Reduced HDL particle size as an additional feature of the atherogenic dyslipidemia of abdominal obesity

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. 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 such as and of M.C. J.P. M. M.A. G.M. of high density lipoprotein studies by and Lipid Res. Scholar, G.R. J. for of have been to and HDL HDL have been characterized on the of size using nondenaturing gradient gel P.J. of high-density by gradient gel Scholar, of high density by a gradient gel Lipid Res. 1994; Scholar). subclasses have been with this and HDL particles to large HDL However, this is because the subclasses were determined only by particle to Thus, the among HDL particle HDL and HDL are not studies using this have between HDL subclasses and metabolic and (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, M. M. S. J. T. High density lipoprotein in and coronary artery Lipid Res. 1995; Scholar, P.T. Krauss R.M. Vranizan K.M. Associations of and with gradient gel of high density lipoprotein in men and Thromb. 1992; Scholar). P.T. Krauss R.M. Vranizan K.M. Associations of and with gradient gel of high density lipoprotein in men and Thromb. 1992; Scholar) have high levels of to associated with CHD risk that low levels in to the low CHD risk in subjects have high HDL Furthermore, an increased has been associated with levels of and lower levels of 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 and fasting plasma insulin concentrations have been with plasma and (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 M. M. S. J. T. High density lipoprotein in and coronary artery Lipid Res. 1995; Scholar) have that a high activity, and were associated with low levels of and with small HDL particle and studies have that CHD risk increased when concentration is decreased to and The distribution of high-density lipoprotein in coronary Scholar, J. C. A. High density and coronary inverse with the particles is to Thromb. Scholar). In the the particles to have a to the effects of increased HDL cholesterol smaller particles B. Moorjani S. Cantin B. Dagenais G.R. Lupien P.J. Després J.P. Associations of and with ischemic heart disease in men. from the Quebec Study.Arterioscler. Thromb. Vasc. Biol. 1997; 17: Scholar). the abdominal obesity has been associated with decreased levels of cholesterol (9Després J.P. Dyslipidaemia and obesity.Baillières Clinical Endocrinology and Metabolism. 1994; 8: 629-660Google Scholar). Furthermore, subjects with and CHD have been characterized by HDL particles with a low cholesterol M. M. S. J. T. High density lipoprotein in and coronary artery Lipid Res. 1995; Scholar). that the HDL particles of insulin-resistant viscerally obese subjects with high TG-low HDL cholesterol dyslipidemia were to reduced in However, this has been the objective of the study was to the of obesity, visceral AT glucose plasma and lipoprotein-lipid concentrations to an average HDL particle size of the distribution of the of HDL by nondenaturing 4–30% gradient gel in a sample of 238 men. Furthermore, because had that the presence of features of the insulin resistance elevated and small LDL as the metabolic were associated with a in CHD risk B. A. P. Cantin B. Dagenais G.R. Lupien P.J. Després J.P. insulin and apolipoprotein B levels and lipoprotein particle size as risk factors for ischemic heart Med. also examined the between HDL size and the features of this atherogenic metabolic and men were from the by the between and were between and of a of subjects were and were not for an document by the The and Regulation of and Scholar) was to which was from the of was in the using the of and G.R. of the determined by Scholar). was from density using the of The of the Biol. Med. Scholar). and were to the the A., The of In of was as for the of visceral a J. 1993; 17: Scholar). of abdominal AT were by computed with a as M. Després J.P. A. S. A. Moorjani S. Lupien P.J. G. C. of adipose tissue distribution by computed in obese with density and J. 1989; Scholar). were from an a for the of plasma and lipoprotein and TG levels were determined in plasma and lipoprotein using a and were from Plasma < were isolated by R.J. H. The distribution and of in Scholar). The HDL was of LDL in the with and M. J. Scholar). was from the HDL M. S. and of subclasses of plasma high density by a Lipid Res. Scholar) with a of from B and concentrations were by the of of by in gel as S. A. F. Lupien P.J. D. C. M. A. in plasma high density lipoprotein concentration in men with Scholar). was in the an were in a in an and for the of plasma glucose and insulin Plasma glucose was H. Med. plasma insulin was by with B. of to and in Scholar). The glucose and insulin the the were determined with the HDL 4–30% gel was for the of HDL size using plasma as M. A. Després J.P. C. B. for HDL particle by gradient gel using Lipid Res. 42: Scholar). were in the using and from of of plasma was the gel in a concentration of and was for a of the of and for for the of by for for and for were for with B in were in a and using the The HDL particle size was with the of plasma of M. A. Després J.P. C. B. for HDL particle by gradient gel using Lipid Res. 42: Scholar). The were by a of the as a of was to HDL particle size using the The average HDL particle size the overall distribution of HDL and is as a using the of by the as M. A. Després J.P. C. B. for HDL particle by gradient gel using Lipid Res. 42: Scholar). average HDL size indicated a of HDL a low average HDL size an increased of HDL particles. and of for the average HDL size by this were and LDL gel was on plasma to the by Krauss and R.M. D.J. of subclasses of plasma low density in Lipid Res. Scholar) and H. J. of age, and on low density lipoprotein subfraction Results from the Scholar) and as A. B. D. A. Moorjani S. F. Lupien P.J. Després J.P. The LDL with plasma lipoprotein levels, visceral obesity, and in 1996; Scholar). was to the on the of average HDL particle size and the was in in which a significant was were to the associations between were computed to the of metabolic to the of the average HDL particle An was to men of this study with low HDL cholesterol levels on the of the of HDL particle size high HDL were using the between HDL and are in HDL particle size was related to and as well as to the levels of and abdominal visceral and AT ≤ ≤ P < 0.0001). were found between HDL particle size and plasma HDL cholesterol and cholesterol levels and P < and significant were between HDL particle size and cholesterol and apolipoprotein HDL particle size the of with and distribution as HDL cholesterol and cholesterol, cholesterol and apolipoprotein with the was found between HDL particle size and a significant relationship between LDL particle size and average HDL particle size was observed P < between HDL and HDL particle size with and visceral and adipose tissue (AT) by computed and < < < < < < < < < < < < < < < < < < P < P in a the relationship of HDL particle size to the metabolic features of abdominal obesity, the sample of 238 men was and of the average HDL particle size distribution as physical and plasma lipoprotein-lipid of HDL particle in the of HDL particle size HDL were characterized by reduced adiposity as by a lower of visceral abdominal AT and decreased and compared with subjects in the lower and < 0.0001). For the plasma lipoprotein-lipid men in the were characterized by decreased plasma levels of cholesterol, TG, TG, LDL TG, and as well as by lower cholesterol/HDL cholesterol and increased plasma levels of HDL cholesterol and cholesterol and increased LDL particle size compared with subjects in the lower of HDL size < Furthermore, men in the for HDL size were characterized by decreased plasma levels of cholesterol, TG, TG, LDL TG, and apolipoprotein B and by a lower cholesterol/HDL cholesterol as well as by increased plasma levels of HDL cholesterol, cholesterol, apolipoprotein and increased LDL particle size compared with subjects in the lower and < is also to that in levels of and LDL cholesterol was observed of HDL particle and lipoprotein-lipid profile of the sample of 238 men on the of HDL particle size from and P < from and P < AT from and P < from P < from and P < from P < from and P < from P < from and P < from P < cholesterol from P < from and P < from P < from and P < from P < from and P < from P < from and P < B from P < from and P < from and P < particle size from P < from and P < particle size from P < from and P < from P < from and P < in a that men in the of HDL particle size were also characterized by lower fasting glucose and insulin concentrations as well as by reduced and responses to a oral glucose compared with men in the lower and of HDL particle size < were also to the of metabolic to the of HDL particle size not in the visceral AT TG, HDL cholesterol, apolipoprotein B, apolipoprotein LDL particle and fasting insulin and glucose levels as well as insulin and glucose of the in HDL particle size was by HDL cholesterol The LDL particle size of the in HDL particle TG levels a significant to from the have that men with the atherogenic metabolic insulin and apolipoprotein B concentrations and LDL were characterized by a in risk of ischemic heart disease B. A. P. Cantin B. Dagenais G.R. Lupien P.J. Després J.P. insulin and apolipoprotein B levels and lipoprotein particle size as risk factors for ischemic heart Med. Scholar). of this atherogenic metabolic have from a sample of men to and for apolipoprotein B, and LDL I. A. C. B. A. J. D. G. D. A. J.P. a of the atherogenic metabolic in Scholar). The of men characterized by the atherogenic metabolic in of HDL particle size is in to of the men in the of HDL particle size HDL were characterized by the presence of the metabolic fasting high apolipoprotein B, and LDL compared with and only in the and of HDL because is a significant between HDL cholesterol levels and HDL particle size 0.61, P < HDL particle size features of an atherogenic among men with reduced HDL cholesterol levels cholesterol For that purpose, a among men in study had HDL cholesterol levels and this on the of the of the average HDL particle size with lower versus HDL particles. for HDL cholesterol levels was also to for the in HDL cholesterol levels, and are in For the levels of HDL cholesterol, men with the particles of HDL particle were characterized by decreased concentrations of cholesterol and by increased levels of cholesterol < Furthermore, were also characterized by decreased LDL particle size < a for increased apolipoprotein B concentrations was with low HDL cholesterol levels and with smaller HDL particles were also characterized by levels of TG and by an increased cholesterol/HDL cholesterol < Thus, of this study that HDL particle size the of CHD risk among men with reduced HDL cholesterol of the of men with low levels of HDL cholesterol on the of the of average HDL particle for HDL-cholesterol by HDL and AT distribution AT cholesterol cholesterol cholesterol cholesterol < cholesterol < HDL particle size < cholesterol P < P < B < particle size < glucose insulin are computed for HDL-cholesterol by P < P < P < P in a are computed studies have an inverse relationship between the concentration of HDL cholesterol and the risk of CHD (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). HDL are of HDL and has been that is the subfraction that (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, M. M. S. J. T. High density lipoprotein in and coronary artery Lipid Res. 1995; Scholar, P.T. Krauss R.M. Vranizan K.M. Associations of and with gradient gel of high density lipoprotein in men and Thromb. 1992; Scholar, B. Moorjani S. Cantin B. Dagenais G.R. Lupien P.J. Després J.P. Associations of and with ischemic heart disease in men. from the Quebec Study.Arterioscler. Thromb. Vasc. Biol. 1997; 17: Scholar, D. P. L. M. C. V. G. I. of a profile increased high-density levels and decreased Scholar). Thus, has been that high levels of are associated with CHD risk that low levels in to the low CHD risk in subjects have high HDL cholesterol P.T. Krauss R.M. Vranizan K.M. Associations of and with gradient gel of high density lipoprotein in men and Thromb. 1992; Scholar). Furthermore, an increased has been associated with lower levels of 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 features of atherogenic have also been associated with low levels of and small HDL particle M. M. S. J. T. High density lipoprotein in and coronary artery Lipid Res. 1995; Scholar). In this to with plasma TG, HDL cholesterol and cholesterol levels, and the ratio, the HDL phenotype appears to represent another feature of atherogenic We also significant between HDL size and of adiposity, the that a high of visceral AT is a factor in the of this atherogenic dyslipidemic obesity, especially abdominal obesity, has been associated with metabolic to the of an atherogenic dyslipidemic which to the increased risk of CHD G.R. adiposity and 1994; the of J. in the that regional AT distribution was an of the of obesity J. Scholar). In this have that visceral obesity is a of the high TG-low HDL cholesterol dyslipidemia associated with and insulin resistance (9Després J.P. Dyslipidaemia and obesity.Baillières Clinical Endocrinology and Metabolism. 1994; 8: 629-660Google Scholar, J.P. obesity as of 1993; Scholar, M.C. Després J.P. A. Moorjani S. D. Lupien P.J. A. C. obesity in associations with glucose plasma and lipoprotein 1992; Scholar). Furthermore, and the high TG-low HDL cholesterol dyslipidemic state have also been associated with an increased risk of CHD 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). has also been that abdominal obesity a of insulin resistance as a of of visceral an increased of to the and an of J.P. obesity as of 1993; Scholar). The the of TG to HDL and LDL the of HDL and LDL to by to the of HDL and LDL particles. We also a relationship between LDL particle size and the average HDL particle that the in the size of lipoprotein the of a metabolic to is also to that significant was found between HDL particle size and LDL cholesterol, to that the of LDL cholesterol not the of are of atherogenic dyslipidemia B. A. P. Cantin B. Dagenais G.R. Lupien P.J. Després J.P. insulin and apolipoprotein B levels and lipoprotein particle size as risk factors for ischemic heart Med. Scholar). was also a correlate of the average HDL particle the that HDL particle size as another feature of the insulin resistance Results of the study that of the HDL particles in the of HDL were also characterized by a more favorable risk factor The by which HDL size CHD risk to However, that this relationship by the of HDL particles to in plasma lipoprotein levels and glucose insulin The relationship of HDL particles to CHD also by in that are in the and of is the in the of from plasma and is in the of a in the of in the of TG by and levels of HDL D. G.R. plasma triglyceride with low density lipoprotein triglyceride and high density the risk for as M. M. S. J. T. High density lipoprotein in and coronary artery Lipid Res. 1995; Scholar, P.J. Krauss R.M. A.P. Reduced cholesterol and elevated in men with abdominal obesity and Thromb. 1992; Scholar, J. P. A. The of lipoprotein and with high density lipoprotein levels in men with a Scholar). Furthermore, CETP and are others in the of For has been that and CETP to HDL levels and particle because the presence of the CETP in apolipoprotein HDL cholesterol and apolipoprotein decreased HDL and increased HDL cholesterol T. A. T. J.L. and to high density lipoprotein levels, particle and in 1993; Scholar). the of an of particles a of particles with an increased average with of apolipoprotein However, are not the only of HDL particle because 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, H. H. H. H. H. M. and in high density lipoprotein subclasses in with of Lipid Res. 1997; Scholar) and (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) factors also levels and distribution of studies have also shown that HDL size is an of metabolic Thus, has been that HDL size by the HDL apolipoprotein to of the in apolipoprotein S. J.L. HDL cholesterol levels are determined by rate, which with of HDL particle of and lipoprotein triglyceride and insulin levels, and Thromb. 1994; 14: Scholar). the the in the metabolic risk profile observed for HDL particle size that HDL particle size by as a overall of CHD We that the average HDL particle size as an additional for of the of CHD this and not such as TG, HDL cholesterol, the cholesterol/HDL cholesterol We have a for the of LDL particle another that CHD risk as have that LDL particle size had to in with features of the insulin-resistant dyslipidemic in to of CHD risk B. A. P. Cantin B. Dagenais G.R. Lupien P.J. Després J.P. insulin and apolipoprotein B levels and lipoprotein particle size as risk factors for ischemic heart Med. Scholar). have to the that not have prospective with CHD studies are clearly to HDL particle size is an CHD risk factor only another correlate of an atherogenic metabolic In of this study that the high TG-low HDL cholesterol dyslipidemic state and an elevated cholesterol/HDL cholesterol ratio, found among viscerally obese are of a reduced HDL particle size by gradient gel electrophoresis. Furthermore, the presence of HDL particles is associated with a high of the features of the atherogenic metabolic Thus, the HDL phenotype is associated with a high risk of a of atherogenic metabolic HDL size represent another of an atherogenic studies are clearly to the of this to the of CHD The to to the subjects for and to the of the Lipid the and the for to this We especially L. G. and C. for in the and of the This was by the and of the and the of and is a of a from the Heart and of is a from the and is a from the of adipose tissue coronary heart disease oral glucose triglycerides