Endothelial Dysfunction and Erectile Dysfunction: Evidence From EASIX Score in NHANES 2001-2004.

This study aimed to explore the relationship between endothelial activation and stress index (EASIX) and all-cause mortality in patients with rheumatoid arthritis (RA), and to further examine whether gamma-glutamyl transferase (GGT) influences this association. We included 2,543 participants with RA from the National Health and Nutrition Examination Survey (NHANES) in this retrospective cohort study. The study outcome was considered to be all-cause mortality. EASIX and GGT levels were measured at baseline (study enrollment) using laboratory data from NHANES. EASIX was divided into two groups based on its median: ≥0.476 and <0.476, while GGT was divided into two groups based on its median: ≥23 U/L and <23 U/L. EASIX was calculated using the formula, lactate dehydrogenase (LDH, U/L) × creatinine (mg/dL)/platelet count (109/L), based on the baseline laboratory measurements. Weighted multivariate Cox regression models were used to assess the associations between EASIX and GGT with the risk of all-cause mortality. Importantly, a moderated analysis of GGT (moderator) was conducted to examine the relationship between EASIX and all-cause mortality among patients with RA. Additionally, subgroup analysis was performed based on age, duration of arthritis, diabetes, and hypertension. A total of 867 individuals developed all-cause mortality over a mean follow-up period of 122.86 ± 3.29 months. After fully adjusting for potential confounding factors, higher EASIX (≥0.476) was positively associated with all-cause mortality (hazard ratio [HR] = 1.42; 95% confidence interval [CI]: 1.18-1.73). However, the association between GGT and all-cause mortality was not significant (p > 0.05). Moderated analysis revealed that higher GGT levels strengthened the correlation between EASIX and all-cause mortality among patients with RA (p = 0.013). The association between EASIX and the risk of all-cause mortality varied depending on GGT levels. The subgroup analysis revealed that GGT moderated the relationship between EASIX and all-cause mortality among RA patients aged 60 years or older (p = 0.007), with a history of arthritis lasting more than 5 years (p = 0.040), or diagnosed with diabetes (p = 0.009) or hypertension (p = 0.016). Competing risks analysis accounting for cardiovascular mortality yielded consistent results (subdistribution hazard ratio [sHR] = 1.39; 95% CI: 1.15-1.69), further supporting the primary findings. High EASIX was positively associated with all-cause mortality in patients with RA, and this association was significantly enhanced by higher GGT levels.

BackgroundVascular endothelial impairment is crucial in diabetes and its cardiovascular complications, but clinically applicable endothelial function markers remain limited. We investigated the Endothelial Activation and Stress Index (EASIX), a novel biomarker calculated from lactate dehydrogenase, creatinine, and platelet count, for predicting mortality in diabetes and prediabetes populations.MethodsThe study analyzed data from 20,285 participants with diabetes or prediabetes enrolled in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Mortality outcomes were tracked through the National Death Index until December 2019. EASIX was calculated as: lactate dehydrogenase (U/L) × creatinine (mg/dL)/platelet count (109/L). We employed multiple statistical approaches, including Kaplan–Meier survival analysis, multivariable Cox proportional hazards models, restricted cubic spline analysis, and stratified analysis to examine the relationship between EASIX and mortality outcomes.ResultsDuring a median follow-up of 90.2 months, 3,432 deaths occurred, including 1,128 cardiovascular-related deaths. Higher EASIX values were significantly associated with increased risks of all-cause and cardiovascular mortality (P for trend < 0.0001). In the fully adjusted model, the highest EASIX quartile (Q4) demonstrated significantly higher risks as compared to the lowest quartile (Q1): all-cause mortality (HR: 1.50, 95% CI 1.33–1.69) and cardiovascular mortality (HR: 1.72, 95% CI 1.38–2.14). Nonlinear relationships were observed between EASIX and mortality outcomes (P for nonlinearity < 0.001). While EASIX predicted outcomes in both populations, diabetic patients showed a more pronounced effect. Subgroup analyses revealed more significant associations in females (HR: 1.36, 95% CI 1.28–1.44) compared to males (HR: 1.18, 95% CI 1.13–1.22), and the association was modified by hypertension status (P for interaction = 0.002).ConclusionEASIX emerges as an independent predictor of all-cause and cardiovascular mortality in diabetes and prediabetes patients. Its accessibility makes it a practical tool for identifying patients requiring intensive monitoring and intervention. The stronger associations in specific subgroups, particularly among diabetic patients and females, underscore the need for targeted approaches.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40001-025-03009-0.

The endothelial activation and stress index (EASIX) can predict endothelial intricacies as well as survival in distinct clinical circumstances. Accordingly, we hypothesize that EASIX may also serve as a predictor for stroke prevalence and mortality outcomes-all-cause mortality (ACM) and cardiovascular mortality (CVM) due to stroke. To validate our hypothesis, we deployed the National Health and Nutrition Examination Survey data. This cohort study employed 1999–2018 NHANES data. To evaluate EASIX effects on stroke risk, weighted logistic regression models were deployed. Meanwhile, we utilized the weighted Cox proportional hazards model for the calculation of hazard ratios (HRs) and 95% confidence intervals (CI) for mortality outcomes. The Kaplan-Meier curves were utilized, seeking the assessment of the interplay between the EASIX and both ACM and CVM among stroke patients. Using restricted cubic spline (RCS) curves, the potential non-linear or linear relations were investigated between the EASIX and both stroke prevalence and mortality outcomes. Subgroup analyses were performed to further assess the interconnection that existed between the EASIX and both stroke presence and its mortality outcomes. Interaction tests between covariates were also performed. Assessment of diagnostic value was done via receiver operating characteristic (ROC) curves. The area under the curve (AUC) was measured to estimate the EASIX predictive values for stroke prevalence and mortality outcomes. Of 43,853 participants, 1674 had a stroke; among them, there were (743/1671, 44.46%) ACM and 225 (13.46%) CVM. After full adjustment, EASIX was positively related to the likelihood of having a stroke (odds ratio [OR] = 1.16, 95% CI: 1.07–1.25). Unlike participants whose EASIX was in the lowest quartile (Q1), those in other quartiles (Q3/Q4) had an increased likelihood of having a stroke (OR = 1.34, 95% CI: 1.04–1.74; OR = 1.54, 95% CI 1.20–1.96, correspondingly). During a median follow-up of 71 months, Cox regression analysis manifested a positive interplay between EASIX and ACM (HR = 1.30, 95% CI: 1.17–1.44) and CVM (HR = 1.29, 95% CI: 1.06–1.58). The results showcased a non-linear interplay between EASIX and stroke presence and mortality outcomes. Additionally, subgroup analysis indicated no significant interactions between EASIX and any categorical covariates for CVM. Nervelessness, significant interaction effects existed between EASIX and the prevalence of stroke in categorical covariates such as hypertension, diabetes, and coronary heart disease (CHD; P < 0.001), as well as between EASIX and ACM in the categorical covariate of gender (P = 0.03). The ROC curves illustrated that the cutoff value of EASIX for stroke incidence and CVM was 0.56, and 0.58 for ACM, with an AUC of 0.663 (95% CI: 0.649–0.677) for stroke prevalence, as well as for ACM with an AUC of 0.620 (95% CI: 0.595–0.649) and for CVM with an AUC of 0.587 (95% CI: 0.549–0.626). The EASIX demonstrated a positive non-linear association with the prevalence and mortality outcomes amongst individuals at the age of 20 years and older who experienced a stroke, as identified in the NHANES dataset. Heightened EASIX scores were significantly related to an escalated risk of both stroke prevalence and mortality outcomes. Collectively, EASIX may be a valuable biomarker for assessing mortality risks in stroke patients and stroke prevalence. Looking forward, implementing EASIX in primary care settings could facilitate the early screening of endothelial function, thereby identifying high-risk patients and guiding appropriate referrals for specialized medical care. This approach can promote patient outcomes and reduce mortality rates among those who have suffered a stroke. Nevertheless, further validation in diverse countries and among various ethnic groups is necessary.

The Prognostic Calculator Easix Predicts Acute Gvhd, Non-Relapse Mortality and Overall Survival in Adult Patients Undergoing Reduced Intensity Conditioning Allogeneic HCT

ABSTRACTEmerging evidence links the Endothelial Activation and Stress Index (EASIX) and mortality risk in coronary artery disease, but its relevance in hypertensive patients remains unclear. This study examines the association between EASIX and all‐cause and cardiovascular mortality in hypertensive individuals. The analysis included 6138 hypertensive patients from seven National Health and Nutrition Examination Survey (NHNES) cycles (2003–2016), with mortality data obtained from the National Death Index (NDI). Over a median follow‐up of 98 months, 1435 (23.4%) participants died, including 400 (6.5%) from cardiovascular causes. Restricted cubic spline analysis revealed a positive association between EASIX and both all‐cause and cardiovascular mortality. Weighted multivariable Cox regression indicated that each 1‐unit increase in EASIX corresponding to a 25% and 23% rise in mortality risk, respectively. Based on the optimal cutoff value determined using the maximally selected rank statistics method, participants were stratified into higher (>0.79) and lower (≤0.79) EASIX groups. Higher EASIX was significantly associated with increased all‐cause mortality risk (HR 1.46, 95% CI 1.23–1.73, p < 0.0001). Higher EASIX scores were associated with increased cardiovascular mortality, especially in former/current smokers and those with diabetes/prediabetes. Time‐dependent receiver operating characteristic analysis assessed the predictive accuracy of EASIX, yielding area under the curve (AUC) for 1‐, 3‐, 5‐, and 10‐year survival of 0.71, 0.67, 0.67, and 0.67 for all‐cause mortality and 0.79, 0.73, 0.73, and 0.71 for cardiovascular mortality. In conclusion, elevated EASIX is independently associated with increased all‐cause and cardiovascular mortality in hypertensive patients, suggesting its potential as a predictive biomarker in clinical practice.

ResumoFundamento A osteoartrite é um tipo prevalente de artrite caracterizada por alterações degenerativas crônicas no sistema músculo-esquelético, que podem resultar em danos articulares e dor crônica.Objetivo Este estudo investigou as associações entre o índice de ativação e estresse endotelial (EASIX) e o aumento do risco de doença cardiovascular aterosclerótica (DCVA) e mortalidade por todas as causas entre pacientes diagnosticados com osteoartrite.Métodos O estudo de coorte abrangeu 2.028 indivíduos com idades entre 40 e 79 anos com osteoartrite, utilizando dados do banco de dados do National Health and Nutrition Examination Surveys (NHANES) abrangendo os anos de 2007 a 2018. O modelo de regressão logística ponderada univariada e o modelo de Cox ponderado foram estabelecidos, respectivamente, para rastrear possíveis fatores de confusão. Um nível de significância de p < 0,05 foi adotado para todas as análises estatísticas.Resultados O estudo revelou um risco elevado de DCVA em correlação com um log (EASIX) aumentado (razão de chances: 1,94, com intervalo de confiança de 95%: 1,57-2,41). Quando comparados a indivíduos com log (EASIX) < -1,29, aqueles com log (EASIX)>-0,78 demonstraram um risco aumentado de DCVA (razão de chances: 2,31, com intervalo de confiança de 95%: 1,68-3,18). Um valor de log (EASIX) mais alto também foi associado a um risco aumentado de mortalidade por todas as causas (razão de risco: 1,59, com intervalo de confiança de 95%: 1,14-2,23). Entre os indivíduos diagnosticados com osteoartrite, aqueles que apresentaram log (EASIX)>-0,78 apresentaram maior risco de morrer por qualquer causa, em comparação aos pacientes com log (EASIX) <-1,29.Conclusão A presença de um alto índice EASIX foi associada a um risco aumentado de DCVA e mortalidade por todas as causas entre pacientes com osteoartrite.

Osteoarthritis is a prevalent type of arthritis characterized by chronic degenerative changes in the musculoskeletal system, which can result in joint damage and chronic pain. This study was to investigate the associations between the endothelial activation and stress index (EASIX) and the increased risk of atherosclerotic cardiovascular disease (ASCVD) and all-cause mortality among patients diagnosed with osteoarthritis. The cohort study encompassed 2028 individuals aged 40-79 years with osteoarthritis, utilizing data from the National Health and Nutrition Examination Surveys (NHANES) database spanning the years 2007 to 2018. The univariate weighted logistic regression model and weighted Cox model were respectively established to screen possible confounders. A significance level of p < 0.05 was adopted for all statistical analyses. The study revealed an elevated risk of ASCVD in correlation with an increased log (EASIX) (Odds Ratio: 1.94, with 95% Confidence Interval:1.57-2.41). When compared to individuals with log (EASIX)< -1.29, those with a log (EASIX) > -0.78 demonstrated a heightened risk of ASCVD (Odds Ratio: 2.31, with 95% Confidence Interval:1.68-3.18). A higher log (EASIX) value was also linked to an increased risk of mortality from all causes (Hazard Ratio: 1.59, with 95% Confidence Interval:1.14 -2.23). Among individuals diagnosed with osteoarthritis, those exhibiting log (EASIX)> -0.78 faced a greater risk of dying from any cause, as compared to patients with log (EASIX) <-1.29. The presence of a high EASIX index was linked to an increased risk of ASCVD and all-cause mortality among patients with osteoarthritis.

Dynamic Easix Scores Closely Predict Non-Relapse Mortality after Allogeneic Hematopoietic Cell Transplantation

The aim of this study is to assess the associations of urinary genistein and endothelial activation and stress index (EASIX) with 10-year atherosclerotic cardiovascular disease (ASCVD) risk. This cross-sectional analysis employed data obtained from the National Health and Nutrition Examination Survey (NHANES). Weighted univariable and multivariable logistic regression models examined EASIX-ASCVD risk correlations, with odds ratio and 95% confidence interval [OR (95%CI)] as effect measures. The potential interactions were explored between EASIX and genistein on 10-year ASCVD risk using additive and multiplicative interaction analyses. The relationships of EASIX and 10-year ASCVD risk were further assessed at different genistein levels. Subgroup analyses examined age, BMI, diabetes, hypertension, and dyslipidemia categories. Totally, 4478 eligible participants were stratified into low-risk (n = 2157) and high-risk (n = 2321) ASCVD groups. Elevated levels of EASIX (OR = 1.35, 95% CI 1.18-1.54), EASIXmedian ≥ 0.427 (OR = 1.40, 95% CI 1.14-1.73), EASIXRCS ≥ 0.434 (OR = 1.45, 95% CI 1.18-1.77), EASIXquartile (0.325-0.427, OR = 1.48, 95% CI 1.05-2.07; 0.427-0.567, OR = 1.51, 95% CI 1.08-2.10; ≥ 0.567, OR = 2.08, 95% CI 1.57-2.77), and log2(EASIX) (OR = 1.32, 95% CI 1.19-1.46) were associated with higher odds of 10-year ASCVD. Low genistein levels presented no significant correlation with 10-year ASCVD risk. The multiplicative interaction between EASIX and genistein levels was significant. When genistein levels < 54.105µg/g, the connections between elevated EASIX levels and higher 10-year ASCVD risk were established in subgroups of age < 60years, BMI ≥ 25kg/m2, non-diabetes, hypertension, and dyslipidemia. Elevated EASIX levels correlated with a higher 10-year ASCVD risk. Whether genistein modulates this association requires further validation, which may have potential implications for ASCVD prevention strategies in the general population.

Endothelial dysfunction (ED) is a key pathophysiological mechanism in cardiovascular diseases (CVD). The Endothelial Activation and Stress Index (EASIX), derived from routine laboratory markers, has been proposed as a surrogate indicator of endothelial stress. However, its relevance to CVD burden and long-term outcomes in the general population remains uncertain. We analyzed data from 38,713 adults aged ≥20years enrolled in the U.S. National Health and Nutrition Examination Survey (NHANES, 1999-2018), representing approximately 1.7 billion individuals after weighting. EASIX was calculated as [LDH (U/L)×creatinine (mg/dL)] / platelet count (109/L) and log₂-transformed. Weighted logistic regression assessed the association between EASIX and CVD prevalence, while weighted Cox models examined its relationship with all-cause (ACM) and cardiovascular mortality (CVM). Restricted cubic spline analyses evaluated potential nonlinear trends, and subgroup analyses tested effect modification. Among 38,713 participants, 4131 had CVD. Higher EASIX values were independently associated with greater CVD prevalence (adjusted OR=1.43, 95% CI: 1.34-1.53). Each log₂ increase in EASIX corresponded to higher risks of ACM (HR=1.39, 95% CI: 1.28-1.51) and CVM (HR=1.54, 95% CI: 1.38-1.72). Individuals in the top EASIX quartile exhibited more than double the mortality risks compared with those in the lowest quartile. Associations were nonlinear and consistent across most subgroups. EASIX demonstrated independent, nonlinear associations with both CVD prevalence and long-term mortality. These findings highlight EASIX as a practical, cost-efficient biomarker for cardiovascular risk stratification in population settings.

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

ObjectiveTo investigate the association between Endothelial Activation and Stress Index (EASIX) and diabetic retinopathy (DR) among patients with diabetic kidney disease (DKD).MethodsA cross-sectional study was conducted based on the National Health and Nutrition Examination Survey (NHANES) database. Participants were divided into quartiles according to EASIX scores. Survey-weighted generalized linear models (SWGLMs) were used to evaluate the association between EASIX and DR, with restricted cubic spline (RCS) analysis to examine non-linear relationships. Stratified analyses were performed by gender, race, age, Body Mass Index (BMI), smoking status, alcohol consumption, blood pressure, and renal function.ResultsAfter multivariate adjustment, each unit increase in EASIX was associated with a 32% higher risk of DR (OR: 1.32, 95% CI: 1.04–1.69, P = 0.024). In quartile analysis, compared with the first quartile, the fourth quartile showed a trend toward increased DR risk (OR: 1.60, 95% CI: 0.99–2.59, P = 0.054), with a significant dose-response trend (P for trend = 0.040). RCS analysis revealed a significant overall association between EASIX and DR (P for overall < 0.001), while the non-linear association was not significant (P for nonlinear = 0.075). Stratified analyses demonstrated that this association remained consistent across different population characteristics.ConclusionEASIX is significantly associated with DR in DKD patients and may serve as a potential marker for DR risk assessment.

ABSTRACTIntroductionEvidence suggests that the Endothelial Activation and Stress Index (EASIX) predicts mortality in endothelium‐related conditions, but its link to mortality risk in diabetes remains unclear. This study investigates the association between EASIX and mortality risk in diabetes patients.MethodsWe included 3,252 diabetes patients from seven National Health and Nutrition Examination Survey cycles (2003–2016). Mortality data were sourced from National Death Index records. Restricted cubic spline (RCS) regression assessed the EASIX‐mortality risk relationship, while the maximally selected rank statistics method (MSRSM) identified the optimal EASIX cutoff for survival outcomes. Weighted multivariable Cox regression models evaluated the association of EASIX with all‐cause and cardiovascular mortality.ResultsOver a median follow‐up of 91 months, 895 (27.5%) of 3,252 diabetes patients died, including 260 (8.0%) from cardiovascular and 635 (19.5%) from noncardiovascular causes. RCS analysis showed a positive association between EASIX and both all‐cause and cardiovascular mortality. Each one‐unit EASIX increase raised all‐cause and cardiovascular mortality risks by 27% and 24%, respectively. MSRSM classified patients into higher (>0.70) and lower (≤0.70) EASIX groups. Those with higher EASIX had a significantly greater risk of all‐cause (HR 1.56, 95% CI 1.21–2.01) and cardiovascular mortality (HR 2.05, 95% CI 1.33–3.16). Time‐dependent receiver operating characteristic analysis showed AUCs for 1‐, 3‐, 5‐, and 10‐year survival were 0.78, 0.72, 0.70, and 0.69 (all‐cause) and 0.90, 0.81, 0.76, and 0.73 (cardiovascular).ConclusionsElevated EASIX is independently associated with increased all‐cause and cardiovascular mortality in diabetes patients, highlighting its potential as a valuable clinical biomarker.

This study investigated the association between the Endothelial Activation and Stress Index (EASIX) and both the prevalence and mortality of breast cancer (BC). Further, it explored the potential mediating role of the Systemic Inflammation Response Index (SIRI). Data were obtained from the National Health and Nutrition Examination Survey 2001 to 2018. Weighted logistic regression models were used to examine the association between EASIX and BC prevalence, while mediation analysis evaluated the contribution of SIRI. Weighted Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for BC mortality, and Kaplan-Meier curves compared survival across EASIX levels. Restricted cubic spline regression assessed linearity, and subgroup analyses tested consistency across covariates. Among 21,329 participants, 593 BC cases were identified. Each 1-unit increase in EASIX was associated with a 39% higher BC risk (odds ratios [ORs] = 1.39, 95% CI: 1.07-1.82, P = .016). Compared with the lowest tertile (T1), the risk was elevated in T2 (OR = 1.61, 95% CI: 1.15-2.26, P = .006) and markedly higher in T3 (OR = 3.07, 95% CI: 2.28-4.14, P < .001). SIRI showed a modest but significant mediating effect, explaining 2.26% of the association (P = .034). No significant interactions were detected. In Cox models, each 1-standard deviation increase in EASIX was associated with a 56% higher risk of all-cause mortality (HR = 1.56, 95% CI: 1.47-1.65, P < .001) and a 104% higher risk among BC patients (HR = 2.04, 95% CI: 1.40-2.98, P < .001). Compared with T1, all-cause mortality increased by 59% in T2 (HR = 1.59) and more than 3-fold in T3 (HR = 3.11). BC-specific mortality was also higher in T3 (HR = 1.16, 95% CI: 1.05-1.27, P = .012). Restricted cubic spline analyses confirmed a linear positive association between EASIX and both BC prevalence and mortality. Elevated EASIX was significantly associated with higher BC prevalence and mortality, partly mediated by systemic inflammation. EASIX may serve as a valuable biomarker for risk assessment and prognosis in BC.

This study aimed to explore the association between the ratio of 4-pyridoxine (4-PA) to pyridoxal 5'-phosphate (PLP) (4-PA/PLP) and diabetic retinopathy (DR) and further assess the mediating effect of Endothelial Activation and Stress Index (EASIX) on the association between 4-PA/PLP and DR. In this cross-sectional study, 1,698 patients with diabetes from the National Health and Nutrition Examination Survey were included. According to the median, 4-PA/PLP was categorized into a high-level group (≥0.89) and a low-level group (<0.89). As the EASIX had a skewed distribution, it was log-transformed before analysis. Weighted logistic regression models were used to investigate the association of 4-PA/PLP with EASIX and DR and the mediating effect of EASIX on the association between 4-PA/PLP and DR. The distribution-of-product method was adopted to assess the mediating effect. Subgroup analysis was performed based on the age and duration of diabetes. A total of 362 diabetic patients were classified as having DR. After adjusting for all covariates, a higher level of 4-PA/PLP was associated with an increased level of log EASIX [odds ratio (OR) = 1.56, 95% confidence interval (CI): 1.06-2.30]. A higher ratio of 4-PA/PLP was associated with increased odds of DR compared to the reference group with lower levels of 4-PA/PLP (OR = 1.94, 95%CI: 1.40-2.67). In addition, we found that log EASIX may play a mediating role in the 4-PA/PLP and DR, with a 95% CI of distribution of product of 0.31 (95% CI: 0.02-0.67). The proportion of mediation was 69.06%. The mediating effect of log EASIX was also observed in individuals with diabetes who were aged≥60 years (proportion of mediation: 50.63%) or had a duration of diabetes ≥10 years (proportion of mediation: 71.83%). This study found a positive association between high levels of 4-PA/PLP and an increased risk of DR, with the relationship being partially mediated by log EASIX.