scholarly journals HDL in the 21st Century: A Multifunctional Roadmap for Future HDL Research

Circulation ◽  
2021 ◽  
Vol 143 (23) ◽  
pp. 2293-2309
Author(s):  
Anand Rohatgi ◽  
Marit Westerterp ◽  
Arnold von Eckardstein ◽  
Alan Remaley ◽  
Kerry-Anne Rye
Keyword(s):  
Cardiovascular Risk ◽  
High Density Lipoprotein ◽  
Therapeutic Target ◽  
Density Lipoprotein ◽  
High Density ◽  
Atherogenic Dyslipidemia ◽  
Optimal Time ◽  
Bioactive Lipids ◽  
Hdl Function ◽  
Increased Risk

Low high-density lipoprotein cholesterol (HDL-C) characterizes an atherogenic dyslipidemia that reflects adverse lifestyle choices, impaired metabolism, and increased cardiovascular risk. Low HDL-C is also associated with increased risk of inflammatory disorders, malignancy, diabetes, and other diseases. This epidemiologic evidence has not translated to raising HDL-C as a viable therapeutic target, partly because HDL-C does not reflect high-density lipoprotein (HDL) function. Mendelian randomization analyses that have found no evidence of a causal relationship between HDL-C levels and cardiovascular risk have decreased interest in increasing HDL-C levels as a therapeutic target. HDLs comprise distinct subpopulations of particles of varying size, charge, and composition that have several dynamic and context-dependent functions, especially with respect to acute and chronic inflammatory states. These functions include reverse cholesterol transport, inhibition of inflammation and oxidation, and antidiabetic properties. HDLs can be anti-inflammatory (which may protect against atherosclerosis and diabetes) and proinflammatory (which may help clear pathogens in sepsis). The molecular regulation of HDLs is complex, as evidenced by their association with multiple proteins, as well as bioactive lipids and noncoding RNAs. Clinical investigations of HDL biomarkers (HDL-C, HDL particle number, and apolipoprotein A through I) have revealed nonlinear relationships with cardiovascular outcomes, differential relationships by sex and ethnicity, and differential patterns with coronary versus noncoronary events. Novel HDL markers may also have relevance for heart failure, cancer, and diabetes. HDL function markers (namely, cholesterol efflux capacity) are associated with coronary disease, but they remain research tools. Therapeutics that manipulate aspects of HDL metabolism remain the holy grail. None has proven to be successful, but most have targeted HDL-C, not metrics of HDL function. Future therapeutic strategies should focus on optimizing HDL function in the right patients at the optimal time in their disease course. We provide a framework to help the research and clinical communities, as well as funding agencies and stakeholders, obtain insights into current thinking on these topics, and what we predict will be an exciting future for research and development on HDLs.

scholarly journals Obesity-Related Changes in High-Density Lipoprotein Metabolism and Function

2020 ◽  
Vol 21 (23) ◽  
pp. 8985
Author(s):  
Julia T. Stadler ◽  
Gunther Marsche
Keyword(s):  
High Density Lipoprotein ◽  
Virgin Olive Oil ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
High Density ◽  
Atherogenic Dyslipidemia ◽  
Hdl Function ◽  
Increased Risk ◽  
And Function ◽  
The Impact

In obese individuals, atherogenic dyslipidemia is a very common and important factor in the increased risk of cardiovascular disease. Adiposity-associated dyslipidemia is characterized by low high-density lipoprotein cholesterol (HDL-C) levels and an increase in triglyceride-rich lipoproteins. Several factors and mechanisms are involved in lowering HDL-C levels in the obese state and HDL quantity and quality is closely related to adiponectin levels and the bioactive lipid sphingosine-1-phosphate. Recent studies have shown that obesity profoundly alters HDL metabolism, resulting in altered HDL subclass distribution, composition, and function. Importantly, weight loss through gastric bypass surgery and Mediterranean diet, especially when enriched with virgin olive oil, is associated with increased HDL-C levels and significantly improved metrics of HDL function. A thorough understanding of the underlying mechanisms is crucial for a better understanding of the impact of obesity on lipoprotein metabolism and for the development of appropriate therapeutic approaches. The objective of this review article was to summarize the newly identified changes in the metabolism, composition, and function of HDL in obesity and to discuss possible pathophysiological consequences.

Abstract 407: Atherogenic Dyslipidemia in Patients with Diabetes Mellitus May Have Distinct High Density Lipoprotein Function

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Wenliang Song ◽  
Jing Du ◽  
Li Qin ◽  
Stuart Zarich ◽  
Sachin Majumdar ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Platelet Aggregation ◽  
High Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Profiles ◽  
High Density ◽  
Atherogenic Dyslipidemia ◽  
Platelet Apoptosis ◽  
Hdl Function ◽  
Two Populations

There is growing evidence suggesting that high-density lipoprotein (HDL) function is more important than the HDL cholesterol (HDL-C) levels. HDL particles are highly heterogeneous and their function may also differ among different patient populations. There are two populations that are recognized tohave significant residual cardiovascular risk despite intensive statin therapy: atherogenic dyslipidaemia and diabetes mellitus. Atherogenic dyslipidemia and diabetes have significant homology with regards to lipid profiles. However, systemic epidemiological studies that describes the overlapping profiles between atherogenic dyslipidemia and diabetes is lacking. The function and types of HDL in these two populations needs to be carefully elucidated. HDL has many functions includingreverse cholesterol transport, anti-oxidant activity and anti-inflammatory activity. HDL may also exert “antiplatelet effects”but the mechanism is unclear.We assessed the prevalence of atherogenic dyslipidemia in diabetes mellitus using data from the National Health and Nutrition Examination Survery (NHANES) and data from Yale New Haven Health (YNHH). We found that atherogenic dyslipidemia and diabetes mellitushave overlapping lipid profiles but are clearly two distinct conditions. In our preliminary studies, we found that HDL inhibits platelet aggregation and activation. Very interestingly, we found HDL can induce mitochondria dependent platelet apoptosis. The antiplatelet effect of HDL, as observed by others in the past, may arise fromapoptotic platelets that do not aggregate, and thus the inhibition of platelet aggregation. Whether HDL subtypes from atherogenic dyslipidemia and diabetes patient have differential effects on platelet apoptosis are currently being investigated.

Assessment of the carotid artery intima-media complex through ultrasonography and the relationship with Pathobiological Determinants of Atherosclerosis in Youth

2015 ◽  
Vol 26 (7) ◽  
pp. 1333-1342 ◽  
Author(s):  
Thacira D. A. Ramos ◽  
Tatianne M. E. Dantas ◽  
Mônica O. S. Simões ◽  
Danielle F. Carvalho ◽  
Carla C. M. Medeiros
Keyword(s):  
Blood Pressure ◽  
Body Mass Index ◽  
Cardiovascular Risk ◽  
Carotid Artery ◽  
High Density Lipoprotein ◽  
High Density Lipoprotein Cholesterol ◽  
Density Lipoprotein ◽  
High Density ◽  
Z Score ◽  
High Cardiovascular Risk

AbstractObjectiveTo evaluate the presence of carotid thickening and its relationship with the Pathobiological Determinants of Atherosclerosis in Youth score.MethodsWe carried out a cross-sectional study involving 512 brazilian adolescents. Variables such as sex, body mass index, concentrations of non-high-density lipoprotein and high-density lipoprotein cholesterol, blood pressure, blood glucose and glycated haemoglobin A1c levels that make up the score, and carotid thickening through the intima-media complex measured by ultrasound were evaluated. We adopted two cut-off points to evaluate carotid thickening, being considered altered for those higher or equal to the z-score 2+ and ⩾75th percentile. The association was assessed using the χ2 test and univariate and multivariate logistic regression analyses.ResultsHigh cardiovascular risk was present in 10.2% of the adolescents; carotid thickness was present in 4.3% determined by the z-score 2+ and in 25.0% determined by the 75th percentile. When measured by the z-score, carotid thickening was associated with high systolic blood pressure (p=0.024), high-non-high density lipoprotein cholesterol (p=0.039), and high cardiovascular risk assessed by the score and by the 75th percentile, with body mass index >30 (p=0.005). In the multivariate analysis, high cardiovascular risk was found to be independently associated with the presence of carotid thickness evaluated by the z-score, with risk four times greater (p=0.010) of presenting with this condition compared with individuals with low risk, and this fact was not observed when factors were analysed alone.ConclusionThe presence of high cardiovascular risk in adolescents assessed by the Pathobiological Determinants of Atherosclerosis in Youth score was associated with marked thickening of the carotid artery in healthy adolescents.

scholarly journals High serum non-high-density lipoprotein and the risk of ischemic stroke: A systematic review

2021 ◽  
Vol 20 (1) ◽  
pp. 15-20
Author(s):  
Nyoman Tyas Apsari ◽  
◽  
Kumara Tini ◽  
I Putu Eka Widyadharma ◽  
◽  
...  
Keyword(s):  
Systematic Review ◽  
Ischemic Stroke ◽  
High Density Lipoprotein ◽  
Large Population ◽  
Density Lipoprotein ◽  
High Serum ◽  
High Density ◽  
Inclusion Criteria ◽  
Increased Risk ◽  
The Relationship

Objectives. High levels of non high density lipoprotein cholesterol (non-HDL-C) are known to contribute to an increased risk of ischemic stroke. This systematic review was conducted to identify the relationship between high non-HDL-C levels and the risk of ischemic stroke. Material and methods. This systematic review using PRISMA (preferred reporting items for systematic reviews and meta-analyses) statement guideline, with a pre-determined search strategy. The search was conducted in Pubmed Central (PMC) and Pubmed from 2009 until 2020 with inclusion criteria, patients with a diagnosis of ischemic stroke, age >18 years, with non-HDL-C levels. The title and abstract of these articles were reviewed for relevance, based on inclusion criteria. This systematic review using STROBE to evaluate the quality in individual study which consists of 22 domains. Results. In the final stage, this systematic review identifies six cohort study consisting 166.720 participants. Overall, the quality in individual studies based on STROBE is good. We reported that there are two studies report that high non-HDL-C levels can significantly increase the risk of ischemic stroke. Meanwhile, there are four studies that report there was no significant relationship between high non-HDL-C levels and the risk of ischemic stroke. Conclusions. Overall, this systematic review provides the result about relationship between high levels of nonHDL-C and the risk of ischemic stroke, there are two studies with a larger population support that high levels of non-HDL-C can increase the risk of ischemic stroke. However, further studies is needed with a large population that specifically identify the relationship between non-HDL-C levels and risk of ischemic stroke and makes a better adjustments for confounding variables.

scholarly journals Monocyte/High-Density Lipoprotein Ratio Predicts the Prognosis of Large Artery Atherosclerosis Ischemic Stroke

2021 ◽  
Vol 12 ◽  
Author(s):  
Youyu Li ◽  
Daqing Chen ◽  
Laifang Sun ◽  
Zhibo Chen ◽  
Weiwei Quan
Keyword(s):  
Ischemic Stroke ◽  
High Density Lipoprotein ◽  
Functional Outcome ◽  
Multivariate Logistic Regression Analysis ◽  
Density Lipoprotein ◽  
High Density ◽  
Large Artery ◽  
Poor Functional Outcome ◽  
Outcome Group ◽  
Increased Risk

Objective: Monocyte to high-density lipoprotein ratio is considered as a new inflammatory marker and has been used to predict the severity of coronary heart disease and the incidence of adverse cardiovascular events (ACEs). However, there is a lack of data relative to large artery atherosclerosis (LAA) ischemic stroke. We investigated whether the monocyte to high-density lipoprotein (HDL) ratio (MHR) is related to the 3-month functional prognosis of LAA ischemic stroke.Materials and Methods: A retrospective analysis was conducted on 316 LAA ischemic stroke patients. The 3-month functional outcome was divided into good and poor according to the modified Rankin Scale (mRS) score. Multivariate logistic regression analysis was performed to evaluate the correlation between MHR and prognosis of ischemic stroke.Results: The MHR level of poor functional outcome group was higher than that of the good functional outcome group [0.44 (0.3, 0.55) vs. 0.38 (0.27, 0.5), P = 0.025]. Logistic stepwise multiple regression revealed that MHR [odds ratio (OR) 9.464, 95%CI 2.257–39.678, P = 0.002] was an independent risk factor for the 3-month poor outcome of LAA ischemic stroke. Compared to the lower MHR tertile, the upper MHR tertile had a 3.03-fold increase (95% CI 1.475–6.225, P = 0.003) in the odds of poor functional outcome after adjustment for potential confounders. Moreover, a multivariable-adjusted restricted cubic spline (RCS) showed a positive close to a linear pattern of this association.Conclusion: Elevated MHR was independently associated with an increased risk of poor 3-month functional outcome of patients with LAA ischemic stroke.

scholarly journals The Role of level and function of High Density Lipoprotein (HDL) in Cardiovascular Diseases

2020 ◽  
pp. 118-127
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
High Density Lipoprotein ◽  
Inverse Relationship ◽  
Density Lipoprotein ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
High Density ◽  
Peripheral Tissues ◽  
Hdl Function

High-density lipoprotein (HDL) is a set of particles with heterogeneous structures that have different functions due to various compounds including surface charge, size, lipid, and protein compounds. Several prospective epidemiological studies have demonstrated that there is a clear inverse relationship between serum HDL concentration and risk of coronary heart disease, despite this relationship, clinical evidence has only challenged the usefulness of higher levels of HDL-C in predicting the risk of cardiovascular diseases (CVD) and have proven that the structure of HDL is altered and loosed function. Therefore, extensive research is needed to identify new agents and biomarkers to improve HDL function and reduce the risk of cardiovascular disease. Given that the most important function of HDL is to transfer excess cholesterol from peripheral tissues and macrophage cells through a receptor called ABCA1 and direct it to the liver, plays an important role in protecting the formation of atherosclerotic plaque. This molecule can provide a strong protective effect against oxidative damage caused by free radicals with intermittent inhibition of the production of pro-inflammatory oxidized lipids in the intima layer of arteries. There is an inverse relationship between the ability to efflux cholesterol and the prevalence of CVD. The ability to remove cholesterol from macrophages by HDL, it is a crucial criterion for determining HDL performance, and it has a strong inverse relationship with carotid intima-media thickness and coronary artery stenosis in angiography independent of HDL level. Key Words: High Density Lipoprotein; Cardiovascular Disease; Atherosclerosis; Lipoprotein

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