Association of Endothelial Activation and Stress Index (EASIX) with long-term mortality in type 2 diabetes patients with coronary heart disease: A prospective national cohort study.
Elevated EASIX levels are independently associated with higher all-cause and cardiovascular mortality in patients with T2DM and CHD, and its inclusion in risk assessment protocols enhances the predictive value for long-term clinical outcomes.
Key Findings
Results
Higher EASIX quartile was significantly associated with increased all-cause mortality in patients with T2DM and CHD.
In fully adjusted models, the highest EASIX quartile had a hazard ratio of 1.93 (95% CI = 1.48–2.50) for all-cause mortality compared with the lowest quartile.
During a median follow-up of 111 months, 617 all-cause deaths occurred among 909 participants.
Study used multivariable Cox regression to assess the association between EASIX and all-cause mortality.
The study population was drawn from the National Health and Nutrition Examination Survey (NHANES) 1999–2010, followed until 2019.
Results
Higher EASIX quartile was significantly associated with increased cardiovascular mortality in patients with T2DM and CHD.
In fully adjusted models, the highest EASIX quartile had a subdistribution hazard ratio of 1.56 (95% CI = 1.05–2.33) for cardiovascular mortality compared with the lowest quartile.
251 cardiovascular deaths occurred during the median follow-up of 111 months.
Fine-Gray competing-risk models were used to assess the association between EASIX and cardiovascular mortality.
Cardiovascular mortality was analyzed as a competing-risk outcome to account for non-cardiovascular deaths.
Results
Restricted cubic spline analysis revealed a significant nonlinear positive relationship between EASIX and mortality.
The relationship between EASIX and both all-cause and cardiovascular mortality was nonlinear and positive.
Restricted cubic spline analysis was used to model the dose-response relationship between EASIX levels and mortality outcomes.
The nonlinear association was statistically significant for both outcomes.
Results
Adding EASIX to a base risk model significantly improved prognostic accuracy for both all-cause and cardiovascular mortality.
The base model consisted of age, HbA1c, and estimated glomerular filtration rate (eGFR).
Adding EASIX to the base model significantly improved the time-dependent C-statistic, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) for both outcomes.
All improvements in model performance metrics were statistically significant (all P < .001).
Time-dependent C-statistic, NRI, and IDI were used to evaluate incremental prognostic value.
Methods
EASIX was calculated as a composite biomarker using lactate dehydrogenase, creatinine, and platelet count.
EASIX incorporates three routinely measured clinical laboratory values: lactate dehydrogenase, creatinine, and platelet count.
EASIX is described as a 'novel composite biomarker' for endothelial activation and stress.
The study analyzed 909 participants with both T2DM and CHD from NHANES 1999–2010.
Endothelial dysfunction is described as prevalent in T2DM with CHD, increasing cardiovascular risk.
Results
The study population experienced high long-term mortality, with the majority of participants dying during follow-up.
909 participants with T2DM and CHD were followed for a median of 111 months (approximately 9.25 years).
617 all-cause deaths and 251 cardiovascular deaths occurred during follow-up.
617 of 909 participants (approximately 68%) died from any cause during the follow-up period.
Participants were drawn from a prospective national cohort (NHANES 1999–2010), followed through 2019.
What This Means
This research suggests that a blood-based score called EASIX — calculated from three routine lab values (lactate dehydrogenase, creatinine, and platelet count) — can help predict the risk of death in people who have both type 2 diabetes and coronary heart disease. Using data from nearly 910 Americans followed for about nine years on average, researchers found that people with the highest EASIX scores were roughly twice as likely to die from any cause and about 1.5 times as likely to die from a cardiovascular cause compared to those with the lowest scores, even after accounting for other health factors.
The relationship between EASIX and mortality was not simply linear — risk increased in a curved, nonlinear pattern as EASIX rose. Importantly, when EASIX was added to a standard risk model that already included age, blood sugar control (HbA1c), and kidney function (eGFR), the model became meaningfully better at predicting who would die and from what cause. All improvements in prediction were highly statistically significant.
This research suggests that EASIX, which reflects how stressed and activated the lining of blood vessels is, could be a useful and inexpensive addition to routine risk assessment for people living with both diabetes and heart disease. Because it relies on tests already commonly ordered in clinical practice, it could potentially be incorporated into existing care without additional costs or procedures. However, further research in other populations and clinical settings would be needed before widespread adoption.
Liu C, Zhang D, Zhu W, Fan K. (2026). Association of Endothelial Activation and Stress Index (EASIX) with long-term mortality in type 2 diabetes patients with coronary heart disease: A prospective national cohort study.. Medicine. https://doi.org/10.1097/MD.0000000000051166