title: Relation of increased prebeta-1 high-density lipoprotein levels to risk of coronary heart disease.
abstract: 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.
authors.affiliation: Applied Quantitative Genotherapeutics, Pfizer Pharmaceuticals, Cambridge, Massachusetts, USA.
authors.forename: Lin T
authors.initials: LT
authors.lastname: Guey
authors.forename: Clive R
authors.initials: CR
authors.lastname: Pullinger
authors.forename: Brian Y
authors.initials: BY
authors.lastname: Ishida
authors.forename: Patricia M
authors.initials: PM
authors.lastname: O'Connor
authors.forename: Christian
authors.initials: C
authors.lastname: Zellner
authors.forename: Omar L
authors.initials: OL
authors.lastname: Francone
authors.forename: Jason M
authors.initials: JM
authors.lastname: Laramie
authors.forename: Josefina M
authors.initials: JM
authors.lastname: Naya-Vigne
authors.forename: Ketevan A
authors.initials: KA
authors.lastname: Siradze
authors.forename: Prakash
authors.initials: P
authors.lastname: Deedwania
authors.forename: Rita F
authors.initials: RF
authors.lastname: Redberg
authors.forename: Philip H
authors.initials: PH
authors.lastname: Frost
authors.forename: Albert B
authors.initials: AB
authors.lastname: Seymour
authors.forename: John P
authors.initials: JP
authors.lastname: Kane
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Malloy
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003327:Coronary Disease / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D005260:Female; D053442:High-Density Lipoproteins, Pre-beta / Q000097:blood*; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D011237:Predictive Value of Tests; D012307:Risk Factors
chemical_list: D053442:High-Density Lipoproteins, Pre-beta