The association of ulceration of the foot with cardiovascular and all-cause mortality in patients with diabetes: a meta-analysis.

Aims/hypothesis: It is well established that diabetes mellitus increases the risk of cardiovascular disease (CVD) and all-cause mortality. Observational studies suggest that a history of diabetic foot ulceration (DFU) may increase this risk further still. We sought to determine to what extent DFU is associated with excess risk over and above diabetes.
Methods: We identified studies reporting on associations of DFU with CVD and all-cause mortality. We obtained data on incident events of all-cause mortality, fatal myocardial infarction and fatal stroke. Study-specific estimates were pooled using a random-effects meta-analysis and the statistical heterogeneity of included studies was assessed using the I (2) statistic.
Results: The eight studies included reported on 3,619 events of all-cause mortality during 81,116 person-years of follow-up. DFU was associated with an increased risk of all-cause mortality (RR 1.89, 95% CI 1.60, 2.23), fatal myocardial infarction (2.22, 95% CI 1.09, 4.53) and fatal stroke (1.41, 95% CI 0.61, 3.24). CVD mortality accounted for a similar proportion of deaths in DFU and non-DFU patients.
Conclusions/interpretation: Patients with DFU have an excess risk of all-cause mortality, compared with patients with diabetes without a history of DFU. This risk is attributable, in part, to a greater burden of CVD. If this result is validated in other studies, strategies should evaluate the role of further aggressive CVD risk modification and ulcer prevention in those with DFU.