Heart failure (HF), the terminal phase of cardiovascular disease, is a prevalent mortality cause among the elderly (1). Globally, it impacts nearly 40 million individuals. Annually, heart failure is the cause of death for 10% to 30% of affected patients (2). Factors such as population growth and aging have led to a consistent increase in heart failure patients (3). Early identification of mortality risk in patients with heart failure can substantially enhance their life quality and survival chances.

Several factors have been identified that correlate with mortality rates in patients with HF. For instance, Grodin et al., analyzing data from TOPCAT, deduced that diminished serum chloride levels independently elevate cardiovascular and all-cause mortality risk in HF patients with preserved ejection fraction (HFpEF) (4). However, this study only included HF patients with standard ejection fraction values, implying that the findings can't be generalized to all HF patients with low chloride levels. Beltowski et al. investigated the relationship between microalbuminuria and mortality in acute HF patients. They classified 426 HF patients who presented at the emergency department into three categories based on their left ventricular ejection fraction: the HF patients with preserved ejection fraction (HFpEF) group, HF with mildly reduced ejection fraction (HFmEF) group, and the HF with reduced ejection fraction (HFrEF) group. They found that AURC only prognosticated outcomes for patients in the HFmEF and HFrEF groups (5). Nonetheless, this study's limited sample size and the focus solely on acute heart failure patients restrict its broader clinical applicability. Therefore, identifying a more stable and readily available index to gauge mortality risk is imperative for optimizing elderly HF patient care.

Inflammation plays a pivotal role in the pathogenesis of HF and is a central process in its pathophysiology. Previous studies show that inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor (TNFα), and interleukin (IL-6), contribute to cardiovascular system adaptability during the early phases of HF (6, 7). However, these markers exacerbate HF's advanced stages by promoting myocardial fibrosis. These findings underline the detrimental effects of elevated pro-inflammatory cytokines on outcomes and cardiac remodeling in HF patients. Therefore,we hypothesized that MLR holds significant implications for the development and progression of HF, particularly in elderly patients. Yet, the relationship between MLR and HF in the elderly remains to be elucidated. Therefore, this study investigated the clinical relevance and prognostic value of MLR in elderly patients with HF.

Our analysis drew upon data from the Sichuan Zigong Heart Failure Database (8). From our assessment, this study presents a novel observation: a concurrent rise in MLR as HF mortality escalates. We discerned a significant correlation between MLR and 3-month mortality among patients with HF. Once potential confounders were accounted for, MLR emerged as a salient predictor of 3-month mortality within this cohort. These findings underscore the potential utility of MLR as a prognostic tool for both HF progression and 3-month mortality.

The results of this study suggest a positive association between MLR and 3-month mortality in elderly HF patients. To mitigate the effects of potential confounders, we employed three distinct Cox regression models to elucidate the relationship between MLR and 3-month mortality in this demographic. Upon complete adjustments in the model 3, the effect value was established at 3.16 (1.33–7.53). This translates to a 216% elevation in the 3-month mortality risk among elderly HF patients for each unit increment in MLR. Based on prevailing clinical consensus, once adjustments for potential confounders have been made, any effect value alteration of MLR by 10% or greater firmly establishes a potent positive correlation between MLR and 3-month mortality in elderly patients with HF. For a more nuanced sensitivity analysis, we bifurcated MLR into two categories, and the resultant data exhibited both stability and reliability. Furthermore, our subgroup analysis, which factored in variables such as age, gender, and co-morbidity index, displayed consistent results across all subgroups, devoid of any interactions. The K-M survival curves, adjusted per model 3, showcased the differential in the 3-month mortality rate between varying MLR levels among elderly HF patients. The results were consistent with trend validation.

Previous studies have highlighted the mononuclear lymphocyte ratio (MLR) as a pivotal risk determinant for conditions such as pneumonia, cancer, depression, and cardiovascular ailments, especially in its role in the progression and outcome prediction of cardiovascular diseases (9–13). Mirna et al. conducted a retrospective cohort study involving 202 myocarditis patients and revealed MLR to be a more salient factor concerning hospitalization duration than conventional inflammatory markers like CRP, white blood cell count, IL-6, or calcitonin gene (14). Gijsberts et al. identified a correlation between elevated MLR and increased levels of NT-proBNP in patients undergoing coronary arteriography, citing it as an independent predictor for heart failure patients’ readmission after an average follow-up of 1.3 years (15). Nevertheless, the prognostic implications of MLR for elderly Chinese HF patients remain underexplored. Hence, our analysis aimed to bridge this knowledge gap. Aligning with our conclusions, prior studies have ascertained that an admission-time MLR is linked with a multivariate-adjusted risk of readmission or mortality. A retrospective cohort study involving 678 patients diagnosed with non-ST-segment elevation myocardial infarction (NSTEMI) who underwent percutaneous coronary intervention (PCI) in Beijing, China, established that heightened MLR levels independently forecasted long-term major adverse cardiac events (MACE) for patients with NSTEMI (16). Zhai et al. observed that, among patients in a cardiac intensive care unit, those in the highest MLR quartile group exhibited the steepest mortality rates (7.8% in the lowest group vs. 16.3% in the highest group, p < 0.001) (6). Oh et al. highlighted that in patients with chronic kidney disease (CKD), the high MLR cohort faced an escalated risk for composite cardiovascular disease (CVD) events, inclusive of cardiovascular disease onset, heart failure, CVD mortality, and all-cause mortality, with an HR of 1.27 (95% CI, 1.1–1.48) (7). Delcea et al. juxtaposed the neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) to discern the most clinically pertinent metrics for forecasting hospitalization outcomes in heart failure patients (17). Their results pinpointed all three metrics as independent mortality predictors in such patients but uniquely distinguished MLR as an independent prognosticator for in-hospital mortality (HR 1.68, 95% CI 1.22–2.32, p = 0.002). Another study investigated 171 heart failure (HF) patients, primarily examining the prognostic value of NLR,MLR,and LMR in predicting major adverse cardiovascular events (MACE) and mortality across different LVEF categories.Their findings demonstrated that patients with HFrEF and HFmrEF exhibited significantly higher NLR and MLR levels but lower LMR levels. While MACE incidence was similar across groups, the HFrEF group had a significantly higher mortality rate (18). The evidence suggests a potential correlation between MLR and heart failure. Consequently, we hypothesized that a reduction in MLR levels might lead to a decline in 3-month mortality among heart failure patients, presenting a pioneering avenue to enhance their health outcomes potentially. However, it's imperative that additional prospective studies be conducted to verify if these findings hold true across a more extensive population.

There are some aspects worth mentioning in the present study compared with previous studies. Since the Sichuan Zigong Heart Failure Database only includes the Chinese population, previous studies have remained uncharted regarding the relationship between MLR and 3-month mortality in Chinese patients with heart failure. For a more graphic depiction of this relationship amongst elderly heart failure patients, we crafted a K-M survival curve.

Also, this study has some limitations. Even as our results signify a positive correlation of MLR with 3-month mortality in elderly patients with heart failure, the retrospective nature of our cohort study inherently introduces biases. Hence, imminent prospective evaluations are requisite to clarify this relationship. Additionally, as the Sichuan Zigong Heart Failure Database is localized to the Chinese population, generalizing our findings about MLR and 3-month mortality in older heart failure patients to other populations remains tentative.First, healthcare-access patterns in China may differ from European cohorts universal-coverage systems. Second, ethnicity-specific factors like dietary sodium intake or ACEI prescription rates could influence leukocyte indices' prognostic utility.While the inflammatory mechanism linking MLR to mortality may be universal, the optimal prognostic thresholds require age- and ethnicity-specific calibration (19) Furthermore,the lack of data on medication dosages and the important variable of left ventricular ejection fraction (LVEF) in this database may impact the study results, despite our comprehensive assessment of the clinical condition of heart failure patients using other key indicators.The prognostic value of MLR may vary by heart failure subtypes: inflammatory markers such as MLR may play a dominant role in HFrEF (LVEF ≤ 40%), whereas diastolic dysfunction might be more critical in HFpEF. Failure to stratify by LVEF could obscure these subtype-specific associations (18). The lack of LVEF data may introduce confounding, as patients with reduced vs. preserved LVEF have distinct risk profiles. However, the inclusion of BNP in our multivariate model may partially mitigate this, as it correlates with EF and overall HF severity (20). The lack of medication data (beta-blockers and RAAS inhibitors) represents a key limitation, as these therapies are known to modify mortality risk in heart failure. Their potential confounding effects cannot be excluded.Future prospective studies should systematically capture medication data and ejection fraction (EF) values to better control for this confounder.

The findings from this retrospective cohort study indicate that the MLR at admission was directly correlated with the 3-month mortality risk in elderly patients with HF. MLR serves as a straightforward yet productive inflammatory marker that can be routinely detected in clinical settings, warranting the scrutiny of healthcare practitioners. However, the precise underlying mechanism and its applicability to diverse populations remain to be elucidated. It is imperative to undertake randomized controlled trials with larger sample sizes to furnish robust evidence for clinical practice guidelines.