Heart failure (HF) has become a significant global public health challenge, with its prevalence steadily increasing, largely driven by the accelerating aging of the population worldwide (1). HF patients have a poor prognosis, with an annual mortality rate reaching up to 33%, and studies encompassing all adult age groups report an overall mortality rate of 24% (2). Moreover, the frequent hospitalizations associated with HF not only impose a substantial burden on healthcare resources but also have a profound negative impact on patients’ quality of life (3).

Malnutrition is highly prevalent among HF patients, with an estimated incidence ranging from 15 to 90%, depending on the assessment method used (4). Several mechanisms contribute to malnutrition in HF, including activation of the renin-angiotensin-aldosterone system (RAAS), involvement of inflammatory mediators, reduced cardiac output, and appetite loss due to dyspnea or intestinal edema (5). In addition, chronic illness, prolonged physical inactivity, and extended bed rest can lead to muscle wasting, further exacerbating malnutrition (6). Studies indicate that HF patients with malnutrition have nearly twice the all-cause mortality rate compared to their well-nourished counterparts, highlighting the critical role of malnutrition in increasing mortality risk (7).

Systemic inflammation is widely recognized as a key pathophysiological feature of both acute and chronic HF, playing a pivotal role in disease progression, exacerbation, and the development of complications (8). Recent studies have highlighted a significant link between inflammatory biomarkers and the prognosis of HF (9). As a result, indices that evaluate both inflammation and nutritional status in a comprehensive manner hold promise as more effective prognostic tools.

There is growing interest in inflammation- and nutrition-related indicators. The Advanced Lung Cancer Inflammation Index (ALI) serves as a composite biomarker that assesses inflammation and nutritional status. Originally designed to evaluate the degree of systemic inflammation in patients with metastatic non-small cell lung cancer (NSCLC) (10), ALI is computed using the formula: body mass index (BMI) multiplied by serum albumin (Alb) divided by the neutrophil to lymphocyte ratio (NLR). Due to its effectiveness in reflecting the body’s inflammatory and nutritional states, ALI has been applied in various disease populations similarly impacted by nutrition and inflammation, including cancer (11), rheumatoid arthritis (12), and diabetes (13). The red cell distribution width-to-albumin ratio (RAR = RDW/albumin) is a novel composite biomarker that reflects both inflammatory and nutritional status. In recent years, multiple studies have demonstrated that RAR is closely associated with mortality risk in a range of critical conditions, including acute myocardial infarction (14), acute respiratory failure (15), and sepsis (16). It has shown strong prognostic utility in these clinical settings.

Additionally, there has been extensive research on other inflammation- and nutrition-related indices, including the monocyte-to-albumin ratio (MAR), neutrophil-to-albumin ratio (NAR), prognostic nutritional index (PNI), geriatric nutritional risk index (GNRI), hemoglobin-albumin-lymphocyte-platelet (HALP) score, and controlling nutritional status (CONUT) score (17, 18). Different inflammation- and nutrition-related biomarkers may reflect distinct pathophysiological aspects of HF, and their predictive value and clinical utility may vary. However, comprehensive evidence on the association between these derived indicators and HF-related mortality is currently lacking, and no studies have systematically compared the prognostic value of these indices for predicting all-cause and cardiovascular mortality in HF patients. Furthermore, while some studies suggest that inflammation- and nutrition-related indicators may be valuable for survival prediction in HF, the optimal prognostic marker remains uncertain.

Therefore, this study utilized data from the nationally representative National Health and Nutrition Examination Survey (NHANES) cohort to investigate the association between inflammation- and nutrition-related indicators and HF prognosis. By systematically evaluating and comparing the prognostic value of these indices, this study aims to clarify their clinical significance and provide more comprehensive evidence to support risk stratification and precision management in HF patients.

This study employed multiple analytical approaches to explore the relationships between various inflammation/nutrition indicators and mortality outcomes in heart failure (HF) patients, analyzing cohort data from 1,500 individuals. After false discovery rate (FDR) correction for multiple testing, the vast majority of these markers remained robust independent predictors of mortality, although the associations for NAR and HALP with cardiovascular mortality were not significant. Restricted cubic spline (RCS) analysis revealed linear or nonlinear relationships between these markers and mortality risk. Time-dependent ROC curve analysis indicated that RAR exhibited the highest predictive value for 1-year all-cause and cardiovascular mortality, whereas ALI demonstrated superior predictive performance for 3-year, 5-year, and 10-year mortality. Furthermore, random survival forest (RSF) analysis, validated through a training-validation set split, consistently identified ALI as the top-ranking predictor, underscoring its stable and prominent role in risk stratification. Stratified analysis reinforced the prognostic value of ALI across different populations, suggesting its stable predictive capability and broad clinical applicability for risk stratification in HF patients. Subgroup analysis showed that RAR had a stronger prognostic value in male patients.

The loss of significance for NAR and HALP after FDR correction (q > 0.05) for cardiovascular mortality is likely attributable to diminished statistical power following stringent multiple testing adjustment. Associations with more modest effect sizes may not survive this correction, which does not negate their potential biological relevance but indicates that their evidence is less robust than that for stronger predictors like RAR and ALI in our cohort.

MAR and NAR, as emerging composite biomarkers of inflammation and nutritional status, may conceptually be inspired by other ratio-based indices (such as NLR and PLR). The significance of these markers in cancer prognosis (19, 20) has been well established and is gradually being extended to inflammatory diseases (21, 22) and cardiovascular conditions (23, 24). This study is the first to evaluate the prognostic value of MAR and NAR for both all-cause and cardiovascular mortality in patients with HF.

The prognostic utility of PNI (25), RAR (26), HALP score (27), ALI (28), GNRI (29), and CONUT score (30) in HF patients has been discussed in previous studies. Consistent with prior findings, our study confirmed that these markers are independent prognostic indicators for HF patients. However, no previous research has systematically compared multiple inflammation/nutrition markers to evaluate their prognostic roles and relative advantages in HF prognosis. Our findings indicate that RAR was the most effective predictor of 1-year mortality, while ALI exhibited the highest predictive value for 3-year, 5-year, and 10-year mortality, potentially reflecting distinct mechanisms influencing short-term versus long-term prognosis.

A possible explanation for this discrepancy is that RAR integrates red blood cell distribution width (RDW) and albumin levels, primarily reflecting acute inflammatory responses, nutritional status, and hemodynamic changes, which may have a more immediate impact on short-term mortality risk in HF patients (26). RDW represents variability in red blood cell volume and is associated with impaired bone marrow hematopoiesis, heightened inflammatory responses, and reduced oxygen-carrying capacity. Elevated RDW may indicate inflammation activation, iron metabolism disorders, and shortened red blood cell lifespan, all of which can accelerate disease progression and contribute to increased short-term mortality risk in HF patients (31). Previous studies have demonstrated that elevated RDW is closely related to short-term hospitalization rates and mortality in HF and may serve as an important predictor of acute HF decompensation or sudden cardiac death (32, 33). Moreover, decreased albumin levels reflect acute malnutrition and heightened inflammation (34). Albumin is a critical marker of chronic inflammation and nutritional status, and low albumin levels indicate acute disease exacerbation, fluid retention, and hepatic dysfunction, potentially leading to higher short-term mortality risk (35). In acute decompensated HF (e.g., congestion, hypoperfusion, hepatic congestion), serum albumin levels typically decrease (36). Therefore, low albumin levels in the short term may serve as a key predictor of poor prognosis. Given that RAR combines RDW, which reflects erythrocyte variability and systemic inflammation, with albumin, which indicates malnutrition, it may be particularly sensitive for predicting short-term mortality risk, such as 1-year mortality.

In contrast, ALI is composed of BMI, albumin, and the neutrophil-to-lymphocyte ratio (NLR), offering a more comprehensive reflection of chronic inflammation, nutritional status, and immune dysregulation, which could have a more significant impact on the long-term progression of HF. NLR, a key component of ALI, reflects chronic inflammation and immune imbalance, both of which are recognized as important drivers of HF progression (37, 38). HF patients with prolonged survival often experience chronic inflammation, immune dysfunction, and cardiac remodeling—factors that may hold greater predictive value in the long term (39, 40). Additionally, albumin and BMI, core components of ALI, provide long-term insights into a patient’s metabolic reserves, muscle mass, and chronic pathological state. Low BMI and hypoalbuminemia are associated with HF-related cachexia, muscle loss (sarcopenia), and chronic energy expenditure syndromes, all of which are critical determinants of long-term mortality (41–44). Thus, the components of ALI are more indicative of chronic inflammation and nutritional status, making them potentially more stable markers for long-term mortality risk assessment. This explains why ALI exhibited superior predictive performance for 3-year, 5-year, and 10-year mortality, suggesting its suitability for long-term prognosis evaluation.

Inflammation is a well-established contributor to HF progression, with significant impact on disease trajectory and outcomes. Targeted interventions including anti-inflammatory therapies (45) and dietary adjustments (46) have shown promise in reducing cardiovascular events and improving prognosis in HF patients. Similarly, improving nutritional status is a modifiable and clinically important goal (47), given its strong association with mortality. It is noteworthy that nutritional status, rather than body mass index (BMI) alone, is a key modulator of heart failure prognosis. Emerging evidence (48) indicates that the protective effect of obesity in HF patients is confined to those who are well-nourished, while this association vanishes in malnourished individuals. This underscores the limitations of the BMI-based “obesity paradox” for prognostic evaluation, as evidence (49) highlights that nutritional status, rather than BMI alone, is a more central factor in risk stratification. Compared to single markers such as C-reactive protein (CRP) or BMI, composite indices offer a multidimensional approach to risk assessment and allow dynamic monitoring of treatment effects. The prognostic value of RAR and ALI may vary across HF subgroups. In acute decompensated HF, characterized by intense systemic inflammation and rapid nutritional decline, RAR may provide a sensitive and practical tool for short-term risk stratification. Elevated RAR reflects both inflammation and hypoalbuminemia, enabling early identification of high-risk patients who may benefit from timely interventions such as anti-inflammatory therapy and nutritional support. In patients with chronic HF, long-term outcomes are more influenced by low-grade inflammation and progressive malnutrition. In this population, ALI appears to be a stronger predictor of long-term mortality. Persistently low ALI may signal the need for optimized disease management, including adjustments to anti-inflammatory and neurohormonal therapies (such as SGLT2 inhibitors, ARNI), individualized dietary strategies, and the consideration of novel therapies like GLP-1 receptor agonists, which have recently demonstrated efficacy in improving symptoms and physical function in patients with HFpEF (50). Integrating ALI into routine risk assessment for stable HF may help guide personalized, prevention-oriented care.

Future research should further investigate the underlying mechanisms connecting ALI and RAR to HF progression and assess their potential role in guiding individualized therapeutic strategies.

In summary, ALI demonstrated the strongest predictive value for long-term prognosis and may aid in guiding long-term pharmacologic adjustments and nutritional optimization strategies in patients with stable heart failure. In contrast, RAR showed the highest accuracy in predicting 1-year mortality and may facilitate early identification of high-risk individuals, enabling timely initiation of anti-inflammatory or nutritional interventions. These findings suggest that ALI and RAR hold potential as practical tools for clinical risk stratification at different stages of heart failure. Prospective studies are warranted to validate these results and to further explore whether ALI- and RAR-based interventions can improve outcomes in the heart failure population.