Dataset Information

A comparison of the theoretical relationship between HDL size and the ratio of HDL cholesterol to apolipoprotein A-I with experimental results from the Women's Health Study.

ABSTRACT: BACKGROUND:HDL size and composition vary among individuals and may be associated with cardiovascular disease and diabetes. We investigated the theoretical relationship between HDL size and composition using an updated version of the spherical model of lipoprotein structure proposed by Shen et al. (Proc Natl Acad Sci U S A 1977;74:837-41.) and compared its predictions with experimental data from the Women's Health Study (WHS). METHODS:The Shen model was updated to predict the relationship between HDL diameter and the ratio of HDL-cholesterol (HDL-C) to apolipoprotein A-I (ApoA-I) plasma concentrations (HDL-C/ApoA-I ratio). In the WHS (n = 26 772), nuclear magnetic resonance spectroscopy (NMR) was used to measure the mean HDL diameter (d(mean,NMR)) and particle concentration (HDL-P); HDL-C and ApoA-I (mg/dL) were measured by standardized assays. RESULTS:The updated Shen model predicts a quasilinear increase of HDL diameter with the HDL-C/ApoA-I ratio, consistent with the d(mean,NMR) values from WHS, which ranged between 8.0 and 10.8 nm and correlated positively with the HDL-C/ApoA-I ratio (r = 0.608, P < 2.2 × 10(-16)). The WHS data were further described by a linear regression equation: d(WHS) = 4.66 nm + 12.31(HDL-C/Apo-I), where d(WHS) is expressed in nanometers. The validity of this equation for estimating HDL size was assessed with data from cholesteryl ester transfer protein deficiency and pharmacologic inhibition. We also illustrate how HDL-P can be estimated from the HDL size and ApoA-I concentration. CONCLUSIONS:This study provides a large-scale experimental examination of the updated Shen model. The results offer new insights into HDL structure, composition and remodeling and suggest that the HDL-C/ApoA-I ratio might be a readily available biomarker for estimating HDL size and HDL-P.

SUBMITTER: Mazer NA

PROVIDER: S-EPMC3669243 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A comparison of the theoretical relationship between HDL size and the ratio of HDL cholesterol to apolipoprotein A-I with experimental results from the Women's Health Study.

Mazer Norman A NA Giulianini Franco F Paynter Nina P NP Jordan Paul P Mora Samia S

Clinical chemistry 20130220 6

<h4>Background</h4>HDL size and composition vary among individuals and may be associated with cardiovascular disease and diabetes. We investigated the theoretical relationship between HDL size and composition using an updated version of the spherical model of lipoprotein structure proposed by Shen et al. (Proc Natl Acad Sci U S A 1977;74:837-41.) and compared its predictions with experimental data from the Women's Health Study (WHS).<h4>Methods</h4>The Shen model was updated to predict the relat ...[more]

PMID: 23426429

Similar Datasets

Project description:AimsThe total cholesterol (TC)/high-density lipoprotein (HDL) cholesterol ratio may carry additional information not available in more commonly used single cholesterol measures. Analysis of discordance between lipid parameters might help assess the impact of such additional information on the risk of atherosclerotic cardiovascular disease. We aimed to investigate the role of the TC/HDL-cholesterol ratio in determining atherosclerotic cardiovascular disease risk when discordant with low-density lipoprotein (LDL) cholesterol and non-HDL-cholesterol.MethodsWe studied 14,403 Atherosclerosis Risk in Communities (ARIC) study participants who were free of atherosclerotic cardiovascular disease at baseline. TC/HDL-cholesterol discordance with LDL-cholesterol (estimated by the novel Martin/Hopkins method) and non-HDL-cholesterol was assessed at five visits and determined by being at or above the median for each lipid parameter. We constructed Cox proportional hazard models to estimate the risk for incident atherosclerotic cardiovascular disease events associated with each lipid concordance/discordance category using a time-varying approach.ResultsMean age of participants was 54.1 years, 56% women and 25% black. There were 2634 atherosclerotic cardiovascular disease events over a median (interquartile range) follow-up of 24.2 (16.0-25.4) years. Among individuals with LDL-cholesterol and non-HDL-cholesterol less than the median, 26% and 21% had discordant TC/HDL-cholesterol at or above the median, respectively. These individuals had a 24% (hazard ratio (HR) 1.24, 95% confidence interval (CI) 1.09, 1.41) and 29% (HR 1.29, 95% CI 1.13, 1.46) greater risk of incident atherosclerotic cardiovascular disease, respectively, compared to those with TC/HDL-cholesterol less than the median after multivariable adjustment. In individuals with diabetes with LDL-cholesterol or non-HDL-cholesterol less than the median, discordant TC/HDL-cholesterol at or above the median was more prevalent at 48% and 38%, respectively.ConclusionClinically significant discordance exists between TC/HDL-cholesterol, available from the standard lipid profile, and the routinely used non-HDL-cholesterol and LDL-cholesterol. Such discordance may help inform atherosclerotic cardiovascular disease risk management, particularly in individuals with diabetes in whom discordance is more common.

Project description:AimsPlasma levels of apolipoprotein B (apoB), the main surface protein on LDL particles, and LDL-C, the amount of cholesterol in those particles, are closely correlated and, considered separately, are positive risk factors. Plasma levels of apolipoprotein A(1), the main surface protein on HDL particles, and HDL-C, the amount of cholesterol in those particles, are also closely correlated with each other and, considered separately, are negative risk factors. The interdependence of these four risk factors is unclear.Methods and resultsCase-control study among 3510 acute myocardial infarction patients (without prior vascular disease, diabetes, or statin use) in UK hospitals and 9805 controls. Relative risks (age, sex, smoking, and obesity-adjusted) were more strongly related to apoB than to LDL-C and, given apoB, more strongly negatively related to apoA(1) than to HDL-C. The ratio apoB/apoA(1) was uncorrelated with time since symptom onset in cases, was reproducible in samples collected a few years apart in controls (correlation 0.81), and encapsulated almost all the predictive power of these four measurements. Its effect was continuous, substantial throughout the UK normal range [relative risk, top vs. bottom decile of this ratio, 7.3 (95% CI 5.8-9.2)] and varied little with age. The ratio apoB/apoA(1) was substantially more informative about risk (chi(1)(2) = 550) than were commonly used measures such as LDL-C/HDL-C, total/HDL cholesterol, non-HDL cholesterol, and total cholesterol (chi(1)(2) = 407, 334, 204, and 105, respectively). Given apoB and apoA(1), the relationship with risk of LDL-C was reversed, and this reversal was strengthened by appropriate allowance for random measurement errors in two correlated variables. Given usual apoB, lower LDL-C (consistent with smaller LDL particles) was associated with higher risk (P < 0.0001). During the first 8 h after symptom onset HDL-C increased by about 10%, precluding reliable assessment of the joint relationship of apoA(1) and pre-onset HDL-C with risk in such retrospective case-control studies.ConclusionApolipoprotein ratios are more informative about risk than lipid fractions are. This suggests that, among lipoprotein particles of a particular type (LDL or HDL), some smaller and larger subtypes differ in their effects on risk. Direct measurements of even more specific subtypes of lipoprotein particles may be even more informative about risk.

Dataset Information

A comparison of the theoretical relationship between HDL size and the ratio of HDL cholesterol to apolipoprotein A-I with experimental results from the Women's Health Study.

Publications

A comparison of the theoretical relationship between HDL size and the ratio of HDL cholesterol to apolipoprotein A-I with experimental results from the Women's Health Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets