Increased risk of major adverse cardiovascular events in patients with deep and infected diabetes-related foot ulcers.

Aims/hypothesis: Diabetes-related foot ulceration (DFU) is associated with increased cardiovascular risk, but the mechanisms remain unclear. Inflammation and infection are mediators of CVD, which may be important in DFU.

Methods: Prospectively collected data from patients attending a multidisciplinary DFU service were analysed. A deep ulcer was defined as one that reached muscle, tendon or deeper structures. Patients were categorised into four DFU groups: not deep and no infection (D-/I-), not deep but infected (D-/I+), deep with no infection (D+/I-) or deep with infection (D+/I+). Incident major adverse cardiovascular events (MACE) were defined as hospitalisation for myocardial infarction, stroke or transient ischaemic attack, or heart failure. Survival analyses were performed using the logrank test and multivariate Cox regression.

Results: Of 513 patients, 241 (47.0%) were in the D-/I- group, 110 (21.4%) were in the D-/I+ group, 35 (6.8%) were in the D+/I- group and 127 (24.8%) were in the D+/I+ group. MACE or all-cause mortality occurred in 75 patients (14.6%), and MACE alone occurred in 46 patients (9.0%) after median follow-up of 381 days (IQR 220-551) and 404 days (IQR 228-576), respectively. Infection was associated with significantly higher MACE or all-cause mortality (21.5% vs 8.7%; p<0.001) and MACE alone (13.5% vs 5.1%; p=0.003). MACE or all-cause mortality was significantly higher in the D+/I+ group (D-/I- 7.9%; D-/I+ 15.5%; D+/I- 14.3%; D+/I+ 26.8%; p<0.001), as was MACE alone (D-/I- 5.0%; D-/I+ 10.9%; D+/I- 5.7%; D+/I+ 15.7%; p=0.017). Infection and a deep ulcer were independent predictors of adverse outcomes.

Conclusions/interpretation: Deep and/or infected DFUs are associated with increased cardiovascular risk compared with DFUs that are not deep or infected. These findings provide a potential mechanistic explanation that requires investigation.