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Impaired High-Density Lipoprotein Function in Patients With Heart Failure.

ABSTRACT: 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.

SUBMITTER: Emmens JE

PROVIDER: S-EPMC8200730 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe prevalence of ischaemic heart failure (HF) continues to increase. Diabetes mellitus (DM) concomitant with ischaemic HF increases the risk of major adverse cardiovascular events (MACEs). As a promising predictor for cardiovascular diseases, the predictive value of the monocyte to high-density lipoprotein cholesterol ratio (MHR) for MACE in the ischaemic HF with DM cohort has never been investigated before.ObjectiveWe aimed to investigate the MHR as a predictor for MACE in ischaemic HF patients with DM who underwent percutaneous coronary intervention (PCI).MethodsThis observational study enrolled 1049 patients with ischaemic HF and DM undergoing PCI from June 2017 to June 2019. The baseline data were collected. MACEs, including all-cause mortality, nonfatal myocardial infarction, and any revascularization, were recorded within the 36-month follow-up. The characteristics and incidence of MACE were analysed in four groups stratified by the quartiles of MHR. The hazard ratio for MACE was analysed with Cox regression models. The incidence of MACE in the four groups was evaluated by Kaplan‒Meier survival analysis. Restricted cubic spline analysis was performed to determine the nonlinear correlation between the MHR and MACE.ResultsAfter the 36-month follow-up, 407 patients (38.8%) experienced MACEs. The incidence of MACE was significantly higher among patients in the upper MHR quartile than among those in the lower MHR quartiles (23.4% vs. 36.0% vs. 41.4% and 54.6%; P < 0.001, respectively), which was consistent with the Kaplan‒Meier survival analyses (P < 0.0001). A multivariate Cox regression model showed that the MHR was an independent risk factor for MACE after variables were adjusted (adjusted HR: 2.11; 95% CI 1.47-3.03; P < 0.001). Its predictive effects on MACE showed no interaction with hypercholesterolemia (P > 0.05).ConclusionThe MHR was a significant and independent predictor of MACEs in ischaemic HF patients with DM undergoing PCI.

Project description:High-density lipoprotein (HDL) may provide cardiovascular protection by promoting reverse cholesterol transport from macrophages. We hypothesized that the capacity of HDL to accept cholesterol from macrophages would serve as a predictor of atherosclerotic burden.We measured cholesterol efflux capacity in 203 healthy volunteers who underwent assessment of carotid artery intima-media thickness, 442 patients with angiographically confirmed coronary artery disease, and 351 patients without such angiographically confirmed disease. We quantified efflux capacity by using a validated ex vivo system that involved incubation of macrophages with apolipoprotein B-depleted serum from the study participants.The levels of HDL cholesterol and apolipoprotein A-I were significant determinants of cholesterol efflux capacity but accounted for less than 40% of the observed variation. An inverse relationship was noted between efflux capacity and carotid intima-media thickness both before and after adjustment for the HDL cholesterol level. Furthermore, efflux capacity was a strong inverse predictor of coronary disease status (adjusted odds ratio for coronary disease per 1-SD increase in efflux capacity, 0.70; 95% confidence interval [CI], 0.59 to 0.83; P<0.001). This relationship was attenuated, but remained significant, after additional adjustment for the HDL cholesterol level (odds ratio per 1-SD increase, 0.75; 95% CI, 0.63 to 0.90; P=0.002) or apolipoprotein A-I level (odds ratio per 1-SD increase, 0.74; 95% CI, 0.61 to 0.89; P=0.002). Additional studies showed enhanced efflux capacity in patients with the metabolic syndrome and low HDL cholesterol levels who were treated with pioglitazone, but not in patients with hypercholesterolemia who were treated with statins.Cholesterol efflux capacity from macrophages, a metric of HDL function, has a strong inverse association with both carotid intima-media thickness and the likelihood of angiographic coronary artery disease, independently of the HDL cholesterol level. (Funded by the National Heart, Lung, and Blood Institute and others.).

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Impaired High-Density Lipoprotein Function in Patients With Heart Failure.

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