# Potential causes and significance of elevated blood ketone levels in patients with heart failure with preserved ejection fraction

## TL;DR

Elevated blood ketones in heart failure patients may indicate metabolic issues and could help improve diagnosis when combined with other markers.

## Contribution

The study identifies blood ketones as a potential diagnostic indicator in heart failure with preserved ejection fraction.

## Key findings

- HFpEF patients had higher acetoacetate levels associated with BMI and blood pressure.
- Combining acetoacetate and NT-proBNP improved diagnostic accuracy (AUC = 0.9117).
- Ketone levels showed no correlation with NYHA functional class in HFpEF patients.

## Abstract

The diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging. Given the critical role of metabolic disturbance and energy expenditure in HFpEF pathophysiology, we investigated the clinical significance and diagnostic value of blood ketone bodies in these patients.

This case–control study enrolled 160 participants, comprising 80 HFpEF patients and 80 matched healthy controls. Baseline characteristics, levels of blood ketones (acetoacetate, β-hydroxybutyrate, acetone), and NT-proBNP were compared. Multivariate linear regression and correlation analyses were employed to assess the associations between ketone levels, clinical parameters, and NT-proBNP. The diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis.

Compared to controls, HFpEF patients showed significant differences in age, heart rate, BMI, and blood pressure. Multivariate regression revealed a significant linear association between BMI, systolic blood pressure, and acetoacetate levels in the HFpEF group. A weak inverse correlation was found between acetoacetate and NT-proBNP levels. However, no correlation was observed between ketone levels and NYHA functional class. ROC analysis demonstrated that the combination of acetoacetate and NT-proBNP yielded the highest diagnostic efficacy (AUC = 0.9117), superior to NT-proBNP alone (AUC = 0.8328) or any ketone body alone.

Unlike nutritional ketosis, elevated blood ketone levels in patients with HFpEF likely reflect impaired metabolic efficiency rather than a marker of cardiac function. Nevertheless, this phenomenon has diagnostic significance: combining acetoacetate with NT-proBNP can markedly improve diagnostic performance.