scholarly journals High-Density Lipoprotein (HDL) Triglyceride and Oxidized HDL: New Lipid Biomarkers of Lipoprotein-Related Atherosclerotic Cardiovascular Disease

Antioxidants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 362 ◽  
Author(s):  
Fumiaki Ito ◽  
Tomoyuki Ito
Keyword(s):  
Cardiovascular Disease ◽  
High Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Peroxide ◽  
Hdl Cholesterol ◽  
High Density ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipid Panel ◽  
Lipid Markers ◽  
Dysfunctional Hdl

Lipid markers are well-established predictors of vascular disease. The most frequently measured lipid markers are total cholesterol, high-density lipoprotein (HDL)-cholesterol (HDL-C), LDL cholesterol (LDL-C), and triglyceride. HDL reduces atherosclerosis by multiple mechanisms, leading to a reduced risk of cardiovascular disease, and HDL-C, as a metric of HDL quantity, is inversely associated with cardiovascular disease, independent of LDL-C. However, the quality of the HDL appears to be more important than its quantity, because HDL loses its antiatherogenic functions due to changes in its composition and becomes “dysfunctional HDL”. Although there is evidence of the existence of “dysfunctional HDL”, biomarkers for monitoring dysfunctional HDL in clinical practice have not yet been established. In this review, we propose a new lipid panel for the assessment of dysfunctional HDL and lipoprotein-related atherosclerotic cardiovascular disease. The lipid panel includes the measurement of lipid peroxide and triglyceride contents within HDL particles.

scholarly journals Roles of Reconstituted High-Density Lipoprotein Nanoparticles in Cardiovascular Disease: A New Paradigm for Drug Discovery

2020 ◽  
Vol 21 (3) ◽  
pp. 739 ◽  
Author(s):  
Jiansheng Huang ◽  
Dongdong Wang ◽  
Li-Hao Huang ◽  
Hui Huang
Keyword(s):  
Cardiovascular Disease ◽  
High Density Lipoprotein ◽  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
Inverse Correlation ◽  
Hdl Cholesterol ◽  
High Density ◽  
Atherosclerotic Cardiovascular Disease ◽  
New Paradigm

Epidemiological results revealed that there is an inverse correlation between high-density lipoprotein (HDL) cholesterol levels and risks of atherosclerotic cardiovascular disease (ASCVD). Mounting evidence supports that HDLs are atheroprotective, therefore, many therapeutic approaches have been developed to increase HDL cholesterol (HDL-C) levels. Nevertheless, HDL-raising therapies, such as cholesteryl ester transfer protein (CETP) inhibitors, failed to ameliorate cardiovascular outcomes in clinical trials, thereby casting doubt on the treatment of cardiovascular disease (CVD) by increasing HDL-C levels. Therefore, HDL-targeted interventional studies were shifted to increasing the number of HDL particles capable of promoting ATP-binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux. One such approach was the development of reconstituted HDL (rHDL) particles that promote ABCA1-mediated cholesterol efflux from lipid-enriched macrophages. Here, we explore the manipulation of rHDL nanoparticles as a strategy for the treatment of CVD. In addition, we discuss technological capabilities and the challenge of relating preclinical in vivo mice research to clinical studies. Finally, by drawing lessons from developing rHDL nanoparticles, we also incorporate the viabilities and advantages of the development of a molecular imaging probe with HDL nanoparticles when applied to ASCVD, as well as gaps in technology and knowledge required for putting the HDL-targeted therapeutics into full gear.

scholarly journals High-Density Lipoproteins and Cardiovascular Disease: The Good, the Bad and the Future

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 857
Author(s):  
Josep Julve ◽  
Joan Carles Escolà-Gil
Keyword(s):  
Cardiovascular Disease ◽  
High Density Lipoprotein ◽  
High Density Lipoprotein Cholesterol ◽  
Density Lipoprotein ◽  
Epidemiological Studies ◽  
High Density ◽  
High Density Lipoproteins ◽  
Atherosclerotic Cardiovascular Disease ◽  
Plasma High Density ◽  
Low Levels

Epidemiological studies have shown that low levels of plasma high-density lipoprotein cholesterol (HDL-C) are associated with increased atherosclerotic cardiovascular disease (CVD) [...]

The Yin and Yang of High-density Lipoprotein and Atherosclerotic Cardiovascular Disease: Focusing on Functionality and Cholesterol Efflux to Reframe the HDL Hypothesis

2021 ◽  
Vol 28 ◽  
Author(s):  
Shiva Ganjali ◽  
Gerald F. Watts ◽  
Maciej Banach ◽  
Željko Reiner ◽  
Petr Nachtigal ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
High Density Lipoprotein ◽  
Cholesterol Efflux ◽  
Association Studies ◽  
Plasma Concentrations ◽  
Density Lipoprotein ◽  
High Density ◽  
Atherosclerotic Cardiovascular Disease ◽  
Genome Wide Association Studies ◽  
Increased Risk

Abstract: The inverse relationship between low plasma high-density lipoprotein cholesterol (HDL-C) concentrations and increased risk of Atherosclerotic Cardiovascular Disease (ASCVD) is well-known. However, plasma HDL-C concentrations are highly variable in subjects with ASCVD. In clinical outcome trials, pharmacotherapies that increase HDL-C concentrations are not associated with a reduction in ASCVD events. A causal relationship between HDL-C and ASCVD has also been questioned by Mendelian randomization studies and genome-wide association studies of genetic variants associated with plasma HDL-C concentrations. The U-shaped association between plasma HDL-C concentrations and mortality observed in several epidemiological studies implicates both low and very high plasma HDL-C concentrations in the etiology of ASCVD and non-ASCVD mortality. These data do not collectively support a causal association between HDL-C and ASCVD risk. Therefore, the hypothesis concerning the association between HDL and ASCVD has shifted from focus on plasma concentrations to the concept of functionality, in particular cellular cholesterol efflux and HDL holoparticle transport. In this review, we focus on these new concepts and provide a new framework for understanding and testing the role of HDL in ASCVD.

scholarly journals Interaction between adipocytes and high-density lipoprotein:new insights into the mechanism of obesity-induced dyslipidemia and atherosclerosis

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Tianhua Zhang ◽  
Jin Chen ◽  
Xiaoyu Tang ◽  
Qin Luo ◽  
Danyan Xu ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Adipose Tissue ◽  
Hormone Secretion ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
Atherosclerotic Cardiovascular Disease ◽  
Nutritional Disorder ◽  
Hdl Function ◽  
And Function

AbstractObesity is the most common nutritional disorder worldwide and is associated with dyslipidemia and atherosclerotic cardiovascular disease. The hallmark of dyslipidemia in obesity is low high density lipoprotein (HDL) cholesterol (HDL-C) levels. Moreover, the quality of HDL is also changed in the obese setting. However, there are still some disputes on the explanations for this phenomenon. There is increasing evidence that adipose tissue, as an energy storage tissue, participates in several metabolism activities, such as hormone secretion and cholesterol efflux. It can influence overall reverse cholesterol transport and plasma HDL-C level. In obesity individuals, the changes in morphology and function of adipose tissue affect plasma HDL-C levels and HDL function, thus, adipose tissue should be the main target for the treatment of HDL metabolism in obesity. In this review, we will summarize the cross-talk between adipocytes and HDL related to cardiovascular disease and focus on the new insights of the potential mechanism underlying obesity and HDL dysfunction.

scholarly journals Novel Insights From Human Studies on the Role of High-Density Lipoprotein in Mortality and Noncardiovascular Disease

2020 ◽  
Author(s):  
Christian M. Madsen ◽  
Anette Varbo ◽  
Børge G. Nordestgaard
Keyword(s):  
Cardiovascular Disease ◽  
High Density Lipoprotein ◽  
Therapeutic Potential ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
Cancer Type ◽  
Health And Disease ◽  
And Function

The vast majority of research about HDL (high-density lipoprotein) has for decades revolved around the possible role of HDL in atherosclerosis and its therapeutic potential within cardiovascular disease prevention; however, failures with therapies aimed at increasing HDL cholesterol has left questions as to what the role and function of HDL in human health and disease is. Recent observational studies have further shown that extreme high HDL cholesterol is associated with high mortality leading to speculations that HDL could in some instances be harmful. In addition, evidence from observational, and to a lesser extent genetic, studies has emerged indicating that HDL might be associated with the development of other major noncardiovascular diseases, such as infectious disease, autoimmune disease, cancer, type 2 diabetes, kidney disease, and lung disease. In this review, we discuss (1) the association between extreme high HDL cholesterol and mortality and (2) the emerging human evidence linking HDL to several major diseases outside the realm of cardiovascular disease.

scholarly journals CORRELATION OF SERUM HIGH-DENSITY LIPOPROTEIN CHOLESTEROL AND HOMOCYSTEINE LEVEL IN PATIENT WITH ACUTE MYOCARDIAL INFARCTION

2019 ◽  
Vol 25 (1) ◽  
pp. 99
Author(s):  
Yayie Dwina Putri ◽  
Tuty Prihandani ◽  
Lillah Lillah ◽  
Rismawati Yaswir
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Acute Myocardial Infarction ◽  
High Density Lipoprotein ◽  
Homocysteine Level ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
The Mean ◽  
Spearman’S Correlation

Acute Myocardial Infarction (AMI), one of the primary manifestation of coronary heart disease, is a significat cause of death worldwide. Hyperhomocysteinemia, a risk factor for cardiovascular disease, is caused by nutritional or genetic disturbances in homocysteine metabolism. The role of hyperhomocysteinemia in altered lipid metabolism presumed holds the key to an increased risk of cardiovascular disease. Hyperhomocysteinemia causes the reduction of serum High-Density Lipoprotein (HDL) cholesterol level by inhibiting hepatic synthesis of apo-A1 (significant apolipoprotein HDL). The aim of this study was to know the correlation between hyperhomocysteinemia and decreased HDL cholesterol levels for the management of cardiovascular disease risk factors. This research was an analytical study with cross-sectional design in 40 patients AMI who meet the inclusion and exclusion criteria and conduct blood test at the Central Laboratory of Hospital Dr. M. Djamil Padang and Biomedical Laboratory Faculty of Medicine Andalas University. The study was conducted in May 2016-Agustus 2017. Homocysteine level was measured by ELISA method. High-Density Lipoprotein level was performed by enzymatic colorimetric method. Data were analyzed by Spearman’s correlation test. Research subjects were 40 people with male gender 30 (75%) and female 10 (25%), mean age 61.08 (11.09) year. The mean level of HDL cholesterol in patients with AMI is 41.93 ± 13.12 mg/dL. The mean level of homocysteine in patients with AMI is 25.36 ± 22.2 µmol/L. Spearman’s correlation test showed a strong correlation between the levels of homocysteine and HDL cholesterol with r=-0.603 and p<0.01.

scholarly journals Associations Between High-Density Lipoprotein Particles and Ischemic Events by Vascular Domain, Sex, and Ethnicity

Circulation ◽  
2020 ◽  
Vol 142 (7) ◽  
pp. 657-669 ◽  
Author(s):  
Kavisha Singh ◽  
Alvin Chandra ◽  
Thomas Sperry ◽  
Parag H. Joshi ◽  
Amit Khera ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Ischemic Stroke ◽  
High Density Lipoprotein ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Large Population ◽  
Density Lipoprotein ◽  
High Density ◽  
Cholesterol Concentration ◽  
Atherosclerotic Cardiovascular Disease

Background: High-density lipoprotein (HDL) cholesterol concentration (HDL-C) is an established atheroprotective marker, in particular for coronary artery disease; however, HDL particle concentration (HDL-P) may better predict risk. The associations of HDL-C and HDL-P with ischemic stroke and myocardial infarction (MI) among women and Blacks have not been well studied. We hypothesized that HDL-P would consistently be associated with MI and stroke among women and Blacks compared with HDL-C. Methods: We analyzed individual-level participant data in a pooled cohort of 4 large population studies without baseline atherosclerotic cardiovascular disease: DHS (Dallas Heart Study; n=2535), ARIC (Atherosclerosis Risk in Communities; n=1595), MESA (Multi-Ethnic Study of Atherosclerosis; n=6632), and PREVEND (Prevention of Renal and Vascular Endstage Disease; n=5022). HDL markers were analyzed in adjusted Cox proportional hazard models for MI and ischemic stroke. Results: In the overall population (n=15 784), HDL-P was inversely associated with the combined outcome of MI and ischemic stroke, adjusted for cardiometabolic risk factors (hazard ratio [HR] for quartile 4 [Q4] versus quartile 1 [Q1], 0.64 [95% CI, 0.52–0.78]), as was HDL-C (HR for Q4 versus Q1, 0.76 [95% CI, 0.61–0.94]). Adjustment for HDL-C did not attenuate the inverse relationship between HDL-P and atherosclerotic cardiovascular disease, whereas adjustment for HDL-P attenuated all associations between HDL-C and events. HDL-P was inversely associated with the individual end points of MI and ischemic stroke in the overall population, including in women. HDL-P was inversely associated with MI among White participants but not among Black participants (HR for Q4 versus Q1 for Whites, 0.49 [95% CI, 0.35–0.69]; for Blacks, 1.22 [95% CI, 0.76–1.98]; P interaction =0.001). Similarly, HDL-C was inversely associated with MI among White participants (HR for Q4 versus Q1, 0.53 [95% CI, 0.36–0.78]) but had a weak direct association with MI among Black participants (HR for Q4 versus Q1, 1.75 [95% CI, 1.08–2.83]; P interaction <0.0001). Conclusions: Compared with HDL-C, HDL-P was consistently associated with MI and ischemic stroke in the overall population. Differential associations of both HDL-C and HDL-P for MI by Black ethnicity suggest that atherosclerotic cardiovascular disease risk may differ by vascular domain and ethnicity. Future studies should examine individual outcomes separately.

scholarly journals Serum modified HDL was associated with cardiovascular disease in a Japanese community-based cohort

2019 ◽  
Vol 29 (Supplement_4) ◽  
Author(s):  
T Okamura ◽  
M Sata ◽  
M Iida ◽  
A Kakino ◽  
S Harada ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
High Density Lipoprotein ◽  
Oxidized Ldl ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Predictive Marker ◽  
High Density ◽  
Apolipoprotein A1 ◽  
Lipid Lowering ◽  
Increased Risk

Abstract Background Previous studies have shown that high density lipoprotein (HDL) is protective against cardiovascular disease (CVD). However, recent studies suggested that function of HDL was more important than HDL cholesterol levels. The present study aimed to clarify the relationship between modified HDL levels and CVD incidence. Methods LOX-1 (lectin-like oxidized LDL receptor) is the receptor that mediates modified LDL (low density lipoprotein) activity; however, some lipoproteins with apolipoprotein A1 (Apo A-1) are also bonded to LOX-1. In this study, serum LOX-1 ligand containing Apo A-1 was defined as modified HDL, which were measured by our new development method. We conducted a nested case-control study in a Japanese cohort study, involving 11,002 community dwellers. During 4.0 years follow-up, we observed 127 new CVD onsets. For each CVD case, age and sex matched three controls were randomly selected (N = 381). Serum samples collected at baseline survey stored at − 80 °C were used for the measurement of modified HDL. We estimated multivariable-adjusted odds ratio (OR) and 95% confidence interval (CI) for the association between modified HDL levels and CVD by conditional logistic regression. Results Modified HDL levels were associated with increased risk of CVD (OR for one unit increase of log transformed modified HDL, 2.05: 95% CI, 1.16-3.62) after adjustment for body mass index, hypertension, diabetes, LDL cholesterol, HDL cholesterol, lipid lowering agents, chronic kidney disease, smoking and alcohol drinking. The magnitude of OR was almost equivalent to those of hypertension and diabetes, which were 2.33 (95% CI, 1.37-3.98) and 2.61 (95% CI, 1.48-4.59), respectively. On the other hands, other lipids markers showed relatively weak associations with CVD. Conclusions Serum modified HDL, i.e., LOX-1 ligand containing Apo A-1, might be a novel predictive marker for CVD in apparently healthy individuals. Key messages Recent epidemiologic studies suggested that function of high-density lipoprotein (HDL) was more important than HDL cholesterol level itself to predict cardiovascular disease. Modified HDL measured by a novel cell-free, non-fluorescent method as LOX-1 ligand containing Apo A-1, was a predictive marker for CVD after adjusting for other traditional risk factors.

scholarly journals Subpopulations of High-Density Lipoprotein: Friends or Foes in Cardiovascular Disease Risk in Chronic Kidney Disease?

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 554
Author(s):  
Susana Coimbra ◽  
Flávio Reis ◽  
Maria João Valente ◽  
Susana Rocha ◽  
Cristina Catarino ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
High Density Lipoprotein ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Size Composition ◽  
High Density

Dyslipidemia is a major traditional risk factor for cardiovascular disease (CVD) in chronic kidney disease (CKD) patients, although the altered lipid profile does not explain the number and severity of CVD events. High-density lipoprotein (HDL) is a heterogeneous (size, composition, and functionality) population of particles with different atherogenic or atheroprotective properties. HDL-cholesterol concentrations per se may not entirely reflect a beneficial or a risk profile for CVD. Large HDL in CKD patients may have a unique proteome and lipid composition, impairing their cholesterol efflux capacity. This lack of HDL functionality may contribute to the paradoxical coexistence of increased large HDL and enhanced risk for CVD events. Moreover, CKD is associated with inflammation, oxidative stress, diabetes, and/or hypertension that are able to interfere with the anti-inflammatory, antioxidative, and antithrombotic properties of HDL subpopulations. How these changes interfere with HDL functions in CKD is still poorly understood. Further studies are warranted to fully clarify if different HDL subpopulations present different functionalities and/or atheroprotective effects. To achieve this goal, the standardization of techniques would be valuable.

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