Circulating Human Epididymis Protein 4 Predicts 10-Year Mortality and Major Adverse Cardiovascular Events in Patients With Peripheral Artery Disease.
A, M., C, H., K, G., EM, B., L, S., JF, D., R, M., CH, S., H, D., & A, L. (2026). Circulating Human Epididymis Protein 4 Predicts 10-Year Mortality and Major Adverse Cardiovascular Events in Patients With Peripheral Artery Disease.. European journal of clinical investigation. https://doi.org/10.1111/eci.70236
A M, C H, K G, EM B, L S, JF D, et al. Circulating Human Epididymis Protein 4 Predicts 10-Year Mortality and Major Adverse Cardiovascular Events in Patients With Peripheral Artery Disease.. European journal of clinical investigation. 2026; doi: 10.1111/eci.70236
A M, C H, K G, et al. Circulating Human Epididymis Protein 4 Predicts 10-Year Mortality and Major Adverse Cardiovascular Events in Patients With Peripheral Artery Disease.[J]. European journal of clinical investigation. 2026. DOI: 10.1111/eci.70236.
@article{a2026,
author = {Muendlein A and Heinzle C and Geiger K and Brandtner EM and Schnetzer L and Dopheide JF and Mathies R and Saely CH and Drexel H and Leiherer A},
title = {Circulating Human Epididymis Protein 4 Predicts 10-Year Mortality and Major Adverse Cardiovascular Events in Patients With Peripheral Artery Disease.},
journal = {European journal of clinical investigation},
year = {2026},
doi = {10.1111/eci.70236},
note = {PMID: 42227653},
}
TY - JOUR AU - Muendlein A AU - Heinzle C AU - Geiger K AU - Brandtner EM AU - Schnetzer L AU - Dopheide JF AU - Mathies R AU - Saely CH AU - Drexel H AU - Leiherer A TI - Circulating Human Epididymis Protein 4 Predicts 10-Year Mortality and Major Adverse Cardiovascular Events in Patients With Peripheral Artery Disease. T2 - European journal of clinical investigation PY - 2026 DO - 10.1111/eci.70236 AN - PMID:42227653 ER -
BACKGROUND: Human epididymis protein 4 (HE4) has emerged as a biomarker linked to fibrosis and cardiovascular disease. However, its prognostic relevance in peripheral artery disease (PAD) remains unclear. We therefore investigated the association of circulating HE4 with long-term outcomes in patients with PAD. METHODS: In this prospective cohort study, 291 patients with symptomatic PAD were enrolled and followed for 10 years. Serum HE4 concentrations were measured by ELISA at baseline. Primary endpoints were all-cause mortality and major adverse cardiovascular events (MACE); secondary endpoints were cardiovascular and non-cardiovascular mortality. RESULTS: During follow-up, 44.7% of patients died and 41.2% experienced MACE. In univariable models, higher HE4 levels were associated with all-cause mortality and MACE. These associations remained significant after adjustment for established cardiovascular risk factors and renal function: HR 1.35 (95% CI 1.14-1.58; p < 0.001) for all-cause mortality and HR 1.24 (95% CI 1.05-1.46; p = 0.010) for MACE per doubling of HE4. In secondary analyses, HE4 was independently associated with both cardiovascular and non-cardiovascular mortality. Addition of HE4 to established risk factors significantly improved risk discrimination and reclassification for all-cause mortality (NRI = 0.412, p < 0.001; IDI = 0.028, p = 0.004), whereas incremental prognostic value for MACE was not statistically significant. CONCLUSION: Circulating HE4 is a robust and independent predictor of long-term mortality and MACE in patients with PAD, with incremental prognostic value for mortality, primarily in terms of risk reclassification.