Low-Density Lipoprotein Size and Cardiovascular Disease: A Reappraisal

Sacks, Frank M.; Campos, Hannia

doi:10.1210/jc.2003-030636

Cited by 241Lipoproteins and Cardiovascular HealthDiabetes, Cardiovascular Risks, and LipoproteinsCholesterol and Lipid Metabolism

Low-Density Lipoprotein Size and Cardiovascular Disease: A Reappraisal

Sacks, Frank M., Campos, Hannia·2003·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2003-030636

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Abstract

The major lipoprotein types, very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), are composed of many subgroups (1–3). Classifications are based on size (1), density, or apolipoprotein (apo) content (2), or a combination of these (3), and the subfractions that are isolated have distinct metabolic and other functional properties. Thus, it is entirely reasonable to think that subfractions of the major lipoproteins have diverse relationships to coronary heart disease (CHD). Because the classical lipid risk factors by no means perfectly predict CHD in patients, lipoprotein subfractionation has the potential to improve risk prediction. Among the various lipoprotein subfractionation systems, LDL size and density by far have attracted the most basic, clinical, and population research. Several companies offer LDL size measurements to physicians as a diagnostic test for CHD risk. Several lines of evidence implicate small, dense LDL in the etiology of CHD. Small, dense LDL is often increased in relative proportion or concentration in patients with CHD. Small, dense LDL has several characteristics that are linked to atherogenesis: long residence time in plasma, and enhanced oxidizability, arterial proteoglycan binding, and permeability through the endothelial barrier (4). Together, these findings have led to the hypothesis that small, dense LDL is a potent atherogenic lipoprotein that can be used to improve risk prediction, and evaluate response to lipid therapy (5–7). Furthermore, small, dense LDL is often part of a group of high-risk characteristics including high triglycerides, low HDL, diabetes, insulin resistance, obesity, and the metabolic syndrome (8–10). This has led logically to the concept that it contributes to the high rate of CHD in these groups. Yet, the very association between small, dense LDL and these other high-risk conditions challenges proponents of the hypothesis to show a direct, independent relationship between small, dense LDL and CHD. In this article, we evaluate evidence on LDL subclasses in risk assessment and therapy, reaching the conclusion that LDL subclass measurement does not add independent information to that conferred generically by the LDL concentration along with the other standard risk factors.

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Neither LDL size nor the concentration of small, dense LDL particles adds to CVD prediction in multiple variable analysis beyond standard lipid risk factors, although small LDL particles predict cardiovascular risk in univariate analysis.
“Neither LDL size nor the concentration of small, dense LDL particles adds to CVD prediction in multiple variable analysis beyond the standard lipid risk factors, although small LDL particles predict cardiovascular risk in univariate analysis (35)(36)(37).”
From Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline (2012) · cites this paper as [35]
Prospective multivariate studies demonstrate that large LDL predicts atherosclerosis and coronary heart disease.
“Prospective multivariate studies demonstrate that large LDL predicts atherosclerosis and coronary heart disease (35,38,39).”
From Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline (2012) · cites this paper as [35]

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Characterization of lipoprotein in a kindred with familial hypercholesterolemia
Patsch, W., Ostlund, R. E., Kuisk, I., Levy, R., & Schonfeld, G. (1982) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38058-5 · Cited by 48 · see citing works
Development and application of a multicompartmental model to study very low density lipoprotein subfraction metabolism
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Dietary polyunsaturated fat decreases interaction between low density lipoproteins and arterial proteoglycans
Manning, J. M., Gebre, A. K., Edwards, I. J., Wagner, W. D., Rudel, L. L., & Parks, J. S. (1994) · Lipids · doi:10.1007/bf02536098 · Cited by 30 · see citing works
LDL particle size in relation to intima‐media thickness and plaque occurrence in the carotid and femoral arteries in patients with hypercholesterolaemia
Hulthe, J., Wiklund, O., Bondjers, G., & Wikstrand, J. (2000) · Journal of Internal Medicine · doi:10.1046/j.1365-2796.2000.00698.x · Cited by 28 · see citing works
Effect of proteoglycans on lipoprotein-cell interactions: possible contribution to atherogenesis
Camejo, G., Hurt‐Camejo, E., & Bondjers, G. (1990) · Current Opinion in Lipidology · doi:10.1097/00041433-199010000-00006 · Cited by 27 · see citing works
LDL particle size in subjects with previously unsuspected coronary heart disease: relationship with other cardiovascular risk markers
Sherrard, B., Simpson, H., Cameron, J. D., Wahi, S., Jennings, G., & Dart, A. M. (1996) · Atherosclerosis · doi:10.1016/0021-9150(96)05920-5 · Cited by 27 · see citing works
Transvascular Low-Density Lipoprotein Transport in Patients With Diabetes Mellitus (Type 2)
Kornerup, K., Nordestgaard, B. G., Feldt‐Rasmussen, B., Borch‐Johnsen, K., Jensen, K. S., & Jensen, J. S. (2002) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000022849.26083.fa · Cited by 27 · see citing works
Regulation of small dense LDL concentration in Korean and Scottish men and women
Cho, H. K., Shin, G.-J., Ryu, S. K., Jang, Y., Day, S., Stewart, G., Packard, C. J., Shepherd, J., & CASLAKE, M. J. (2002) · Atherosclerosis · doi:10.1016/s0021-9150(02)00058-8 · Cited by 25 · see citing works
Influence of simvastatin on LDL-subtypes in patients with heterozygous familial hypercholesterolemia and in patients with diabetes mellitus and mixed hyperlipoproteinemia
Geiss, H. C., SCHWANDT, P., & Parhofer, K. (2002) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-2002-32150 · Cited by 24 · see citing works
Hypoglycaemic symptoms reported by children with Type 1 diabetes mellitus and by their parents
Ross, L. A., McCrimmon, R. J., Frier, B. M., Kelnar, C. J. H., & Deary, I. J. (1998) · Diabetic Medicine · doi:10.1002/(sici)1096-9136(199810)15:10 · Cited by 24 · see citing works
Native LDL potentiate TNFα and IL-8 production by human mononuclear cells
Netea, M. G., Kullberg, B. J., Demacker, P. N. M., Jacobs, L., Verver-Jansen, T. J. G., Hijmans, A., van Tits, L. J. H., Hoenderop, J. G. J., Willems, P. H. G. M., van der Meer, J. W. M., et al. (2002) · Journal of Lipid Research · doi:10.1194/jlr.m100254-jlr200 · Cited by 16 · see citing works
Risk factors for coronary heart disease in a population with a high prevalence of obesity and diabetes: a case-control study of the Polynesian population of Western Samoa.
Wahi, S., Gatzka, C. D., Sherrard, B., Simpson, H., Collins, V., Dowse, G. K., Zimmet, P., Jennings, G., & Dart, A. M. (1997) · PubMed · Cited by 16 · see citing works
Low-density lipoprotein particle size is not a discriminating marker for atherogenic risk in male offspring of parents with early coronary artery disease
Slyper, A. H., Ивановна, З. С., Schectman, G., Hoffmann, R. G., & Walker, J. A. (1997) · Metabolism · doi:10.1016/s0026-0495(97)90086-x · Cited by 14 · see citing works

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The metabolic syndrome
Eckel, R. H., Alberti, K., Grundy, S. M., & Zimmet, P. (2010) · The Lancet · doi:10.1016/s0140-6736(09)61794-3 · Cited by 6,283 · see citing works
The metabolic syndrome
Eckel, R. H., Grundy, S. M., & Zimmet, P. (2005) · The Lancet · doi:10.1016/s0140-6736(05)66378-7 · Cited by 5,566 · see citing works
Dietary fats and cardiovascular disease: a presidential advisory from the American Heart Association
Sacks, F. M., Lichtenstein, A. H., Wu, J. H. Y., Appel, L. J., Creager, M. A., Kris-Etherton, P. M., Miller, M., Rimm, E. B., Rudel, L. L., Robinson, J. G., et al. (2017) · Circulation · doi:10.1161/cir.0000000000000510 · Cited by 1,386 · see citing works
Self-citation
The Metabolic Syndrome
Grundy, S. M. (2010) · Springer eBooks · doi:10.1007/978-1-4419-5839-6_1 · Cited by 1,225 · see citing works
Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline
Berglund, L., Brunzell, J. D., Goldberg, A. C., Goldberg, I. J., Sacks, F., Murad, M. H., & Stalenhoef, A. F. H. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-3213 · Cited by 887 · see citing works
Self-citation
Overproduction of very low-density lipoproteins is the hallmark of the dyslipidemia in the metabolic syndrome
Adiels, M., Olofsson, S.-O., Taskinen, M.-R., & Borén, J. (2008) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.107.160192 · Cited by 820 · see citing works
Lipoprotein Management in Patients With Cardiometabolic Risk
Brunzell, J. D., Davidson, M. H., Furberg, C. D., Goldberg, R. B., Howard, B. V., Stein, J. H., & Witztum, J. L. (2008) · Diabetes Care · doi:10.2337/dc08-9018 · Cited by 710 · see citing works
Low-Density Lipoprotein and High-Density Lipoprotein Particle Subclasses Predict Coronary Events and Are Favorably Changed by Gemfibrozil Therapy in the Veterans Affairs High-Density Lipoprotein Intervention Trial
Otvos, J. D., Collins, D. E., Freedman, D. S., SHALAUROVA, I. Y., Schaefer, E. J., McNamara, J. R., Bloomfield, H. E., & Robins, S. J. (2006) · Circulation · doi:10.1161/circulationaha.105.565135 · Cited by 542 · see citing works
Lipoprotein Management in Patients With Cardiometabolic Risk
Brunzell, J. D., Davidson, M. H., Furberg, C. D., Goldberg, R. B., Howard, B. V., Stein, J. H., & Witztum, J. L. (2008) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2008.02.034 · Cited by 523 · see citing works
Lipoprotein particle profiles by nuclear magnetic resonance compared with standard lipids and apolipoproteins in predicting incident cardiovascular disease in women.
Mora, S., Otvos, J. D., Rifai, N., Rosenson, R. S., Buring, J. E., & Ridker, P. M. (2009) · Circulation · doi:10.1161/circulationaha.108.816181 · Cited by 490 · see citing works
New insights into the pathophysiology of dyslipidemia in type 2 diabetes
Taskinen, M.-R., & Borén, J. (2015) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.01.039 · Cited by 440 · see citing works
LDL particle subclasses, LDL particle size, and carotid atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA)
Mora, S., Szklo, M., Otvos, J. D., Greenland, P., Psaty, B. M., Goff, D. C., O’Leary, D. H., Saad, M. F., Tsai, M. Y., & Sharrett, A. R. (2007) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2006.05.007 · Cited by 380 · see citing works
The obesity, metabolic syndrome, and type 2 diabetes mellitus pandemic: Part I. Increased cardiovascular disease risk and the importance of atherogenic dyslipidemia in persons with the metabolic syndrome and type 2 diabetes mellitus
Ginsberg, H. N., & MacCallum, P. R. (2009) · Journal of the CardioMetabolic Syndrome · doi:10.1111/j.1559-4572.2008.00044.x · Cited by 331 · see citing works
Assessment and Treatment of Cardiovascular Risk in Prediabetes: Impaired Glucose Tolerance and Impaired Fasting Glucose
DeFronzo, R. A., & Abdul‐Ghani, M. A. (2011) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2011.03.013 · Cited by 318 · see citing works
Increased Small Low-Density Lipoprotein Particle Number
Kathiresan, S., Otvos, J. D., SULLIVAN, L. M., Keyes, M. J., Schaefer, E. J., Wilson, P. W. F., D’Agostino, R. B., Vasan, R. S., & Robins, S. J. (2005) · Circulation · doi:10.1161/circulationaha.105.567107 · Cited by 317 · see citing works
Evaluation of Biomarkers and Surrogate Endpoints in Chronic Disease
Institute of Medicine (2010) · National Academies Press eBooks · doi:10.17226/12869 · Cited by 273 · see citing works
Lipoprotein subfractions and cardiovascular disease risk
Krauss, R. M. (2010) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32833b7756 · Cited by 272 · see citing works
Clinical utility of inflammatory markers and advanced lipoprotein testing: Advice from an expert panel of lipid specialists
Davidson, M. H., Ballantyne, C. M., Jacobson, T. A., Bittner, V. A., Braun, L. T., Brown, A. S., Brown, W. V., Cromwell, W. C., Goldberg, R. B., McKenney, J. M., et al. (2011) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2011.07.005 · Cited by 262 · see citing works
The Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in dyslipidaemic patients
Fruchart, J.-C., Sacks, F. M., Hermans, M. P., Assmann, G., Brown, W. V., Ceska, R., Chapman, M. J., Dodson, P. M., Fioretto, P., Ginsberg, H. N., et al. (2008) · Diabetes and Vascular Disease Research · doi:10.3132/dvdr.2008.046 · Cited by 260 · see citing works
Self-citation
Low-density lipoprotein size and cardiovascular risk assessment
Rizzo, M., & Berneis, K. K. (2005) · QJM · doi:10.1093/qjmed/hci154 · Cited by 257 · see citing works
Discordance of low-density lipoprotein (LDL) cholesterol with alternative LDL-related measures and future coronary events
Mora, S., Buring, J. E., & Ridker, P. M. (2014) · Circulation · doi:10.1161/circulationaha.113.005873 · Cited by 255 · see citing works
Value of Low-Density Lipoprotein Particle Number and Size as Predictors of Coronary Artery Disease in Apparently Healthy Men and Women
El Harchaoui, K., van der Steeg, W. A., Stroes, E. S. G., Kuivenhoven, J. A., Otvos, J. D., Wareham, N. J., Hutten, B. A., Kastelein, J. J. P., Khaw, K.-T., & Boekholdt, S. M. (2007) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2006.09.043 · Cited by 239 · see citing works
Diabetic Dyslipidemia
Chahil, T. J., & Ginsberg, H. N. (2006) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2006.06.002 · Cited by 233 · see citing works
A Renewed Focus on the Association Between Thyroid Hormones and Lipid Metabolism
Duntas, L. H., & Brenta, G. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00511 · Cited by 230 · see citing works
Cardiovascular disease in diabetes, beyond glucose
Eckel, R. H., Bornfeldt, K., & Goldberg, I. J. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.07.001 · Cited by 224 · see citing works
Cardiovascular Disease Under the Influence of Excess Visceral Fat
Després, J. (2007) · Critical Pathways in Cardiology A Journal of Evidence-Based Medicine · doi:10.1097/hpc.0b013e318057d4c9 · Cited by 199 · see citing works
Docosahexaenoic acid supplementation improves fasting and postprandial lipid profiles in hypertriglyceridemic men.
Kelley, D. S., Siegel, D., Vemuri, M., & Mackey, B. E. (2007) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/86.2.324 · Cited by 179 · see citing works
Glycation of LDL by Methylglyoxal Increases Arterial Atherogenicity
Rabbani, N., Godfrey, L., Xue, M., Shaheen, F., Geoffrion, M., Milne, R. W., & Thornalley, P. J. (2011) · Diabetes · doi:10.2337/db11-0085 · Cited by 167 · see citing works
Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in Sprague–Dawley rats
Kesl, S., Poff, A. M., Ward, N. P., Fiorelli, T. N., Ari, C., Putten, A. J. V., Sherwood, J. W., Arnold, P., & D’Agostino, D. P. (2016) · Nutrition & Metabolism · doi:10.1186/s12986-016-0069-y · Cited by 154 · see citing works
Associations between smoking, components of metabolic syndrome and lipoprotein particle size
Slagter, S. N., van Vliet‐Ostaptchouk, J. V., Vonk, J. M., Boezen, H. M., Dullaart, R. P. F., Kobold, A. C. M., Feskens, E. J. M., van Beek, A. P., van der Klauw, M. M., & Wolffenbuttel, B. H. R. (2013) · BMC Medicine · doi:10.1186/1741-7015-11-195 · Cited by 151 · see citing works
REVIEW: Efficacy and Mechanisms of Action of Statins in the Treatment of Diabetic Dyslipidemia
Ginsberg, H. N. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-2084 · Cited by 145 · see citing works
Atherogenic dyslipidemia and oxidative stress: a new look
Rizzo, M., Kotur‐Stevuljević, J., Berneis, K. K., Spinas, G. A., Rini, G. B., Jelić‐Ivanović, Z., Spasojević‐Kalimanovska, V., & Vekić, J. (2009) · Translational research · doi:10.1016/j.trsl.2009.01.008 · Cited by 142 · see citing works
LDL and HDL subclasses in acute ischemic stroke: prediction of risk and short-term mortality.
Zeljković, A., Vekić, J., Spasojević-Kalimanovska, V., Jelić-Ivanović, Z., Bogavac-Stanojević, N., Gulan, B., & Spasić, S. (2010) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2009.11.040 · Cited by 125 · see citing works
Lipids and lipid management in diabetes
Jaiswal, M., Schinske, A., & Pop‐Busui, R. (2013) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2013.12.001 · Cited by 117 · see citing works
The joint effects of apolipoprotein B, apolipoprotein A1, LDL cholesterol, and HDL cholesterol on risk: 3510 cases of acute myocardial infarction and 9805 controls
Parish, S., Peto, R., Palmer, A. J., Clarke, R. T., Lewington, S., Offer, A. R., Whitlock, G., Clark, S., Youngman, L. D., Sleight, P., et al. (2009) · European Heart Journal · doi:10.1093/eurheartj/ehp221 · Cited by 116 · see citing works
Milk-Derived Fatty Acids Are Associated with a More Favorable LDL Particle Size Distribution in Healthy Men
Sjögren, P., Skoglund-Andersson, C., Hamsten, A., Fisher, R. M., Rosell, M., Zdravkovic, S., Vessby, B. O., Fairé, U. D., & Hellénius, M.-L. (2004) · Journal of Nutrition · doi:10.1093/jn/134.7.1729 · Cited by 111 · see citing works
Physical activity, sedentary behavior time and lipid levels in the Observation of Cardiovascular Risk Factors in Luxembourg study
Crichton, G. E., & Alkerwi, A. (2015) · Lipids in Health and Disease · doi:10.1186/s12944-015-0085-3 · Cited by 107 · see citing works
Prevalence of Metabolic Syndrome in Pakistan
Basit, A., & Shera, A. S. (2008) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2008.0005 · Cited by 100 · see citing works
The abnormal lipid profile in obesity and coronary heart disease (CHD) in Pakistani subjects
Shabana, S., Shahid, S. U., & Sarwar, S. (2020) · Lipids in Health and Disease · doi:10.1186/s12944-020-01248-0 · Cited by 105 · see citing works
Endogenous Estrogens Lower Plasma PCSK9 and LDL Cholesterol But Not Lp(a) or Bile Acid Synthesis in Women
Persson, L., Henriksson, P., Westerlund, E., Hovatta, O., Angelin, B., & Rudling, M. J. (2011) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.242461 · Cited by 98 · see citing works
Apolipoprotein B-containing lipoproteins in atherogenesis
Borén, J., Packard, C. J., & Binder, C. J. (2025) · Nature Reviews Cardiology · doi:10.1038/s41569-024-01111-0 · Cited by 104 · see citing works
Mixed Dyslipidemia, Metabolic Syndrome, Diabetes Mellitus, and Cardiovascular Disease: Clinical Implications
Cannon, C. P. (2008) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2008.09.067 · Cited by 96 · see citing works
Is it LDL particle size or number that correlates with risk for cardiovascular disease?
Superko, H. R., & Gadesam, R. (2008) · Current Atherosclerosis Reports · doi:10.1007/s11883-008-0059-2 · Cited by 91 · see citing works
Small, dense low‐density‐lipoproteins and the metabolic syndrome
Rizzo, M., & Berneis, K. K. (2006) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.694 · Cited by 91 · see citing works
Advanced lipoprotein testing and subfractionation are not (yet) ready for routine clinical use
Mora, S. (2009) · Circulation · doi:10.1161/circulationaha.108.819359 · Cited by 89 · see citing works
Thyroid Function and Lipid Subparticle Sizes in Patients with Short-Term Hypothyroidism and a Population-Based Cohort
Pearce, E. N., Wilson, P. W. F., Yang, Q., Vasan, R. S., & Braverman, L. E. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-1987 · Cited by 85 · see citing works
Consensus statement on management of dyslipidemia in Indian subjects
Chandra, K. S., Bansal, M., Nair, T., Iyengar, S. S., Gupta, R., Manchanda, S. C., Mohanan, P. P., Rao, V. D., Manjunath, C. N., Sawhney, J. P. S., et al. (2014) · Indian Heart Journal · doi:10.1016/j.ihj.2014.12.001 · Cited by 84 · see citing works
Liver-Specific Inhibition of Acyl-Coenzyme A:Cholesterol Acyltransferase 2 With Antisense Oligonucleotides Limits Atherosclerosis Development in Apolipoprotein B100–Only Low-Density Lipoprotein Receptor −/− Mice
Bell, T. A., Brown, J. M., Graham, M. J., Lemonidis, K. M., Crooke, R. M., & Rudel, L. L. (2006) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000225289.30767.06 · Cited by 79 · see citing works
Who needs to care about small, dense low-density lipoproteins?
Rizzo, M., & Berneis, K. K. (2007) · International Journal of Clinical Practice · doi:10.1111/j.1742-1241.2007.01596.x · Cited by 77 · see citing works
Narrowing Sex Differences in Lipoprotein Cholesterol Subclasses Following Mid‐Life: The Very Large Database of Lipids (VLDL‐10B)
Swiger, K. J., Martin, S. S., Blaha, M. J., Toth, P. P., Nasir, K., Michos, E. D., Gerstenblith, G., Blumenthal, R. S., & Jones, S. R. (2014) · Journal of the American Heart Association · doi:10.1161/jaha.114.000851 · Cited by 77 · see citing works
The apolipoprotein story
Sacks, F. M. (2006) · Atherosclerosis Supplements · doi:10.1016/j.atherosclerosissup.2006.05.004 · Cited by 75 · see citing works
Self-citation
Lipid Triad or Atherogenic Lipoprotein Phenotype: A Role in Cardiovascular Prevention?
Rizzo, M., & Berneis, K. K. (2005) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.12.237 · Cited by 74 · see citing works
Delayed In Vivo Catabolism of Intermediate-Density Lipoprotein and Low-Density Lipoprotein in Hemodialysis Patients as Potential Cause of Premature Atherosclerosis
Ikewaki, K., Schaefer, J. R., Frischmann, M. E., Okubo, K., Hosoya, T., Mochizuki, S., Dieplinger, B., Trenkwalder, E., Schweer, H., Kronenberg, F., et al. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000188555.60475.c2 · Cited by 74 · see citing works
Lipid Effects of Peroxisome Proliferator-Activated Receptor-Δ Agonist GW501516 in Subjects With Low High-Density Lipoprotein Cholesterol
Olson, E. J., Pearce, G. L., Jones, N. P., & Sprecher, D. L. (2012) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.112.247890 · Cited by 71 · see citing works
The Clinical Relevance of Low-Density-Lipoproteins Size Modulation by Statins
Rizzo, M., & Berneis, K. K. (2006) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-006-8283-x · Cited by 70 · see citing works
LDL particle size and composition and incident cardiovascular disease in a South-European population: The Hortega-Liposcale Follow-up Study
Pichler, G., Amigó, N., Téllez-Plaza, M., Pardo-Cea, M. Á., Dominguez-Lucas, A., Marrachelli, V. G., Monleón, D., Martı́n-Escudero, J. C., Ascaso, J. F., Chaves, F. J., et al. (2018) · International Journal of Cardiology · doi:10.1016/j.ijcard.2018.03.128 · Cited by 67 · see citing works
Ezetimibe alone or in combination with simvastatin increases small dense low-density lipoproteins in healthy men: a randomized trial
Berneis, K. K., Rizzo, M., Berthold, H. K., Spinas, G. A., Krone, W., & Gouni‐Berthold, I. (2010) · European Heart Journal · doi:10.1093/eurheartj/ehq181 · Cited by 69 · see citing works
Mechanisms of the components of the metabolic syndrome that predispose to diabetes and atherosclerotic CVD
Eckel, R. H. (2007) · Proceedings of The Nutrition Society · doi:10.1017/s0029665107005320 · Cited by 68 · see citing works
LDL and HDL subclasses and their relationship with Framingham risk score in middle-aged Serbian population
Vekić, J., Topić, A., Zeljković, A., Jelić‐Ivanović, Z., & Spasojević‐Kalimanovska, V. (2007) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2006.11.013 · Cited by 66 · see citing works
The Contribution of Cardiac Fatty Acid Oxidation to Diabetic Cardiomyopathy Severity
Karwi, Q. G., Sun, Q., & Lopaschuk, G. D. (2021) · Cells · doi:10.3390/cells10113259 · Cited by 65 · see citing works
Impact of menopause and diabetes on atherogenic lipid profile: is it worth to analyse lipoprotein subfractions to assess cardiovascular risk in women?
Fonseca, M. I. H., da Silva, I. T., & Ferreira, S. R. G. (2017) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-017-0221-5 · Cited by 66 · see citing works
Predicting the risk of coronary heart disease
Dent, T. H. S. (2010) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2010.06.019 · Cited by 56 · see citing works
Pathogenesis and Management of the Dyslipidemia of the Metabolic Syndrome
Raal, F. J. (2009) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2008.0079 · Cited by 53 · see citing works
Lipoprotein Subclass Abnormalities and Incident Hypertension in Initially Healthy Women
Paynter, N. P., Sesso, H. D., Conen, D., Otvos, J. D., & Mora, S. (2011) · Clinical Chemistry · doi:10.1373/clinchem.2011.167544 · Cited by 50 · see citing works
Dietary Fat–Induced Alterations in Atherosclerosis Are Abolished by ACAT2-Deficiency in ApoB100 Only, LDLr −/− Mice
Bell, T. A., Kelley, K. L., Wilson, M. D., Sawyer, J. K., & Rudel, L. L. (2007) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.107.142802 · Cited by 50 · see citing works
Effect of alirocumab on specific lipoprotein non-high-density lipoprotein cholesterol and subfractions as measured by the vertical auto profile method: analysis of 3 randomized trials versus placebo
Toth, P. P., Hamon, S., Jones, S. R., Martin, S. S., Joshi, P. H., Kulkarni, K. R., Banerjee, P., Hanotin, C., Roth, E. M., & McKenney, J. M. (2016) · Lipids in Health and Disease · doi:10.1186/s12944-016-0197-4 · Cited by 50 · see citing works
The p. N103K mutation of leptin (LEP) gene and severe early onset obesity in Pakistan
Shabana, S., & Hasnain, S. (2016) · Biological Research · doi:10.1186/s40659-016-0082-7 · Cited by 49 · see citing works
A Mechanistic Systems Pharmacology Model for Prediction of LDL Cholesterol Lowering by PCSK9 Antagonism in Human Dyslipidemic Populations
Gadkar, K., Budha, N., Baruch, A., Davis, J. D., Fielder, P., & Ramanujan, S. (2014) · CPT: Pharmacometrics & Systems Pharmacology · doi:10.1038/psp.2014.47 · Cited by 48 · see citing works
Estrogen Decreases Atherosclerosis in Part by Reducing Hepatic Acyl-CoA:Cholesterol Acyltransferase 2 (ACAT2) in Monkeys
Kavanagh, K., Davis, M. A., Zhang, L., Wilson, M. D., Register, T. C., Adams, M. R., Rudel, L. L., & Wagner, J. D. (2009) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.109.191825 · Cited by 46 · see citing works
Predicting the risk of coronary heart disease. II: The role of novel molecular biomarkers and genetics in estimating risk, and the future of risk prediction
Dent, T. (2010) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2010.06.021 · Cited by 43 · see citing works
Hypothyroidism Results in Small Dense LDL Independent of IRS Traits and Hypertriglyceridemia
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Authors: Sacks, F. M., & Campos, H.
Affiliations: Harvard University (US)
Corresponding author: Sacks, Frank M.
ORCID: Sacks, Frank M.
Campos, Hannia
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2003-10
Volume: 88
Issue: 10
Pages: 4525-4532
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jc.2003-030636
OpenAlex: W2164346577
Cited by: 241
References: 88
Citations by year: 2026: 3 · 2025: 13 · 2024: 4 · 2023: 7 · 2022: 4 · 2021: 9 · 2020: 8 · 2019: 6 · 2018: 5 · 2017: 5 · 2016: 14 · 2015: 8 · 2014: 8 · 2013: 9 · 2012: 10
FWCI: 9.91
Type: journal article
Language: en
Open access: closed
Locations: The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Keywords: small dense LDL, LDL subclasses, coronary artery disease, cardiovascular risk prediction, atherogenesis, metabolic syndrome, HDL cholesterol, triglycerides
MeSH terms: Cardiovascular Diseases, Humans, Cholesterol, LDL, Particle Size

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Low-Density Lipoprotein Size and Cardiovascular Disease: A Reappraisal

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