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

Author(s):  
Christian M. Madsen ◽  
Anette Varbo ◽  
Børge G. Nordestgaard

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.

Antioxidants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 362 ◽  
Author(s):  
Fumiaki Ito ◽  
Tomoyuki Ito

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.


2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Tianhua Zhang ◽  
Jin Chen ◽  
Xiaoyu Tang ◽  
Qin Luo ◽  
Danyan Xu ◽  
...  

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.


Author(s):  
Yayie Dwina Putri ◽  
Tuty Prihandani ◽  
Lillah Lillah ◽  
Rismawati Yaswir

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.


2020 ◽  
Vol 21 (3) ◽  
pp. 739 ◽  
Author(s):  
Jiansheng Huang ◽  
Dongdong Wang ◽  
Li-Hao Huang ◽  
Hui Huang

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.


2019 ◽  
Vol 29 (Supplement_4) ◽  
Author(s):  
T Okamura ◽  
M Sata ◽  
M Iida ◽  
A Kakino ◽  
S Harada ◽  
...  

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.


1982 ◽  
Vol 28 (10) ◽  
pp. 2040-2043 ◽  
Author(s):  
H S Simpson ◽  
F C Ballantyne ◽  
C J Packard ◽  
H G Morgan ◽  
J Shepherd

Abstract Recent interest in the putative protective role of high-density lipoprotein (HDL) and its subfractions against atherosclerosis has highlighted the need for a rapid, simple subfractionation procedure. Here we compared HDL subfractionation by two recently developed polyanionic-precipitation methods with the values obtained by rate zonal ultracentrifugation. A similar result for total HDL cholesterol was obtained by all three methods. However, HDL2 cholesterol as measured by the precipitation procedures was significantly higher than the zonal value, and HDL3 was lower. This reflects the different underlying principles involved in the separations and highlights the need for a clearer understanding of the functional roles of the HDL fractions.


2019 ◽  
Vol 39 (12) ◽  
pp. 2457-2467 ◽  
Author(s):  
Annabelle Rodriguez ◽  
Bernardo L. Trigatti ◽  
Chieko Mineo ◽  
Darcy Knaack ◽  
John T. Wilkins ◽  
...  

The HDL (high-density lipoprotein) Workshop was established in 2009 as a forum for candid discussions among academic basic scientists, clinical investigators, and industry researchers about the role of HDL in cardiovascular disease. This ninth HDL Workshop was held on May 16 to 17, 2019 in Boston, MA, and included outstanding oral presentations from established and emerging investigators. The Workshop featured 5 sessions with topics that tackled the role of HDL in the vasculature, its structural complexity, its role in health and disease states, and its interaction with the intestinal microbiome. The highlight of the program was awarding the Jack Oram Award to the distinguished professor emeritus G.S. Getz from the University of Chicago. The tenth HDL Workshop will be held on May 2020 in Chicago and will continue the focus on intellectually stimulating presentations by established and emerging investigators on novel roles of HDL in cardiovascular and noncardiovascular health and disease states.


Author(s):  
Samar R. El Khoudary ◽  
Xirun Chen ◽  
Alexis Nasr ◽  
Jeff Billheimer ◽  
Maria Mori Brooks ◽  
...  

Objective: The cardioprotective capacity of HDL (high-density lipoprotein) cholesterol postmenopause has been challenged. HDL subclasses, lipid contents, and function might be better predictors of cardiovascular risk than HDL cholesterol. Changes in these measures have not been characterized over the menopause transition (MT) with respect to timing relative to the final menstrual period. Approach and Results: Four hundred seventy-one women with HDL particle (HDL-P) subclasses (nuclear magnetic resonance spectroscopy total, large, medium, and small HDL-P and HDL size), HDL lipid content (HDL phospholipids and triglycerides), and HDL function (cholesterol efflux capacity [HDL-CEC]) measured for a maximum of 5 time points across the MT were included. HDL cholesterol and total HDL-P increased across the MT. Within the 1 to 2 years bracketing the final menstrual period, large HDL-P and HDL size declined while small HDL-P and HDL-triglyceride increased. Although overall HDL-CEC increased across the MT, HDL-CEC per HDL-P declined. Higher concentrations of total, large, and medium HDL-P and greater HDL size were associated with greater HDL-CEC while of small HDL-P were associated with lower HDL-CEC. Associations of large HDL-P and HDL size with HDL-CEC varied significantly across the MT such that higher large HDL-P concentrations and greater HDL size were associated with lower HDL-CEC within the 1 to 2 years around the final menstrual period. Conclusions: Although HDL cholesterol increased over the MT, HDL subclasses and lipid content showed adverse changes. While overall HDL-CEC increased, HDL-CEC per HDL-P declined, consistent with reduced function per particle. Large HDL-P may become less efficient in promoting HDL-CEC during the MT.


Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 554
Author(s):  
Susana Coimbra ◽  
Flávio Reis ◽  
Maria João Valente ◽  
Susana Rocha ◽  
Cristina Catarino ◽  
...  

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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