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Updated: Jun 16, 2025

Author Spotlight: Exploring the Relationship Between Lipotoxicity and HFpEF
Published on: March 29, 2024
Low LCAT activity is linked to acute decompensated heart failure and mortality in patients with CKD
Julia T Stadler1, Thomas Bärnthaler1, Andrea Borenich2
1Division of Pharmacology, Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Medical University of Graz, Graz, Austria.
Insights
Low lecithin-cholesterol acyltransferase (LCAT) activity in chronic kidney disease (CKD) patients is linked to higher mortality and heart failure risk. This finding highlights LCAT
Area of Science:
- Nephrology
- Cardiology
- Biochemistry
Background:
- Chronic kidney disease (CKD) is associated with reduced lecithin-cholesterol acyltransferase (LCAT) activity.
- Decreased LCAT activity may increase cardiovascular mortality risk in CKD patients.
- LCAT is crucial for high-density lipoprotein (HDL) maturation.
Purpose of the Study:
- To investigate the association between LCAT activity and adverse outcomes in non-dialysis CKD patients.
- To explore the relationship between LCAT activity, HDL particle size, and cardiovascular risk.
Main Methods:
- Serum LCAT activity and lipoprotein profiles were measured in 453 non-dialysis CKD patients.
- Nuclear magnetic resonance spectroscopy was used to characterize lipoprotein profiles.
- Patients were followed for a mean of 5.0 ± 2.2 years for adverse outcomes.
Main Results:
- LCAT activity positively correlated with smaller HDL particle size, suggesting a protective role.
- Lower baseline LCAT activity was independently associated with increased risk of all-cause mortality (HR 0.62) and acute decompensated heart failure (ADHF) (HR 0.67).
- LCAT activity was not significantly associated with atherosclerotic events or kidney function decline.
Conclusions:
- Reduced LCAT activity is an independent predictor of mortality and ADHF in CKD patients.
- LCAT activity is linked to HDL subclasses that may offer cardiovascular protection.
- Targeting LCAT activity could be a potential therapeutic strategy in CKD management.
Abstract:
Chronic kidney disease (CKD) is often associated with decreased activity of lecithin-cholesterol acyltransferase (LCAT), an enzyme essential for HDL maturation. This reduction in LCAT activity may potentially contribute to an increased risk of cardiovascular mortality in patients with CKD. The objective of this study was to investigate the association between LCAT activity in patients with CKD and the risk of adverse outcomes. We measured serum LCAT activity and characterized lipoprotein profiles using nuclear magnetic resonance spectroscopy in 453 non-dialysis CKD patients from the CARE FOR HOMe study. LCAT activity correlated directly with smaller HDL particle size, a type of HDL potentially linked to greater cardiovascular protection. Over a mean follow-up of 5.0 ± 2.2 years, baseline LCAT activity was inversely associated with risk of death (standardized HR 0.62, 95% CI 0.50-0.76; P < 0.001) and acute decompensated heart failure (ADHF) (standardized HR 0.67, 95% CI 0.52-0.85; P = 0.001). These associations remained significant even after adjusting for other risk factors. Interestingly, LCAT activity was not associated with the incidence of atherosclerotic cardiovascular events or kidney function decline during the follow-up. To conclude, our findings demonstrate that low LCAT activity is independently associated with all-cause mortality and ADHF in patients with CKD, and is directly linked to smaller, potentially more protective HDL subclasses.
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