Lipoprotein subfractions and cardiovascular disease risk.
ABSTRACT Subfractions of LDL and HDL defined by differences in particle size and density have been associated to varying degrees with risk of cardiovascular disease (CVD). Assessment of these relationships has been clouded by lack of standardization among the various analytic methodologies as well as the strong correlations of the subfractions with each other and with standard lipid and lipoprotein risk markers. This review summarizes the properties of the major LDL and HDL particle subclasses, and recent evidence linking their measurement with risk of atherosclerosis and CVD.
Several recent studies have shown independent relationships of levels of LDL and HDL-size subclasses to risk of both coronary artery and cerebrovascular disease. However, the two largest studies, employing nuclear magnetic resonance and ion mobility, respectively, did not find evidence that these measurements improved risk assessment compared with standard lipoprotein assays. In the latter study, principal component analysis was used to group multiple subfraction measurements into three distinct and statistically independent clusters that were related both to cardiovascular outcomes and to genotypes that may reflect underlying metabolic determinants.
Although there is as yet inconclusive evidence as to the extent to which LDL and HDL subfraction measurements improve clinical assessment of CVD risk beyond standard lipid risk markers, recent studies suggest that more refined analyses of lipoprotein subspecies may lead to further improvements in CVD risk evaluation and particularly in identification of appropriate targets for therapeutic intervention in individual patients.
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ABSTRACT: Despite evidence to the contrary, exercise interventions for obese youth target weight loss as a means for improving health. Using Exercise is Medicine® as a framework, we present a conceptual model for the beneficial effects of exercise independent of weight loss in obese youth and highlight novel biomarkers of cardiometabolic health that could prove useful as interventional targets for this population.
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ABSTRACT: Lipoproteins are protein-lipid nanoparticles that transport lipids in circulation and are central in atherosclerosis and other disorders of lipid metabolism. Apolipoproteins form flexible structural scaffolds and important functional ligands on the particle surface and direct lipoprotein metabolism. Lipoproteins undergo multiple rounds of metabolic remodeling that is crucial to lipid transport. Important aspects of this remodeling, including apolipoprotein dissociation and particle fusion, are mimicked in thermal or chemical denaturation and are modulated by free energy barriers. Here we review the biophysical studies that revealed the kinetic mechanism of lipoprotein stabilization and unraveled its structural basis. The main focus is on high-density lipoprotein (HDL). An inverse correlation between stability and functions of various HDLs in cholesterol transport suggests the functional role of structural disorder. A mechanism for the conformational adaptation of the major HDL proteins, apoA-I and apoA-II, to the increasing lipid load is proposed. Together, these studies help understand why HDL forms discrete subclasses separated by kinetic barriers, which have distinct composition, conformation and functional properties. Understanding these properties may help improve HDL quality and develop novel therapies for cardiovascular disease. Copyright © 2015. Published by Elsevier B.V.FEBS Letters 03/2015; DOI:10.1016/j.febslet.2015.02.028 · 3.34 Impact Factor
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ABSTRACT: A randomised, cross-over, controlled-feeding study was conducted to evaluate the cholesterol-lowering effects of diets containing pistachios as a strategy for increasing total fat (TF) levels v. a control (step I) lower-fat diet. Ex vivo techniques were used to evaluate the effects of pistachio consumption on lipoprotein subclasses and functionality in individuals (n 28) with elevated LDL levels ( ≥ 2·86 mmol/l). The following test diets (SFA approximately 8 % and cholesterol < 300 mg/d) were used: a control diet (25 % TF); a diet comprising one serving of pistachios per d (1PD; 30 % TF); a diet comprising two servings of pistachios per d (2PD; 34 % TF). A significant decrease in small and dense LDL (sdLDL) levels was observed following the 2PD dietary treatment v. the 1PD dietary treatment (P= 0·03) and following the 2PD dietary treatment v. the control treatment (P= 0·001). Furthermore, reductions in sdLDL levels were correlated with reductions in TAG levels (r 0·424, P= 0·025) following the 2PD dietary treatment v. the control treatment. In addition, inclusion of pistachios increased the levels of functional α-1 (P= 0·073) and α-2 (P= 0·056) HDL particles. However, ATP-binding cassette transporter A1-mediated serum cholesterol efflux capacity (P= 0·016) and global serum cholesterol efflux capacity (P= 0·076) were only improved following the 2PD dietary treatment v. the 1PD dietary treatment when baseline C-reactive protein status was low ( < 103μg/l). Moreover, a significant decrease in the TAG:HDL ratio was observed following the 2PD dietary treatment v. the control treatment (P= 0·036). There was a significant increase in β-sitosterol levels (P< 0·0001) with the inclusion of pistachios, confirming adherence to the study protocol. In conclusion, the inclusion of pistachios in a moderate-fat diet favourably affects the cardiometabolic profile in individuals with an increased risk of CVD.British Journal Of Nutrition 07/2014; 112(05):1-9. DOI:10.1017/S0007114514001561 · 3.34 Impact Factor