Reduced HDL particle size as an additional feature of the atherogenic dyslipidemia of abdominal obesity
2001; Elsevier BV; Volume: 42; Issue: 12 Linguagem: Inglês
10.1016/s0022-2275(20)31529-7
ISSN1539-7262
AutoresAgnès Pascot, Isabelle Lemieux, Denis Prud’homme, Angelo Tremblay, André Nadeau, Charles Couillard, Jean Bergeron, Benoı̂t Lamarche, Jean‐Pierre Després,
Tópico(s)Obesity, Physical Activity, Diet
ResumoReduced plasma HDL cholesterol concentration has been associated with an increased risk of coronary heart disease. However, a low HDL cholesterol concentration is usually not observed as an isolated disorder because this condition is often accompanied by additional metabolic alterations. The objective of this study was to document the relevance of assessing HDL particle size as another feature of the atherogenic dyslipidemia found among subjects with visceral obesity and insulin resistance. For that purpose, an average HDL particle size was computed by calculating an integrated HDL particle size using nondenaturing 4–30% gradient gel electrophoresis. Potential associations between this average HDL particle size versus morphometric and metabolic features of visceral obesity were examined in a sample of 238 men. Results of this study indicated that HDL particle size was a significant correlate of several features of an atherogenic dyslipidemic profile such as increased plasma TG, decreased HDL cholesterol, high apolipoprotein B, elevated cholesterol/HDL cholesterol ratio, and small LDL particles as well as increased levels of visceral adipose tissue (AT) (0.33 ≤ |r| ≤ 0.61, P < 0.0001). Thus, men with large HDL particles had a more favorable plasma lipoprotein-lipid profile compared with those with smaller HDL particles. Furthermore, men with large HDL particles were also characterized by reduced overall adiposity and lower levels of visceral AT as well as reduced insulinemic-glycemic responses to an oral glucose load. In conclusion, small HDL particle size appears to represent another feature of the high TG-low HDL cholesterol dyslipidemia found in viscerally obese subjects characterized by hyperinsulinemia.—Pascot, A., I. Lemieux, D. Prud'homme, A. Tremblay, A. Nadeau, C. Couillard, J. Bergeron, B. Lamarche, and J-P. Després. Reduced HDL particle size as an additional feature of the atherogenic dyslipidemia of abdominal obesity. J. Lipid Res. 2001. 42: 2007–2014. Reduced plasma HDL cholesterol concentration has been associated with an increased risk of coronary heart disease. However, a low HDL cholesterol concentration is usually not observed as an isolated disorder because this condition is often accompanied by additional metabolic alterations. The objective of this study was to document the relevance of assessing HDL particle size as another feature of the atherogenic dyslipidemia found among subjects with visceral obesity and insulin resistance. For that purpose, an average HDL particle size was computed by calculating an integrated HDL particle size using nondenaturing 4–30% gradient gel electrophoresis. Potential associations between this average HDL particle size versus morphometric and metabolic features of visceral obesity were examined in a sample of 238 men. Results of this study indicated that HDL particle size was a significant correlate of several features of an atherogenic dyslipidemic profile such as increased plasma TG, decreased HDL cholesterol, high apolipoprotein B, elevated cholesterol/HDL cholesterol ratio, and small LDL particles as well as increased levels of visceral adipose tissue (AT) (0.33 ≤ |r| ≤ 0.61, P < 0.0001). Thus, men with large HDL particles had a more favorable plasma lipoprotein-lipid profile compared with those with smaller HDL particles. Furthermore, men with large HDL particles were also characterized by reduced overall adiposity and lower levels of visceral AT as well as reduced insulinemic-glycemic responses to an oral glucose load. In conclusion, small HDL particle size appears to represent another feature of the high TG-low HDL cholesterol dyslipidemia found in viscerally obese subjects characterized by hyperinsulinemia. —Pascot, A., I. Lemieux, D. Prud'homme, A. Tremblay, A. Nadeau, C. Couillard, J. Bergeron, B. Lamarche, and J-P. Després. Reduced HDL particle size as an additional feature of the atherogenic dyslipidemia of abdominal obesity. J. Lipid Res. 2001. 42: 2007–2014. The inverse relationship between plasma HDL cholesterol concentration and the incidence of coronary heart disease (CHD) is a well-documented phenomenon (1Gordon T. Castelli W.P. Hjottland M.C. Kannel W.B. Dawber T.R. High density lipoprotein as a protective factor against coronary heart disease.Am. J. Med. 1977; 62: 707-714Google Scholar, 2Gordon D.J. Probstfield J.L. Garrison R.J. Neaton J.D. Castelli W.P. Knoke J.D. Jacobs D.R. Bangdiwala S. Tyroler H.A. High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies.Circulation. 1989; 79: 8-15Google Scholar). Plasma HDL cholesterol levels are determined by numerous environmental (3Williams P.T. Haskell W.L. Vranizan K.M. Krauss R.M. The associations of high-density lipoprotein subclasses with insulin and glucose levels, physical activity, resting heart rate, and regional adiposity in men with coronary artery disease: the Stanford Coronary Risk Intervention Project baseline survey.Metabolism. 1995; 44: 106-114Google Scholar, 4Williams P.T. Vranizan K.M. Austin M.A. Krauss R.M. Associations of age, adiposity, alcohol intake, menstrual status, and estrogen therapy with high-density lipoprotein subclasses.Arterioscler. Thromb. 1993; 13: 1654-1661Google Scholar) and genetic (5Freeman D.J. Griffin B.A. Holmes A.P. Lindsay G.M. Gaffney D. Packard C.J. Shepherd J. Regulation of plasma HDL cholesterol and subfraction distribution by genetic and environmental factors. Associations between the TaqI B RFLP in the CETP gene and smoking and obesity.Arterioscler. Thromb. 1994; 14: 336-344Google Scholar) factors. We and others have shown that low HDL cholesterol levels are often accompanied by elevated TG concentrations (6Lamarche B. Després J.P. Moorjani S. Cantin B. Dagenais G.R. Lupien P.J. Triglycerides and HDL-cholesterol as risk factors for ischemic heart disease. Results from the Quebec cardiovascular study.Atherosclerosis. 1996; 119: 235-245Google Scholar, 7Jeppesen J. Hein H.O. Suadicani P. Gyntelberg F. Relation of high TG-low HDL cholesterol and LDL cholesterol to the incidence of ischemic heart disease. An 8-year follow-up in the Copenhagen Male Study.Arterioscler. Thromb. Vasc. Biol. 1997; 17: 1114-1120Google Scholar, 8Tai E.S. Emmanuel S.C. Chew S.K. Tan B.Y. Tan C.E. Isolated low HDL cholesterol: an insulin-resistant state only in the presence of fasting hypertriglyceridemia.Diabetes. 1999; 48: 1088-1092Google Scholar). This high TG-low HDL cholesterol dyslipidemia is a salient feature of the insulin resistance syndrome, which is strongly related to abdominal obesity, especially when accompanied by high levels of visceral adipose tissue (AT) (9Després J.P. Dyslipidaemia and obesity.Baillières Clinical Endocrinology and Metabolism. 1994; 8: 629-660Google Scholar). Furthermore, the high TG-low HDL cholesterol dyslipidemic phenotype has clearly been associated with an increased CHD risk in several prospective studies (7Jeppesen J. Hein H.O. Suadicani P. Gyntelberg F. Relation of high TG-low HDL cholesterol and LDL cholesterol to the incidence of ischemic heart disease. An 8-year follow-up in the Copenhagen Male Study.Arterioscler. Thromb. Vasc. Biol. 1997; 17: 1114-1120Google Scholar, 10Manninen V. Tenkanen L. Koskinen P. Huttunen J.K. Mantari M. Heinonen O.P. Frick M.H. Joint effects of triglyceride and LDL cholesterol concentrations on coronary heart disease risk in the Helsinki Heart Study. Implications for treatment.Circulation. 1992; 85: 37-45Google Scholar, 11Assmann G. Schulte H. Relation of high-density lipoprotein cholesterol and triglycerides to incidence of atherosclerotic coronary artery disease (The PROCAM Experience).Am. J. Cardiol. 1992; 70: 733-737Google Scholar). HDL particles are heterogeneous, and several approaches, such as ultracentrifugation, precipitation, immunoaffinity chromatography, and various types of electrophoresis (12Cheung M.C. Segrest J.P. Albers J.J. Cone J.T. Brouillette C.G. Chung B.H. Kashyap M. Glasscock M.A. Anantharamaiah G.M. Characterization of high density lipoprotein subspecies: structural studies by single vertical spin ultracentrifugation and immunoaffinity chromatography.J. Lipid Res. 1987; 28: 913-929Google Scholar, 13Warnick G.R. Benderson J. Albers J.J. Dextran sulfate-Mg2+ precipitation procedure for quantitation of high-density-lipoprotein cholesterol.Clin. Chem. 1982; 28: 1379-1388Google Scholar), have been used to isolate and characterize HDL subpopulations. Among these methods, HDL have been characterized on the basis of size using nondenaturing polyacrylamide gradient gel electrophoresis (14Blanche P.J. Gong E.L. Forte T.M. Nichols A.V. Characterization of human high-density lipoproteins by gradient gel electrophoresis.Biochim. Biophys. Acta. 1981; 665: 408-419Google Scholar, 15Li Z. McNamara J.R. Ordovas J.M. Schaefer E.J. Analysis of high density lipoproteins by a modified gradient gel electrophoresis method.J. Lipid Res. 1994; 35: 1698-1711Google Scholar). Different subclasses have been identified with this method, namely, HDL3c, HDL3b, HDL3a, HDL2a, and HDL2b (small, dense HDL particles to large HDL particles). However, this classification is subjective because the subclasses were determined only by arbitrary particle sizes without regard to their composition. Thus, the interrelationships among HDL particle size, HDL function, and HDL lipid content are not yet fully defined. Previous studies using this classification have reported relationships between HDL subclasses and different metabolic and anthropometric parameters (3Williams P.T. Haskell W.L. Vranizan K.M. Krauss R.M. The associations of high-density lipoprotein subclasses with insulin and glucose levels, physical activity, resting heart rate, and regional adiposity in men with coronary artery disease: the Stanford Coronary Risk Intervention Project baseline survey.Metabolism. 1995; 44: 106-114Google Scholar, 4Williams P.T. Vranizan K.M. Austin M.A. Krauss R.M. Associations of age, adiposity, alcohol intake, menstrual status, and estrogen therapy with high-density lipoprotein subclasses.Arterioscler. Thromb. 1993; 13: 1654-1661Google Scholar, 16Syvänne M. Ahola M. Lahdenpera S. Kahri J. Kuusi T. Virtanen K.S. Taskinen M.R. High density lipoprotein subfractions in non-insulin-dependent diabetes mellitus and coronary artery disease.J. Lipid Res. 1995; 36: 573-582Google Scholar, 17Williams P.T. Krauss R.M. Vranizan K.M. Stefanick M.L. Wood P.D. Lindgren F.T. Associations of lipoproteins and apolipoproteins with gradient gel electrophoresis estimates of high density lipoprotein subfractions in men and women.Arterioscler. Thromb. 1992; 12: 332-340Google Scholar). Williams et al. (17Williams P.T. Krauss R.M. Vranizan K.M. Stefanick M.L. Wood P.D. Lindgren F.T. Associations of lipoproteins and apolipoproteins with gradient gel electrophoresis estimates of high density lipoprotein subfractions in men and women.Arterioscler. Thromb. 1992; 12: 332-340Google Scholar) have reported high levels of HDL3b to be associated with CHD risk factors, suggesting that low HDL3b levels may contribute in part to the low CHD risk in subjects who have high HDL cholesterol. Furthermore, an increased body mass index (BMI) has been associated with higher levels of HDL3b and lower levels of HDL2b (4Williams P.T. Vranizan K.M. Austin M.A. Krauss R.M. Associations of age, adiposity, alcohol intake, menstrual status, and estrogen therapy with high-density lipoprotein subclasses.Arterioscler. Thromb. 1993; 13: 1654-1661Google Scholar), and fasting plasma insulin concentrations have been inversely correlated with plasma HDL3a, HDL2a, and HDL2b (3Williams P.T. Haskell W.L. Vranizan K.M. Krauss R.M. The associations of high-density lipoprotein subclasses with insulin and glucose levels, physical activity, resting heart rate, and regional adiposity in men with coronary artery disease: the Stanford Coronary Risk Intervention Project baseline survey.Metabolism. 1995; 44: 106-114Google Scholar). In addition, Syvänne et al. (16Syvänne M. Ahola M. Lahdenpera S. Kahri J. Kuusi T. Virtanen K.S. Taskinen M.R. High density lipoprotein subfractions in non-insulin-dependent diabetes mellitus and coronary artery disease.J. Lipid Res. 1995; 36: 573-582Google Scholar) have reported that a high hepatic lipase (HL) activity, hyperinsulinemia, and hypertriglyceridemia were independently associated with low levels of HDL2b and generally with small HDL particle size. Case-control and angiographic studies have suggested that CHD risk may be increased when HDL2b concentration is decreased relative to HDL3c and HDL3b (18Wilson H.M. Patel J.C. Skinner E.R. The distribution of high-density lipoprotein subfractions in coronary survivors.Biochem. Soc. Trans. 1990; 18: 1175-1176Google Scholar, 19Johansson J. Carlson L.A. Landou C. Hamsten A. High density lipoproteins and coronary atherosclerosis. A strong inverse relation with the largest particles is confined to normotriglyceridemic patients.Arterioscler. Thromb. 1991; 11: 174-182Google Scholar). In the Québec Cardiovascular Study, the cholesteryl esterrich HDL2 particles appeared to have a greater contribution to the cardioprotective effects of increased HDL cholesterol than did smaller HDL3 particles (20Lamarche B. Moorjani S. Cantin B. Dagenais G.R. Lupien P.J. Després J.P. Associations of HDL2 and HDL3 subfractions with ischemic heart disease in men. Prospective results from the Quebec Cardiovascular Study.Arterioscler. Thromb. Vasc. Biol. 1997; 17: 1098-1105Google Scholar). On the other hand, abdominal obesity has been associated with decreased levels of HDL2 cholesterol (9Després J.P. Dyslipidaemia and obesity.Baillières Clinical Endocrinology and Metabolism. 1994; 8: 629-660Google Scholar). Furthermore, subjects with type 2 diabetes and CHD have been characterized by small-sized HDL particles with a low cholesterol content (16Syvänne M. Ahola M. Lahdenpera S. Kahri J. Kuusi T. Virtanen K.S. Taskinen M.R. High density lipoprotein subfractions in non-insulin-dependent diabetes mellitus and coronary artery disease.J. Lipid Res. 1995; 36: 573-582Google Scholar). These results suggest that the HDL particles of insulin-resistant viscerally obese subjects with high TG-low HDL cholesterol dyslipidemia were likely to be reduced in size. However, this issue has never been examined. Therefore, the objective of the present study was to examine the potential relationships of obesity, visceral AT accumulation, glucose tolerance, plasma insulin, and lipoprotein-lipid concentrations to an average HDL particle size (a cumulative marker of the distribution of the sizes of HDL particles) obtained by nondenaturing 4–30% gradient gel electrophoresis in a sample of 238 men. Furthermore, because we had previously reported that the presence of some features of the insulin resistance syndrome (hyperinsulinemia, elevated apoB, and small LDL particles, defined as the "atherogenic metabolic triad") were associated with a substantial increase in CHD risk (21Lamarche B. Tchernof A. Mauriège P. Cantin B. Dagenais G.R. Lupien P.J. Després J.P. Fasting insulin and apolipoprotein B levels and low-density lipoprotein particle size as risk factors for ischemic heart disease.J. Am. Med. Assoc. 1998; 279: 1955-1961Google Scholar), we also examined the potential relationships between HDL size and the features of this atherogenic metabolic triad. Two hundred and thirty-eight men were recruited from the Québec City metropolitan area by solicitation through the media between 1987 and 1998. Subjects were between 19 and 68 years of age. Participants covered a wide range of BMI values (18–42 kg/m2). All subjects were healthy, nonsmoking volunteers and were not under treatment for CHD, diabetes, dyslipidemias, or endocrine disorders. All participants signed an informed consent document approved by the Laval University Medical Ethics Committee. The hydrostatic weighing technique (22Behnke A.R. Wilmore J.H. Evaluation and Regulation of Body Build and Composition. Prentice-Hall, Englewood Cliffs, NJ1974: 20-37Google Scholar) was used to measure body density, which was obtained from the mean of six measurements. Pulmonary residual volume was measured before immersion in the hydrostatic tank, using the helium dilution method of Meneely and Kaltreider (23Meneely G.R. Kaltreider N.L. Volume of the lung determined by helium dilution.J. Clin. Invest. 1949; 28: 129-139Google Scholar). Percent body fat was derived from body density using the equation of Siri (24Siri W.E. The gross composition of the body.Adv. Biol. Med. Phys. 1956; 4: 239-280Google Scholar). Height and body weight were measured according to the procedures recommended at the Airlie Conference (25Lohman, T., Roche, A., Martorel, R., 1988. The Airlie (VA) consensus conference standardization of anthropometric measurements. In Standardization of Anthopometric Measurements. Champaign, IL. 39–80.Google Scholar), whereas waist circumference was measured as previously mentioned (26van der Kooy K. Seidell J.C. Techniques for the measurement of visceral fat: a practical guide.Int. J. Obes. Relat. Metab. Disord. 1993; 17: 187-196Google Scholar). Measurements of abdominal AT areas were performed by computed tomography with a Siemens Somatom DHR scanner (Erlangen, Germany), as previously described (27Ferland M. Després J.P. Tremblay A. Pinault S. Nadeau A. Moorjani S. Lupien P.J. Thériault G. Bouchard C. Assessment of adipose tissue distribution by computed axial tomography in obese women: association with body density and anthropometric measurements.Br. J. Nutr. 1989; 61: 139-148Google Scholar). Blood samples were collected from an antecubital vein into vacutainer tubes containing EDTA after a 12-h overnight fast for the measurement of plasma lipid and lipoprotein levels. Cholesterol and TG levels were determined in plasma and lipoprotein fractions using a Technicon RA-500 analyzer (Bayer Corporation, Tarrytown, NY), and enzymatic reagents were obtained from Randox Laboratories Ltd. (Crumlin, UK). Plasma VLDL (d < 1.006 g/ml) were isolated by ultracentrifugation (28Havel R.J. Eder H. Bragdon H.F. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum.J. Clin. Invest. 1955; 34: 1345-1353Google Scholar). The HDL fraction was obtained after precipitation of LDL in the infranatant (d > 1.006 g/ml) with heparin and MnCl2 (29Burstein M. Samaille J. Sur un dosage rapide du cholestérol lié aux beta-lipoprotéines du sérum.Clin. Chim. Acta. 1960; 5: 609-610Google Scholar). HDL2 was then precipitated from the HDL fraction (30Gidez L.I. Miller G.J. Burstein M. Slage S. Eder H.H. Separation and quantitation of subclasses of human plasma high density lipoproteins by a simple precipitation procedure.J. Lipid Res. 1982; 23: 1206-1223Google Scholar) with a 4% solution of low-molecular-weight dextran sulfate (15–20 kDa) obtained from SOCHIBO (Boulogne, France). Apolipoprotein B and A-I concentrations were measured by the rocket immunoelectrophoretic method of Laurell (31Laurell C.B. Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies.Anal. Biochem. 1966; 15: 45-52Google Scholar), as previously described (32Moorjani S. Dupont A. Labrie F. Lupien P.J. Brun D. Gagné C. Giguère M. Bélanger A. Increase in plasma high density lipoprotein concentration following complete androgen blockage in men with prostatic carcinoma.Metabolism. 1987; 36: 244-250Google Scholar). A 75-g OGTT was performed in the morning after an overnight fast. Blood samples were collected in EDTA-containing tubes through a venous catheter placed in an antecubital vein at −15, 0, 15, 30, 45, 60, 90, 120, 150, and 180 min for the determination of plasma glucose and insulin concentrations. Plasma glucose was measured enzymatically (33Richterich R. Dauwalder H. Zur bestimmung der plasmaglukosekonzentration mit der hexokinase-glucose-6-phosphatdehydrogenase-methode.Schweiz. Med. Wochenschr. 1971; 101: 615-618Google Scholar), whereas plasma insulin was measured by radioimmunoassay with polyethylene glycol separation (34Desbuquois B. Aurbach G.D. Use of polyethylene glycol to separate free and antibody-bound peptide hormones in radioimmunoassays.J. Clin. Endocrinol. Metab. 1971; 37: 732-738Google Scholar). The total glucose and insulin areas under the curve during the OGTT were determined with the trapezoid method. HDL size. Nondenaturing 4–30% polyacrylamide gel electrophoresis was performed for the measurement of HDL size using whole plasma kept at −80°C, as recently described (35Pérusse M. Pascot A. Després J.P. Couillard C. Lamarche B. A new method for HDL particle sizing by polyacrylamide gradient gel electrophoresis using whole plasma.J. Lipid Res. 2001; 42: 1331-1334Google Scholar). Briefly, gels were casted in the laboratory using acrylamide and bis-acrylamide (40:1.1) obtained from Bio-Rad (Hercules, CA). A volume of 10 μl of plasma samples was applied onto the gel in a final concentration of 15% sucrose and 0.2% bromophenol blue. Electrophoresis was performed at 4°C for a prerun of 15 min at 125 V before the entry of samples and at 70 V for 20 min for the entry of samples into stacking gel, followed by migration at 100 V for 6 h, at 150 V for 12 h, and finally at 200 V for 1–3 h. Gels were stained for lipids overnight with Sudan black B (Lipostain, Paragon electrophoresis system, Beckman, Montréal, Canada) in 55% ethanol. Gels were restored in a 9% acetic acid, 20% methanol solution and subsequently analyzed using the Imagemaster 1-D Prime computer software (version 3.01; Amersham Pharmacia Biotech, Baie d'Urfé, Québec, Canada). The mean HDL particle size was obtained with the migration of lipid-stainable plasma standards of known diameters (35Pérusse M. Pascot A. Després J.P. Couillard C. Lamarche B. A new method for HDL particle sizing by polyacrylamide gradient gel electrophoresis using whole plasma.J. Lipid Res. 2001; 42: 1331-1334Google Scholar). The lipid-stainable standards used were calibrated by computing a log-linear standard curve of the protein-stainable Pharmacia HMW standards as a function of their relative migration distance (Rf). A similar approach was used to assess HDL particle size using the calibrated lipid-stainable bands. The average HDL particle size represents the overall distribution of HDL subspecies and is calculated as a continuous variable using the migration distance of each peak multiplied by its relative area under the densitometric scan, as recently reported (35Pérusse M. Pascot A. Després J.P. Couillard C. Lamarche B. A new method for HDL particle sizing by polyacrylamide gradient gel electrophoresis using whole plasma.J. Lipid Res. 2001; 42: 1331-1334Google Scholar). A higher average HDL size indicated a greater proportion of "large" HDL particles, whereas a low average HDL size suggested an increased prevalence of "small" HDL particles. Inter- and intra-assay coefficients of variation for the average HDL size assessed by this method were <3% (n = 59) and <1% (n = 20), respectively. LDL size. Nondenaturing 2–16% polyacrylamide gel electrophoresis was performed on whole plasma according to the procedure described by Krauss and Burke (36Krauss R.M. Burke D.J. Identification of multiple subclasses of plasma low density lipoproteins in normal humans.J. Lipid Res. 1982; 23: 97-104Google Scholar) and McNamara et al. (37McNamara J.R. Campos H. Ordovas J.M. Peterson J. Wilson P.W. Schaefer E.J. Effect of gender, age, and lipid status on low density lipoprotein subfraction distribution. Results from the Framingham Offspring Study.Arteriosclerosis. 1987; 7: 483-490Google Scholar) and as previously reported (38Tchernof A. Lamarche B. Prud'homme D. Nadeau A. Moorjani S. Labrie F. Lupien P.J. Després J.P. The dense LDL phenotype. Association with plasma lipoprotein levels, visceral obesity, and hyperinsulinemia in men.Diabetes Care. 1996; 19: 629-637Google Scholar). A general linear model was used to compare the groups divided on the basis of average HDL particle size tertiles, and the Duncan post hoc test was used in situations in which a significant group effect was observed. Pearson correlation coefficients were calculated to quantify the univariate associations between variables. Stepwise multiple regression analyses were computed to sort out the independent contribution of metabolic variables to the variance of the average HDL particle size. An unpaired Student's t-test was performed to compare men of this study with low HDL cholesterol levels further divided into two groups on the basis of the 50th percentile of HDL particle size (low vs. high HDL size). All analyses were performed using the SAS statistical package (SAS Institute, Cary, NC). Correlations between HDL parameters and anthropometric indices are presented in Table 1. HDL particle size was inversely related to BMI and waist girth as well as to the levels of fat mass and abdominal visceral and subcutaneous AT areas (−0.26 ≤ r ≤ −0.32, P < 0.0001). Relationships were found between HDL particle size and plasma HDL cholesterol and HDL2 cholesterol levels (r = 0.61 and 0.64, respectively, P < 0.0001), and significant but weak correlations were noted between HDL particle size and HDL3 cholesterol and apolipoprotein A-I levels. Overall, HDL particle size followed the same pattern of correlations with body fat and body fat distribution indices as HDL cholesterol and HDL2 cholesterol, whereas HDL3 cholesterol and apolipoprotein A-I showed weak or even no correlation with body fat indices. On the other hand, no association was found between HDL particle size and LDL-cholesterol (Fig. 1), whereas a significant relationship between LDL peak particle size and average HDL particle size was observed (Fig. 1, r = 0.55, P < 0.0001).TABLE 1.Correlations between HDL components and HDL particle size with body mass index (BMI), total body fatness, and visceral and subcutaneous adipose tissue (AT) accumulation measured by computed tomography and waist girthHDL-CholesterolHDL2-CholesterolHDL3-CholesterolApolipoprotein A-IHDL SizeBMI−0.35aP < 0.0001.−0.40aP < 0.0001.−0.08−0.01−0.32aP < 0.0001.Fat mass−0.36aP < 0.0001.−0.38aP < 0.0001.−0.13bP = 0.05.−0.04−0.26aP < 0.0001.Visceral AT−0.32aP < 0.0001.−0.32aP < 0.0001.−0.14bP = 0.05.0.02−0.28aP < 0.0001.Subcutaneous AT−0.36aP < 0.0001.−0.40aP < 0.0001.−0.10−0.08−0.27aP < 0.0001.Waist girth−0.36aP < 0.0001.−0.38aP < 0.0001.−0.12−0.03−0.31aP < 0.0001.HDL size0.61aP < 0.0001.0.64aP < 0.0001.0.21bP = 0.05.0.31aP < 0.0001.—a P < 0.0001.b P = 0.05. Open table in a new tab To further explore the relationship of HDL particle size to the metabolic features of abdominal obesity, the sample of 238 men was subdivided into subgroups usingthe 33rd and 66th percentiles of the average HDL particle size distribution as cutoff values. Table 2 shows subjects' physical characteristics and plasma lipoprotein-lipid profiles across tertiles of HDL particle size. Men in the upper tertile of HDL particle size (large HDL particles) were characterized by reduced adiposity as reflected by a lower cross-sectional area of visceral abdominal AT and decreased BMI and total body fat mass compared with subjects in the lower and middle tertiles (P < 0.0001). For the plasma lipoprotein-lipid profile, men in the middle tertile were characterized by decreased plasma levels of VLDL cholesterol, TG, VLDL TG, LDL TG, and apolipoproteinB as well as by lower cholesterol/HDL cholesterol ratio and increased plasma levels of HDL cholesterol and HDL2 cholesterol and increased LDL peak particle size compared with subjects in the lower tertile of HDL size (P < 0.01). Furthermore, men in the upper tertile for HDL size were characterized by decreased plasma levels of VLDL cholesterol, TG, VLDL TG, LDL TG, and apolipoprotein B and by a lower cholesterol/HDL cholesterol ratio as well as by increased plasma levels of HDL cholesterol, HDL2 cholesterol, apolipoprotein A-I, and increased LDL peak particle size compared with subjects in both the lower and middle tertiles (P < 0.01). It is also relevant to point out that no difference in levels of total and LDL cholesterol was observed across tertiles of HDL particle size.TABLE 2.Physical characteristics and lipoprotein-lipid profile of the sample of 238 men classified on the basis of HDL particle size tertilesHDL Particle SizeTertile 1 (n = 79) ( 85.1 Å)Physical characteristicsBMI (kg/m2)29.5 ± 4.4228.5 ± 4.6325.3 ± 4.3bSignificantly different from tertiles 1 and 2; P < 0.005.Fat mass (kg)25.1 ± 9.424.2 ± 10.217.6 ± 9.5bSignificantly different from tertiles 1 and 2; P < 0.005.Visceral AT area (cm2)154 ± 63145 ± 6998 ± 61bSignificantly different from tertiles 1 and 2; P < 0.005.Lipoprotein-lipid profileCholesterol (mmol/l)Total5.35 ± 0.815.22 ± 0.844.90 ± 0.95VLDL0.86 ± 0.370.67 ± 0.44aSignificantly different from tertile 1; P < 0.03.0.41 ± 0.26bSignificantly different from tertiles 1 and 2; P < 0.005.LDL3.63 ± 0.743.56 ± 0.833.35 ± 0.87HDL0.85 ± 0.150.97 ± 0.19aSignificantly different from tertile 1; P < 0.03.1.14 ± 0.22bSignificantly different from tertiles 1 and 2; P < 0.005.HDL20.21 ± 0.100.31 ± 0.14aSignificantly different from tertile 1; P < 0.03.0.45 ± 0.17bSignificantly different from tertiles 1 and 2; P < 0.005.HDL30.64 ± 0.130.67 ± 0.140.69 ± 0.13aSignificantly different from tertile 1; P < 0.03.Cholesterol/HDL cholesterol ratio6.47 ± 1.225.54 ± 1.30aSignificantly different from tertile 1; P < 0.03.4.42 ± 1.12bSignificantly different from tertiles 1 and 2; P < 0.005.Triglycerides (mmol/l)Total2.31 ± 0.831.84 ± 0.76aSignificantly different from tertile 1; P < 0.03.1.25 ± 0.62bSignificantly different from tertiles 1 and 2; P < 0.005.VLDL1.70 ± 0.751.29 ± 0.69aSignificantly different from tertile 1; P < 0.03.0.78 ± 0.54bSignificantly different
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