Pre-diabetes is associated with increased cardiac events in cancer patients prescribed anthracyclines

Abstract

Abstract Background Pre-diabetes, a precedent of overt diabetes and metabolic disorder, is a known risk factor for adverse cardiovascular outcomes. Its impact on adverse cardiovascular outcomes in cancer patients prescribed anthracycline-containing chemotherapy (ACT) is uncertain. Objective To evaluate the association of pre-diabetes with cardiovascular events in cancer patients prescribed ACT. Methods We included cancer patients treated with ACT from 2000-2019, drawn from a previously validated territory-wide database. Patients were subsequently divided into diabetes, pre-diabetes, and normoglycaemia groups based on their baseline glycaemic profile. The primary outcome, major adverse cardiovascular events (MACE), was defined as a composite of hospitalization for heart failure and cardiovascular death. Results Among 12649 patients treated with ACT (55.5% male, median age 62 years), 3997 had pre-diabetes at baseline and 5622 had diabetes. Over a median follow-up of 8.7 years, the incidence of MACE was 211 (7.0%) in the normoglycaemia group, 358 (9.0%) in the pre-diabetes group, and 728 (12.9%) in the diabetes group. Compared with the normoglycaemia group, both pre-diabetes (adjusted hazard ratio [HR] = 1.20, 95% confidence interval [CI] 1.01-1.43) and diabetes (adjusted HR = 1.46, 95% CI 1.24-1.70) were associated with an increased risk of MACE. In the pre-diabetes group, 475 (18%) patients progressed to overt diabetes and exhibited a greater risk of MACE (adjusted HR = 1.76, 95% CI 1.31-2.36) than those who remained prediabetic. Conclusions In cancer patients treated with ACT, pre-diabetes at baseline, and those who progressed to diabetes at follow-up, had an increased risk of MACE. Our findings reveal that pre-diabetes is a key predictor and potential treatment target to reduce the risk of MACE in patients prescribed ACT.