Circulating acetoacetate is associated with poor prognosis in heart failure patients

Abstract

Background: Acetoacetate is used as an alternative energy source in the heart, and has the potential to improve cardiac function. However, the prognostic impact of acetoacetate has not been investigated in heart failure. Methods: This study enrolled consecutive 615 hospitalized patients with heart failure. We investigated the associations between circulating acetoacetate and clinical characteristics or prognosis in HF patients. Results: We divided the patients into two groups based on circulating acetoacetate levels (high group: acetoacetate ≥35 µmoL/L, n = 313; and low group: acetoacetate <35 µmoL/L, n = 302). The high group had an older age (68 vs. 65 years, P = 0.003) and higher log brain natriuretic peptide levels (2.43 vs. 2.23, P < 0.001) compared with the low group. In contrast, there were no significant differences in the prevalence of co-morbidities, including diabetes mellitus, chronic kidney disease, and anemia, between the two groups. During the median follow-up period of 328 days, 66 all-cause deaths occurred. The high group had a worse prognosis compared with the low group (Log rank, P = 0.041). In the Cox proportional hazard analysis, circulating acetoacetate levels (per 10 µmoL/L increase) were associated with all-cause mortality (hazard ratio 1.020, 95% confidence interval 1.010–1.030, P < 0.001). Conclusions: Circulating acetoacetate is associated with all-cause mortality in patients with heart failure. These results provide new insights into the role of alternative cardiac metabolism in heart failure patients, and raise the possibility of acetoacetate as a novel biomarker to predict the prognosis of heart failure patients. Keywords: Acetoacetate, Ketone body, Metabolism, Heart failure, Prognosis