Effects of fatty liver on the size and composition of high-density lipoprotein cholesterol subpopulations in adolescents with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is an emerging disease in the pediatric population. The association between T2DM and non-alcoholic fatty liver disease (NAFLD) has been described. Recent evidence suggests that sizes and composition of high-density lipoprotein (HDL) may be more important that HDL-C levels in predicting coronary heart disease. There is not data regarding the HDL subclasses distribution and composition in T2DM youths with NAFLD. METHODS: This cross-sectional study included 47 adolescents with T2DM and 23 non-diabetic controls of both sexes aged 10 to 18 years. The presence of NAFLD was determined estimated proton density fat fraction (PDFF) by magnetic resonance by spectroscopy. We compared the HDL subclasses distribution (HDL2b, HDL2a, HDL3a HDL3b and HDL3c) and the HDL chemical composition (total protein, triglyceride, phospholipid, cholesteryl esters, and free cholesterol) between the groups of adolescents with T2DM and the control group. RESULTS: Patients with T2DM and NAFLD had a significantly lower proportion HDL2b (P = .040) and a higher proportion of HDL3c (P = .035); higher proportion of TG (P = .032) and a lower CE (P = .002) and FC (P < .001). A negative association was observed between PDFF and the percentages of HDL2b (r2 = -0.341, P = .004) and the average particle size (r2 = -0.327, P = .05), and a positive association with HDL3c subpopulations (r2 = 0.327, P = .015); about composition inside HDL particle, a positive association with PDFF and the TG (r2 = 0.299, P = .013) and negative with CE (r2 = -0.265, P = .030). CONCLUSIONS: In adolescents diagnosed with T2DM, the presence of NAFLD is associated with abnormalities in the distribution of HDL subpopulations and the lipid composition of HDL particles.

A Novel Protein Glycan-Derived Inflammation Biomarker Independently Predicts Cardiovascular Disease and Modifies the Association of HDL Subclasses with Mortality.

BACKGROUND: Evidence suggests that systemic inflammation may adversely impact HDL function. In this study we sought to evaluate the independent and incremental predictive performance of GlycA-a novel serum inflammatory biomarker that is an aggregate measure of enzymatically glycosylated acute phase proteins-and HDL subclasses on adverse events in a retrospective observational study of a secondary prevention population and to understand a priori defined potential interactions between GlycA and HDL subclasses. METHODS: GlycA and HDL subclasses were measured using proton nuclear magnetic resonance spectroscopy in 7617 individuals in the CATHGEN (CATHeterization GENetics) cardiac catheterization biorepository. RESULTS: GlycA was associated with presence [odds ratio (OR) 1.07 (1.02-1.13), P = 0.01] and extent [OR 1.08 (1.03, 1.12) P < 0.0005] of coronary artery disease and with all-cause mortality [hazard ratio (HR) 1.34 (1.29-1.39), P < 0.0001], cardiovascular mortality [1.37 (1.30-1.45), P < 0.0001] and noncardiovascular mortality [1.46 (1.39-1.54) P < 0.0001] in models adjusted for 10 cardiovascular risk factors. GlycA and smaller HDL subclasses had independent but opposite effects on mortality risk prediction, with smaller HDL subclasses being protective [HR 0.69 (0.66-0.72), P < 0.0001]. There was an interaction between GlycA and smaller HDL subclasses-increasing GlycA concentrations attenuated the inverse association of smaller HDL subclasses with mortality. Adding GlycA and smaller HDL subclasses into the GRACE (Global Registry of Acute Coronary Events) and Framingham Heart Study Risk Scores improved mortality risk prediction, discrimination and reclassification. CONCLUSIONS: These findings highlight the interaction of systemic inflammation and HDL with clinical outcomes and may increase precision for clinical risk assessment in secondary prevention populations.

[Clinical Application of Methods for the Qualitative Evaluation of Lipid Abnormalities].

Recent lifestyle and social environment changes in Japan have been accompanied by increasing incidencerates of metabolic disorders, such as dyslipidemia and diabetes. Therefore, the rates of cardiovascular disease due to the progression of atherosclerosis are also increasing, and cardiovascular disease remains the leading cause of death in Japan. In particular, dyslipidemia, represented by hypercholesterolemia, hypertriglyceridemia, and hypoalphalipoproteinemia, is closely related to the onset and progression of atherosclerosis. Total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol have been used as quantitative markers of lipids to evaluate cardiovascular risks. However, these markers are not sufficient to fully assess the risks. Therefore, we focused on qualitative markers that represent lipid abnormalities, and examined the utility of qualitative lipids evaluation as clinical markers of atherosclerotic disorders. Previously, we reported that HDL and LDL subclasses and sterol markers are clinically important for evaluating the pathogenesis and risks of cardiovascular disorders. Moreover, lipoprotein subclasses may be useful as therapeutic markers for cardiovascular disorders, and oxysterols may also be useful as diagnostic markers for dementing disorders and diseases of the central nervous system. These issues remain to befully elucidated in the future.

Association of high-density lipoprotein subclasses and incident coronary heart disease: The Jackson Heart and Framingham Offspring Cohort Studies.

AIMS: We aimed to clarify the associations of high-density lipoprotein cholesterol (HDL-C) subclasses with incident coronary heart disease (CHD) in two large primary prevention cohorts. METHODS: We measured cholesterol at baseline from the two major HDL subfractions (larger, more buoyant HDL2 and smaller, denser HDL3) separated by density gradient ultracentrifugation in 4114 (mean age 53.8 years; 64% female) African American participants from the Jackson Heart Study and 818 (mean age 57.3 years, 52% female) predominantly Caucasian participants from the Framingham Offspring Cohort Study. Multivariable adjusted hazard ratios (HRs) for HDL-C and its subclasses were derived from Cox proportional hazards regression models to estimate associations with incident CHD events including myocardial infarction, CHD death, and revascularization. Analyses were performed for each cohort separately and as a combined population. RESULTS: In models adjusted for cardiovascular risk factors for the combined population, HDL3-C (HR 0.76 per SD increase; 95% confidence interval (CI), 0.62-0.94; p = 0.01), rather than HDL2-C (HR 0.88 per SD; 95% CI, 0.72-1.09; p = 0.24) drove the inverse association of HDL-C (HR 0.79 per SD; 95% CI, 0.64-0.98; p = 0.03) with CHD. Similar associations were seen in multivariable analyses within each cohort including after adjusting for apolipoprotein A1 in the Jackson Heart Study. CONCLUSION: Smaller, denser HDL3-C levels are primarily responsible for the inverse association between HDL-C and incident CHD in this diverse group of primary prevention subjects. These findings have important implications ranging from considerations of HDL biology to interpretations of clinical trials utilizing HDL-C therapeutics.

Differential Association Between HDL Subclasses and the Development of Type 2 Diabetes in a Prospective Study of Japanese Americans.

OBJECTIVE: Recent studies have suggested that HDL cholesterol is inversely associated with the development of type 2 diabetes. However, little is known about the association between different HDL subclasses and the risk for future type 2 diabetes. RESEARCH DESIGN AND METHODS: The study enrolled 406 Japanese Americans (51% male) without diabetes, aged 34-75 years. Oral glucose tolerance tests were performed to determine type 2 diabetes status at baseline, 2.5 years, 5 years, and 10 years after enrollment. HDL2, HDL3, total HDL cholesterol, and visceral adipose tissue (VAT) area by computed tomography were measured at baseline. RESULTS: In univariate analysis, total HDL and HDL2 cholesterol were inversely associated with the incidence of type 2 diabetes, but HDL3 cholesterol was not. In multivariate analysis, total HDL cholesterol (odds ratio per 1-SD increment, 0.72 [95% CI 0.52-0.995], P = 0.047) and HDL2 cholesterol (odds ratio per 1-SD increment, 0.64 [95% CI 0.44-0.93], P = 0.018) were inversely associated with the risk for type 2 diabetes independent of age, sex, BMI, waist circumference, family history of diabetes, lifestyle factors, systolic blood pressure, lipid-lowering medication use, triglyceride level, HOMA-insulin resistance, and 2-h glucose; however, HDL3 cholesterol was not associated with diabetes risk. The association between diabetes risk and total HDL and HDL2 cholesterol became insignificant after adjustment for VAT area. CONCLUSIONS: Subjects with higher HDL2 cholesterol were at lower risk for incident type 2 diabetes, but this association was confounded by and not independent of VAT. Higher HDL3 cholesterol was not associated with diabetes risk.

HDL particle subpopulations: Focus on biological function.

Low levels of high-density lipoprotein-cholesterol (HDL-C) constitute an independent biomarker of cardiovascular morbi-mortality. However, recent advances have drastically modified the classical and limited view of HDL as a carrier of 'good cholesterol', and have revealed unexpected levels of complexity in the circulating HDL particle pool. HDL particles are indeed highly heterogeneous in structure, intravascular metabolism and biological activity. This review describes recent progress in our understanding of HDL subpopulations and their biological activities, and focuses on relationships between the structural, compositional and functional heterogeneity of HDL particles.

HDL cholesterol subclasses, myocardial infarction, and mortality in secondary prevention: the Lipoprotein Investigators Collaborative.

AIMS: High-density lipoprotein (HDL) is highly heterogeneous and the link of its subclasses to prognosis remains controversial. We aimed to rigorously examine the associations of HDL subclasses with prognosis in secondary prevention. METHODS AND RESULTS: We collaboratively analysed data from two, complementary prospective cohorts: the TRIUMPH study of 2465 acute myocardial infarction patients, and the IHCS study of 2414 patients who underwent coronary angiography. All patients had baseline HDL subclassification by vertical-spin density gradient ultracentrifugation. Given non-linearity, we stratified by tertiles of HDL-C and its two major subclasses (HDL2-C, HDL3-C), then compared multivariable-adjusted hazard ratios for mortality and mortality/myocardial infarction. Patients were middle-aged to elderly (TRIUMPH: 58.2 ± 12.2 years; IHCS: 62.6 ± 12.6 years), and the majority were men (TRIUMPH: 68.0%; IHCS: 65.5%). IHCS had lower mean HDL-C levels (34.6 ± 10.1 mg/dL) compared with TRIUMPH (40 ± 10.6 mg/dL). HDL3-C accounted for >3/4 of HDL-C (mean HDL3-C/HDL-C 0.78 ± 0.05 in both cohorts). During 2 years of follow-up in TRIUMPH, 226 (9.2%) deaths occurred, while death/myocardial infarction occurred in 401 (16.6%) IHCS patients over 5 years. No independent associations with outcomes were observed for HDL-C or HDL2-C. In contrast, the lowest tertile of HDL3-C was independently associated with >50% higher risk in each cohort (TRIUMPH: with middle tertile as reference, fully adjusted HR for mortality of HDL3-C, 1.57; 95% CI, 1.13-2.18; IHCS: fully adjusted HR for mortality/myocardial infarction, 1.55; 95% CI, 1.20-2.00). CONCLUSION: In secondary prevention, increased risk for long-term hard clinical events is associated with low HDL3-C, but not HDL2-C or HDL-C, highlighting the potential value of subclassifying HDL-C.

Validation of a novel homogeneous assay for of HDL3-C measurement.

BACKGROUND: Low serum concentration of high density lipoprotein2 cholesterol (HDL2-C) is associated with increased risk of cardiovascular events. HDL2-C is calculated indirectly by subtracting high density lipoprotein3 cholesterol (HDL3-C) from total high density lipoprotein cholesterol (HDL-C). However, the special equipment and long assay times required for HDL3-C measurement have hindered the use of HDL2-C clinically. Here, we report the validation of a simple and rapid homogeneous assay for HDL3-C that is adaptable to clinical chemistry analyzers. MATERIALS AND METHODS: Method comparison based on 2740 serum specimens spanning the physiological range of HDL3-C was analyzed in singlicate to evaluate and validate a new homogeneous assay from Denka Seiken against the conventional dextran sulfate precipitation method. This study was performed over five days. Serum pools were prepared for the analysis of precision over 5 days (5 measurements per day), linearity, and interference (hemoglobin, bilirubin, and triglycerides) evaluation. RESULT: The homogeneous method had good within-run precision at concentrations of 24, 36, and 46 mg/dl, yielding standard deviations (SD) of 0.2 (0.9%) 0.4 (1.2%), and 0.5 (1.1%), respectively. Between-day precision, performed over 5 days using the same serum pools, yielded SD of 0.3 (1.4%), 1.0 (2.8%), and 0.9 (2.0%), respectively. The assay was linear from 1 to 100 mg/dl and correlated very well with the dextran sulfate precipitation method. There was no interference from hemoglobin up to 500 mg/dl, bilirubin up to 25 mg/dl, or triglycerides up to 1500 mg/dl. CONCLUSION: This homogeneous HDL3-C assay quantitatively measures HDL3-C in serum samples and has excellent precision, and can be implemented on an automated chemistry analyzer, thereby facilitating rapid measurement (~10 min) of a large number of samples in a standard clinical laboratory without the need for additional expensive equipment, laboratory space, or specially-trained staff.

[Studies of influences of blood glucose controlling on the changes of lipid profiles, ApoB100, ApoAI and HDL subclass of newly diagnosed type 2 diabetes].

This study was aimed to observe if the lipid profiles, apoprotein B100 (ApoB100), ApoAI, high density lipoprotein (HDL) and its subclasses could be improved by controlling the blood glucose. Fifty-three patients with newly diagnosed type 2 diabetic were divided into four groups, diet and exercise group (n = 13), continuous subcutaneous insulin infusion (CSII) group (n = 14), multiple daily insulin injection group (MDI, n = 13), and oral hypoglycaemic agents group (n = 13). Fasting blood glucose (FPG), glycated hemoglobin A1c (HbA1c), lipid profiles, ApoB100, ApoAI and HDL subclasses were measured at beginning and a month later. Forty-three patients finished the testing. The levels of FPG, HbA1c, triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and ApoB100 were decreased significantly (P < 0.05) in all groups, and ApoAI/ApoB100 increased obviously (P < 0.05). Comparatively matured HDL subclasses such as HDL2b were increased (P < 0.05), and comparatively infantile HDL subclasses such as HDL3b were decreased (P < 0.05). Therapy with hyperglycemic agents improved TG, TC, LDL-C, ApoB100, ApoAI/ApoB100, and HDL2b significantly (P < 0.05), but intervention with the diet and exercise group alone did not improve lipid profiles, apolipoproteins, and HDL subclasses (P > 0.05). Meanwhile, therapy with insulin intensive therapy (MDI, CSII) group had the most powerful effect on decreasing ApoB100 concentration (P < 0.05). The results suggested that lipid profiles, apolipoproteins, and quantity and quality of HDL subclasses might be improved by blood glucose controlling.

Lipoprotein subclass profiles in young adults born preterm at very low birth weight.

BACKGROUND: Adults born preterm at very low birth weight (VLBW ≤ 1500g) have increased risk factors for cardiovascular diseases including high blood pressure and impaired glucose regulation. Non-optimal lipoprotein profile is generally also likely to affect the increased cardiovascular risk, but lipoprotein subclass level data on adults born at VLBW are sparse. SUBJECTS AND METHODS: We studied 162 subjects born at VLBW and 169 term-born controls, aged 19 to 27 years. Total lipid, triglyceride and cholesterol concentrations of 14 lipoprotein subclasses were determined by proton nuclear magnetic resonance spectroscopy in the fasting state and in 2-hour serum samples from an oral glucose tolerance test. FINDINGS: In comparison to controls, VLBW subjects had significantly higher fasting concentration of triglycerides in chylomicrons and largest very-low-density lipoprotein particles [XXL-VLDL-TG, difference 0.026 (95% CI: 0.004 to 0.049), P=0.024], and of triglycerides in small high-density lipoprotein particles [S-HDL-TG, 0.026 (95% CI: 0.002 to 0.051), P=0.037]. The seemingly important role of triglycerides was further supported by principal component analysis in which the first component was characterized by multiple lipoprotein triglyceride measures. CONCLUSIONS: Young adults born at VLBW and their peers born at term had triglyceride-related differences in both VLDL and HDL subclasses. These differences suggest that the increased risk factors for cardiovascular diseases among the VLBW individuals in adulthood may partly relate to impaired triglyceride metabolism.

HDL subfractions analysis: a new laboratory diagnostic assay for patients with cardiovascular diseases and dyslipoproteinemia.

OBJECTIVE: The HDL family forms a protective part of plasma lipoproteins. It consists of large HDL, intermediate HDL, and small HDL subclasses. The large HDL and intermediate HDL subclasses are considered anti-atherogenic parts of the HDL family. The atherogenicity of the small HDL subclass is currently the subject of much discussion. In the patient group with the diagnosis of cardiovascular disease (arterial hypertension, coronary heart disease) and in individuals with a non-atherogenic hypercholesterolemia, a type of lipoprotein profile (either a non-atherogenic phenotype A, or an atherogenic phenotype B) was identified, and a concentration of small dense LDL (sdLDL) was analyzed. The aim of this study was to identify the major representative of the HDL subclasses in the individuals with cardiovascular diseases, who had an atherogenic lipoprotein phenotype B, and in the individuals with the diagnosis of non-atherogenic hyper-betalipoproteinemia LDL1,2, who had a non-atherogenic lipoprotein phenotype A. METHODS: Identification of the specific lipoprotein phenotype and a quantitative analysis of small dense LDL was performed by an electrophoresis method on polyacrylamide gel (PAG), using the Lipoprint LDL system. For a quantitative analysis of HDL subclasses, i.e., large HDL, intermediatete HDL, and small HDL, in subjects with newly diagnosed cardiovascular diseases (arterial hypertension and coronary heart disease), and in subjects with a non-atherogenic hypercholesterolemia (hyper-betalipoproteinemia LDL1,2), we used an innovative electrophoresis method on polyacrylamide gel (PAG), the Lipoprint HDL system. With regard to lipids, total cholesterol and triglycerides in plasma were analyzed by an enzymatic CHOD PAP method. A control group consisted of a group of healthy normolipidemic volunteers without signs of clinically manifested impairment of the cardiovascular system. RESULTS: In the patient group with the diagnosis of arterial hypertension (p<0.0002) and coronary heart disease (p<0.0001), (both are classified as cardiovascular diseases), the large HDL subclass was significantly decreased and the small HDL subclass was increased (p<0.0001). The concentration of the intermediate HDL subclass did not differ from that of the control group. These results were in accordance with an atherogenic lipoprotein phenotype B in individuals with the diagnosis of cardiovascular diseases, where, using a Lipoprint LDL analysis, a high concentration of atherogenic small dense LDL (p<0.0001) was found. Thus, it seems that the small HDL subclass represents an atherogenic part of the HDL family. Conversely, an increased concentration of total HDL (p<0.0001), large HDL (p<0.005), and intermediate HDL subclasses (p<0.0001) was found in a group of subjects with a non-atherogenic hyper-betalipoproteinemia LDL1,2.The concentration of the small HDL subclass did not differ from that of the control group. In this non-atherogenic lipoprotein profile, only traces of atherogenic small dense LDL were identified. CONCLUSIONS: The advantages of this new method includes: (i) Identification of ten HDL subfractions with Lipoprint HDL analysis (large HDL1-3, intermediate HDL 4-7, and small HDL 8-10) . (ii) Discovery of a high concentration of small HDL in plasma lipoproteins in patients with cardovascular diseases with an atherogenic lipoprotein phenotype B, confirms that the atherogenic subclass of HDL family is attributable to small HDL. (iii) Presence of a low concentration of small HDL in non-atherogenic hypercholesterolemia also confirms the atherogenic characteristics of the small HDL subclass per se. (iv) Presence of small dense LDL is definitive to diagnose an atherogenic lipoprotein profile. It is valid for hyperlipidemia and for normolipidemia as well.

Associations between serum lipid levels and chronic low back pain.

BACKGROUND: Low back pain may be related to abnormal lipid levels because of atherosclerosis in arteries supplying the lumbar region. METHODS: In the cross-sectional HUNT 2 study in the Norwegian county of Nord-Trøndelag, lipid levels were measured in 33,962 women and 30,031 men. A total of 8954 women (26%) and 6273 men (21%) reported suffering from low back pain continuously for at least 3 months in the past year. RESULTS: In age-adjusted analyses, the prevalence of low back pain was inversely associated with HDL cholesterol and positively associated with triglycerides, with stronger associations in women than in men. Relatively weak associations remained in women after adjustment for smoking, physical activity, education, work status, blood pressure, and body mass, but no associations remained among men. Total cholesterol levels were unrelated to low back pain in either sex after age adjustment. CONCLUSIONS: The results are partly consistent with the atherosclerosis hypothesis.

High-density lipoprotein subclasses are a potential intermediary between alcohol intake and reduced risk of cardiovascular disease: the Rancho Bernardo Study.

We conducted a cross-sectional study of NMR-derived HDL subclasses and alcohol intake among 2171 community-dwelling older adults with a large proportion of daily or near-daily alcohol consumers (44 %). We aimed to assess whether, in addition to increasing total HDL, alcohol may induce a beneficial shift in HDL particle size distribution. Participants were categorised based on reported alcohol intake (g per week) and on frequency (none, < 3 times/week, 3-4 times/week, ≥ 5 times/week). The association between alcohol intake and lipoprotein fractions was examined using sex-specific linear regression models adjusted for age, BMI, diabetes, current smoking, exercise and hormone therapy in women. There was a stepwise gradient with the highest weekly alcohol consumption associated with the highest total HDL size and greatest number of medium and large HDL particles, as well as higher total HDL concentrations (all P < 0.001); total small HDL did not differ. Alcohol-HDL size associations were similar in both sexes and did not differ by use of hormone replacement therapy in women. In conclusion, regular alcohol consumers had a higher number and percentage of large HDL particles than non-drinkers. These results suggest that one way that alcohol may decrease CVD is through potentially favourable changes in lipoprotein subclass composition.

Enzymatic assessment of cholesterol on electrophoresis gels for estimating HDL size distribution and plasma concentrations of HDL subclasses.

The aim of this study was to develop an enzymatic cholesterol staining method to determine HDL subclasses in a polyacrylamide gradient gel electrophoresis, which further allows staining by protein in the same electrophoresis lane. HDLs from 120 healthy individuals were separated through nondenaturing PAGE. HDLs were stained for cholesterol using an enzymatic semisolid mixture. Once the gels were unstained, they were stained again for proteins with Coomassie blue. The proportions of HDL subclasses were determined by densitometry. HDL subclasses were transformed to concentrations using as reference HDL-cholesterol plasma levels. This method is comparable in linearity and reproducibility to Coomassie blue staining, although it provides quantitative data. As expected, HDL size distribution shifted toward larger particles when determined by cholesterol as compared with protein. With this method, we observed different proportions of HDL subclasses between men and women as compared with Coomassie blue staining. We described a method to determine HDL size distribution by enzymatic cholesterol staining on polyacrylamide gels. The method allows the quantification of the cholesterol plasma concentration of each HDL subclass with the possibility to further stain the protein in the same sample. The combination of HDL staining by cholesterol and protein on electrophoresis gels provides information that may have clinical relevance.

A simple and precise method for measuring HDL-cholesterol subfractions by a single precipitation followed by homogenous HDL-cholesterol assay.

HDL consists of two major subfractions, HDL2 and HDL3. This paper describes a simple method for assaying HDL subspecies by combining a single precipitation with a direct high density lipoprotein-cholesterol (HDL-C) assay. A precipitation reagent (0.06 ml) containing 1,071 U/ml heparin, 500 mmol/l MnCl2) and 12 mg/ml dextran sulfate was added to a serum (0.3 ml). The sample was incubated and centrifuged at 10,000 rpm for 10 min. HDL3-C was measured by a homogenous HDL-C assay in the supernatant, and HDL2-C was estimated by subtracting the HDL3-C from the direct HDL-C. The HDL3-C and HDL2-C values determined by the precipitation method were identical to those determined by ultracentrifugation, and there were excellent correlations between the methods in the measurements of HDL3-C and HDL2-C (r = 0.933 and 0.978, respectively; n = 102). The two methods also proved to be highly correlated in the measurement of apolipoprotein A-I and A-II in HDL subfractions. The HDL-C subfractions determined by ultracentrifugation were more closely associated with the homogenous HDL-C assay than with the total cholesterol assay, especially in the hypertriglyceridemic samples. Our method is far simpler and more precise than the classical dual precipitation method for HDL-C subfractions, and it can be easily performed in a routine chemical laboratory.

Relationship between plasma apolipoproteinB concentrations, apolipoproteinB/apolipoproeinA-I and HDL subclasses distribution.

BACKGROUND: To analyze the relationship between plasma apoB100 concentrations, apoB100/apoA-I ratio and the alteration of HDL subclasses distribution. METHODS: The apoA-I contents of plasma HDL subclasses were quantitated by 2-dimensional gel electrophoresis coupled with immunodetection in 506 subjects. RESULTS: The subjects in the highest tertile of apoB100 groups had significantly higher small-sized prebeta(1)-HDL, however lower large-sized HDL(2a), HDL(2b) than the subjects in the lowest tertile of apoB100 group. Furthermore, a significant down in the HDL(2b)/prebeta(1)-HDL values (from 6.8 to 1.6) with a rise in apoB100/apoA-I ratio (from 0.4 to 1.4) were observed. Compared to subjects with apoB100/apoA-I ratio<0.9, the subjects with apoB100/apoA-I ratio > or =0.9 had significantly higher small-sized prebeta(1)-HDL whereas lower HDL(3a), HDL(3b) and large-sized HDL(2a), HDL(2b.) Pearson correlation revealed that concentrations of apoB100 were positively correlated with prebeta(1)-HDL but negatively correlated with HDL(2a) and HDL(2b), and in multivariate analysis, all HDL subclasses were independently associated with the apoB100/apoA-I ratio. CONCLUSION: The apoB100 concentrations, especially apoB100/apoA-I ratio could reflect sensitively the alteration of HDL subclasses distribution. And HDL subclasses distribution characteristics of hyperlipidemic subjects appeared in the subjects with apoB100/apoA-I ratio > or =0.9, which indicated the efficiency of RCT was weakened and the maturation of HDL was blocked.