TY - JOUR
T1 - Impaired high-density lipoprotein function in patients with heart failure
AU - Emmens, Johanna E.
AU - Jia, Congzhuo
AU - Ng, Leong L.
AU - van Veldhuisen, Dirk J.
AU - Dickstein, Kenneth
AU - Anker, Stefan D.
AU - Lang, Chim C.
AU - Cleland, John G. F.
AU - Voors, Adriaan A.
AU - de Boer, Rudolf A.
AU - Tietge, Uwe J. F.
N1 - Funding Information:
This work was supported by the European Commission [FP7-242209-BIOSTAT-CHF; EudraCT 2010-020808-29].
Funding Information:
Dr Jia was supported by a fellowship from the Chinese Scholarship Council. SDA reports receiving fees from Bayer, Boehringer Ingelheim, Cardiac Dimension, Impulse Dynamics, Novartis, Servier, St. Jude Medical, and Vifor Pharma; and grant support from Abbott Vascular and Vifor Pharma. Dr Lang received consultancy fees or research grants from Amgen, Applied Therapeutics, Astra Zenenca, Boehringher Ingelheim, MSD, and Novartis. Dr Filippatos participated in committees of trials and registries sponsored by Novartis, Servier, Bayer, BI, Vifor, and Medtronic. Dr Voors received consultancy fees or research grants from Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, GSK, Merck, Myokardia, Novartis, Roche Diagnostics, and Servier. Dr de Boer received speaker fees from Abbott, AstraZeneca, Novartis, and Roche. Dr Tietge received consultancy fees from AstraZeneca. The University Medical Center Groningen, which employs several of the authors, has received research grants or fees from AstraZeneca, Abbott, Bristol-Myers Squibb, Novartis, Novo Nordisk, and Roche. The remaining authors have no disclosures to report.
Publisher Copyright:
© 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
PY - 2021/5/4
Y1 - 2021/5/4
N2 - Background: We recently showed that, in patients with heart failure, lower high-density lipoprotein (HDL) cholesterol concentration was a strong predictor of death or hospitalization for heart failure. In a follow-up study, we suggested that this association could be partly explained by HDL proteome composition. However, whether the emerging concept of HDL function contributes to the prognosis of patients with heart failure has not been addressed.Methods and Results: We measured 3 key protective HDL function metrics, namely, cholesterol efflux, antioxidative capacity, and anti-inflammatory capacity, at baseline and after 9 months in 446 randomly selected patients with heart failure from BIOSTAT-CHF (A Systems Biology Study to Tailored Treatment in Chronic Heart Failure). Additionally, the relationship between HDL functionality and HDL proteome composition was determined in 86 patients with heart failure. From baseline to 9 months, HDL cholesterol concentrations were unchanged, but HDL cholesterol efflux and anti-inflammatory capacity declined (both P<0.001). In contrast, antioxidative capacity increased (P<0.001). Higher HDL cholesterol efflux was associated with lower mortality after adjusting for BIOSTAT-CHF risk models and log HDL cholesterol (hazard ratio, 0.81; 95% CI, 0.71-0.92; P=0.001). Other functionality measures were not associated with outcome. Several HDL proteins correlated with HDL functionality, mainly with cholesterol efflux. Apolipoprotein A1 emerged as the main protein associated with all 3 HDL functionality measures.Conclusions: Better HDL cholesterol efflux at baseline was associated with lower mortality during follow-up, independent of HDL cholesterol. HDL cholesterol efflux and anti-inflammatory capacity declined during follow-up in patients with heart failure. Measures of HDL function may provide clinical information in addition to HDL cholesterol concentration in patients with heart failure.
AB - Background: We recently showed that, in patients with heart failure, lower high-density lipoprotein (HDL) cholesterol concentration was a strong predictor of death or hospitalization for heart failure. In a follow-up study, we suggested that this association could be partly explained by HDL proteome composition. However, whether the emerging concept of HDL function contributes to the prognosis of patients with heart failure has not been addressed.Methods and Results: We measured 3 key protective HDL function metrics, namely, cholesterol efflux, antioxidative capacity, and anti-inflammatory capacity, at baseline and after 9 months in 446 randomly selected patients with heart failure from BIOSTAT-CHF (A Systems Biology Study to Tailored Treatment in Chronic Heart Failure). Additionally, the relationship between HDL functionality and HDL proteome composition was determined in 86 patients with heart failure. From baseline to 9 months, HDL cholesterol concentrations were unchanged, but HDL cholesterol efflux and anti-inflammatory capacity declined (both P<0.001). In contrast, antioxidative capacity increased (P<0.001). Higher HDL cholesterol efflux was associated with lower mortality after adjusting for BIOSTAT-CHF risk models and log HDL cholesterol (hazard ratio, 0.81; 95% CI, 0.71-0.92; P=0.001). Other functionality measures were not associated with outcome. Several HDL proteins correlated with HDL functionality, mainly with cholesterol efflux. Apolipoprotein A1 emerged as the main protein associated with all 3 HDL functionality measures.Conclusions: Better HDL cholesterol efflux at baseline was associated with lower mortality during follow-up, independent of HDL cholesterol. HDL cholesterol efflux and anti-inflammatory capacity declined during follow-up in patients with heart failure. Measures of HDL function may provide clinical information in addition to HDL cholesterol concentration in patients with heart failure.
KW - cholesterol efflux
KW - functionality
KW - high‐density lipoprotein
KW - outcome
KW - proteome
UR - http://www.scopus.com/inward/record.url?scp=85105769123&partnerID=8YFLogxK
U2 - 10.1161/JAHA.120.019123
DO - 10.1161/JAHA.120.019123
M3 - Article
C2 - 33870728
SN - 2047-9980
VL - 10
JO - Journal of the American Heart Association Cardiovascular and Cerebrovascular Disease (JAHA)
JF - Journal of the American Heart Association Cardiovascular and Cerebrovascular Disease (JAHA)
IS - 9
M1 - e019123
ER -