Relation of increased prebeta-1 high-density lipoprotein levels to risk of coronary heart disease.

Preβ-1 high-density lipoprotein (HDL) plays a key role in reverse cholesterol transport by promoting cholesterol efflux. Our aims were (1) to test previous associations between preβ-1 HDL and coronary heart disease (CHD) and (2) to investigate whether preβ-1 HDL levels also are associated with risk of myocardial infarction (MI). Plasma preβ-1 HDL was measured by an ultrafiltration-isotope dilution technique in 1,255 subjects recruited from the University of California-San Francisco Lipid and Cardiovascular Clinics and collaborating cardiologists. Preβ-1 HDL was significantly and positively associated with CHD and MI even after adjustment for established risk factors. Inclusion of preβ-1 HDL in a multivariable model for CHD led to a modest improvement in reclassification of subjects (net reclassification index 0.15, p = 0.01; integrated discrimination improvement 0.003, p = 0.2). In contrast, incorporation of preβ-1 HDL into a risk model of MI alone significantly improved reclassification of subjects (net reclassification index 0.21, p = 0.008; integrated discrimination improvement 0.01, p = 0.02), suggesting that preβ-1 HDL has more discriminatory power for MI than for CHD in our study population. In conclusion, these results confirm previous associations between preβ-1 HDL and CHD in a large well-characterized clinical cohort. Also, this is the first study in which preβ-1 HDL was identified as a novel and independent predictor of MI above and beyond traditional CHD risk factors.

[1]  B. Perret,et al.  Hepatic lipase induces the formation of pre-beta 1 high density lipoprotein (HDL) from triacylglycerol-rich HDL2. A study comparing liver perfusion to in vitro incubation with lipases. , 1994, The Journal of biological chemistry.

[2]  C. Fielding,et al.  Early incorporation of cell-derived cholesterol into pre-beta-migrating high-density lipoprotein. , 1988, Biochemistry.

[3]  J. Kane,et al.  Characteristics of human lipoproteins isolated by selected-affinity immunosorption of apolipoprotein A-I. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Robert L Wilensky,et al.  Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. , 2011, The New England journal of medicine.

[5]  N. Gharavi,et al.  Inflammation and metabolic disorders , 2008, Current opinion in clinical nutrition and metabolic care.

[6]  M. Pencina,et al.  Evaluating the added predictive ability of a new marker: From area under the ROC curve to reclassification and beyond , 2008, Statistics in medicine.

[7]  T. Miida,et al.  Pre beta 1-high-density lipoprotein increases in coronary artery disease. , 1996, Clinical chemistry.

[8]  J. Albers,et al.  Dextran sulfate-Mg2+ precipitation procedure for quantitation of high-density-lipoprotein cholesterol. , 1982, Clinical chemistry.

[9]  S. Kunitake,et al.  Interconversion between apolipoprotein A-I-containing lipoproteins of pre-beta and alpha electrophoretic mobilities. , 1992, Journal of lipid research.

[10]  M. Jauhiainen,et al.  Degradation of Phospholipid Transfer Protein (PLTP) and PLTP-generated Pre-β-high Density Lipoprotein by Mast Cell Chymase Impairs High Affinity Efflux of Cholesterol from Macrophage Foam Cells* , 2003, The Journal of Biological Chemistry.

[11]  O. Francone,et al.  Increased prebeta-HDL levels, cholesterol efflux, and LCAT-mediated esterification in mice expressing the human cholesteryl ester transfer protein (CETP) and human apolipoprotein A-I (apoA-I) transgenes. , 1996, Journal of lipid research.

[12]  R. Levy,et al.  Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. , 1972, Clinical chemistry.

[13]  Weiqun,et al.  Familial ligand-defective apolipoprotein B. Identification of a new mutation that decreases LDL receptor binding affinity. , 1995, The Journal of clinical investigation.

[14]  Nancy R. Cook,et al.  Use and Misuse of the Receiver Operating Characteristic Curve in Risk Prediction , 2007, Circulation.

[15]  D. Sviridov,et al.  Delineation of the role of pre-beta 1-HDL in cholesterol efflux using isolated pre-beta 1-HDL. , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[16]  Serkalem Demissie,et al.  Value of High-Density Lipoprotein (HDL) Subpopulations in Predicting Recurrent Cardiovascular Events in the Veterans Affairs HDL Intervention Trial , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[17]  M. N. Poy,et al.  Apolipoprotein M is required for preβ-HDL formation and cholesterol efflux to HDL and protects against atherosclerosis , 2005, Nature Medicine.

[18]  P. Duchateau,et al.  Prebeta-1 HDL in plasma of normolipidemic individuals: influences of plasma lipoproteins, age, and gender. , 1998, Journal of lipid research.

[19]  J. Kane,et al.  Apolipoprotein A-I-containing lipoproteins with pre-beta electrophoretic mobility. , 1985, Journal of lipid research.

[20]  A. Tall,et al.  Increased prebeta-high density lipoprotein, apolipoprotein AI, and phospholipid in mice expressing the human phospholipid transfer protein and human apolipoprotein AI transgenes. , 1996, The Journal of clinical investigation.

[21]  E. Brinton,et al.  Very small apolipoprotein A-I-containing particles from human plasma: isolation and quantification by high-performance size-exclusion chromatography. , 2000, Clinical chemistry.

[22]  H. Bloomfield,et al.  Relation of gemfibrozil treatment and high-density lipoprotein subpopulation profile with cardiovascular events in the Veterans Affairs High-Density Lipoprotein Intervention Trial. , 2008, Metabolism: clinical and experimental.

[23]  D. Rader,et al.  The Ability to Promote Efflux Via ABCA1 Determines the Capacity of Serum Specimens With Similar High-Density Lipoprotein Cholesterol to Remove Cholesterol From Macrophages , 2010, Arteriosclerosis, thrombosis, and vascular biology.

[24]  P. Duchateau,et al.  Measurement of prebeta-1 HDL in human plasma by an ultrafiltration-isotope dilution technique. , 1997, Analytical biochemistry.

[25]  S. Kunitake,et al.  Heterogeneity of high-density lipoproteins and apolipoprotein A-I as related to quantification of apolipoprotein A-I. , 1996, Methods in enzymology.

[26]  M. Pape,et al.  Secretion of pre-beta-migrating apoA-I by cynomolgus monkey hepatocytes in culture. , 1991, Journal of lipid research.

[27]  A. Tall,et al.  HDL, ABC transporters, and cholesterol efflux: implications for the treatment of atherosclerosis. , 2008, Cell metabolism.

[28]  Børge G Nordestgaard,et al.  High pre-beta1 HDL concentrations and low lecithin: cholesterol acyltransferase activities are strong positive risk markers for ischemic heart disease and independent of HDL-cholesterol. , 2010, Clinical chemistry.

[29]  D. Reboussin,et al.  Plasma Levels of HDL Subpopulations and Remnant Lipoproteins Predict the Extent of Angiographically-Defined Coronary Artery Disease in Postmenopausal Women , 2008, Arteriosclerosis, thrombosis, and vascular biology.

[30]  L. Cupples,et al.  High-Density Lipoprotein Subpopulation Profile and Coronary Heart Disease Prevalence in Male Participants of the Framingham Offspring Study , 2004, Arteriosclerosis, thrombosis, and vascular biology.