Oxidized HDL Increase Risk of Heart Failure with Preserved Ejection Fraction: Study

A recent study published in the Clinical Research in Cardiology journal linked impaired high-density lipoprotein (HDL) function to an increased risk of heart failure with preserved ejection fraction (HFpEF). The study highlights the critical role of oxidative stress and inflammation in the pathophysiology of HFpEF by emphasizing the significance of oxidized HDL (nHDLox).

This research analyzed the HDL antioxidant function in 366 patients with suspected heart failure, including 88 diagnosed with HFpEF. The antioxidant function of HDL was assessed using a validated cell-free biochemical assay. By measuring the lipid peroxide content of HDL (HDLox) normalized by HDL cholesterol levels (HDL-C) and comparing it with control values from healthy participants, this study identified a clear association between increased nHDLox levels and HFpEF.

The key findings revealed that patients with HFpEF had, on average, 15% higher levels of nHDLox when compared to participants without heart failure. These elevated levels of oxidized HDL suggest diminished antioxidant function in HFpEF patients. Also, even after adjusting for variables like age, sex, kidney function, diabetes, hypertension, atrial fibrillation, and other cardiovascular risk factors, nHDLox remained an independent predictor of HFpEF.

Every standard deviation (SD) increase in nHDLox was associated with a 67% greater risk of HFpEF when compared to the individuals without heart failure. These findings underline the potential of nHDLox as a biomarker for early detection of HFpEF and emphasize its importance in guiding future therapeutic strategies.

HFpEF, is a heterogeneous clinical syndrome with limited treatment options. Current approaches primarily focus on symptom management rather than targeting the underlying causes. The discovery of impaired HDL antioxidant function as a risk factor opens new avenues for addressing HFpEF through early intervention.

Overall, the findings of this research suggest that restoring or improving HDL function could serve as a promising therapeutic target. Strategies to reduce oxidative stress and inflammation may hold the key to reduce the progression of HFpEF. While further studies and trials are needed to explore the mechanisms and treatment possibilities, this research provides a significant step forward in understanding the complex biology of heart failure.

Reference:

Sasko, B., Kelesidis, T., Kostin, S., Scharow, L., Mueller, R., Jaensch, M., Wintrich, J., Christ, M., Ritter, O., Ukena, C., & Pagonas, N. (2025). Reduced antioxidant high-density lipoprotein function in heart failure with preserved ejection fraction. Clinical Research in Cardiology: Official Journal of the German Cardiac Society. https://doi.org/10.1007/s00392-024-02583-3