With the transformation of social structure, population aging has been escalating year by year, accompanied by a rising trend in the prevalence and mortality of coronary heart disease (CHD). As of 2019, the global burden of CHD had reached approximately 197 million patients, making it one of the most prevalent cardiovascular diseases (CVD) and the second leading cause of death in China (1). From 1990 to 2017, the global age-standardized mortality rate for CHD increased by 20.6%, with the most substantial rises observed in Africa and other low- to middle-income nations (2). Projections indicate a persistent upward trend in CHD mortality. This disease imposes substantial physical, psychological, and socioeconomic burdens, adversely affecting individual well-being, family welfare, and healthcare expenditures. The early identification of risk factors and timely detection of high-risk individuals are pivotal for the implementation of effective preventive strategies and tailored interventions.

As our understanding of CHD pathogenesis deepens, there is an increasing focus on the multiple potential factors influencing CHD development. Well-recognized risk factors for CHD include hypertension, insulin resistance, dyslipidemia [elevated low-density lipoprotein cholesterol (LDL-c) or reduced high-density lipoprotein cholesterol (HDL-c)], smoking, excessive alcohol intake, overweight/obesity, psychological stress, and advanced age (3–5). With the exception of age (a non-modifiable risk factor), other determinants can be effectively managed via lifestyle adjustments, stress reduction, and pharmacologic interventions to slow CHD progression (6, 7). HDL-c remains the most significant protective factor against CHD among parameters measured in routine lipid panels (8). HDL-c plays a central role in reverse cholesterol transport, shuttling extrahepatic cholesterol to the liver for catabolism, exerting functions of inhibiting LDL oxidation and platelet activation, and serving as a key anti-atherosclerotic lipoprotein (9). HDL-c has long been considered inversely related to CHD risk. In other words, low levels of HDL-c are a risk factor for CHD, which has been confirmed by several previous studies (10, 11).

Albumin (ALB), the most abundant water-soluble protein in plasma, plays a pivotal role in maintaining osmotic pressure, functioning as an antioxidant, acting as a biological buffer, and mediating transport of endogenous and exogenous substances. It exhibits both antioxidant and anti-inflammatory activities (12). ALB serves as a key biomarker for nutritional status and chronic inflammatory states, with reduced levels commonly linked to chronic pathologies and malnutrition (13). Numerous observational studies and meta-analyses have demonstrated a negative association between serum albumin levels and cardiovascular outcomes (14). Numerous observational investigations and meta-analytic syntheses have consistently evidenced an inverse association between serum ALB concentrations and cardiovascular event rates (15, 16). Accumulating evidence indicates that hypoalbuminemia is associated with heightened risks of major adverse cardiovascular events (MACE) and in-hospital mortality (16). Oduncu et al. (17) demonstrated that admission serum ALB levels strongly predicted clinical outcomes in ST-segment elevation myocardial infarction (STEMI) patients treated with percutaneous coronary intervention (PCI). Hypoalbuminemia (lower serum ALB concentration) is closely associated with elevated cardiovascular risk. Pooled data from meta-analyses indicate that each 2.5 g/L decrease in serum ALB is associated with a 24%–56% higher mortality odds ratio, encompassing both all-cause and cardiovascular-specific mortality outcomes (18). Serum ALB concentration strongly and independently predicts in-hospital all-cause mortality, demonstrating a negative association with mortality (19). Numerous prior studies have established that low serum ALB is a robust predictor of CHD. A representative analysis has demonstrated a significant correlation between serum ALB levels and CHD risk, whereby lower ALB concentrations are associated with an elevated risk of CHD (20).

Both ALB and HDL-c correlate with the onset and progression of CHD, yet their combined relationship with CHD remains underexplored. Two new combined indicators of nutritional status and lipid metabolism, namely, ALB multiplied by HDL-c (AHM) and ALB–HDL-c ratio (AHR), may hold importance in CHD prediction. These findings, by identifying novel predictive biomarkers, may enable more timely clinical interventions for CHD patients.

Through the development of a multivariate logistic regression model, this study identified male gender, hypertension, T2DM, and smoking as independent risk factors for CHD. In contrast, higher levels of HDL-c, ALB, and AHM were significantly associated with a reduced risk of CHD, highlighting their protective roles. After controlling for confounding variables, multivariate logistic regression identified AHM as an independent protective factor against CHD. ROC curve analysis demonstrated that AHM achieved an AUC of 0.808 (95% CI: 0.791–0.825), significantly outperforming other indicators in diagnosing CHD. The GS score, a validated angiographic scoring system, has been widely used to quantify the severity of coronary lesions in CHD. Notably, we observed a significant negative correlation between AHM and GS, suggesting its potential role in early risk stratification for CHD patients. Subgroup analyses indicated that AHM conferred the highest predictive accuracy for CHD among individuals under 60 years, highlighting its age-specific utility.

CHD is a common CVD, and its natural history usually begins with AS, a chronic, lipid-driven inflammatory arterial disease (24). Abnormal lipid metabolism is one of the major risk factors for AS (25). Therefore, it is meaningful to evaluate serum lipid profiles in patients with CHD. Previous studies have confirmed that HDL-c is negatively correlated with CHD (26, 27). The landmark Framingham study showed that compared with high HDL-c levels, low HDL-c levels increased the risk of CHD. It also confirmed a strong negative correlation between HDL-c levels and CHD risk, with HDL-c being the strongest predictor among the evaluated lipid risk factors (28). Gu et al. (29) analyzed six large prospective studies and found that patients with CHD exhibited significantly lower HDL-c levels compared with those of participants in a case–control study. Among 267,500 Chinese participants, lower HDL-c concentrations (<50 mg/dl, 1.3 mmol/L) were significantly associated with an increased risk of stroke. Notably, each 1 mmol/L increase in HDL-c was associated with a 16% reduction in ischemic stroke risk and a 21% reduction in hemorrhagic stroke risk. Our study found that HDL-c levels were significantly lower in the CHD group compared with those in the control group, with HDL-c demonstrating a significant negative correlation with GS scores (P < 0.05). Univariate logistic regression analysis identified HDL-c as a protective factor against CHD. This protective effect likely stems from structural and functional impairments of HDL-c, which are induced by acute and chronic inflammation in CHD patients. Apolipoprotein A-1 is an important component of HDL-c, primarily responsible for lipid transport and metabolism (30, 31). During inflammation, serum amyloid A (SAA) levels rise and displace apoA-1 from HDL particles, impairing cholesterol efflux and promoting the entrapment of HDL in arterial walls. This process exacerbates oxidative modification of HDL particles, diminishing their anti-atherosclerotic capacity by impairing cholesterol efflux and antioxidant functions (32).

ALB is an important protein present in human plasma. The liver is the only site of ALB synthesis, and its production is regulated by factors such as nutritional status, inflammation, osmotic pressure, and hormones (12). ALB performs diverse physiological roles, including maintenance of plasma colloid osmotic pressure, transport of hydrophobic substances (e.g., bilirubin, fatty acids, and drugs), and exertion of anti-inflammatory and antioxidant activities (33, 34). Hypoalbuminemia may increase blood viscosity and compromise vascular endothelial function, thereby potentially predisposing to ischemia–reperfusion injury through impaired microvascular perfusion. These effects—combined with increased thrombotic propensity and enhanced inflammatory vulnerability—likely contribute to the pathogenesis of AS by promoting lipid deposition, vascular inflammation, and plaque instability (35). Vincent et al. (36) demonstrated that individuals with declining serum ALB concentrations—even when levels remained within the normal reference range—had a significantly elevated risk of CVD. Serum ALB levels are significantly inversely correlated with CVD incidence and progression. Clinical data show that lower ALB concentrations are associated with more severe coronary artery disease, with ALB levels decreasing progressively as disease severity increases (37). A 15-year cohort study found that hypoproteinemia was an independent predictor of cardiovascular and cerebrovascular disease (38). The results showed that serum ALB levels were significantly lower in the CHD group than those in the control group (P < 0.05), consistent with previous findings.

In summary, the well-documented negative association between ALB, HDL-c, and CHD reflects their roles in inflammation–nutrition balance and vascular protection. The synthesis and excretion of these proteins are intricately regulated by nutritional status (e.g., amino acid availability for ALB), inflammatory cytokines (e.g., IL-6 suppression of ALB and HDL dysfunction), and metabolic hormones (e.g., thyroid hormone modulation of HDL biogenesis). Understanding these regulatory networks may uncover novel therapeutic targets for CHD prevention. HDL-c levels are inversely correlated with conditions such as chronic renal failure, T2DM, and liver cirrhosis, reflecting dysregulated lipoprotein metabolism in these diseases (39). Malnutrition, inflammation, diabetes, liver disease, and infection can reduce albumin production, thereby leading to hypoalbuminemia. Each factor exerts distinct effects (40). Thus, it warrants clinical consideration that limitations exist in evaluating CHD risk using HDL-c or ALB alone, given their susceptibility to confounding factors such as inflammation, nutrition, and comorbidities. Therefore, we have developed a new composite indicator, the atherosclerosis heart marker (AHM), and analyzed its sensitivity and specificity for the diagnosis of CHD. This study introduces AHM as a novel composite indicator integrating serum ALB (a nutritional marker) and HDL-c (a lipid parameter), potentially providing broader predictive value than individual biomarkers. Univariate and multivariate analyses consistently identified AHM as a significant predictor of CHD risk among the examined factors. AHM was an independent risk factor for CHD. The area under the ROC curve (AUC) for AHM was significantly higher than that for HDL-c (0.808 vs. 0.777, P < 0.001). To assess the association between AHM and coronary artery stenosis severity, we used the GS score system to quantify lesion severity. AHM showed a negative correlation with GS scores and emerged as an independent risk factor for multivessel CHD. These findings demonstrate AHM's utility in quantifying coronary artery stenosis, as evidenced by its strong negative correlation with GS scores (Pearson r = −0.150, P < 0.001) and higher diagnostic accuracy than single markers.

Our study conferred several strengths. First, we for the first time elucidated the potential of AHM in identifying CHD, establishing its significant negative correlation with coronary stenosis severity. As a readily accessible biomarker from routine blood tests, AHM has the potential to enable clinicians to detect CHD at earlier stages and refine risk stratification, supported by its high sensitivity (75.7%) for preclinical atherosclerosis. Second, all patients underwent gold-standard CAG, with CHD diagnosed based on ≥50% luminal stenosis; those initially diagnosed by coronary computed tomography angiography (CCTA) were excluded to minimize diagnostic bias. However, this study also had limitations. First, the retrospective design inherently resulted in incomplete laboratory data for certain patients—particularly lipid profiles and inflammatory markers—and unmeasured confounders (e.g., family history, socioeconomic status, and lifestyle factors) were not adjusted for in the multivariate analysis, potentially introducing residual confounding bias. Second, current studies lack specific clinical reference values for AHM in assessing CHD and coronary stenosis severity. Large-sample studies are needed to establish risk assessment thresholds, thereby enabling precise risk stratification and optimized management of CHD patients. Finally, the study's single-center design and small sample size represent limitations. Future large-scale, multicenter prospective trials are needed to validate the clinical utility of this indicator and establish population-specific reference ranges for AHM.

AHM was significantly linked to an elevated risk of CHD. The lower the AHM level, the greater the CHD occurrence rate. AHM is associated not only with the occurrence of CHD but also with the severity of coronary artery stenosis. The ratio serves as a practical clinical indicator, combining accessibility, cost-effectiveness, minimal invasiveness, and widespread adoption. Its clinical value lies in facilitating early CHD detection, disease severity assessment, timely intervention, and prognostic improvement, making it suitable for broader clinical implementation.