Relation of Increased Prebeta-1 High-Density Lipoprotein Levels to Risk of Coronary Heart Disease
Applied Quantitative Genotherapeutics, Pfizer Pharmaceuticals, Cambridge, Massachusetts, USA. The American journal of cardiology
(Impact Factor: 3.28).
08/2011; 108(3):360-6. DOI: 10.1016/j.amjcard.2011.03.054
Preβ-1 high-density lipoprotein (HDL) plays a key role in reverse cholesterol transport by promoting cholesterol efflux. Our aims were (1) to test previous associations between preβ-1 HDL and coronary heart disease (CHD) and (2) to investigate whether preβ-1 HDL levels also are associated with risk of myocardial infarction (MI). Plasma preβ-1 HDL was measured by an ultrafiltration-isotope dilution technique in 1,255 subjects recruited from the University of California-San Francisco Lipid and Cardiovascular Clinics and collaborating cardiologists. Preβ-1 HDL was significantly and positively associated with CHD and MI even after adjustment for established risk factors. Inclusion of preβ-1 HDL in a multivariable model for CHD led to a modest improvement in reclassification of subjects (net reclassification index 0.15, p = 0.01; integrated discrimination improvement 0.003, p = 0.2). In contrast, incorporation of preβ-1 HDL into a risk model of MI alone significantly improved reclassification of subjects (net reclassification index 0.21, p = 0.008; integrated discrimination improvement 0.01, p = 0.02), suggesting that preβ-1 HDL has more discriminatory power for MI than for CHD in our study population. In conclusion, these results confirm previous associations between preβ-1 HDL and CHD in a large well-characterized clinical cohort. Also, this is the first study in which preβ-1 HDL was identified as a novel and independent predictor of MI above and beyond traditional CHD risk factors.
Available from: ncbi.nlm.nih.gov
- "CHD patients often have increased small discoidal HDL particles and decreased large α-1 and α-2 HDL particles
. The preβ1-HDL was identified as a novel and independent predictor of myocardial infarction (MI) above and beyond traditional CHD risk factors
. Other study showed that small HDL particle size was associated with an increased CHD risk, but this association was largely explained by traditional risk factors
[Show abstract] [Hide abstract]
ABSTRACT: A higher prevalence of coronary heart disease (CHD) in people with diabetes. We investigated the high-density lipoprotein (HDL) subclass profiles and alterations of particle size in CHD patients with diabetes or without diabetes.
Plasma HDL subclasses were quantified in CHD by 1-dimensional gel electrophoresis coupled with immunodetection.
Although the particle size of HDL tend to small, the mean levels of low density lipoprotein cholesterol(LDL-C) and total cholesterol (TC) have achieved normal or desirable for CHD patients with or without diabetes who administered statins therapy. Fasting plasma glucose (FPG), triglyceride (TG), TC, LDL-C concentrations, and HDL3 (HDL3b and 3a) contents along with Gensini Score were significantly higher; but those of HDL-C, HDL2b+preβ2, and HDL2a were significantly lower in CHD patients with diabetes versus CHD patients without diabetes; The preβ1-HDL contents did not differ significantly between these groups. Multivariate regression analysis revealed that Gensini Score was significantly and independently predicted by HDL2a, and HDL2b+preβ2.
The abnormality of HDL subpopulations distribution and particle size may contribute to CHD risk in diabetes patients. The HDL subclasses distribution may help in severity of coronary artery and risk stratification, especially in CHD patients with therapeutic LDL, TG and HDL levels.
[Show abstract] [Hide abstract]
ABSTRACT: Lipid-poor or lipid-free high density lipoprotein (HDL) particles, designated pre ß-HDL, stimulate removal of cell-derived cholesterol to the extracellular compartment, which is an initial step in the reverse cholesterol transport pathway. Pre ß-HDL levels may be elevated in subjects with established cardiovascular disease. We determined the relationship of carotid intima media thickness (IMT), a marker of subclinical atherosclerosis, with pre ß-HDL in subjects without clinically manifest cardiovascular disease.
IMT and plasma pre ß-HDL, assayed by crossed immuno-electrophoresis, were determined in 70 non-diabetic subjects (aged 56±9 years; non-smokers only; 27 women).
IMT was correlated positively with pre ß-HDL, both expressed as plasma apolipoprotein (apo) A-I concentration (r=0.271, p=0.023) and as% of apo A-I (r=0.341, p=0.004). In contrast, IMT was correlated inversely with HDL cholesterol (r=-0.253, p=0.035). IMT was also related positively to pre ß-HDL after adjustment for age, sex, systolic blood pressure (in apoA-I concentration, ß=0.203, p=0.043; in% of plasma apoA-I, ß=0.235, p=0.023). IMT remained associated with pre ß-HDL after additional adjustment for either body mass index, plasma glucose, cholesterol, triglycerides, HDL cholesterol, apoA-I and apoB.
Subclinical atherosclerosis may relate to higher plasma pre ß-HDL independently of apoA-I and HDL cholesterol levels.
Available from: press.endocrine.org
[Show abstract] [Hide abstract]
ABSTRACT: Mifepristone is a glucocorticoid and progestin antagonist under investigation for the treatment of Cushing's syndrome. Mifepristone decreases high-density lipoprotein (HDL) cholesterol (HDL-C) levels in treated patients, but the clinical significance of this is unclear because recent studies suggest that functional properties of HDL predict cardiovascular disease status better than does HDL-C concentration.
The aim of the study was to characterize the impact of mifepristone administration on HDL particle concentration and function.
We conducted a double-blind, randomized, placebo-controlled trial at a single-site, clinical research center.
Thirty healthy postmenopausal female volunteers participated in the study.
Individuals were randomized to receive daily oral mifepristone (600 mg) or placebo for 6 wk.
We measured HDL-C, serum HDL particle concentration, and HDL-mediated cholesterol efflux by treatment group.
As expected, ACTH, cortisol, estradiol, and testosterone levels increased in the mifepristone group. Mifepristone treatment decreased HDL-C and HDL particle concentration by 26 and 25%, respectively, but did not alter pre-β HDL concentration. In contrast, the serum HDL-mediated cholesterol efflux decreased with mifepristone treatment by only 12%, resulting in an effective increase of the efflux capacity per HDL particle. No changes were observed in cholesterol ester transfer protein or lecithin:cholesterol acyltransferase activity.
Treatment with mifepristone reduced HDL-C, HDL particle concentration, and serum HDL cholesterol efflux in postmenopausal women. However, on a per particle basis, the efflux capacity of serum HDL increased. These observations support the concept that a decrease in HDL-C may not represent proportional impairment of HDL function.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.