Modification of High-Density Lipoprotein Functions by Diet and Other Lifestyle Changes: A Systematic Review of Randomized Controlled Trials

High-density lipoprotein (HDL) functional traits have emerged as relevant elements that may explain HDL antiatherogenic capacity better than HDL cholesterol levels. These properties have been improved in several lifestyle intervention trials. The aim of this systematic review is to summarize the results of such trials of the most commonly used dietary modifications (fatty acids, cholesterol, antioxidants, alcohol, and calorie restriction) and physical activity. Articles were screened from the Medline database until March 2021, and 118 randomized controlled trials were selected. Results from HDL functions and associated functional components were extracted, including cholesterol efflux capacity, cholesteryl ester transfer protein, lecithin-cholesterol acyltransferase, HDL antioxidant capacity, HDL oxidation status, paraoxonase-1 activity, HDL anti-inflammatory and endothelial protection capacity, HDL-associated phospholipase A2, HDL-associated serum amyloid A, and HDL-alpha-1-antitrypsin. In mainly short-term clinical trials, the consumption of monounsaturated and polyunsaturated fatty acids (particularly omega-3 in fish), and dietary antioxidants showed benefits to HDL functionality, especially in subjects with cardiovascular risk factors. In this regard, antioxidant-rich dietary patterns were able to improve HDL function in both healthy individuals and subjects at high cardiovascular risk. In addition, in randomized trial assays performed mainly in healthy individuals, reverse cholesterol transport with ethanol in moderate quantities enhanced HDL function. Nevertheless, the evidence summarized was of unclear quality and short-term nature and presented heterogeneity in lifestyle modifications, trial designs, and biochemical techniques for the assessment of HDL functions. Such findings should therefore be interpreted with caution. Large-scale, long-term, randomized, controlled trials in different populations and individuals with diverse pathologies are warranted.

Dietary Strategies to Improve Cardiovascular Health: Focus on Increasing High-Density Lipoprotein Functionality

Cardiovascular disease is one of the leading causes of morbidity and mortality worldwide, with increasing incidence. A cornerstone of cardiovascular disease prevention is lifestyle modification through dietary changes to influence various risk factors such as obesity, hypertension and diabetes. The effects of diet on cardiovascular health are complex. Some dietary components and metabolites directly affect the composition and structure of high-density lipoproteins (HDL) and increase anti-inflammatory and vasoprotective properties. HDLs are composed of distinct subpopulations of particles of varying size and composition that have several dynamic and context-dependent functions. The identification of potential dietary components that improve HDL functionality is currently an important research goal. One of the best-studied diets for cardiovascular health is the Mediterranean diet, consisting of fish, olive oil, fruits, vegetables, whole grains, legumes/nuts, and moderate consumption of alcohol, most commonly red wine. The Mediterranean diet, especially when supplemented with extra virgin olive oil rich in phenolic compounds, has been shown to markedly improve metrics of HDL functionality and reduce the burden, or even prevent the development of cardiovascular disease. Particularly, the phenolic compounds of extra virgin olive oil seem to exert the significant positive effects on HDL function. Moreover, supplementation of anthocyanins as well as antioxidants such as lycopene or the omega−3 fatty acid eicosapentaenoic acid improve parameters of HDL function. In this review, we aim to highlight recent discoveries on beneficial dietary patterns as well as nutritional components and their effects on cardiovascular health, focusing on HDL function.

Serum cholesterol efflux capacity is associated with coronary plaque progression in patients with coronary heart disease

Background Coronary plaque progression is a major risk factor of adverse cardiac events in patients with coronary heart disease (CHD). Emerging evidence showed that attenuated high-density lipoprotein (HDL) function measured by cholesterol efflux capacity (CEC) was associated with development of atherosclerosis independent of HDL cholesterol level. In this study, we sought to investigate whether CEC is a predictor for coronary plaque progression in CHD patients. Methods We consecutively enrolled CHD patients from January 2017 to August 2019 in our Hospital who underwent elective percutaneous coronary intervention and had at least one non-target coronary lesion. Follow-up coronary angiography were performed at around 12 months. Fluorescence-labeled cholesterol and J774 macrophages were used to measure the CEC of ApoB-depleted serum sample from all patients. Quantitative coronary angiography (QCA) was performed both at baseline and follow-up to analyze the plaque progression. Results A total of 430 CHD patients with 586 non-target coronary lesions were included in the final analysis. During a mean follow-up time of 381.04±59.52 days, patients with decreased CEC presented more severe plaque progression (net luminal loss in highest to lowest CEC quartile: 0.22±0.42mm vs 0.20±0.41mm vs 0.13±0.36mm vs 0.11±0.34mm, p=0.035). In multivariate analysis, baseline CEC was independently associated with coronary plaque progression after adjustment for traditional risk factors including HDL cholesterol and ApoA-I, no matter treated as categorical variable (OR: 0.382 [95% CI 0.180–0.781] for highest to lowest quartile) or continuous variable (OR: 0.522 [95% CI 0.373–0.714] for per SD increase]. Furthermore, CEC demonstrated a better power in predicting coronary plaque progression compared with HDL cholesterol concentration (AUC=0.644 vs 0.514). Conclusions This study suggests that HDL function reflected by serum CEC is an independent predictor for coronary plaque progression in CHD patients. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation of China, Shanghai Municipal Commission of Health and Family Planning

High-density lipoprotein lipid peroxidation in association with presence of coronary artery disease and atrial fibrillation in a large cross-sectional study

Background The function of high-density lipoprotein (HDL) cholesterol may play a more important role in the prevention of cardiovascular disease compared to the concentration of the HDL. Cardiovascular diseases such as coronary artery disease (CAD) and atrial fibrillation (AF) have been linked to impaired HDL function. Purpose The aim of the present study is to assess a biochemical measure of the antioxidant function of HDL and its association with presence of CAD and AF. Methods Patients admitted for elective cardiac catheterization were recruited in this cross-sectional study. Out of 1231 participants that were included in the analyses, 727 patients had confirmed CAD (CAD group), 369 patients had no CAD (no CAD group) and 129 persons were included as a control group. HDL function was measured in sera by determination of HDL-lipid peroxidation content (HDLox) assessed by a validated fluorometric cell-free biochemical assay and was normalized for the levels of HDL cholesterol (normalized HDLox/HDL-C ratio or nHDLox; no units). Results are expressed as median with interquartile range. Associations of nHDLox with presence of CAD and AF were assessed by univariate and multivariate analyses. Results Participants in the CAD group had higher levels of nHDLox (0.80, 0.61–1.03) compared to the no CAD (0.70, 0.55–0.93) and control (0.66, 0.55–1.03, no units, p<0.001) group. Out of 1206 participants, 233 (19%) had AF and 973 (81%) had no AF. Patients with AF have also higher nHDLox (0.82, 0.60–10.03) compared to persons without AF (0.73, 0.58–0.98, p=0.03). In univariate analysis nHDLox was associated with CAD (p<0.001). In multivariate analysis adjusted for age, gender, CAD, BMI and hypertension, nHDLox was a strong independent predictor of atrial fibrillation (p=0.015) but was not an independent predictor of CAD (p>0.05) Conclusions Reduced antioxidant function of HDL (increased HDLox measured by a biochemical assay), a metric of HDL function, is increased in patients with atherosclerosis and manifested CAD and is also associated with the presence of atrial fibrillation independent of the presence of CAD. FUNDunding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Medical School of Brandenburg-MHB Fontane

Independent Effects of Kidney Function and Cholesterol Efflux on Cardiovascular Mortality

BackgroundImpaired renal function is associated with cardiovascular and all-cause mortality. In the general population, HDL-cholesterol is associated with cardiovascular events, which is not true in patients with chronic kidney disease (CKD). This has been attributed to abnormal HDL function in CKD.MethodsIn this study, we analyzed the association between kidney function, cholesterol efflux capacity as one of the major HDL functions and cardiovascular mortality in 2469 patients of the Ludwigshafen Risk and Cardiovascular Health Study who all underwent coronary angiography.ResultsWe found a strong association between cholesterol efflux capacity and kidney function. Additionally, a genetic score of 53 SNPs associated with GRF and the uromodulin SNP rs12917707 was correlated inversely with cholesterol efflux. However, adjustment for eGFR and uromodulin as markers of kidney function did not affect the relationship between cholesterol efflux and cardiovascular mortality.ConclusionsWe suggest that impaired renal function lowers cholesterol efflux, but that this is not mediating the effects of impaired kidney function on cardiovascular mortality. Other mechanisms of low cellular cholesterol efflux may causally be involved in adverse cardiovascular outcomes.Trial registrationThe study was approved by the Ethics Committee at the “Aerztekammer Rheinland-Pfalz” and was performed conform to the declaration of Helsinki (837.255.97 [1394], approved January 8th, 1999).