Class Note for BME 510 at UA
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DIABETESMETABOLISM RESEARCH AND REVIEWS Diabetes Metab Res Rev 2007 23 14720 REVIEW ARTICLE Published online 2 November 2006 in Wiley Intersdence wwwintersciencew eycom DOI 101002dmrr694 Small dense lowdensitylipoproteins and the metabolic syndrome39r Manfredi Rizzo 1 Kaspar Berneisz 1Department of Clinical Medicine and Emerging Diseases University of Palermo Italy 2Division of Endocrinology and Diabetology University Hospital Zurich Switzerland Correspondence to Manfredi Rizzo Dipartimento di Medicina Clinica e delle Patologie Emergenti Universita di Palermo Via del Vespro 141 901277Palermo Italy Eimail mrizzo unipait lThis article was published online on End November 2006 An error was subsequently identi ed and corrected by an erratum notice that was published online on DOI 725 This printed version incorporates the amendment identi ed by the erratum notice WILEY InterScrence rUVEF cmgm m we Received 27FebruaryZUU Accepted 17 September 2006 Copyright 2006 John Wiley amp Sons Ltd Summary Small dense lowedensityelipoproteins LDL are associated with increased risk for cardiovascular diseases and diabetes mellitus and a reduction in LDL size has been reported in patients with coronary and nonecoronary forms of atherosclerosis LDL size has been accepted as an important predictor of cardiovascular events and progression of coronary artery disease as well as an emerging cardiovascular risk factor by the National Cholesterol Education Program Adult Treatment Panel 111 Small dense LDL with elevated triglyceride levels and low HDLecholesterol concentrations constitute the atherogenic lipoprotein phenotype ALP a form of atherogenic dyslipidemia that is a feature of type 2 diabetes and the metabolic syndrome LDL size and subclasses show speci c alterations in patients with the metabolic syndrome that probably signi cantly increase their cardiovascular risk however so far it has not been recommended to incorporate LDL size measurements in treatment plans when hypolipidemic therapies are installed Patients with type 2 diabetes are at high cardiovascular risk and it is still on debate if the treatment goals may be identical or whether there are distinct groups with different cardiovascular risks and hence with different treatment goals Measurements beyond traditional lipids such as measurements on the presence of small dense LDL in patients with the metabolic syndrome may help to identify cardiovascular risk subgroups In addition it might be possible in the future to individualize hypolipidemic treatments if more than the traditional lipids are taken into account LDL size measurement may potentially help to assess cardiovascular risk within the metabolic syndrome and adapt the treatment goals thereafter Copyright 2006 John Wiley 81 Sons Ltd Keywords small dense LDL atherosclerosis prevention diabetes metabolic syndrome Introduction In the past years several expert groups have suggested that diagnostic criteria be used in clinical practice to identify patients with metabolic syndrome and these de nitions have been somewhat different 178 As recently stated by the joint American Heart Association and National Heart Lung and Blood Institute in the Scienti c Statement on Diagnosis and Management of the Metabolic Syndrome 8 all the proposed classi cations have in common the concept that the metabolic syndrome represent a constellation of interrelated risk factors of metabolic origin metabolic risk factors that appear to directly promote the development of atherosclerotic cardiovascular disease The metabolic risk factors include elevated blood pressure elevated plasma glucose and atherogenic dyslipidemia which consists of an aggregation of lipoprotein abnormalities including elevated plasma LDL Heterogeneity and Metabolic Syndrome quot5L3 39 I g 30 g 1 16 E I J I DA u 7 I 1 I 20 i I 39 7 l14 E l I I E5 i 39l 2 1 Q 10 I J M10 5 I I I I I I I Figure 1 LDL heterogeneity and plasma triglyceride and HDLcholesterol concentrations ALP atherogenic lipoprotein phenotype as modi ed from 70 triglyceride levels increased small dense lowedensitye lipoproteins LDL and reduced highdensityelipoproteins HDLecholesterol concentrations This form of dyslipidemia also known as atherogenic lipoprotein phenotype ALFY Figure 1 or lipid triad represents a partially heritable trait and is associated with increased cardiovascular risk 9711 It has been suggested that the clinical importance of the ALP proba bly exceeds that of LDLecholesterol because many more patients with coronary artery disease are found to have this trait compared to those with hypercholesterolaemia 1213 LDL in humans do not show a normal but a bimodal distribution and can be separated into larger more buoyant and smaller more dense particles 10 Small dense LDL are associated with increased risk for cardiovascular disease and diabetes mellitus reviewed in 1415 and their predominance has been accepted as an emerging cardiovascular risk factor by the National Cholesterol Education Program Adult Treatment Panel III 3 Heterogeneity of LDL particles LDL comprise distinct multiple subclasses that differ in size density physicochemical composition metabolic behaviour and atherogenicity There are at least four major subspecies of LDL large LDLAI medium LDLAII small LDLAHI very small LDLAIV 1617 LDL subclasses show differences in the surface lipid content and certain features of the apolipoprotein B100 structure and probably contribute to size changes ofthese particles On the basis of the measurement of peak particle diameter or ultracentrifugal density individuals generally cluster into two broad subgroups the majority with a predominance of larger or medium sized LDL LDL pattern A and a substantial minority with a higher proportion of smaller LDL particles LDL pattern B 101617 It has been suggested that there are parallel metabolic channels within the delipidation cascade from very low densityelipoproteins VLDL to LDL 17 and a metabolic relationship between large VLDL particles and small LDL Copyright 2006 John Wiley amp Sons Ltd 15 particles has been demonstrated using stable isotopes in subjects with a predominance of small dense LDL Studies have not yet identi ed the speci c precursors of individual LDL subclasses but several data suggest that separate pathways may be responsible for the generation of distinct LDL particles 18 Inverse correlations of changes in large LDL LDLAI and small LDL LDLAIH and of changes of medium sized LDL LDLAH and very small LDL LDLAIV in dietary intervention studies raise the possibility of precursoreproduct relationships between distinct LDL subclasses 17 Figure 2 Particleesize distribution of plasma LDL subfractions can be measured by different laboratory techniques including analytical preparative and noneequilibrium density gradient ultracentrifugation as well as nuclear magnetic resonance 19 However the most common procedure is represented by the gradient gel electrophoresis of whole plasma 20 Assignment of LDL subclass phenotypes is based on particle diameter of the major plasma LDL peak LDL pattern A larger more buoyant LDL is de ned as an LDL subclass pattern with the major gradient gel peak at a particle diameter of 258 A or greater whereas the major peak of LDL pattern B small dense LDL is at a particle diameter of less than 258 A It has been shown that LDL phenotype is genetically in uenced with a heritability ranging from 35 to 45 A 80 607 r7059plt00001 40 20 e A LDLAIII mgdL 40 e 50 780 780 760 V40 720 0 20 40 60 A LDLrl mgum 03 60 r O r 0 47 plt0 0001 40 r 207 A LDLAIV mgdl 20 40 l l l l l l l l 780 760 V40 720 0 20 40 60 A LDLVII mgan Figure 2 Reciprocal relationships between diet induced changes in LDL subclasses as measured by analytical ultracentrifugation as modi ed from 17 Diabetes Metab Res Rev 2007 23 14720 DOI 101002dn1n 16 and the predominance of small dense LDL is commonly found in conjunctionwith familial disorders of lipoprotein metabolism that are associated with increased risk of premature coronary artery disease 17 The prevalence of the pattern B phenotype is approximately 30 in adult men 5710 in young men and women lt20 years and approximately 15725 in postmenopausal women but a number of nonegenetic environmental factors may in uence the expression of this phenotype including abdominal adiposity oral contraceptive use and dietary factors 20 Small dense LDL and cardiovascular risk Acute myocardial infarction and the ALP seem to share a similar array of interrelated metabolic aberrations including modifications in plasma lipids and lipoproteins as well as a relative resistance to insulinemediated glucose uptake The common lipid alterations observed during the acute phase of myocardial infarction include a rise of triglyceride levels and a fall of total LDL and HDLecholesterol concentrations 21723 and such modifications have a great clinical relevance since they must be taken into account in making therapeutic decisions 24 We recently found 25 in a group of subjects admitted to hospital for a myocardial infarction and followed until the discharge and three months after the event that the reduction of LDL peak particle size is premature and persist during the hospitalization with a significant increase three months after the myocardial infarction In addition the timing of these changes seemed to precede those of all other lipoproteins Notably it has been recently shown that even angina itself on the background of coronary artery spasm without atherosclerosis may lower LDL size 26 Small dense LDL seem to be associated even to none coronary forms of atherosclerosis reviewed in 27 It has been shown that smaller LDL particles represent a risk factor for peripheral arterial disease in the absence or presence of diabetes 28 The association between carotid disease and small dense LDL has been found in healthy subjects 29732 and in different categories of patients with familial combined hyperlipidemia familial hypercholesterolemia vascular dementia Alzheimer s disease insulin resistance or type 2 diabetes 33737 In addition it has been recently shown that carotid atherosclerosis regression or progression may be linked to LDL size 343738 Several reasons have been suggested for the atheroe genicity of small dense LDL Smaller denser LDL are taken up more easily by arterial tissue than larger LDL 39 suggesting greater transendothelial transport of smaller particles In addition smaller LDL particles may also have decreased receptoremediated uptake increased proteoe glycan binding and reduced sialic acid content 4041 Further it has been shown that oxidative susceptibility Copyright 2006 John Wiley amp Sons Ltd M Rizzo and K Berneis increases and antioxidant concentrations decrease with decreasing LDL size 42 To date the magnitude and independence of the association of LDL size with cardiovascular diseases has been tested in more than 50 studies including cross sectional and prospective epidemiologic as well as clinical intervention trials reviewed in 43 The vast majority but not all of these trials demonstrate a significant univariate association of small dense LDL with increased coronary heart disease CHD risk However LDL size is rarely a significant and independent predictor of CHD risk after multivariate adjustments for confounding variables in particular plasma triglyceride levels and HDL cholesterol concentrations Therefore it cannot be excluded that the increased risk associated with smaller LDL size in univariate analyses may be a consequence of the broader pathophysiology of which small dense LDL is a part eg high triglycerides low HDL cholesterol increased LDL particle number obesity insulin resistance diabetes metabolic syndrome rather than a re ection of an intrinsic increased atherogenic potential and a clear causal relationship between small dense LDL and increased cardiovascular risk based on the present knowledge cannot be proved Small dense LDL and diabetes Hypertriglyceridemia low HDL cholesterol and an increased fraction of small dense LDL particles charace terize diabetic dyslipidemia 44746 while LDL or total cholesterol are generally not increased in patients with diabetes except for a slight increase of LDLecholesterol in women 47 In addition small dense LDL are associ7 ated with the cluster of risk factors found in the insulin resistance syndrome 48 Interestingly subjects with predominance of small dense LDL have a greater than twofold increased risk for developing type 2 diabetes mellitus independently of age sex glucose tolerance and body mass index and an increase of peak LDL size was associated with a 16 decrease in the risk of developing type 2 diabetes mellitus 49 It has also been shown that patients with the insulin resistance syndrome have an elevated prevalence of the LDL pattern B phenotype 50 and this has been confirmed for diabetes in both men and women 4551 Figure 3 In addition using a euglycemic clamp technique to categorize individuals as insulinesensitive insulineresistant or type 2 diabetic more severe states of insulin resistance were associated with smaller LDL particle size 52 Table 1 Recently we investigated the clinical significance of LDL size and LDL subclasses in patients with type 2 diabetes 37 Diabetic patients with manifest CHD had decreased LDL particle sizes and altered LDL subclass distributions that is specifically more LDLIII and less LDLel and LDLII as compared to diabetic patients without established CHD Multivariate analysis revealed that LDL size was the strongest marker of CHD as compared to nine Diabetes Metub Res Rev 2007 23 14720 DOI 101002dmn LDL Heterogeneity and Metabolic Syndrome Men 60 50 40 30 20 10 o PatternA Intermediate Pattern B Pattern LDL size phenotype p lt 0025 with vs without diabetes D Without diabetes I Mth diabetes 17 Women 100 80 60 40 20 0 Pattern A Intermediate Pattern B Pattern LDL size phenotype p lt 001 with vs without diabetes Figure 3 LDL phenotypes in men and women with diabetes as modi ed from 4551 Table1 LDL subclass particle concentrations mean I SD in nmolL by nuclear magnetic resonance in insulinsensitive IS insulinresistant IR and type 2 diabetic DM subjects as modified from 52 IR vs IS DM vs IS IS IR DM p p 2 Large 589 i 325 534 i 357 385 i 418 04457 00058 Intermediate 238i316 213i271 385i425 07218 00312 Small 366 i 398 668 i 599 805 i 712 00088 00002 other established cardiovascular risk factors including plasma lipids and lipoproteins Increased intima media thickness IMT is considered a reliable surrogate marker of early atherosclerosis and it has been shown to correlate signi cantly with the presence of CHD and to predict coronary events 53 55 In addition signi cant relationships of IMT with other lipid parameters such as LDLcholesterol and apoB have been demonstrated 5657 In our study described above 37 LDL size was signi cantly associated with carotid IMT in patients with type 2 diabetes and LDL size was the second strongest predictor of IMT after smoking when compared to nine other cardiovascular risk factors and the strongest of all lipid parameters In summary LDL size seems to represent a marker of clinical apparent CHD and nonapparent IMT atherosclerosis in type 2 diabetes However the potential clinical value in this population that is at high risk of car diovascular events 58 needs to be shown in prospective studies before routine laboratory measurements of LDL size can be recommended Small dense LDL and the metabolic syndrome Small dense LDL with low HDLcholesterol and ele vated trygliceride concentrations constitute the three components of atherogenic dyslipidemia that is strongly associated with the metabolic syndrome 38 how ever scienti c guidelines so far support recommendations Copyright 2006 John Wiley 8 Sons Ltd to manage HDLcholesterol and trygliceride levels only 38 Beyond this lipoprotein pro le small dense LDL may be even independently associated with the metabolic syndrome Hulthe et al 32 assessed the prevalence of metabolic syndrome in a populationbased sample of 58 year old healthy men using the WHO de nition 1 The authors found that LDL size was signi cantly smaller in subjects with the metabolic syndrome in relation to those without it Figure 4 In addition they found that subjects with pattern B had signi cantly higher mean values for body mass index blood pressure heart rate serum cholesterol triglyceride levels and plasma insulin and lower HDL levels compared with subjects with pattern A Subjects with pattern B had also a higher prevalence of moderate to large plaques in the carotid artery compared with subjects with pattern A Interestingly decreasing LDL peak particle size was signi cantly associated with increasing IMT of the common carotid artery the carotid artery bulb and the common femoral artery There was a statistically signi cant association between plaque occurrence and size and the LDL peak particle diameter in both the carotid and femoral arteries a 270 plt0001 Va 2 268 I 266 2 264 Q 39 I E 262 cu g 260 8 I S 256 1 Metabolic No metabolic syndrome Subjects syndrome but 31 ri5k factors with no risk factors 1162 F252 1177 Figure 4 LDL size in patients with the metabolic syndrome as modi ed from 32 Diabetes Metab Res Rev 2007 23 14720 DOI 101002dmrr 18 However Haffner et al have already shown in 1995 that LDL size is decreased in subjects with multiple metabolic disorders Since no exact de nition was available at that time regarding the metabolic syndrome the authors 59 decided to examine the association of LDL size and pattern to speci c insulin proinsulin increased triglyceride decreased HDL hypertension and impaired glucose tolerance in 488 nonediabetic subjects They found that LDL size decreased in a stepwise fashion with the increasing number of the metabolic disorders described above zero 2626 j 94 one 2570 j 93 two 2564 i 94 three 2490 j 91 and four 2449 i 90 A These results were similar in men and women in none Hispanic whites and Mexican Americans Notably the association between LDL size and the number of metabolic disorders remained statistically signi cant even after adjustment for obesity body fat distribution gender ethnicity proinsulin and insulin concentrations Other studies 6061 have more recently indirectly assessed the levels ofsmall dense LDL in subjects with the metabolic syndrome using recent evidences that support the use of the triglycerideHDLecholesterol ratio for the prediction of LDL pattern B 6263 Many issues on the accuracy may be questioned but this indirect measure holds the great advantages of being inexpensive as well as being used in routine practice In summary LDL size and subclasses show speci c alterations in patients with the metabolic syndrome that probably signi cantly increase their cardiovascular risk however so far it has not been recommended by the international scienti c societies to incorporate LDL size measurements in treatment plans when hypolipidemic therapies are installed However measurements beyond traditional lipids such as on the presence of small dense LDL in patients with the metabolic syndrome may help to identify cardiovascular risk subgroups In addition it might be possible in future to individualize hypolipidemic treatments if more than the traditional lipids are taken into account Particularly LDL size measurements may help to assess cardiovascular risk within the metabolic syndrome and adapt the treatment goals thereafter Conclusions Small dense LDL are associated with increased risk for cardiovascular disease and diabetes mellitus and a reduction in LDL size has been reported in patients with acute myocardial infarction with angina pectoris as well as in those with nonecoronary forms of atherosclerosis LDL size seems also to be an important predictor of cardiovascular events and progression of coronary artery disease and the predominance of small dense LDL has been accepted as an emerging cardiovascular risk factor by the National Cholesterol Education Program Adult Treatment Panel III 3 In addition small dense LDL with elevated triglyceride levels and low HDLecholesterol concentrations constitute the ALP 9711 a form of Copyright 2006 John Wiley amp Sons Ltd M Rizzo and K Berneis atherogenic dyslipidemia that is a feature of type 2 diabetes and the metabolic syndrome 38 As recently stated by the joint American Heart Association and National Heart Lung and Blood Institute Scienti c Statement on Diagnosis and Management of the Metabolic Syndrome atherogenic dyslipidemia can become a target for lipidelowering therapy after the goal for LDLecholesterol has been attained In other words as long as LDLecholesterol remains above goal level LDL cholesterol is the primary target of therapy even in the metabolic syndrome 8 However this point is still on debate since this approach may leave a substantial excess risk for cardio vascular disease in patients with this type of dyslipidemia 111364 As recently reported 64 even if modi ca7 tion of the atherogenic lipid triad is probably one of the most effective methods of reducing cardiovascular risk therapy for atherogenic dyslipidemia is often directed to rst lowering serum LDLecholesterol levels usually by statins Yet results of recent trials evaluating statins have been mixed even showing no signi cant effect on cardio vascular outcomes in subgroups of patients with diabetes and the recent Collaborative Atorvastatin Diabetes Study showed that atorvastatin can reduce cardiovascular events in a trial speci cally designed for a diabetic population though the population had to have at least one other risk factor in addition to diabetes 65 By contrast brates are potentially well suited for the management of dyslipidemia associated with type 2 diabetes and the metabolic syndrome as they are usually more effective than statins in normalizing serum levels of HDL cholesterol and triglycerides 64 In addition brates are much more effective compared to statins in modifying LDL size and subclasses towards less atherogenic particles 43 Promising results have been obtained from several trials using brates such as the Beza brate Infarction Prevention study 66 and the Veterans Affairs Cooperative Studies Program HDLPC Intervention Trial with gem brozil 67 In addition new ndings are available from the feno brate intervention and event lowering in diabetes FIELD trial 68 a clinical outcomes trial speci cally designed to evaluate feno brate in a large population of patients with type 2 diabetes many of them with the metabolic syndrome This multinational randomized controlled trial included 9795 participants aged 50775 years all with type 2 diabetes mellitus and not taking statin therapy at study entry The primary outcome was coronary events coronary heart disease death or nonefatal myocardial infarction and the secondary outcome was total cardiovascular events the composite of cardiovascular death myocardial infarction stroke and coronary and carotid revascularization The results of the study were somehow disappointing feno brate did not signi cantly reduce the risk of coronary events as the primary outcome and reduced only total cardiovascular events mainly due to fewer nonefatal myocardial infarctions and revascularizations However it has to be emphasized that a very large portion of patients with the ALP was Diabetes Metab Res Rev 2007 23 14720 DOI 101002dmn LDL Heterogeneity and Metabolic Syndrome excluded according to the inclusion criteria of study totalecholesterol concentration of 30765 mmolL and a totalecholesterolHDLecholesterol ratio of 40 or more or plasma triglyceride of 10750 mmolL In other words this study probably excluded exactly the type of patients that would bene t most from brate therapy In conclusion LDL size and subclasses show peculiar alterations in patients with the metabolic syndrome that probably signi cantly increases their cardiovascular risk however so far it is not recommended by the international scienti c societies to treat such alterations with lipid lowering molecules or with other agents However mea7 surements beyond traditional lipids such as on the pres ence of small dense LDL in patients with the metabolic syndrome may help to identify cardiovascular risk sub groups and it has been recently suggested that patients at very high cardiovascular risk should be managed carefully and potentially treated more aggressively 69 To justify the routine measurement of LDL size large clinical endpoint studies are necessary these studies should investigate whether certain pharmacological there apies are more effective in reducing cardiovascular more bidity and mortality in pattern B compared with pattern A patients independently from LDLecholesterol Therefore it might be possible in future to individualize hypolipie demic treatments if more than the traditional lipids are taken into account LDL size measurement may potentially help to assess cardiovascular risk within the metabolic syndrome and adapt the treatment goals thereafter Acknowledgements Kaspar Berneis was supported by a researdi grant from the Swiss National Foundation 3200BOy1052581 References 1 World Health Organization Dq inition Diagnosis and Classification ofDiabetes Mellitus and its Complications Report of a WHO Consultation World Health Organization Geneva 1999 2 Balkau B Charles MA Comment on the provisional report from the WHO consultation European Group for the Study of Insulin Resistance EGIR Diabet Med 1999 16 4427443 3 National Cholesterol Education Program NCEP Expert panel on detection evaluation and treatment ofhigh blood cholesterol in adults adult treatment panel 111 Third report of the National Cholesterol Education Program NCEP expert panel on detection evaluation and treatment of high blood cholesterol in adults Adult Treatment Panel III nal report Circulation 2002 106 314373421 4 Einhorn D Reaven GM Cobin RH et al American college of endocrinology position statement on the insulin resistance syndrome Endocr Pract 2003 9 2377252 5 Grundy SM Brewer HB Jr Cleeman JI Smith SC Jr Lenfant C American Heart Association National Heart Lung and Blood Institute De nition of metabolic syndrome report of the National Heart Lung and Blood InstituteAmerican Heart Association conference on scienti c issues related to de nition Circulation 2004 109 4337438 6 International Diabetes Federation Worldwide de nition of the metabolic syndrome Available at httpwwwidforg webdatad3ocsI39DFJVIetasyndromede nitionpdf 2005 7 Kahn R Buse J Ferrannini E Stern M American Diabetes Association European Association for the Study of Diabetes Copyright 2006 John Wiley amp Sons Ltd 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 19 The metabolic syndrome time for a critical appraisal joint statement from the American Diabetes Association and the European Association for the Study of Diabetes Diabetes Care 2005 28 228972304 Grundy SM Cleeman JI Daniels SR etal American Heart Association National Heart Lung and Blood Institute Diagnosis and management ofthe metabolic syndrome an American Heart AssociationNational Heart Lung and Blood Institute Scienti c Statement Circulation 2005 112 273572752 Austin MA King MC Vranizan KM Krauss RM Atherogenic lipoprotein phenotype A proposed genetic marker for coronary heart disease risk Circulation 1990 82 4957506 Krauss RM Dietary and genetic probes of atherogenic dyslipidemia Arterioscler Thromb Vasc Biol 2005 25 226572272 Rizzo M Berneis K Lipid triad or atherogenic lipoprotein phenotype a role in cardiovascular prevention JAtheroscler Thromb 2005 12 2377239 Sattar N Petrie JR Jaap AJ The atherogenic lipoprotein phenotype and vascular endothelial dysfunction Atherosclerosis 1998 138 2297235 Superko HR Beyond LDL cholesterol reduction Circulation 1996 94 235172354 Berneis K Rizzo M LDL size does it matter Swiss Med Wkly 2004 134 7207724 Rizzo M Berneis K Should we measure routinely the LDL peak particle size IntJ Card 2006 107 1667170 Krauss RM Burke DJ Identi cation of multiple subclasses of plasma low density lipoproteins in normal humans J Lipid Res 1982 23 977104 Berneis KK Krauss RM Metabolic origins and clinical signi cance of LDL heterogeneity J Lipid Res 2002 43 136371379 Rizzo M Taylor JM Barbagallo CM Berneis K Blanche PJ Krauss RM Effects on lipoprotein subclasses of combined expression of human hepatic lipase and human apoB in transgenic rabbits Arterioscler Thromb Vasc Biol 2004 24 1417146 Sacks FM Campos H Lowrdensity lipoprotein size and cardiovascular disease a reappraisal J Clin Endocrinol Metab 2003 88 452574532 Rizzo M Barbagallo CM Severino M et al Lowrdensityr lipoproteins particle size in a population living in a small Mediterranean island EurJ Clin Invest 2003 33 1267133 Avogaro P Bon GB Cazzolato G et al Variations in apolipoproteins B and A1 during the course of myocardial infarctionEurJ Clin Invest 1978 8 1217129 Rosenson RS Myocardial injury the acute phase response and lipoprotein metabolism JAm Coll Cardiol 1993 22 9337940 Carlsson R Lindberg G Westin L Israelsson B Serum lipids four weeks after acute myocardial infarction are a valid basis for lipid lowering intervention in patients receiving thrombolysis BrHeartJ 1995 74 18720 Kingswood JC Williams S Owens DR How soon after myocardial infarction should plasma lipid values be assessed BrMedJ 1984 289 165171653 Barbagallo CM Rizzo M Cefalu AB et al Changes in plasma lipids and lowrdensity lipoprotein peak partide size during and after myocardial infarctionAm J Cardiol 2002 89 4607462 Miwa K Low density lipoprotein particles are small in patients with coronary VaSOSpaSm IntJ Cardiol 2003 87 1937201 Rizzo M Berneis K Corrado E Novo S The signi cance oflowr density lipoproteins size in vascular diseases IntAngiol 2006 25 479 O Neal DN Lewicki J Ansari MZ et al Lipid levels and peripheral vascular disease in diabetic and nonrdiabetic subjects Atherosclerosis 1998 136 178 SkoglundrAndersson C Tang R Bond MG de Faire U Hamsten A Karpe F LDL particle size distribution is associated with carotid intimarmedia thickness in healthy 507yearrold men Arterioscler Thromb Vasc Biol 1999 19 242272430 Bokemark L Wikstrand J Attvall S Hulthe J Wedel H FagerbergB Insulin resistance and intimarmedia thickness in the carotid and femoral arteries of clinically healthy 587yearrold men The Atherosclerosis and Insulin Resistance Study AIR JIntern Med 2001 249 59767 Hallman DM Brown SA Ballantyne CM Sharrett AR Boerr winkle E Relationship between lowrdensity lipoprotein subr classes and asymptomatic atherosclerosis in subjects from the Diabetes Metab Res Rev 2007 23 14720 DOI 101002dn1n 20 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 Atherosclerosis Risk in Communities ARIC Study Biomarkers 2004 9 1907202 Hulthe J Bokemark L Wikstrand J Fagerberg B The metabolic syndrome LDL partide size and atherosclerosis the Atherosclerosis and Insulin Resistance AIR studyArterioscler Thromb Vasc Biol 2000 20 214072147 Liu MVL Ylitalo K Nuotio I Salonen R Salonen JT Taskir nen MR Association between carotid intimarmedia thickness and lowrdensity lipoprotein size and susceptibility of lowr density lipoprotein to oxidation in asymptomatic members of familial combined hyperlipidemia families Stroke 2002 33 125571260 van Tits LJ Smilde TJ van Wissen S de Graaf J Kastelein JJ StalenhoefAF Effects of atorvastatin and simvastatin on lowr density lipoprotein subfraction pro le lowrdensity lipoprotein oxidizability and antibodies to oxidized lowrdensity lipoprotein in relation to carotid intima media thickness in familial hypercholesterolemiaJInvestig Med 2004 52 1777184 Watanabe T Koba S Kawamura M et al Small dense lowr density lipoprotein and carotid atherosclerosis in relation to vascular dementia Metabolism 2004 53 4767482 Hulthe J Wiklund O Olsson G et al Computerized measurement of LDL particle size in human serum Reproducibility studies and evaluation of LDL particle size in relation to metabolic variables and the occurrence of atherosclerosis Scand J Clin Lab Invest 1999 59 6497661 Berneis K Jeanneret C Muser J Felix B Miserez AR Lowr density lipoprotein size and subclasses are markers of dinically apparent and nonrapparent atherosclerosis in type 2 diabetes Metabolism 2005 54 2277234 Wallenfeldt K Bokemark L Wikstrand J Hulthe J Fagerberg B Apolipoprotein Bapolipoprotein A71 in relation to the metabolic syndrome and change in carotid artery intimarmedia thick ness during 3 years in middleraged men Stroke 2004 35 224872252 Bjornheden T Babyi A Bondjers G Wiklund O Accumulation of lipoprotein fractions and subfractions in the arterial wall determined in an in vitro perfusion systemAthemsclerosis 1996 123 43756 Galeano NF Aeraideri M Keyserman F Rumsey SC Deckelr baum RJ Small dense low density lipoprotein has increased af nity for LDL receptorrindependent cell surface binding sites a potential mechanism for increased atherogenicity J Lipid Res 1998 39 126371273 Camejo G Lopez A Lopez F Quinones J Interaction of low density lipoproteins with arterial proteoglycans The role of charge and sialic acid contentAtherosclerosis 1985 55 937105 Tribble DL Rizzo M Chait A Lewis DM Blanche PJ Krauss RM Enhanced oxidative susceptibility and reduced antioxidant content of metabolic precursors of small dense lowrdensity lipoproteinsAmJMed 2001 110 1037110 Rizzo M Berneis K Lowrdensityrlipoproteins size and cardiovascular risk assessment QJMrIntJMed 2006 99 1714 Reaven GM Banting lecture Role ofinsulin resistance in human disease Diabetes 1988 37 159571607 Selby JV Austin MA Newman B et al LDL subclass phenotypes and the insulin resistance syndrome in Women Circulation 1993 88 3817387 Syvanne M Taskinen MR Lipids and lipoproteins as coronary risk factors in nonrinsulinr dependent diabetes mellitus Lancet 1997 350Suppl 1 512075123 UK Prospective Diabetes Study 27 Plasma Lipids and lipoproteins at diagnosis of NIDDM by age and sex Diabetes Care 1997 20 168371687 Friedlander Y Kidron M Caslake M Lamb T McConnell M Barr On H Low density lipoprotein particle size and risk factors of insulin resistance syndrome Atherosclerosis 2000 148 1417149 Austin MA Mykkanen L Kuusisto J et al Prospective study of small LDLs as a risk factor for nonrinsulin dependent diar betes mellitus in elderly men and Women Circulation 1995 921177071778 Reaven GM Chen YD Jeppesen J Maheux P Krauss RM Insulin resistance and hyperinsulinemia in individuals with small dense low density lipoprotein particles J Clin Invest 1993 92 1417146 Feingold KR Grunfeld C Pang M Doerrler W Krauss RM LDL subclass phenotypes and triglyceride metabolism in nonrinsulinr dependent diabetesArterioscler Thromb 1992 12 149671502 Copyright 2006 John Wiley amp Sons Ltd 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 M Rizzo and K Berneis Garvey WT Kwon S Zheng D et al Effects of insulin resistance and type 2 diabetes on lipoprotein subclass particle size and concentration determined by nuclear magnetic resonance Diabetes 2003 52 4537462 Chambless LE Heiss G Folsom AR et al Association ofcoronary heart disease incidence with carotid arterial wall thickness and major risk factors the Atherosclerosis Risk in Communities ARIC Study 198771993AmJEpidemiol1997 14614837494 Craven TE Ryu JE Espeland MA etal Evaluation of the associations between carotid artery atherosclerosis and coronary artery stenosis A casercontrol study Circulation 1990 82 12307 1242 Wofford J39L Kahl FR Howard GR McKinney WM Toole JF Crouse JR III Relation of extent of extracranial carotid artery atherosclerosis as measured by Brmode ultrasound to the extent of coronary atherosclerosis Arterioscler Thromb 1991 1 1 17867 1794 Goya K Kitamura T Inaba M et al Risk factors for asymptomatic atherosclerosis in Japanese type 2 diabetic patients without diabetic microvascular complications Metabolism 2003 52 130271306 Niskanen L Rauramaa R Miettinen H Haffner SM Mercuri M Uusitupa M Carotid artery intimarmedia thickness in elderly patients with NIDDM and in nondiabetic subjects Stroke 1996 27 198671992 Rizzo M Barbagallo CM Noto D et al Diabetes family history and extension of coronary atherosclerosis are strong predictors of adverse events after PTCA a one year followrup study Nutr Metab Cardiovasc Dis 2005 15 3617367 Haffner SM Mykkanen L Robbins D et al A preponderance of small dense LDL is associated with speci c insulin proinsulin and the components of the insulin resistance syndrome in non diabetic subjects Diabetologia 1995 38 132871336 Garin MC Kalix B Morabia A James RW Small dense lipoprotein partides and reduced paraoxonaser1 in patients with the metabolic syndromeJ Clin EndocrinolMetab 2005 90 226472269 Slapikas R Luksiene D Slapikiene B Babarskiene MR Gryr bauskiene R Linoniene L Prevalence of cardiovascular risk factors in coronary heart disease patients with different lowr density lipoprotein phenotypes Medicina Kaunas 2005 41 925793 1 Hanak V Munoz J Teague J Stanley A Jr Bittner V Accuracy of the triglyceride to highrdensity lipoprotein cholesterol ratio for prediction of the lowrdensity lipoprotein phenotype BAm J Cardiol 2004 94 2197222 McLaughlin T Reaven G Abbasi F etal Is there a simple way to identify insulinrresistant individuals at increased risk of cardiovascular disease Am J Cardiol 2005 96 3997404 Nesto RW Beyond lowrdensity lipoprotein addressing the atherogenic lipid triad in type 2 diabetes mellitus and the metabolic syndromeAm J Cardiovasc Drugs 2005 5 3797387 Colhoun HM Betteridge DJ Durrington PN etal CARDS investigators Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study CARDS multicentre randomised placebo controlled trial Lancet 2004 364 6857696 Tenenbaum A Motro M Fisman EZTanne DBoyko VBehar S Beza brate for the secondary prevention of myocardial infarction in patients with metabolic syndrome Arch Intern Med 2005 1652 115471160 Rubins HB Robins SJ Collins D etal Gem brozil for the secondary prevention of coronary heart disease in men with low levels of high density lipoprotein cholesterol ve
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