Association between the Endothelial Activation and Stress Index (EASIX) and all-cause and cardiovascular mortality in patients with diabetes and prediabetes
Abstract Background Vascular 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 dehyd...
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BMC
2025-08-01
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| Series: | European Journal of Medical Research |
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| Online Access: | https://doi.org/10.1186/s40001-025-03009-0 |
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| author | Enfa Zhao Yiqing Chen Hang Xie Ruimeng Wang Yuan Gao Bingtian Dong Chaoxue Zhang |
| author_facet | Enfa Zhao Yiqing Chen Hang Xie Ruimeng Wang Yuan Gao Bingtian Dong Chaoxue Zhang |
| author_sort | Enfa Zhao |
| collection | DOAJ |
| description | Abstract Background Vascular 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. Methods The 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. Results During 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). Conclusion EASIX 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. |
| format | Article |
| id | doaj-art-e7b9d25b0bcb450f982ea1d90a79e8d3 |
| institution | Kabale University |
| issn | 2047-783X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj-art-e7b9d25b0bcb450f982ea1d90a79e8d32025-08-20T03:42:27ZengBMCEuropean Journal of Medical Research2047-783X2025-08-0130111210.1186/s40001-025-03009-0Association between the Endothelial Activation and Stress Index (EASIX) and all-cause and cardiovascular mortality in patients with diabetes and prediabetesEnfa Zhao0Yiqing Chen1Hang Xie2Ruimeng Wang3Yuan Gao4Bingtian Dong5Chaoxue Zhang6Department of Ultrasound, the First Affiliated Hospital of Anhui Medical UniversityDepartment of Endocrinology, the First Affiliated Hospital of Anhui Medical UniversityDepartment of Cardiovascular Medicine, The First Affiliated Hospital of Xi’an Jiaotong UniversitySecond Clinical Medical College, Anhui Medical UniversityDepartment of Ultrasound, the First Affiliated Hospital of Anhui Medical UniversityDepartment of Ultrasound, the First Affiliated Hospital of Anhui Medical UniversityDepartment of Ultrasound, the First Affiliated Hospital of Anhui Medical UniversityAbstract Background Vascular 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. Methods The 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. Results During 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). Conclusion EASIX 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.https://doi.org/10.1186/s40001-025-03009-0Endothelial Activation and Stress IndexAll-cause mortalityCardiovascular mortalityDiabetesPrediabetes |
| spellingShingle | Enfa Zhao Yiqing Chen Hang Xie Ruimeng Wang Yuan Gao Bingtian Dong Chaoxue Zhang Association between the Endothelial Activation and Stress Index (EASIX) and all-cause and cardiovascular mortality in patients with diabetes and prediabetes European Journal of Medical Research Endothelial Activation and Stress Index All-cause mortality Cardiovascular mortality Diabetes Prediabetes |
| title | Association between the Endothelial Activation and Stress Index (EASIX) and all-cause and cardiovascular mortality in patients with diabetes and prediabetes |
| title_full | Association between the Endothelial Activation and Stress Index (EASIX) and all-cause and cardiovascular mortality in patients with diabetes and prediabetes |
| title_fullStr | Association between the Endothelial Activation and Stress Index (EASIX) and all-cause and cardiovascular mortality in patients with diabetes and prediabetes |
| title_full_unstemmed | Association between the Endothelial Activation and Stress Index (EASIX) and all-cause and cardiovascular mortality in patients with diabetes and prediabetes |
| title_short | Association between the Endothelial Activation and Stress Index (EASIX) and all-cause and cardiovascular mortality in patients with diabetes and prediabetes |
| title_sort | association between the endothelial activation and stress index easix and all cause and cardiovascular mortality in patients with diabetes and prediabetes |
| topic | Endothelial Activation and Stress Index All-cause mortality Cardiovascular mortality Diabetes Prediabetes |
| url | https://doi.org/10.1186/s40001-025-03009-0 |
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