title: Remnant Lipoprotein Cholesterol and Incident Coronary Heart Disease: The Jackson Heart and Framingham Offspring Cohort Studies.
abstract: Remnant lipoproteins (RLPs), the triglyceride-enriched precursors to low-density lipoprotein, are an emerging risk factor for coronary heart disease (CHD). We sought to determine the association of RLP cholesterol (RLP-C) levels with incident CHD in 2 diverse, prospective, longitudinal observational US cohorts.
  
  
  
  We analyzed cholesterol levels from serum lipoprotein samples separated via density gradient ultracentrifugation in 4114 US black participants (mean age 53.8 years, 64% women) from the Jackson Heart Study and a random sample of 818 predominantly white participants (mean age 57.3 years, 52% women) from the Framingham Offspring Cohort Study. Multivariable-adjusted hazard ratios (HRs) for RLP-C (the sum of very low-density lipoprotein3 cholesterol and intermediate-density lipoprotein cholesterol) were derived to estimate associations with incident CHD events consisting of myocardial infarction, CHD death, and revascularizations for each cohort separately and as a combined population. There were 146 CHD events in the combined population. After adjustments for age, sex, body mass index, smoking, blood pressure, diabetes, and lipid-lowering therapy for the combined population, RLP-C (HR 1.23 per 1-SD increase, 95% CI 1.06-1.42, P<0.01) and intermediate-density lipoprotein cholesterol (HR 1.26 per 1-SD increase, 95% CI 1.08-1.47, P<0.01) predicted CHD during an 8-year follow-up. Associations were attenuated by high-density lipoprotein cholesterol and ultimately lost significance with inclusion of real low-density lipoprotein cholesterol, which excludes Lp(a) and IDL cholesterol fractions. Similar associations were seen in multivariable analyses within each cohort.
  
  
  
  RLP-C levels are predictive of incident CHD in this diverse group of primary prevention subjects. Interventions aimed at reducing RLP-C to prevent CHD warrant further intensive investigation.
  
  
  
  URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00415415.
authors.affiliation: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX parag.joshi@utsouthwestern.edu.
authors.forename: Parag H
authors.initials: PH
authors.lastname: Joshi
authors.affiliation: Royal Brompton and Harefield NHS Trust, London, UK.
authors.forename: Arif A
authors.initials: AA
authors.lastname: Khokhar
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Massaro
authors.affiliation: Center of Biostatistics & Bioinformatics, University of Mississippi Medical Center, Jackson, MS Jackson Heart Study, University of Mississippi Medical Center, Jackson, MS.
authors.forename: Seth T
authors.initials: ST
authors.lastname: Lirette
authors.affiliation: Center of Biostatistics & Bioinformatics, University of Mississippi Medical Center, Jackson, MS Jackson Heart Study, University of Mississippi Medical Center, Jackson, MS.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Griswold
authors.affiliation: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD.
authors.forename: Seth S
authors.initials: SS
authors.lastname: Martin
authors.affiliation: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Blaha
authors.affiliation: Atherotech Diagnostics Laboratory, Birmingham, AL.
authors.forename: Krishnaji R
authors.initials: KR
authors.lastname: Kulkarni
authors.affiliation: Jackson Heart Study, University of Mississippi Medical Center, Jackson, MS.
authors.forename: Adolfo
authors.initials: A
authors.lastname: Correa
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA.
authors.forename: Ralph B
authors.initials: RB
authors.lastname: D'Agostino
authors.affiliation: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Jones
authors.affiliation: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD CGH Medical Center, Sterling, IL University of Illinois School of Medicine, Peoria, IL.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Toth
mesh_terms: D000328:Adult; D000368:Aged; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood*; D015331:Cohort Studies; D003327:Coronary Disease / Q000097:blood / Q000453:epidemiology* / Q000401:mortality; D005260:Female; D006801:Humans; D015994:Incidence; D017270:Lipoprotein(a) / Q000097:blood; D008074:Lipoproteins / Q000097:blood*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000097:blood / Q000453:epidemiology*; D009204:Myocardial Revascularization / Q000706:statistics & numerical data*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood*; D014481:United States / Q000453:epidemiology
chemical_list: D008076:Cholesterol, HDL; D015243:Cholesterol, VLDL; D017270:Lipoprotein(a); D008074:Lipoproteins; D014280:Triglycerides; C030104:lipoprotein cholesterol; C112017:remnant-like particle cholesterol; D002784:Cholesterol
keywords: coronary heart disease; lipids; primary prevention; remnant lipoprotein cholesterol; triglycerides