. Second, due to the retrospective nature of this study, comprehensive surgical information, such as collateral blood vessels, degree of stenosis, and number of stents, which may significantly influence patient prognosis, was not fully obtainable. Lastly, incomplete follow-up data may have introduced selection bias. Therefore, further large-scale, multicenter prospective studies are necessary to validate the relationship between the new nutritional index and the prognosis of patients with CHD after PCI.

5 Conclusion

In conclusion, the new nutritional index, which incorporates albumin and the NLR demonstrates greater predictive efficiency than individual nutritional and inflammatory markers in assessing the prognostic of patients with coronary heart disease following PCI. This new index not only predicts patient outcomes but also holds significant clinical utility. Specifically, a value below 17.9509 indicates an elevated risk of poor prognosis, highlighting the need for early intervention in these patients.