Authors: Mark Zwerus; Cees J. Tack; Jeannette Roeleveld; Rene Ottens; Famke Wagenaar; Steven Teerenstra; Teba Alnima; Radboud University Medical Centre
Background: Diabetes-related foot ulcers (DFUs) are associated with increased cardiovascular risk and mortality. This study aims to assess the risk of major adverse cardiovascular events (MACE) and mortality in patients with an active diabetic foot ulcer and the impact of selected risk factors, including healing time.
Methods: Retrospectively collected data from patients attending the multidisciplinary DFU unit of the Radboud University Medical Centre with a new DFU between January 2022 and January 2025 and a follow-up of at least 3 months were analysed. Logrank tests with Kaplan-Meier curves and multivariate Cox regressions were performed to explore risk factors for mortality, MACE and healing time.
Results: 174 people were included with a median healing time of 15 weeks (IQR 6-25). Mortality occurred in 38 patients (21%) of which 15 patients during an active ulcer (8,8%; relative risk 39,5%). Mortality was significant higher in patients with an active DFU (HR 5,76; 95% CI 2.68, 12.36; p<0,001), peripheral artery disease (HR 1,30; 95% CI 1.12, 1.79; p=0,013), MACE during follow-up (HR 1,39; 95% CI 1.20, 1,76; p=0,005) and hospitalization due to infection (HR 1,45; 95% CI 1.23, 1,87; p=0,017). MACE occurred in 34 patients (19,5%) of which 16 patients during the active phase of DFU (9,1%; relative risk 47,1%). Having a medical history of prior cardiovascular event was significantly associated with developing MACE during follow-up (HR 1,21; 95% CI 1.06, 1.69; p=0,011). Healing time was significantly prolonged in patients with hindfoot ulcers (HR 1,82; 95% CI 1.08, 3.06; p=0,024) and (neuro)ischemic ulcers (HR 2,47; 95% CI 1.66, 3,70; p=<0,001), contributing to the effect of peripheral artery disease (HR 1,66; 95% CI 1.08, 2,56; p=0,019).
Discussion/Conclusion: Cardiovascular morbidity and mortality is increased in patients with a DFU, but it seems even higher during the active phase of a foot ulcer. Ulcers on the hindfoot and neuro-ischemic ulcers are associated with prolonged healing time.