Global Burden of Disease studies indicate that ischemic heart disease remains a primary disease burden across nations and regions. Notably, coronary artery disease (CAD) has emerged as the most prevalent cardiovascular disorder in both developed and developing regions, characterized by high mortality rates and posing a serious threat to public health security (1–3).

An increasing number of studies indicate that the onset of CAD is trending toward younger age groups (4, 5). According to the National Cholesterol Education Program Adult Treatment Panel III guidelines (NCEP-ATP III), premature CAD (PCAD) is defined as CAD occurring in males aged <55 years and females aged <65 years (6). Research has shown that PCAD constitutes 31% of total CAD cases (7). However, compared to patients with mature CAD (MCAD), those with PCAD have a higher incidence of acute coronary syndrome (ACS), as well as increased mortality rates and a poorer long-term prognosis (8–10).

In clinical practice, a phenomenon has been observed: many patients ultimately hospitalized for PCAD report having undergone annual health check-ups before hospitalization, yet none of these examinations included coronary artery screening. The reasons may be that the patients had no symptoms, lacked high-risk factors, or that coronary artery screening is not part of routine physical examinations. Consequently, these patients are often not identified as high-risk by current risk stratification guidelines or traditional risk assessment tools (11, 12), leading to hospitalization for acute cardiovascular events or even death within the subsequent year. Therefore, it is necessary to look for clues in routine health check-ups to guide and assess whether further coronary artery screening is needed, a measure that should be put on the agenda.

Over the past two decades, the conceptualization of CAD-associated atherosclerosis has progressively shifted toward recognition as a chronic, low-grade, lipid-driven inflammatory disorder of the arterial wall. Accumulating evidence indicates that atherosclerosis constitutes a chronic inflammatory arterial pathology, fundamentally mediated by inflammatory mechanisms involving multiple cytokines and biochemical mediators linked to CAD initiation, progression, and clinical outcomes (13–15).

In recent years, numerous diagnostic indicator models for cardiovascular diseases have been proposed, such as the monocyte-to-high-density lipoprotein cholesterol ratio (MHR), lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to- lymphocyte ratio (PLR), apolipoprotein B to apolipoprotein A-1 ratio (apoB/apoA-1), and the low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (LDL-c/HDL-c) (16, 17). These models primarily integrate both protective and risk factors as indicators, leveraging their combined diagnostic power for risk assessment. Compared to individual parameters alone, they exhibit improved diagnostic value through a comprehensive integration of the effects of protective and risk factors.

Some scholars believe that MHR (18–20), LMR (21–23), NLR (24, 25), PLR (26, 27), apoB/apoA-1 (28, 29), and LDL-c/HDL-c (30) have a certain degree of diagnostic effect on CAD, but there is no clear conclusion regarding the diagnostic value of these models for PCAD. This study will explore the diagnostic value of MHR, LMR, NLR, PLR, apoB/apoA-1, and LDL-c/HDL-c for PCAD in order to find reliable diagnostic indicators and provide reference for the screening of PCAD.

CAD is increasingly affecting younger populations. With changes in lifestyle, the increased prevalence of metabolic diseases, and shifts in exposure patterns to risk factors, the characteristics and risk factors of CAD onset have also changed (31, 32). The risk factors for PCAD also differ from those for MCAD (33). CAD is a chronic inflammatory disease characterized by coronary artery stenosis and remodeling, resulting from the interaction of genetic and environmental factors (34, 35). Over the past two decades, the perspective on atherosclerosis has gradually shifted towards it being a lipid-driven, chronic, low-grade inflammatory disease of the arterial wall. Inflammatory factors and lipid factors are involved in its occurrence, progression, and prognosis (36). Therefore, in this study, we investigated the correlation between PCAD and inflammatory/lipid ratios. We found that MHR, NLR, apoB/apoA-1, and LDL-c/HDL-c all demonstrated diagnostic value for PCAD. Specifically, the apoB/apoA-1 ratio demonstrated the greatest diagnostic value. Its diagnostic power was further enhanced when combined with clinical risk factors. Furthermore, this diagnostic value was particularly pronounced in the ACS subgroup.

Our study showed that the PCAD group was younger than the angiographically normal control group. This age difference may be related to the higher proportion of males in the PCAD group, as the age inclusion criteria for males were lower than those for females. Furthermore, the younger age of the PCAD group better reflects its premature onset characteristics. This is because numerous studies have demonstrated that the onset of CAD and many of its risk factors are positively correlated with age (i.e., older age is associated with higher disease risk, more risk factors, and greater severity) (37–40). Paradoxically, the PCAD group, being the diseased group, was younger than the angiographically normal control group. This further underscores that the PCAD group possesses pathogenic factors that defy age-related distribution patterns compared to the angiographically normal controls. This paradox will further emphasize the significance of abnormal findings in the subsequent comparison of risk factors between the PCAD group and the angiographically normal control group.

Our study found that the PCAD group had a higher proportion of smokers, alcohol consumers, individuals with diabetes, and individuals with a family history of hypertension, diabetes, and CAD compared to the control group. This aligns with the established clinical understanding of CAD risk factors (34). The higher prevalence of family history of hypertension and diabetes likely involves complex interactions between genetic factors and environmental influences (41–43). Notably, no significant difference in the proportion of hypertension itself was observed between the two groups in this study. This finding is inconsistent with the widely accepted concept that hypertension is a causative factor for CAD, and with the majority of studies reporting a higher prevalence of hypertension among CAD patients (44, 45). This discrepancy may be related to regional variations in the prevalence of hypertension. Alternatively, it could be attributed to the relatively preserved cardiovascular status in younger patients, including their greater compensatory capacity to resist adverse stimuli, enhanced ability to clear inflammatory mediators, and stronger vascular barrier function. Furthermore, as a chronic disease, hypertension requires a longer duration to exert its pathogenic effects on the cardiovascular system. Therefore, hypertension itself may have limited reference value for predicting PCAD onset. Nevertheless, strict blood pressure control remains crucial for young patients, as the risk of developing CAD increases with advancing age and prolonged duration of hypertension.

Regarding laboratory parameters in PCAD, research is relatively scarce. This study found that PCAD patients had elevated levels of Neutrophil, Lymphocyte, Monocyte, UA, TG, and apoB, while levels of apoA-1 and HDL-c were decreased. These alterations align with the characteristic features of CAD pathogenesis and are even more pronounced in PCAD (16). Notably, PLR showed no significant difference between groups ( Table 1 ), and LMR failed to demonstrate independent association with PCAD in regression models ( Figure 3 ). This apparent non-significance may reflect pathophysiological specificity: PLR’s focus on platelet activation aligns poorly with the chronic monocyte-driven inflammation of young-onset PCAD, while LMR’s signal is attenuated by compensatory lymphocyte preservation and monocyte subset differentiation better captured by ratios like MHR. Furthermore, in this study, PLT count, TC, and LDL-c levels in the PCAD group showed no significant difference compared to the angiographically normal control group. This finding differs from the results of Duran M’s study (46). Duran M’s research indicated that young patients (< 60 years old with stable angina) had lower PLT counts and higher TC and LDL-c levels compared to angiographically normal controls, and identified LDL-c as an independent risk factor for young patients. The discrepancy between the two studies may be related to differences in the inclusion criteria of the study populations and ethnic variations. Differences in lifestyle and dietary habits associated with geographical regions could also have played a role. Consequently, the results of this study only suggest that PLT count, TC, and LDL-c may contribute less to PCAD development in the Chinese population of the Zunyi region.

Research on diagnostic models specifically for PCAD is relatively scarce, and there is no established mainstream consensus; most findings are extrapolated from studies on CAD. This study found that the apoB/apoA-1 diagnostic model demonstrated the greatest value for predicting PCAD. This diagnostic value was further enhanced when combined with certain clinical risk factors and was particularly pronounced within the ACS subgroup.

ApoB is the core structural protein of atherogenic lipoproteins (such as Lp (a), LDL, VLDL), and atherosclerosis is the underlying cause of heart attacks. The infiltration and retention of apoB-containing lipoproteins within the arterial wall constitute a key initiating event that triggers inflammation and promotes the development of atherosclerosis. Following penetration through damaged endothelium, apoB-containing lipoproteins become oxidized to form ox-LDL, which activates macrophage scavenger receptors (e.g., CD36), promoting foam cell formation. ApoB also activates the NLRP3 inflammasome, leading to the release of IL-1β and IL-18, thereby intensifying the inflammatory microenvironment within plaques. Furthermore, apoB levels are associated with an enlarging lipid core and thinning fibrous cap, increasing the risk of plaque rupture (47, 48). Consequently, some researchers posit that apoB is a more accurate marker of cardiovascular risk than LDL-c or non-HDL-c (49). ApoA-1 is the primary protein component of HDL-c, well-known for its roles in regulating cholesterol transport, modulating inflammation and immune responses, and preventing atherosclerosis. ApoA-1 facilitates cholesterol efflux from cells via ABCA1/ABCG1 transporters, reducing lipid deposition in the vascular wall. ApoA-1 can inhibit the NF-κB pathway and macrophage polarization, thereby attenuating plaque inflammation. It also enhances mitophagy through the JAK2/STAT3 pathway, improving oxidative stress (50, 51). In summary, apoB drives atherosclerotic progression through multiple pathways, including lipid retention, inflammation activation, plaque destabilization, and genetic regulation, whereas ApoA-1 exerts opposing protective effects. Both are critical factors influencing atherosclerosis in its early stages. The apoB/apoA-1 ratio model integrates the diagnostic capabilities of both markers and can serve as a diagnostic model for PCAD.

In recent years, numerous innovative diagnostic approaches have emerged for PCAD, including but not limited to machine learning algorithms (52), IL-6 gene polymorphism screening (53) and electrochemical biosensors (54). While demonstrating promising diagnostic efficacy, their clinical implementation nevertheless faces substantial barriers. These include prohibitive per-test costs ($50–$1000), dependency on specialized instrumentation, and operational complexities that hinder integration into routine screening protocols. By contrast, the apoB/apoA-1 ratio model leverages existing lipid profiling infrastructure, utilizing validated thresholds to enable cost-effective risk stratification (<$5 per test). This positions it as a pragmatic solution for large-scale screening of non-traditional risk cohorts, particularly individuals with isolated familial predisposition. The findings of this study therefore establish a framework for incorporating coronary risk assessment into standard physical examinations, with the biomarker models investigated offering exceptional economic viability and clinical deployability through their accessibility via routine laboratory assays.

As a cross-sectional analysis, this research primarily establishes the diagnostic utility of inflammatory ratios for identifying existing PCAD. While the developed models demonstrate strong discriminatory capacity within this context, their true predictive capability for incident PCAD remains to be validated. Robust validation of this predictive capability requires future prospective cohort studies incorporating pre-diagnosis biomarker measurements and longitudinal follow-up prior to disease onset. Furthermore, the single-center retrospective design inherently limits the generalizability of our findings—confounding factors such as genetic predispositions (e.g., lipid metabolism polymorphisms unique to the Southwestern Han population), lifestyle patterns (high-salt and high-fat diets, capsaicin intake), environmental exposures (trace element distribution in karst topography), regional patient characteristics, healthcare practice variations, and selection biases may influence the conclusions.

Therefore, although these initial results highlight the significant potential of apoB/apoA-1 and its combined model for diagnosis, their clinical translation necessitates validation in multi-center prospective cohorts with predefined endpoints and external datasets to confirm generalizability and establish real-world clinical utility. Additionally, while we investigated several established inflammatory ratios and traditional risk factors, the range of potential predictors examined could be expanded and refined in future research, and a larger sample size would enhance the statistical power and stability of the models, particularly for subgroup analyses.

Future research should aim to: conduct multi-center prospective studies with pre-diagnostic biomarker assessment to validate the predictive value of these ratios for incident PCAD; incorporate external validation cohorts; explore the integration of a broader spectrum of novel biomarkers and risk factors; and investigate the cost-effectiveness and clinical impact of implementing apoB/apoA-1 screening in routine health assessments for early PCAD detection.

The apoB/apoA-1 outperformed MHR, NLR, and LDL-c/HDL-c as an inflammatory biomarker in PCAD. Its diagnostic capacity was notably enhanced in ACS subgroups. A comprehensive model combining apoB/apoA-1 with traditional risk factors demonstrated exceptional accuracy. Incorporating this biomarker into routine screening protocols could significantly strengthen preventive strategies.