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. 2026 May 18;14(4):qfag035. doi: 10.1093/sexmed/qfag035

Endothelial activation and stress index is independently associated with arteriogenic erectile dysfunction: a cross-sectional study

Chuan Xu 1, Yuyang Zhang 2, Xu Wu 3, Guodong Liu 4, Hao Geng 5, Dongdong Tang 6, Xiansheng Zhang 7,✉
PMCID: PMC13181756  PMID: 42157972

Abstract

Introduction

Arteriogenic erectile dysfunction (AED) is the vascular subtype of erectile dysfunction and is closely linked to endothelial dysfunction. The Endothelial Activation and Stress Index (EASIX), calculated from lactate dehydrogenase (LDH), creatinine, and platelet count, has been recognized as a surrogate marker of endothelial injury in several vascular-related conditions. The aim of this study is to explore the association between EASIX and AED.

Methods

In this cross-sectional study, 193 men were enrolled, including 94 patients diagnosed with AED and 99 controls. Erectile function was assessed using the International Index of Erectile Function-5 (IIEF-5), nocturnal penile tumescence and rigidity, and color duplex Doppler ultrasonography. EASIX was calculated as LDH × creatinine/platelet count. Multivariate logistic regression analysis was performed to evaluate the association between EASIX and AED after adjusting for potential confounders. Receiver operating characteristic (ROC) curve analysis was conducted to assess diagnostic performance.

Results

EASIX levels were significantly higher in the AED group compared to controls (1.13 [0.72–1.55] vs. 0.79 [0.58–1.01], P < .001). In multivariate logistic regression analysis adjusting for age, body mass index, smoking status, metabolic parameters, testosterone levels, and comorbidities, EASIX remained independently associated with AED (OR 1.339, 95% CI 1.239–1.448, P < .001). When analyzed by quartiles, participants in the highest EASIX quartile had a significantly increased likelihood of AED compared with the lowest quartile (P < .001). A significant negative correlation was observed between EASIX and IIEF-5 score (r = −0.291, P = .004). ROC analysis demonstrated that EASIX had moderate diagnostic performance for identifying AED (AUC 0.728, 95% CI 0.656–0.799), which was higher than LDH (AUC 0.680) and creatinine (AUC 0.689).

Conclusion

EASIX was significantly associated with AED and demonstrated moderate diagnostic performance. Prospective studies are warranted to validate its clinical applicability.

Keywords: endothelial activation and stress index, arteriogenic erectile dysfunction, endothelial dysfunction, vascular erectile dysfunction, biomarker

Introduction

Erectile dysfunction (ED) is defined as the persistent inability to achieve or maintain an erection sufficient for satisfactory sexual intercourse, a condition that significantly affects both physical and emotional well-being.1–3 As a prevalent condition, the incidence of ED increases with age, with studies revealing that 10% of men over 35 years of age experience ED, and another 25% report occasional episodes of erectile difficulties. This prevalence continues to rise dramatically with aging, with up to 75% of men experiencing ED by the age of 70.4 Beyond the physical implications, ED can have profound effects on the quality of life, leading to psychological distress, relationship issues, and reduced self-esteem.5–7 The multifactorial nature of ED involves complex interactions between psychological, hormonal, and vascular factors, with increasing evidence suggesting that age-related vascular changes play a significant role in its onset and progression.8 As the population ages, the burden of ED will continue to grow, necessitating effective screening and management strategies.

Penile erection is primarily a vascular event, dependent on the proper function of the blood vessels within the penis, a highly vascularized organ. Among the different pathogenic mechanisms of ED, vascular pathologies represent the most common cause, accounting for 60%-80% of ED.9 Vascular ED, particularly arteriogenic ED (AED), is commonly caused by endothelial dysfunction,10 which impairs the dilation of blood vessels and reduces blood flow. Among various forms of vasculogenic ED, AED is most closely associated with endothelial dysfunction and atherosclerosis.11,12 Endothelial dysfunction plays a critical role in the development of AED and is also an early indicator of cardiovascular disease (CVD).13,14 Studies have shown that ED, particularly AED, can precede the clinical signs of atherosclerosis and serve as an early marker of cardiovascular risk.15,16 The strong association between AED and CVD highlights the importance of evaluating erectile function as part of cardiovascular health assessment, as endothelial dysfunction is a shared underlying factor for both conditions.

Therefore, the activation and stress response of endothelial cells play a central role in the progression of AED. Recognizing biomarkers that objectively reflect the extent of endothelial injury is crucial for assessing the risk of AED in patients. The Endothelial Activation and Stress Index (EASIX) is a novel endothelial function marker that integrates lactate dehydrogenase (LDH), creatinine, and platelet count. Due to its simple calculation and cost-effectiveness, EASIX has emerged as an innovative biomarker reflecting endothelial dysfunction and inflammatory responses.17 Initially developed to assess the severity of endothelial injury in stem cell transplant patients, EASIX has been shown to be elevated in conditions related to thrombotic microangiopathies caused by endothelial dysfunction.18 Previous studies have demonstrated that elevated EASIX is associated with increased mortality risk in allogeneic stem cell transplant recipients, linked to endothelial dysfunction-induced thrombotic microvascular damage.19,20 In addition, EASIX has been significantly correlated with morbidity and mortality in various conditions, serving as a predictor for stroke,21 coronary artery disease,22 and hypertension.23

Is a higher EASIX score associated with an increased risk of AED in patients with ED? Given the critical role of endothelial dysfunction in AED and the established association between EASIX and endothelial injury in other vascular diseases, we hypothesize that EASIX may serve as a valuable biomarker for identifying AED. Our study specifically focuses on AED because it is the subtype of ED most closely associated with endothelial dysfunction. Among the various types of ED, AED is considered the vascular type that most directly reflects underlying endothelial damage. Therefore, investigating the association between EASIX and AED offers insight into the potential of EASIX as a biomarker for vascular-related ED. The primary objective of this study is to evaluate the association between EASIX levels and the presence of AED, and to assess its diagnostic performance compared to individual biomarkers such as LDH, creatinine, and platelet count. We hypothesize that elevated EASIX values are associated with an increased likelihood of AED, providing a simple and accessible tool for early detection and risk assessment of vascular-related ED.

Methods

Study design

This study is a prospective, cross-sectional clinical study conducted from December 2024 to January 2026. We consecutively recruited male patients (aged 18-65 years) who visited the urology/andrology outpatient clinics at the local hospital, presenting with ED as their primary complaint. Erectile function was assessed using the International Index of Erectile Function (IIEF-5).24 A score of ≤21 was used to diagnose ED. The control group was recruited from the hospital’s health check-up center and was subject to the same inclusion and exclusion criteria. These men had no reported symptoms of ED prior to enrollment, and their IIEF-5 scores >21.

Exclusion criteria included: a history of pelvic or perineal surgery; diagnosed hormonal disorders (eg, hypothyroidism, hyperthyroidism, testosterone deficiency, or hyperprolactinemia); neurological diseases; alcohol abuse; any known renal disease, including chronic kidney disease, documented renal impairment, or persistent proteinuria/albuminuria; acute infections; or use of medications known to affect sexual function (eg, antipsychotics, antidepressants, or phosphodiesterase type 5 inhibitors). Participants using medications that affect endothelial function (eg, steroids, immunosuppressants, chemotherapeutic agents) or platelet function (eg, antiplatelet drugs) were also excluded. The study protocol was approved by the ethics committee of the local ethics committee (Approval No. PJ2024-11-82), and written informed consent was obtained from all participants before enrollment.

Data collection and variables

In this study, baseline demographic and clinical data were collected from all participants, including age, body mass index (BMI), smoking history, physical activity, and comorbidities such as cardiovascular disease (CVD) and diabetes mellitus (DM), which were recorded using structured questionnaires and medical history reviews.

Fasting blood samples were collected from all participants to measure several biomarkers associated with endothelial function and vascular health. LDH levels were measured using a colorimetric method based on the enzymatic reduction of nicotinamide adenine dinucleotide (NAD+) to nicotinamide adenine dinucleotide (NADH). Serum creatinine was measured via an enzymatic colorimetric method based on the Jaffe reaction, which assesses kidney function and is linked to endothelial health. Platelet count (PLT) was determined using an automated hematology analyzer (Sysmex XN-900, Sysmex Corporation, Kobe, Japan), which uses light scattering properties to count platelets, an important marker of vascular function. Other serum parameters, including total cholesterol (TC), triglycerides (TG), and fasting blood glucose (FBG), were measured using direct assays and the glucose oxidase method, respectively. Total testosterone (TT) levels were quantified using chemiluminescent immunoassays (CLIA), a highly sensitive method for hormone measurement. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation, based on serum creatinine levels, age, gender, and race. The EASIX was calculated using the formula: LDH (U/L) × Creatinine (mg/dL)/PLT (109/L).

Comorbidities such as CVD and DM were diagnosed based on self-reports of medical history, including a history of heart disease, stroke, or use of related medications such as antihypertensives, statins, and antidiabetic drugs. Participants with these conditions were categorized accordingly. All laboratory tests were conducted at the hospital’s central laboratory, which adheres to national medical standards to ensure the accuracy and consistency of the results.

Assessment of AED

All enrolled participants with ED underwent nocturnal penile tumescence and rigidity (NPTR) monitoring using the RigiScan™ device (GOTOP Medical, Minneapolis, MN, USA) for two consecutive nights under standardized sleep conditions. During this period, participants were instructed to avoid any activities that could interfere with nocturnal erections. The NPTR parameters measured included baseline rigidity, tip rigidity, tumescence, event counts, and the duration of the longest erection episode. A normal NPTR result was defined by meeting at least one of the following criteria: (i) three or more erectile events lasting ≥10 min with tip rigidity ≥70%, or (ii) an increase in penile circumference of ≥3 cm at the base or ≥ 2 cm at the tip. If neither criterion was met, the NPTR result was classified as abnormal.

Patients with abnormal NPTR findings were subsequently assessed using color duplex Doppler ultrasonography (CDDU) to evaluate penile hemodynamics. After intra-cavernosal injection (ICI) of 20 μg alprostadil (Caverject®, Pfizer, New York, USA), CDDU was performed by trained radiologists using the Aixplorer™ ultrasound system (Supersonic Imagine S.A., Aix-en-Provence, France) at our center. Radiologists adhered to a standardized examination protocol and predefined diagnostic criteria for evaluating penile hemodynamics. Peak systolic velocity (PSV) and end-diastolic velocity (EDV) of both cavernous arteries were measured initially in the flaccid state and every 5 min up to 25 min post-ICI administration. A PSV threshold of <30 cm/s and EDV <5 cm/s were used to diagnose AED.25

Statistical analysis

All statistical analyses were performed using SPSS software (version 23.0, IBM Corp., Armonk, NY, USA). Descriptive statistics were used to summarize the baseline demographic and clinical characteristics of the study participants. Continuous variables were expressed as means ± standard deviations (SD) or medians with interquartile ranges (IQR) based on the normality of the data. The normality of data was assessed using the Shapiro–Wilk test. For normally distributed variables, comparisons between the AED group and the control group were made using independent t-tests, while the Mann–Whitney U test was used for non-normally distributed variables. Categorical variables were presented as frequencies and percentages, and comparisons between groups were performed using the chi-square test.

Univariable logistic regression analyses were first performed to evaluate the association between each variable and AED. Variables with P < .10 in univariable analysis, along with clinically relevant factors, were included in the multivariable logistic regression model. We performed multivariate logistic regression analysis to evaluate the association between EASIX and the presence of AED. The regression model was adjusted for potential confounders, including age, BMI, smoking status, regular exercise, FBG, TC, TG, TT, eGFR, CVD, and DM. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for EASIX score. To assess the diagnostic performance of EASIX in identifying AED, we performed receiver operating characteristic (ROC) curve analysis. The optimal cut-off values for EASIX, LDH, creatinine, and platelet count were determined using Youden’s index, and the area under the curve (AUC) with 95% CI was reported. In addition, among participants diagnosed with AED, Spearman’s correlation coefficient was conducted to evaluate the association between EASIX and IIEF-5 scores. All statistical tests were two-tailed, and statistical significance was defined as a P-value of <.05.

Results

Demographic and clinical characteristics

A detailed flowchart of patient selection, including exclusion criteria and diagnostic procedures, is presented in Figure 1. As shown in Figure 1, a total of 193 participants were enrolled in the study, with 94 diagnosed with AED and 99 in the control group. The demographic and clinical characteristics are summarized in Table 1. The mean age was 37.46 ± 6.66 years for the AED group and 35.34 ± 6.50 years for the control group (P = .027). BMI was similar between the two groups: 24.98 ± 2.41 kg/m2 in the AED group and 24.64 ± 1.60 kg/m2 in controls (P = .245). Smoking prevalence was higher in the AED group (38.30%) compared to the control group (33.33%) (P = .472). CVD was more common in the AED group (36.17%) than in controls (23.23%) (P = .049), while DM was similar between groups (P = .581).

Figure 1.

For image description, please refer to the figure legend and surrounding text.

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Flow diagram illustrating the recruitment and selection process of study participants. Abbreviations: IIEF-5, international index of erectile function-5; ED, erectile dysfunction; NPTR, nocturnal penile tumescence and rigidity; CDDU, color duplex Doppler ultrasonography; AED, arteriogenic erectile dysfunction.

Table 1.

Demographic and clinical characteristics of participants.

AED (n = 94) Control (n = 99) P
Age (years) 37.46 ± 6.66 35.34 ± 6.50 .027 a
BMI (kg/m2) 24.98 ± 2.41 24.64 ± 1.60 .245a
Smoking, n (%) 36 (38.30) 33 (33.33) .472b
Regular exercise, n (%) 29 (30.85) 35 (35.35) .507b
FBG (mmol/L) 5.01 ± 0.53 5.10 ± 0.51 .234a
TC (mmol/L)c 3.99 (3.56-4.42) 3.58 (3.13-4.04) .025 d
TG (mmol/L)c 1.39 (1.15-1.63) 1.29 (1.09-1.50) .045 d
TT (nmol/L) 17.33 ± 4.09 18.25 ± 4.07 .121a
eGFR (mL/min/1.73 m2) 92.83 ± 3.88 93.82 ± 3.15 .052a
LDH (U/L) 267.19 ± 76.69 217.04 ± 72.84 <.001 a
Creatinine (mg/dL) 1.07 ± 0.22 0.93 ± 0.17 <.001 a
Platelet (109/L)c 261 (206-316) 241 (209-274) .220d
EASIX scorec 1.13 (0.72-1.55) 0.79 (0.58-1.01) <.001 d
CVD, n (%) 34 (36.17) 23 (23.23) .049 b
DM, n (%) 16 (17.02) 14 (14.14) .581b
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Values are percentages or mean ± SD unless noted otherwise.

a

Independent sample t tests.

b

Chi-square test. Bold indicates P < .05.

c

Values are presented as median with interquartile range. Regular exercise: Twice a week, at least 30 min each time.

d

Mann–Whitney U test was used.

Abbreviations: AED, arteriogenic erectile dysfunction; BMI, Body Mass Index; FBG, fasting blood glucose; TC, Total Cholesterol; TG, Triglyceride; TT, Total Testosterone; eGFR, estimated glomerular filtration rate; LDH, Lactate dehydrogenase; EASIX, Endothelial Activation and Stress Index; CVD, cardiovascular disease; DM, diabetes mellitus.

The bolded P value indicates that P < 0.05.

Key biomarkers showed significant differences: the AED group had higher LDH (267.19 ± 76.69 U/L) and creatinine (1.07 ± 0.22 mg/dL) compared to control group (P < .001 for both). EASIX scores were also higher in the AED group (1.13 [0.72–1.55]) compared to the control group (0.79 [0.58–1.01]) (P < .001).

Association between EASIX and AED

Univariable logistic regression analyses are presented in Supplementary Table S1. Variables such as age and TG were significantly associated with AED, while TC, eGFR, and CVD showed borderline significance. As shown in Table 2, multivariate logistic regression analysis was conducted to assess the association between the EASIX and the presence of AED. The model was adjusted for potential confounders, including age, BMI, smoking status, regular exercise, FBG, TC, TG, TT, eGFR, CVD, and DM.

Table 2.

Multivariate logistic regression analysis for AED.

Variable Adjusted model
OR 95% CI P
EASIX score (continuous) 1.339 1.239-1.448 <.001
EASIX score (Quartiles)
Q1 (<0.62) Reference Reference Reference
Q2 (0.62-0.92) 1.024 0.972-1.086 .093
Q3 (0.92-1.22) 1.624 1.260-2.843 <.001
Q4 (>1.22) 2.688 1.789-4.554 <.001
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Statistical analysis:

Adjusted model: adjusted for age, BMI, smoking status, regular exercise, FBG, TC, TG, TT, eGFR, CVD, and DM.

Abbreviations: AED, arteriogenic erectile dysfunction; BMI, Body Mass Index; FBG, fasting blood glucose; TC, Total Cholesterol; TG, Triglyceride; TT, Total Testosterone; eGFR, estimated glomerular filtration rate; EASIX, Endothelial Activation and Stress Index; CVD, cardiovascular disease; DM, diabetes mellitus.

The analysis revealed that EASIX was significantly associated with the likelihood of having AED. The OR for EASIX as a continuous variable was 1.339 (95% CI: 1.239-1.448, P < .001), indicating that for every unit increase in EASIX, the odds of having AED increased by 33.9%. Further analysis of EASIX in quartiles demonstrated a dose-dependent relationship with AED risk. Compared to the reference group (Q1: EASIX <0.62), participants in Q3 (EASIX 0.92-1.22) had an OR of 1.624 (95% CI: 1.260-2.843, P < .001), and those in Q4 (EASIX >1.22) had an OR of 2.688 (95% CI: 1.789-4.554, P < .001). Therefore, compared with the reference group (Q1: EASIX <0.62), a significantly increased risk of AED was observed in the Q3 and Q4 groups, while no significant association was found in Q2. These results indicate that the increased risk of AED is primarily evident when EASIX exceeds ~0.92.

Correlation and diagnostic performance

As shown in Figure 2, we conducted a correlation analysis between EASIX and IIEF-5 score. A statistically significant but weak negative correlation was observed between EASIX and IIEF-5 scores (r = −0.291, P = .004), indicating that higher EASIX values were associated with worse erectile function. This supports the hypothesis that endothelial dysfunction, as reflected by EASIX, is linked to the severity of ED in patients with AED.

Figure 2.

For image description, please refer to the figure legend and surrounding text.

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Correlation between EASIX and IIEF-5 score. Scatter plot showing the correlation between the EASIX and IIEF-5 score. Abbreviations: EASIX,endothelial activation and stress index; IIEF-5, international index of erectile function-5.

The diagnostic performance of EASIX and other biomarkers for identifying AED was assessed using ROC curve analysis (Table 3). The optimal cut-off for EASIX was 1.070, with a sensitivity of 60.5% and specificity of 76.8%, yielding an AUC of 0.728 (95% CI: 0.656-0.799, P < .001). In comparison, LDH had an AUC of 0.680, creatinine an AUC of 0.689, and platelet count showed a poor AUC of 0.551. Figure 3 demonstrates that EASIX had the highest AUC, outperforming LDH and creatinine, indicating its superior diagnostic ability for AED.

Table 3.

Diagnostic performance of LDH, Creatinine, Platelet, and EASIX score for identifying AED.

Indicator Optimal Cut-off Specificity Sensitivity AUC (95%CI) P-value
LDH (U/L) 218.5 0.535 0.777 0.680 (0.604-0.755) <.001
Creatinine (mg/dL) 1.045 0.778 0.532 0.689 (0.615-0.764) <.001
Platelet (109/L) - - - 0.551 (0.467-0.635) .220
EASIX score 1.070 0.768 0.605 0.728 (0.656-0.799) <.001
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Abbreviations: AED, arteriogenic erectile dysfunction; LDH, Lactate dehydrogenase; EASIX, Endothelial Activation and Stress Index; AUC, Area Under the Curve; CI, Confidence Interval.

Figure 3.

For image description, please refer to the figure legend and surrounding text.

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ROC curves for identifying AED. ROC curves of EASIX, LDH, creatinine, and PLT for discriminating AED. Abbreviations: ROC, receiver operating characteristic; AED, arteriogenic erectile dysfunction; EASIX, endothelial activation and stress index; LDH, lactate dehydrogenase; PLT, platelet count.

Discussion

In this study, we explored the association between the EASIX and AED. Our results demonstrate that EASIX levels were significantly higher in the AED group compared to controls, indicating a potential link between endothelial dysfunction and AED. Multivariate logistic regression analysis confirmed that EASIX was independently associated with AED, with higher EASIX values corresponding to an increased likelihood of AED. Furthermore, EASIX showed moderate diagnostic performance for identifying AED, outperforming traditional biomarkers such as LDH and creatinine, as evidenced by ROC curve analysis. These findings suggest that EASIX may serve as a valuable biomarker for identifying patients with AED, with potential applications in clinical settings for risk assessment and early detection.

Previous studies have primarily focused on specific biomarkers such as TC, TG, or inflammatory markers in the context of ED.26–29 However, limited research has explored the relationship between LDH and creatinine levels and ED. Serum creatinine levels, for example, can reflect a variety of factors that may influence erectile function, such as age, race, muscle mass, diet, and underlying conditions like CKD and CVD.30 Elevated creatinine can indicate poor renal function,31 which is often linked to endothelial dysfunction and vascular impairment, both of which are key factors in the development of AED. In our study, we observed that both LDH and creatinine levels were significantly higher in the AED group compared to controls. LDH is a marker of cellular injury, and its elevated levels suggest ongoing endothelial damage,32 which has been shown to be associated with vascular ED. Creatinine, commonly used to assess kidney function, may provide insight into the systemic endothelial dysfunction that contributes to the pathogenesis of AED. The combination of these markers in the calculation of EASIX further strengthens its potential as a comprehensive biomarker for endothelial stress in AED.

EASIX, as a composite marker derived from LDH, creatinine, and platelet count, reflects multiple dimensions of endothelial dysfunction, inflammation, and microvascular injury.22 Given that endothelial dysfunction is a central pathophysiological mechanism underlying AED, the observed association between EASIX and AED is biologically plausible. LDH, one of the components of EASIX, is released into the circulation when cellular integrity is compromised. Damage to vascular endothelial cells may lead to increased LDH levels, reflecting ongoing tissue injury and endothelial stress. Elevated LDH has been associated with vascular inflammation and microvascular impairment, both of which are relevant to penile arterial insufficiency.33 Serum creatinine, another component of EASIX, may provide indirect insight into systemic microvascular function. Increased creatinine levels can indicate renal microvascular dysfunction, which shares common pathophysiological pathways with systemic endothelial injury.34 The coexistence of renal dysfunction and endothelial damage may therefore contribute to the elevated EASIX levels observed in patients with AED. Platelet count, the denominator in the EASIX formula, is also closely linked to endothelial integrity. Endothelial injury and complement activation may lead to platelet consumption and alterations in platelet dynamics. Exposure of subendothelial collagen, along with increased levels of tissue factor and von Willebrand factor secondary to endothelial damage, promotes platelet activation and aggregation.35 These processes are central to microvascular dysfunction and may further impair penile blood flow. Importantly, EASIX has been recognized as a prognostic biomarker in several endothelial-driven diseases.36 Previous studies have demonstrated significant correlations between EASIX and circulating markers of endothelial activation, including CXCL8, IL-18, CXCL9, soluble thrombomodulin, angiopoietin-2, tumor necrosis factor-related molecules, and insulin-like growth factor-1.18,20,37,38 These findings support the concept that EASIX reflects endothelial activation and stress burden at a systemic level. Since penile erection depends critically on intact endothelial nitric oxide signaling and adequate arterial inflow, systemic endothelial stress39—as reflected by elevated EASIX—may parallel the vascular abnormalities observed in AED. While causality cannot be inferred from the present cross-sectional study, the mechanistic overlap between endothelial dysfunction and AED provides a coherent biological framework supporting the association observed in our analysis.

EASIX demonstrated moderate discriminative ability and may have potential as an adjunctive indicator for AED risk assessment; however, its clinical applicability remains limited and requires further validation in prospective studies. Because EASIX is derived from routinely measured laboratory parameters—LDH, creatinine, and platelet count—it can be easily calculated without additional testing burden or cost, which enhances its feasibility in everyday clinical practice. Given the close association between AED and systemic vascular dysfunction, EASIX may provide supplementary information reflecting endothelial stress and microvascular impairment. This may be particularly relevant in patients with coexisting cardiovascular risk factors, in whom vascular evaluation is clinically meaningful. While EASIX is not intended to replace established diagnostic modalities such as penile Doppler ultrasonography, it may help identify individuals with a higher likelihood of vascular-related ED and support clinical decision-making regarding further hemodynamic assessment. Further prospective and multicenter studies are needed to validate these findings and to clarify whether EASIX may have additional value in risk stratification or longitudinal monitoring.

Several limitations of this study should be acknowledged. First, the cross-sectional design precludes any inference of causal relationships between EASIX and AED. Although a significant association was observed, longitudinal studies are required to determine the temporal relationship between elevated EASIX levels and the development of AED. Second, this was a single-center study with a relatively moderate sample size, which may limit the generalizability of the findings to other populations. Multicenter studies involving larger and more diverse cohorts are needed to validate the reproducibility and external applicability of our results. Third, although we adjusted for several important confounding variables, residual confounding cannot be completely excluded. Factors such as dietary patterns, and unmeasured inflammatory markers may have influenced the observed associations. Finally, EASIX was evaluated at a single time point, and dynamic changes over time were not assessed. Whether longitudinal variations in EASIX are associated with changes in erectile function warrants further investigation.

Conclusion

In conclusion, this study demonstrated that the EASIX was significantly associated with AED. Higher EASIX levels were independently linked to an increased likelihood of AED and showed moderate diagnostic performance in identifying vascular-related ED. These findings suggest that EASIX may serve as a simple and accessible adjunctive biomarker reflecting endothelial stress in patients with AED. Further prospective and multicenter studies are warranted to validate these results and clarify its potential clinical utility.

Supplementary Material

Table_S1_qfag035
table_s1_qfag035.docx (16.8KB, docx)

Acknowledgments

Not applicable.

Contributor Information

Chuan Xu, Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China.

Yuyang Zhang, Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China.

Xu Wu, Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China.

Guodong Liu, Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China.

Hao Geng, Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China.

Dongdong Tang, Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China.

Xiansheng Zhang, Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China.

Author contributions

Chuan Xu, Yuyang Zhang, Xu Wu and Xiansheng Zhang: Conceptualization, Methodology, Writing—Original Draft, Funding Acquisition; Chuan Xu, Guodong Liu, Hao Geng, Dongdong Tang, and Xiansheng Zhang: Data Curation, Formal Analysis, Visualization; Chuan Xu, Yuyang Zhang, Xu Wu, Guodong Liu, and Xiansheng Zhang: Investigation, Validation, Writing—Review & Editing; Xiansheng Zhang, Dongdong Tang, and Yuyang Zhang: Project Administration, Resources, Supervision; All authors have read and agreed to the published version of the manuscript.

Funding

Our work received support from The National Natural Science Foundation of China (Grants 82071637 and 82371635).

Conflicts of interest

The authors declare no competing interests.

Data availability

The data are currently not publicly available due to participant privacy, but, if necessary, they are available from the corresponding author upon reasonable request.

Ethics approval and consent to participate

This study was performed in line with the principles of the Declaration of Helsinki. The study was approved by the Ethics Committee of the First Affiliated Hospital of Anhui Medical University. All study participants submitted written informed consent.

Consent for publication

Not applicable.

References

  • 1. Najari  BB, Kashanian  JA. Erectile dysfunction. JAMA.  2016;316(17):1838. 10.1001/jama.2016.12284 [DOI] [PubMed] [Google Scholar]
  • 2. Shamloul  R, Ghanem  H. Erectile dysfunction. Lancet.  2013;381(9861):153–165. 10.1016/S0140-6736(12)60520-0 [DOI] [PubMed] [Google Scholar]
  • 3. Selvin  E, Burnett  AL, Platz  EA. Prevalence and risk factors for erectile dysfunction in the US. Am J Med. 2007;120(2):151–157. 10.1016/j.amjmed.2006.06.010 [DOI] [PubMed] [Google Scholar]
  • 4. Camacho  ME, Reyes-Ortiz  CA. Sexual dysfunction in the elderly: age or disease?  Int J Impot Res. 2005;17(Suppl 1):S52–S56. 10.1038/sj.ijir.3901429 [DOI] [PubMed] [Google Scholar]
  • 5. Maiorino  MI, Bellastella  G, Esposito  K. Diabetes and sexual dysfunction: current perspectives. Diabetes Metab Syndr Obes. 2014;7:95–105. 10.2147/DMSO.S36455 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. Saigal  CS, Wessells  H, Pace  J, Schonlau  M, Wilt  TJ. Predictors and prevalence of erectile dysfunction in a racially diverse population. Arch Intern Med. 2006;166(2):207–212. 10.1001/archinte.166.2.207 [DOI] [PubMed] [Google Scholar]
  • 7. McMahon  CG. Current diagnosis and management of erectile dysfunction. Med J Aust. 2019;210(10):469–476. 10.5694/mja2.50167 [DOI] [PubMed] [Google Scholar]
  • 8. Lowenstein  L, Damti  A, Pillar  G, Shott  S, Blumenfeld  Z. Evaluation of endothelial function in women with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol. 2007;134(2):208–212. 10.1016/j.ejogrb.2007.02.011 [DOI] [PubMed] [Google Scholar]
  • 9. Brotons  FB, Campos  JC, Gonzalez-Correales  R, Martín-Morales  A, Moncada  I, Pomerol  JM. Core document on erectile dysfunction: key aspects in the care of a patient with erectile dysfunction. Int J Impot Res. 2004;16(Suppl 2):S26–S39. 10.1038/sj.ijir.3901240 [DOI] [PubMed] [Google Scholar]
  • 10. Bertini  A, Pozzi  E, Fallara  G, et al.  The atherosclerotic cardiovascular disease risk score is a reliable tool to identify patients with arteriogenic erectile dysfunction. Andrology.  2023;11(7):1451–1459. 10.1111/andr.13437 [DOI] [PubMed] [Google Scholar]
  • 11. Ghiadoni  L, Taddei  S, Virdis  A. Hypertension and endothelial dysfunction: therapeutic approach. Curr Vasc Pharmacol. 2012;10(1):42–60. 10.2174/157016112798829823 [DOI] [PubMed] [Google Scholar]
  • 12. Chung  RY, Chan  D, Woo  J, et al.  Erectile dysfunction is associated with subsequent cardiovascular and respiratory mortality in cohort of 1,436 Chinese elderly men. J Sex Med. 2015;12(7):1568–1576. 10.1111/jsm.12918 [DOI] [PubMed] [Google Scholar]
  • 13. Lojanapiwat  B, Weerusawin  T, Kuanprasert  S. Erectile dysfunction as a sentinel marker of endothelial dysfunction disease. Singapore Med J. 2009;50(7):698–701. [PubMed] [Google Scholar]
  • 14. Shah  NP, Cainzos-Achirica  M, Feldman  DI, et al.  Cardiovascular disease prevention in men with vascular erectile dysfunction: the view of the preventive cardiologist. Am J Med. 2016;129(3):251–259. 10.1016/j.amjmed.2015.08.038 [DOI] [PubMed] [Google Scholar]
  • 15. Bal  K, Oder  M, Sahin  AS, et al.  Prevalence of metabolic syndrome and its association with erectile dysfunction among urologic patients: metabolic backgrounds of erectile dysfunction. Urology.  2007;69(2):356–360. 10.1016/j.urology.2006.09.057 [DOI] [PubMed] [Google Scholar]
  • 16. Shiri  R, Koskimäki  J, Hakama  M, et al.  Effect of life-style factors on incidence of erectile dysfunction. Int J Impot Res. 2004;16(5):389–394. 10.1038/sj.ijir.3901196 [DOI] [PubMed] [Google Scholar]
  • 17. Xu  HB, Ye  Y, Xue  F, Wu  J, Suo  Z, Zhang  H. Association between endothelial activation and stress index and 28-day mortality in septic ICU patients: a retrospective cohort study. Int J Med Sci. 2023;20(9):1165–1173. 10.7150/ijms.85870 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18. Luft  T, Benner  A, Terzer  T, et al.  EASIX and mortality after allogeneic stem cell transplantation. Bone Marrow Transplant. 2020;55(3):553–561. 10.1038/s41409-019-0703-1 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19. Penack  O, Luft  T, Peczynski  C, et al.  Endothelial activation and stress index (EASIX) to predict mortality after allogeneic stem cell transplantation: a prospective study. J Immunother Cancer. 2024;12(1):e007635. 10.1136/jitc-2023-007635 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20. Kordelas  L, Terzer  T, Gooley  T, et al.  EASIX-1year and late mortality after allogeneic stem cell transplantation. Blood Adv. 2023;7(18):5374–5381. 10.1182/bloodadvances.2022008617 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21. Huang  Y, Li  Z, Wang  J, Wang  D, Yin  X. Endothelial activation and stress index is a reliable predictor for the prevalence and mortality outcomes of stroke. Sci Rep. 2025;15(1):23285. 10.1038/s41598-025-06595-5 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22. Finke  D, Hund  H, Frey  N, Luft  T, Lehmann  LH. EASIX (endothelial activation and stress index) predicts mortality in patients with coronary artery disease. Clin Res Cardiol. 2025;114(8):1008–1018. 10.1007/s00392-024-02534-y [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. Dong  G, Wu  T, Gu  X, Wu  L. Endothelial activation and stress index predicts all-cause and cardiovascular mortality in hypertensive individuals: a Nationwide study. J Clin Hypertens (Greenwich). 2025;27(4):e70057. 10.1111/jch.70057 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24. Rosen  RC, Riley  A, Wagner  G, Osterloh  IH, Kirkpatrick  J, Mishra  A. The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology.  1997;49(6):822–830. 10.1016/S0090-4295(97)00238-0 [DOI] [PubMed] [Google Scholar]
  • 25. Flores  JM, West  M, Mulhall  JP. Efficient use of penile doppler ultrasound for investigating men with erectile dysfunction. J Sex Med. 2024;21(8):734–739. 10.1093/jsxmed/qdae070 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26. Wei  M, Macera  CA, Davis  DR, Hornung  CA, Nankin  HR, Blair  SN. Total cholesterol and high density lipoprotein cholesterol as important predictors of erectile dysfunction. Am J Epidemiol. 1994;140(10):930–937. 10.1093/oxfordjournals.aje.a117181 [DOI] [PubMed] [Google Scholar]
  • 27. Chen  C, Zhai  H, Huang  G, et al.  Is lower low-density lipoprotein cholesterol associated with lower androgen and erectile dysfunction in men?  Nutr Metab Cardiovasc Dis. 2018;28(12):1304–1310. 10.1016/j.numecd.2018.08.006 [DOI] [PubMed] [Google Scholar]
  • 28. Feldman  HA, Goldstein  I, Hatzichristou  DG, Krane  RJ, McKinlay  JB. Impotence and its medical and psychosocial correlates: results of the Massachusetts male aging study. J Urol. 1994;151(1):54–61. 10.1016/S0022-5347(17)34871-1 [DOI] [PubMed] [Google Scholar]
  • 29. Esposito  K, Giugliano  F, Di Palo  C, et al.  Effect of lifestyle changes on erectile dysfunction in obese men: a randomized controlled trial. Jama.  2004;291(24):2978–2984. 10.1001/jama.291.24.2978 [DOI] [PubMed] [Google Scholar]
  • 30. Zhou  S, Wang  P, Sun  L, et al.  Lower serum creatinine to cystatin C ratio associated with increased incidence of frailty in community-dwelling elderly men but not in elderly women. Aging Clin Exp Res. 2024;36(1):140. 10.1007/s40520-024-02787-7 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31. Bohlouli  A, Tarzamni  MK, Zomorodi  A, Abdollahifard  S, Hashemi  B, Nezami  N. Remnant kidney function and size in living unrelated kidney donors after nephrectomy. Saudi J Kidney Dis Transpl. 2010;21(2):246–250. [PubMed] [Google Scholar]
  • 32. Gilli  SC, Bastos  SO, Benites  BD, Costa  FF, Saad  ST. LDH and age are associated with hemolysis-endothelial dysfunction in HbSC patients. Blood Cells Mol Dis. 2016;59:119–123. 10.1016/j.bcmd.2016.04.012 [DOI] [PubMed] [Google Scholar]
  • 33. Parra-Bonilla  G, Alvarez  DF, Alexeyev  M, Vasauskas  A, Stevens  T. Lactate dehydrogenase a expression is necessary to sustain rapid angiogenesis of pulmonary microvascular endothelium. PLoS One. 2013;8(9):e75984. 10.1371/journal.pone.0075984 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34. Cofiell  R, Kukreja  A, Bedard  K, et al.  Eculizumab reduces complement activation, inflammation, endothelial damage, thrombosis, and renal injury markers in aHUS. Blood.  2015;125(21):3253–3262. 10.1182/blood-2014-09-600411 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35. Carrizzo  A, Izzo  C, Oliveti  M, et al.  The main determinants of diabetes mellitus vascular complications: endothelial dysfunction and platelet Hyperaggregation. Int J Mol Sci. 2018;19(10):2968. 10.3390/ijms19102968 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36. Luft  T, Benner  A, Jodele  S, et al.  EASIX in patients with acute graft-versus-host disease: a retrospective cohort analysis. Lancet Haematol. 2017;4(9):e414–e423. 10.1016/S2352-3026(17)30108-4 [DOI] [PubMed] [Google Scholar]
  • 37. Luft  T, Wendtner  CM, Kosely  F, et al.  EASIX for prediction of outcome in hospitalized SARS-CoV-2 infected patients. Front Immunol. 2021;12:634416. 10.3389/fimmu.2021.634416 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38. Dai  H, Penack  O, Radujkovic  A, et al.  Early bilirubinemia after allogeneic stem cell transplantation-an endothelial complication. Bone Marrow Transplant. 2021;56(7):1573–1583. 10.1038/s41409-020-01186-6 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39. Liu  C, Lu  K, Tao  T, et al.  Endothelial nitric oxide synthase polymorphisms and erectile dysfunction: a meta-analysis. J Sex Med. 2015;12(6):1319–1328. 10.1111/jsm.12896 [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Table_S1_qfag035
table_s1_qfag035.docx (16.8KB, docx)

Data Availability Statement

The data are currently not publicly available due to participant privacy, but, if necessary, they are available from the corresponding author upon reasonable request.

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