Psoriasis is a chronic immune-mediated inflammatory dermatosis affecting approximately 2-3% of the global population (1–3). Clinically, it is characterized by well-demarcated erythematosquamous plaques, typically distributed symmetrically on extensor surfaces (elbows, knees), scalp, and lumbosacral regions, though extensive cutaneous involvement may occur (4, 5). Beyond its cutaneous manifestations, psoriasis exerts a substantial impact on a patient’s quality of life and imposes significant socioeconomic burdens (6). Despite considerable advances in therapeutic options, post-treatment relapse rates exceed 90% (7, 8), and the patients frequently develop comorbid arthritis, metabolic syndrome, and cardiovascular complications (9–11). Current understanding of psoriasis pathogenesis implicates multifaceted interactions between immune dysregulation, genetic susceptibility, autoantigens presentation, and environmental triggers (12, 13). However, the precise molecular and cellular mechanisms remain remains incompletely understood. While biological therapies have revolutionized management, approximately 40% of patients continue to exhibit suboptimal or non-durable responses, highlighting an unmet need for clinically actionable biomarkers to facilitate personalized therapeutic strategies (14, 15).

The neutrophil-to-high-density lipoprotein cholesterol ratio (NHR) has emerged as a novel dual-functional inflammatory-metabolic biomarker, offering unique advantages by concurrently assessing innate immune activation through neutrophils and lipid metabolic disorders. Although previous studies have independently confirmed the association of neutrophils (key inflammatory mediators) and high-density lipoprotein (HDL) cholesterol (a regulator of lipid metabolism and inflammatory) with psoriasis, the combined predictive value of these two components has not been thoroughly investigated (16, 17). Mechanistically, neutrophil extracellular traps (NETs) containing LL-37 and RNA components can directly contribute to the formation of psoriatic plaques (20). HDL typically exerts anti-inflammatory effects by modulating macrophages activity (21). However, in patients with psoriasis, HDL displays pro-inflammatory changes and impaired cholesterol efflux capacity (22). These findings suggest a dual disturbance in inflammation and metabolism that may synergistically exacerbate the development of psoriasis. Moreover, recent studies have shown that NHR demonstrates superior predictive performance compared to other inflammatory-metabolic indicators such as the monocyte-to-HDL ratio (MHR) and neutrophil-to-lymphocyte ratio (NLR), emphasizing its potential clinical utility (23).

Although NHR has shown prognostic utility in cardiovascular and metabolic diseases, its role in immune-mediated inflammatory diseases, particularly psoriasis, remains underexplored (18–20). This cross-sectional study, based on the National Health and Nutrition Examination Survey (NHANES) database, is the first to systematically evaluate the association between NHR and psoriasis. The findings offer new insights into the interplay between inflammation and metabolism in the pathogenesis of psoriasis and support the potential of NHR as a novel biomarker for clinical risk stratification and individualized therapeutic strategies.

To the best of our knowledge, this is the first cross-sectional study to investigate the association between NHR and psoriasis using data from the NHANES database. Weighted multivariable logistic regression analyses of 21,723 participants identified an independent positive association between NHR and psoriasis risk, consistent across both unadjusted and partially adjusted models. Subgroup analyses further confirmed the robustness of this association across various demographic and clinical subpopulations, with alcohol consumption identified as a potential effect modifier. The sensitivity analyses demonstrated that the NHR possesses both temporal stability and is robust to confounding, supporting its utility as a biomarker for psoriasis risk. These findings provide novel insights into the inflammatory-metabolic interplay underlying psoriasis and underscore the potential utility of NHR as a biomarker for risk stratification and early intervention.

Recent advancements have highlighted the clinical relevance of novel biomarkers in disease prediction and management. As a composite inflammatory-metabolic marker, NHR uniquely integrates peripheral neutrophil counts and HDL-C levels, providing a multidimensional perspective on the interplay between inflammation and lipid metabolism (26, 27). Notably, NHR has demonstrated superior predictive performance over monocyte-to-HDL ratio and neutrophil-to-lymphocyte ratio across a range of pathological conditions (18, 28). For example, Tian et al. (2025) identified elevated NHR as a predictor of aortic dissection and aneurysm risk, implicating vascular inflammatory pathways (29). Similarly, NHR was associated with disease severity in patients with acute biliary pancreatitis (30), while Du et al. (2025) reported a 34% increased risk of renal stone in individuals within the highest NHR tertile (95% CI: 1.15–1.57, p < 0.001) (31). Collectively, these findings support the role of elevated NHR as a marker of both neutrophil-mediated inflammation and HDL-C dysfunction, consistent with our observed association between NHR and psoriasis risk.

The observed dose-response relationship between NHR and psoriasis risk, although not yet fully elucidated mechanistically, is supported by established biological frameworks. Neutrophils play a central role in psoriasis pathogenesis and contribute to disease progression through multiple pathways: (1) activated neutrophils secrete cytokines within IL-23/IL-17 axis, promoting Th17 cell differentiation and keratinocyte hyperproliferation (32); (2) neutrophil extracellular traps, composed of DNA-LL37 complexes and histones, activate plasmacytoid dendritic cells via Toll-like receptor 9 signaling, leading to increased production of TNF-α/IL-6 release, and further activation of keratinocytes and T-cells (33, 34); (3) NADPH oxidase 2-dependent reactive oxygen species induces keratinocyte necroptosis, thereby compromising epidermal barrier integrity (35). Simultaneously, HDL in patients with psoriasis demonstrates pro-inflammatory properties and reduced cholesterol efflux capacity (36). Moreover, prospective data from the UK Biobank indicate an inverse association between HDL-C levels and psoriasis risk (37). Collectively, these mechanisms support the “neutrophil activation–HDL dysfunction” axis as a biologically plausible pathway underlying the association between NHR and psoriatic pathology.

Furthermore, the study found that elevated NHR was more strongly associated with psoriasis risk among participants who did not consume alcohol. This observation may be explained by the absence the dual protective effects associated with low-to-moderate alcohol intake in this group. First, low-dose ethanol has been shown to exert anti-inflammatory effects via the gut microbiota-acetate-GPR43 axis. This pathway inhibits neutrophil reactive oxygen species production and endoplasmic reticulum stress, thereby reducing the formation of NET (38). Second, moderate alcohol consumption has been reported to increase HDL-C levels by enhancing the transport of apolipoprotein A-I and A-II, which improve HDL function (39). Together, these mechanisms suggest that low-to-moderate alcohol consumption may help alleviate psoriasis-related inflammation and metabolic disturbances by reducing NET formation and enhancing HDL function. However, it is important to note that excessive alcohol intake may negate these potential benefits, and that individual responses vary significantly (40, 41).

The characteristics of the study population may have influenced the observed associations. In this study, the term “drinkers” referred to individuals who consumed at least 12 alcoholic beverages per year. This category includes participants with very low levels of alcohol intake, which may attenuate the potential protective effects of low-to-moderate alcohol consumption. Considering these factors, elevated NHR was found to be significantly and strongly associated with psoriasis risk in the non-drinking group.

This study has several strengths. First, it is the first systematic evaluation of NHR in the context of chronic inflammatory skin disease. Second, the use of a nationally representative NHANES cohort enhances the generalizability of the findings. Third, rigorous multivariable adjustments were employed to minimize potential confounding, and stratified analyses were conducted to account for population heterogeneity. However, several limitations should be acknowledged. First, the cross-sectional design limits the ability to draw causal inferences. Second, psoriasis diagnoses were based on self-reported reports, which may induce potential misclassification bias. Future prospective cohort studies and mechanistic experiments are needed to validate the predictive utility of NHR and to elucidate its molecular effects on keratinocyte biology. Moreover, as the current analysis was restricted to U.S. adult males, future multicenter studies across diverse healthcare systems and ethnic populations are necessary to confirm the generalizability of NHR as a biomarker for psoriasis.

Clinically, the accessibility and low cost of NHR make it a practical tool for psoriasis risk assessment. Early interventions targeting metabolic-inflammatory pathways in individuals with elevated NHR may help prevent or slow disease progression. Moreover, longitudinal monitoring of NHR could enhance the prediction of therapeutic response to biologics, thereby contributing to the advancement of personalized management in psoriasis.

This study reveals a significant positive association between the NHR and psoriasis risk. Our findings provide translational evidence supporting early risk stratification and precision interventions in psoriasis, highlighting the role of inflammatory-metabolic interplay. Future prospective cohort studies involving larger and more diverse populations are needed to confirm this relationship and further elucidate its underlying mechanisms.