Female disadvantage in risk of adverse outcomes after incident diabetic foot hospitalizations: A population cohort study.

BACKGROUND Diabetic foot disease (DFD) is more prevalent among males and is associated with an excess-risk of cardiovascular events or mortality. AIMS This study explores the risk of next cardiovascular events, renal failure and all-cause mortality after incident DFD hospitalizations, separately in males and females to detect any gender difference in a cohort of 322,140 persons with diabetes retrospectively followed-up through administrative data-sources in Tuscany, Italy over years 2011-2018. METHODS The hazard ratio (HR) for incident adverse outcomes after first hospitalizations for DFD categorized as: major/minor amputations (No.=449;3.89%), lower limbs' revascularizations (LLR: No.=2854;24.75%) and lower-extremity-arterial-disease (LEAD) with no procedures (LEAD-no proc: No.=6282;54.49%), was compared to risk of patients with background-DFD (ulcers, infections, Charcot-neuroarthropathy: No.=1,944;16.86%). RESULTS DFD incidence-rate was higher among males compared to females [1.57(95% CI:1.54-1.61) vs. 0.97(0.94-1.00)/100,000p-years]. After DFD the overall risk of coronary artery disease was significantly associated to male gender and that of stroke to female gender. LEAD-no proc and LLR were associated with risk of stroke risk only in females and with coronary artery disease at a significantly higher extent among women. Incident renal failure was not associated with any DFD category. Amputations and LEAD-no proc, significantly predicted mortality risk only in females while LLR reduced such risk in both genders. Females had a greater risk of composite outcome (death or cardiovascular events). When compared with background-DFD the risk was by 34% higher after amputations [HR: 1.34(1.04-1.72)] and by 10% higher after LEAD-no proc: [HR:1.10(1.03-1.18)] for LEAD-no proc, overall confirming that after incident DFD more strictly associated with vascular pathogenesis females are burdened by a greater excess-risk of adverse events. CONCLUSIONS After incident DFD hospitalizations, females with DFD associated with amputations or with arterial disease are burdened by a greater excess risk of subsequent adverse cardiovascular events, compared with those with background DFD.