Association 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: 2.73). 05/2012; 19(5):444-52. DOI: 10.5551/jat.11445
Source: PubMed


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.

Download full-text


Available from: Masayasu Yoneda, Jun 26, 2015
  • Source
    • "Using NMR, the multi-ethnic study of atherosclerosis [22] showed that, compared with total cholesterol and LDL cholesterol, abnormalities in HDL-C and sdLDL-C are more strongly and consistently associated with common carotid artery IMT in patients with moderate chronic kidney disease. Regarding sdLDL-C quantification by simple precipitation methods, Shoji et al. reported that carotid artery IMT was strongly correlated with sdLDL-C in subjects with dyslipidemia , diabetes mellitus, hypertension, and chronic kidney disease, as well as in smokers [23]. Notably, sdLDL-C concentrations were found to be positively correlated with carotid artery IMT as measured by homogenous assay only in Japanese Americans [21]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Small dense low-density lipoprotein cholesterol (sdLDL-C) concentrations correlate more strongly with coronary heart disease than other LDL-C and large LDL particle concentrations. We investigated the association between carotid artery intima-media thickness (IMT) and sdLDL-C concentrations in Japanese subjects. Methods: Carotid artery IMT, blood pressure (BP), fasting plasma sdLDL-C, glucose metabolism, lipid, and C-reactive protein levels were measured in 97 native Japanese subjects. Carotid artery IMT was assessed by ultrasonography, and sdLDL-C concentrations were measured by a homogenous assay. Pearson’s correlation coefficient analyses and multiple regression analyses were used to examine the relationships between carotid artery IMT values, sdLDL-C values, and other clinical variables. Results: After multiple regression analysis, including age, sex, body mass index, systolic BP, diastolic BP, fasting plasma glucose, HbA1c, estimated glomerular filtration rate (eGFR), total-C, high-density lipoprotein (HDL)-C, triglyceride, LDL-C, non-HDL-C, large buoyant LDL-C, and sdLDL-C, carotid artery IMT remained significantly associated with age, systolic BP, diastolic BP, and sdLDL-C, whereas sdLDL-C remained significantly associated with age, total-C, HDL-C, triglycerides, and carotid artery IMT. Conclusions: When measured by a homogenous assay, carotid artery IMT may have a closer relationship with sdLDL-C concentrations than other lipid parameters in Japanese subjects. sdLDL-C may be a potentially useful risk marker when assessing carotid artery IMT in Japanese subjects.
    Clinica chimica acta; international journal of clinical chemistry 01/2015; 442:110-114. DOI:10.1016/j.cca.2015.01.010. · 2.82 Impact Factor
  • Source
    • "Therefore, the HDL2 subfraction seem to be more atherosclerotic protective than the HDL3 subfraction (McPherson et al., 2006). A inverse correlation has been established between the HDL2 subfraction and atherosclerosis where an increase in the HDL2 subfraction results in decrease in its atherosclerosis (Maeda et al., 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: According to literature, the High Density Lipoprotein 2 (HDL2) cholesterol is a better predictor of cardiovascular disease than total HDL. Thus, this study was undertaken to evaluate the interest of HDL2 in the management of Type 2 Diabetes Mellitus (T2DM) patients recruited at University Hospital Yalgado Ouedraogo of Ouagadougou (Burkina Faso, West Africa).The distribution of type 2 diabetes group according to cardiovascular complications reported 37.9% with microvascular complications and 36.4% with macrovascular complications. The total cholesterol, triglyceride, HDL cholesterol and HDL3 cholesterol were significantly higher in type 2 diabetes population compared to control group (p<0.001). On the contrary, a significant decrease of HDL2 cholesterol and LDL cholesterol were observed in T2DM group compared to control group (p<0.05). The decrease of HDL2 cholesterol according to the cardiovascular risk factors was significant in obesity, diabetes duration up to 10 years and hypercholesterolemia. The HDL2 cholesterol variations according to diabetes complications showed significant decrease in metabolic syndrome and hypertension (p<0.001). The HDL2 cholesterol measurement was useful for evaluating cardiovascular risk in diabetics, because in this study only its level was significantly decreased, while total cholesterol and HDL3 cholesterol levels increased and LDL cholesterol level was within normal limits. Therefore, the HDL2 might be including in T2DM management. Indeed, the reagents are available from local providers and the quality control has validated this affordable method for resource limited laboratories.
  • Source
    • "Small, dense LDL (sLDL) cholesterol is a subclass of LDL. In recent years, a large number of epidemiologic and clinical studies have shown the role elevated sLDL levels play in the initiation of As and that it is a risk factor in coronary heart disease.4,5 "
    [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. DOI:10.1016/j.curtheres.2013.11.006 · 0.45 Impact Factor
Show more