Article

Associations between small dense LDL, HDL subfractions (HDL2, HDL3) and risk of atherosclerosis in Japanese-Americans.

Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Japan.
Journal of atherosclerosis and thrombosis (Impact Factor: 2.93). 05/2012; 19(5):444-52. DOI: 10.5551/jat.11445
Source: PubMed

ABSTRACT Small dense low-density lipoprotein (sdLDL) has been suggested to be more atherogenic than large buoyant LDL. High-density lipoprotein (HDL) consists of two major subfractions (HDL2, HDL3), and just as controversy remains regarding which of the two is the more powerful negative risk factor for atherosclerosis, associations between sdLDL and these HDL subfractions are unclear.
We measured sdLDL cholesterol (sdLDL-C), HDL2 cholesterol (HDL2-C) and HDL3 cholesterol (HDL3-C) by a newly developed method in 481 Japanese-Americans who were not using lipid-lowering medication, and examined the associations of these cholesterol concentrations with variables related to atherosclerosis.
In multivariate analysis, sdLDL-C was positively correlated with the body mass index (BMI), fasting glucose and insulin, 2-h glucose, HOMA-IR, high sensitivity C-reactive protein (hsCRP), and carotid artery intima-media thickness (IMT) after adjustment for age and sex. In particular, sdLDL-C was positively correlated with IMT, even after adjustment for sex, age, smoking status, hypertension, diabetes mellitus and hsCRP. HDL2-C was more closely inversely correlated than total HDL-C with BMI, fasting glucose and insulin, 2-h glucose, HOMA-IR, and hsCRP, whereas HDL3-C was not correlated with these factors. Additionally, HDL2-C was more closely correlated than total HDL-C or HDL3-C with sdLDL-C, LDL-C, triglycerides (TG), and apolipoprotein B (apoB).
SdLDL-C was closely associated with insulin resistance and glucose tolerance, lending credence to its potential as a useful risk marker in assessing carotid artery IMT and the present degree of atherosclerosis in Japanese-Americans. The findings also suggest that subjects with higher HDL2-C levels were better protected from atherosclerosis.

0 Bookmarks
 · 
233 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Coronary heart disease (CHD) is the leading cause of death in the United States, yet assessing risk of its development remains challenging. The present study evaluates a new automated assay of small dense low-density lipoprotein cholesterol content (sdLDL-C) and whether sdLDL-C is a risk factor for CHD compared with LDL-C or small LDL particle concentrations derived from nuclear magnetic resonance spectroscopy. sdLDL-C was measured using a new automated enzymatic method, and small LDL concentrations were obtained by nuclear magnetic resonance in 4387 Multi-Ethnic Study of Atherosclerosis participants. Cox regression analysis estimated hazard ratios for developing CHD for 8.5 years after adjustments for age, race, sex, systolic blood pressure, hypertension medication use, high-density lipoprotein cholesterol, and triglycerides. Elevated sdLDL-C was a risk factor for CHD in normoglycemic individuals. Those in the top sdLDL-C quartile showed higher risk of incident CHD (hazard ratio, 2.41; P=0.0037) compared with those in the bottom quartile and indicated greater CHD risk than the corresponding quartile of LDL-C (hazard ratio, 1.75; P=0.019). The association of sdLDL-C with CHD risk remained significant when LDL-C (<2.57 mmol/L) was included in a multivariate model (hazard ratio, 2.37; P=0.012). Nuclear magnetic resonance-derived small LDL concentrations did not convey a significant risk of CHD. Those with impaired fasting glucose or diabetes mellitus showed higher sdLDL-C and small LDL concentrations but neither was associated with higher CHD risk in these individuals. This new automated method for sdLDL-C identifies risk for CHD that would remain undetected using standard lipid measures, but only in normoglycemic, nondiabetic individuals.
    Arteriosclerosis Thrombosis and Vascular Biology 11/2013; · 6.34 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Atherogenic dyslipidemia characterized by abnormal changes in plasma lipid profile such as low high-density lipoprotein (HDL) and increased triglyceride (TG) levels is strongly associated with atherosclerotic diseases. We aimed to evaluate the levels of pro- and antiatherogenic lipids and erythrocyte membrane cholesterol (EMC) content in normo- and dyslipidemic subjects to investigate whether EMC content could be a useful marker for clinical presentation of atherogenic dyslipidemia. Low-density lipoprotein (LDL), HDL and their subfraction levels and erythrocyte lipid content were determined in 64 normolipidemic (NLs), 42 hypercholesterolemic (HCs) and 42 mixed-type dyslipidemic subjects (MTDs). Plasma atherogenic lipid indices [small-dense LDL (sdLDL)/less-dense HDL (LHDL), TC/HDL-C, TG/HDL-C and Apo B/AI] were higher in MTDs compared to NLs (p < 0.001). The highest sdLDL level was observed in HCs (p < 0.01). Despite a slight increase in EMC level in dyslipidemic subgroups, the difference was not statistically significant. A significant negative correlation, however, was observed between EMC and sdLDL/LHDL in HCs (p < 0.035, r = -0.386). Receiver operating characteristic curves to predict sdLDL level showed that TG and EMC levels had higher area under curve values compared to other parameters in HCs. We showed that diameters of larger LDL and HDL particles tend to shift toward smaller values in MTDs. Our results suggest that EMC content and TG levels may be a useful predictor for sdLDL level in hypercholesterolemic patients.
    Journal of Membrane Biology 11/2013; · 2.48 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective We aimed to investigate how losartan exerts protective effects on human umbilical vein endothelial cell injury induced by small, dense, LDL (sLDL) cholesterol particles. Methods sLDL cholesterol was isolated by a 2-steps method and the nuclear translocation and activation of nuclear factor-κB (NF-κB) in endothelial cells was observed by confocal microscopy and electrophoretic mobility shift assays. Results Losartan greatly inhibited the nuclear translocation of NF-κB induced by sLDL cholesterol in a dose-dependent manner. Conclusions sLDL cholesterol may be involved in endothelial dysfunction possibly through NF-κB activation; losartan protects against sLDL cholesterol-inducing endothelial cell injury by inhibiting NF-κB activation, suggesting that losartan may play a role in the prevention and treatment of cardiovascular disease.
    Current Therapeutic Research 12/2014; 76:17–20. · 0.45 Impact Factor