Erectile dysfunction (ED) is defined as the persistent inability to achieve or maintain an erection sufficient for satisfactory sexual performance (1). It is one of the most common male sexual disorders, currently affecting approximately 150 million men worldwide, and this number is projected to exceed 300 million by 2025 (2). The prevalence of ED increases progressively with age and is strongly associated with multiple risk factors, including cardiovascular disease (CVD), metabolic syndrome, diabetes, and lifestyle habits such as smoking and physical inactivity (3–6). It is estimated that approximately 25%–70% of ED cases can be attributed to vascular causes, collectively referred to as vasculogenic erectile dysfunction (7), which encompasses arteriogenic (AED), venogenic (VED), and mixed forms (8). Among these, arteriogenic ED (AED) represents the predominant subtype, primarily resulting from structural or functional impairment of penile arteries (9). Clinical and epidemiological studies have identified several major risk factors for vasculogenic ED, including hypertension, diabetes, and dyslipidemia, all of which contribute to endothelial dysfunction within the penile vasculature (10).

Given the high prevalence of ED and its profound impact on quality of life, elucidating its underlying mechanisms and identifying novel predictive biomarkers have become major research priorities. Among the proposed mechanisms contributing to ED, inflammation plays a pivotal role. Chronic low-grade inflammation is closely linked to endothelial dysfunction, a key component in the pathogenesis of vasculogenic ED (11). The inflammatory process disrupts nitric oxide (NO) synthesis and bioavailability, leading to impaired vasodilation and reduced penile blood flow (12). Numerous studies have highlighted the association between inflammatory markers and ED. For instance, C-reactive protein (CRP), a widely recognized indicator of systemic inflammation, has been consistently correlated with ED severity (13). Similarly, hematologic ratios such as the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) have emerged as important predictors of ED, reflecting the balance between pro-inflammatory and anti-inflammatory pathways (14). Although growing evidence supports a strong link between inflammation and erectile dysfunction, the search for more comprehensive and integrative biomarkers that capture both inflammatory and metabolic components remain ongoing.

In recent years, the neutrophil percentage-to-albumin ratio (NPAR) has attracted increasing attention as a novel composite indicator reflecting both inflammatory and nutritional status. As classic cellular effectors, neutrophils play a central role in regulating inflammatory responses and mediating tissue injury during immune activation (15). Conversely, serum albumin acts as a key modulator of anti-inflammatory, antioxidant, and anticoagulant activity, and is inversely correlated with systemic inflammation (16, 17). Hypoalbuminemia also reflects poor nutritional status, which has been associated with adverse outcomes across a variety of chronic conditions (18). Recent studies have demonstrated that elevated NPAR levels are strongly associated with increased mortality in chronic obstructive pulmonary disease, CVD, and malignancies (19–21). By integrating both inflammatory and nutritional information, NPAR provides a more comprehensive reflection of systemic homeostasis and may serve as a valuable prognostic biomarker for disease outcomes.

However, to date, no study has examined the potential relationship between NPAR and ED, particularly AED—a subtype closely linked to systemic vascular and inflammatory processes. Given that NPAR simultaneously reflects both inflammatory activation and nutritional imbalance, it may provide a more integrated perspective on the pathophysiological mechanisms underlying AED. We therefore designed this study to investigate the association between NPAR and AED, and to evaluate whether NPAR could serve as an independent predictor and diagnostic biomarker for AED.

In this cross-sectional study, we explored the relationship between the NPAR and AED. Our findings showed that NPAR levels were significantly higher in patients with AED compared with healthy controls. After adjusting for potential confounders, NPAR remained independently associated with the presence of AED, indicating that elevated NPAR values may reflect systemic inflammatory and nutritional disturbances that coexist with AED. Furthermore, ROC analysis demonstrated that NPAR had a greater discriminative ability for identifying AED than WBC or its individual components (NP and albumin) and other inflammation biomarkers (CRP and NLR). These results suggest that NPAR, as an integrated index, provides a more comprehensive reflection of the inflammatory and nutritional state related to vascular impairment in ED, supporting its potential utility as a convenient and informative hematologic parameter for clinical assessment.

Inflammation plays a pivotal role in the pathophysiology of ED. Among the extensively studied inflammatory markers, CRP is one of the most established indicators of systemic inflammation. Elevated CRP levels have been consistently associated with a higher prevalence of ED, as CRP is a known mediator of endothelial impairment, which is fundamental to normal erectile physiology. In addition, the NLR has been identified as a predictor of cardiovascular and inflammatory disorders, and recent studies have demonstrated a significant association between elevated NLR and ED (27). A higher NLR reflects a predominance of pro-inflammatory neutrophils, which may contribute to endothelial injury and vascular dysfunction. Similarly, the PLR has been proposed as another inflammation-related marker that reflects both inflammatory and thrombotic activity. Studies have shown that elevated PLR levels are associated with an increased risk of ED, suggesting that systemic inflammation and enhanced platelet activation may be involved in the pathogenesis of ED (28, 29). However, to date, no study has investigated the relationship between the NPAR and erectile dysfunction, particularly AED.

The NPAR integrates two critical biomarkers—NP and serum albumin level—and has increasingly been recognized as a reliable indicator of systemic inflammation in various chronic conditions. Previous studies have demonstrated that elevated NPAR levels are associated with adverse outcomes in cardiovascular diseases, including higher mortality and the progression of heart failure (30, 31). In addition, increased NPAR has been linked to a greater risk of chronic kidney disease (CKD). Given its composite nature, NPAR provides a comprehensive reflection of both pro-inflammatory and anti-inflammatory balance, combining the effects of neutrophil elevation and hypoalbuminemia. Our findings extend the existing evidence by showing that NPAR is independently associated with erectile dysfunction, particularly the arteriogenic subtype.

The potential mechanisms linking NPAR to AED may relate to the biological roles of its two components—neutrophils and albumin. Neutrophils are key mediators of the innate immune response and play a central role in the inflammatory cascade (32). Their activation results in the release of pro-inflammatory cytokines, reactive oxygen species (ROS), and other factors that contribute to endothelial dysfunction and vascular injury (33). Conversely, serum albumin is not merely a marker of nutritional status but also an important anti-inflammatory and antioxidant regulator. Lower albumin concentrations often indicate chronic inflammation and poor health status, and have been associated with adverse cardiovascular outcomes, endothelial impairment, and increased mortality (16, 17). The combined effect of elevated neutrophils and reduced albumin therefore offers an integrated perspective on systemic inflammation and vascular health. The strong association observed between NPAR and AED in our study may reflect this dual impact on endothelial function and vascular integrity.

Although the ROC analysis yielded a higher AUC for NPAR (0.742), these values remain insufficient for NPAR to function as an independent diagnostic tool. In interpreting the diagnostic performance of NPAR, it is important to emphasize that this biomarker is not intended to function as a standalone diagnostic or screening tool for AED. This is consistent with the biological nature of NPAR: as an inflammation- and nutrition-based composite index, it reflects systemic processes associated with endothelial impairment, but it cannot directly characterize penile hemodynamics. Rather than serving as a diagnostic test, the clinical value of NPAR lies in risk stratification. Elevated NPAR levels may suggest a greater inflammatory burden and a higher likelihood of vascular involvement among patients presenting with ED, thereby identifying individuals who may benefit from further cardiovascular or metabolic evaluation. This concept parallels the use of other inflammatory markers such as CRP or NLR, which do not offer high diagnostic accuracy but remain clinically valuable for estimating vascular risk. Notably, the robustness of this association across multiple clinically relevant subgroups—including different age categories, smoking statuses, and cardiovascular comorbidity profiles—suggests that NPAR may provide vascular risk information that is broadly applicable across diverse ED populations. The consistent findings across subgroups further strengthen the interpretation that NPAR reflects a systemic pathophysiological process rather than a phenomenon confined to a specific patient subset. Accordingly, NPAR should be viewed as a complementary biomarker—providing additional biological context to the hemodynamic information obtained through CDDU—rather than a substitute for Doppler ultrasound. Thus, while NPAR contributes meaningfully to the understanding of vascular risk in ED, its diagnostic and therapeutic implications should be interpreted within the broader framework of multifactorial ED assessment, and further studies are warranted to determine whether NPAR-guided strategies may improve clinical decision-making or long-term vascular outcomes.

Several limitations of this study should be acknowledged. First, the cross-sectional design precludes the establishment of a causal relationship between NPAR and AED. Second, although we adjusted for several major confounders, residual or unmeasured factors—such as diet, oxidative stress markers, and subclinical inflammation—may still have influenced the results. Third, the sample size was relatively modest and limited to patients recruited from specific clinical centers, which may restrict the generalizability of our findings. Fourth, cardiovascular outcomes and longitudinal follow-up data were unavailable; therefore, the current results cannot establish whether higher NPAR identifies AED patients at greater risk of future cardiovascular events. Another limitation relates to the demographic characteristics of the study population. Most participants in our cohort were relatively young and within the normal BMI range. This distribution reflects the typical attendance pattern of outpatient urology and andrology clinics in China, where older men or individuals with obesity are often reluctant to seek medical attention for sexual dysfunction due to cultural stigma and low health-seeking behavior. As a result, patients aged over 50–60 years—who comprise a large proportion of ED cases in the general population—were underrepresented. Therefore, the generalizability of our findings to older or overweight/obese populations may be limited. Future studies involving broader, community-based recruitment across diverse age and metabolic profiles are needed to validate these results. Finally, Renal dysfunction is an established risk factor for ED and may also influence systemic inflammatory and nutritional markers such as NPAR. In the present study, patients with any known kidney disease, including chronic kidney disease or persistent proteinuria/albuminuria, were excluded at baseline, and serum albumin levels were within the normal range across groups, making overt renal protein loss unlikely. However, creatinine and eGFR were not uniformly available across all centers, and subclinical renal impairment cannot be completely ruled out. Therefore, the absence of standardized renal function measurements represents a limitation and should be addressed in future studies. Despite these limitations, this study is, to our knowledge, the first to demonstrate a significant association between NPAR and AED. Our findings suggest that NPAR, a simple and cost-effective laboratory index combining inflammatory and nutritional information, may serve as a useful hematologic parameter for identifying individuals at higher vascular risk among ED patients. Future prospective and mechanistic studies are warranted to confirm these associations and to clarify the underlying biological pathways linking systemic inflammation, nutritional status, and vascular ED.

In summary, this study demonstrated that the NPAR is significantly associated with AED. Elevated NPAR levels may reflect an imbalance between systemic inflammation and nutritional status that accompanies vascular impairment in ED. Compared with WBC and its individual components, NPAR showed superior discriminatory performance in identifying AED, highlighting its potential as a simple, inexpensive, and accessible hematologic indicator for clinical evaluation. Further prospective studies are warranted to validate these findings and to elucidate the underlying mechanisms linking NPAR to vascular erectile dysfunction.