Cardiovascular disease (CVD) has become one of the most important public health problems in the world, and it is also one of the most important causes of death in the world, among which the prevalence and mortality of coronary heart disease (CHD) are the highest [1, 2]. Although the medical treatment and surgical treatment of CHD have become standardized, the prognosis is still not optimistic, and the mortality rate is still gradually rising in patients with CHD [3]. Therefore, screening and early intervention of reversible risk factors is very important to improve the prognosis and quality of life of patients with CHD.

Serum albumin is the most abundant multifunctional protein in the blood. It not only plays a vital role in the regulation of colloid osmotic pressure, but also has antioxidant properties, and can also respond to various diseases as an acute phase reaction protein [4, 5, 6, 7]. However, unlike other acute phase reactive proteins, its concentration is at a low level in the acute phase [5]. In addition, albumin is a biomarker reflecting nutritional status. Hypoalbuminemia is due mainly to the decline in liver synthesis, decreased intake and chronic inflammation, which can be seen in many diseases [8, 9]. Recent research has indicated that serum albumin is strongly associated with the outcome and mortality of many chronic diseases, including cirrhosis, chronic heart failure and chronic obstructive pulmonary disease [10, 11, 12, 13, 14, 15]. Moreover, serum albumin and its composite indicators play a significant role in assessing cardiovascular risk and predicting clinical outcomes [16]. Several studies have demonstrated that serum albumin, whether used alone or in combination with other clinical parameters, is strongly associated with no-reflow and new-onset atrial fibrillation following percutaneous coronary intervention in patients with acute myocardial infarction [17, 18]. It has also been linked to left ventricular hypertrophy in individuals with hypertension [19]. Additionally, lower albumin levels have been shown to predict long-term all-cause mortality in patients with dual-chamber permanent pacemakers [20]. However, the relationship between serum albumin and mortality risk in patients with coronary heart disease remains unclear.

Therefore, based on the current research background and knowledge gaps, and to provide therapeutic strategies for the management of albumin in the prognosis of CHD, we used data from the 1999–2015 National Health and Nutrition Examination Survey (NHANES), to examine the association between serum albumin levels and the death risks for CHD patients.

In this large, retrospective cohort study, our findings indicated that serum albumin was significantly associated with both all-cause mortality and cardiovascular death among those suffering from CHD. Moreover, this association presented a linear negative correlation pattern. These results not only emphasized the significance of serum albumin in the prognostic assessment and care of CHD patients, but also suggested that for individuals with hypoalbuminemia, appropriate supplementation of exogenous albumin might have potential clinical value in improving the prognosis of patients with CHD and even CVD. However, whether higher concentrations of serum albumin will improve patient outcomes will require further study to identify those subgroups of patients who will benefit most from this therapy.

Several studies have verified the relationship between serum albumin and the prognosis of certain chronic diseases. In a clinical trial involving 559 participants, Feng et al. [10] demonstrated an independent negative correlation between 4-year all-cause mortality and baseline serum albumin levels in heart failure patients. In a cohort study of 3398 patients with severe chronic obstructive pulmonary disease, Ling et al. [11] identified a negative relationship between serum albumin levels and in-hospital mortality. In a case-control study of 1383 patients with nonalcoholic fatty liver diagnosed hepatic biopsies, Takahashi et al. [23] found that individuals with moderate or lower serum albumin levels had a higher likelihood of death or requiring a liver transplant compared to those with higher serum albumin levels. Another large prospective cohort study also reported that acute inpatients with serum albumin levels $\le$3.4 g/dL faced a greater risk of all-cause mortality or ischemic events compared to those with serum albumin levels $>$3.4 g/dL [24]. In addition, two recent prospective single-center studies in the emergency department of an Italian hospital showed that the serum albumin level measured on admission could independently predict the mortality of patients with acute infection 30 days after discharge, and that serum albumin had a higher predictive value for 30-day mortality in patients with a low to medium organ failure assessment score [25, 26]. Thomas et al. [27] found that reduced albumin levels were independently linked to higher mortality rates 5 and 9 years after follow-up in 331 patients over 55 of age with an intra-capsular fracture of the femoral neck, and they identified 42 g/L as the optimal threshold of serum albumin for predicting patient survival, these results were helpful for decision-making in patients undergoing total hip replacement or hemiarthroplasty. In addition, in a prospective cohort study involving 1000 patients with ischemic stroke, higher serum albumin levels were significantly linked to a lower risk of death, emphasizing its potential clinical role as a prognostic marker in this patient group [28]. While these studies did not include CHD patients, our findings align with their results, confirming a strong association between serum albumin levels and the risk of both all-cause and cardiovascular mortality. These studies added further evidence for the detrimental effects of hypoalbuminemia in CVD, and that low serum albumin should be considered as a risk factor for increased mortality in patients with CHD. However, it is still unknown what the safe concentration of serum albumin should be in patients with CHD. A recent study questioned the safety of higher the serum albumin levels. In the PRACTICE study, a 60-month follow-up of 14,994 coronary artery disease patients revealed a U-shaped relationship between serum albumin and the risks of major adverse cardiovascular events. After adjusting for confounders, albumin levels below 45 g/L were linked to lower risks, while levels above 50 g/L were associated with higher risks [29]. They found that albumin levels below 35 g/L were independently related to higher all-cause and cardiac death risk [29]. In addition to its role as an individual biomarker, serum albumin also contributes to several composite indices that have shown strong associations with poor outcomes in cardiopulmonary diseases. Among these, the prognostic nutritional index (PNI) and the Naples scoring systems have drawn increasing attention. Forexample, in a study involving 221 patients with heart failure who had implantable cardioverter-defibrillators, reported that lower PNI scores were significantly linked to higher all-cause mortality [30]. Likewise, Şaylık et al. [31], in a cohort of 1889 patients with acute ST-segment elevation myocardial infarction, found that the Naples Score independently predicted long-term mortality and improved the prognostic accuracy beyond traditional models. Another study also demonstrated that the Naples prognostic score was an independent predictor of long-term mortality in patients with acute pulmonary embolism [32]. These findings collectively suggest that serum albumin, whether assessed on its own or as part of a composite risk score, holds substantial prognostic value in the context of CVD. It is worth noting that while a significant association was observed, causality cannot be inferred from this observational study. Serum albumin may not be a direct causal factor but rather a surrogate marker of underlying pathophysiological conditions, such as chronic inflammation, malnutrition, or systemic illness. Hypoalbuminemia could reflect a catabolic state, liver dysfunction, or ongoing inflammatory processes, all of which may contribute to poor outcomes in CHD patients. This highlights the importance of interpreting our findings within the broader clinical and biological context. Besides, subgroup analysis revealed a more pronounced inverse association between serum albumin levels and both all-cause and cardiovascular mortality in non-hypertensive individuals compared to those with hypertension, suggesting a potentially meaningful but borderline significant protective effect. This pattern may reflect the complex interplay between hypertension, vascular damage, albuminuria, and systemic inflammation, all of which could modulate the prognostic value of serum albumin. Further investigation is warranted to understand how hypertension-related pathophysiology might attenuate the protective association of albumin in CHD patients.

Our study has several limitations. First, the study population reflected a small percentage of the American population. Second, due to the limitations of population survey data, the research data did not include echocardiography and coronary angiography data. Thirdly, due to the limitation of the database, we failed to investigate the association between serum albumin and additional outcomes of individuals with CHD, such as major adverse cardiovascular events. Fourth, serum albumin levels were measured at baseline during the NHANES survey, while CHD diagnosis was based on self-reported or physician-confirmed history, meaning that albumin measurements may have occurred after the onset of CHD. This raises the possibility of reverse causality—where CHD itself may contribute to lower albumin levels through mechanisms such as chronic inflammation or malnutrition—potentially biasing the observed associations. Fifth, due to the limitations of the NHANES dataset, we were unable to compare serum albumin with other established cardiovascular biomarkers, such as B-type natriuretic peptide or high-sensitivity troponin, which were not systematically collected. This limits our ability to evaluate the relative prognostic value of albumin in the context of risk stratification. We have acknowledged this as a limitation and suggest that future studies incorporate a wider range of biomarkers for a more comprehensive assessment. Sixth, although our study covered a 16-year period, the NHANES dataset does not provide dynamic measures of serum albumin or detailed records of evolving CHD management strategies over time. As a result, we were unable to assess whether secular trends in albumin levels or treatment practices influenced the observed associations. We have acknowledged this limitation and suggest that future research based on long-term follow-up data is needed to explore the potential impact of temporal changes. Finally, we might have overlooked some potential risk factors, such as genetic susceptibility, socioeconomic status, dietary nutrition, and environmental factors, associated with increased risk in CHD patients.

In this retrospective cohort study utilizing the survey data from the general population, we discovered not only that serum albumin levels were significantly associated with the likelihood of all-cause and cardiovascular mortality in individuals with CHD, but also that this association exhibited a linear negative correlation pattern. These results help to define the effects of serum albumin on CVD, and remind us of the importance to monitor serum albumin levels in patients with CHD to improve the adverse outcomes of patients with CVD.

All raw data used in this study can be accessed on the NHANES website (https://wwwn.cdc.gov/nchs/nhanes/default.aspx).

JT: Conceptualization, Investigation, Data curation, Formal analysis, Visualization, Writing-original draft, Writing-review & editing, Validation, Funding acquisition, Project administration, Supervision. TW: Conceptualization, Methodology, Software, Data curation, Formal analysis, Writing-review and editing. QW, QH, FY, XX, and PZ: Conceptualization, Validation, Writing-review and editing. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

The research scheme was approved by the National Center for Health Statistics of the Center for Disease Control and Prevention Institutional Review Board (Protocol #98-12, #2005-06). Participants have signed the informed consent form. The research program and content were in line with the Declaration of Helsinki.

Not applicable.

This research received no external funding.

The authors declare no conflict of interest.