title: Use of lipoprotein particle measures for assessing coronary heart disease risk post-American Heart Association/American College of Cardiology guidelines: the Multi-Ethnic Study of Atherosclerosis.
abstract: OBJECTIVE
  The American College of Cardiology and American Heart Association have issued guidelines indicating that the contribution of apolipoprotein B-100 (ApoB) to cardiovascular risk assessment remains uncertain. The present analysis evaluates whether lipoprotein particle measures convey risk of coronary heart disease (CHD) in 4679 Multi-Ethnic Study of Atherosclerosis (MESA) participants.
  
  
  RESULTS
  Cox regression analysis was performed to determine associations between lipids or lipoproteins and primary CHD events. After adjustment for nonlipid variables, lipoprotein particle levels in fourth quartiles were found to convey significantly greater risk of incident CHD when compared to first quartile levels (hazard ratio [HR]; 95% confidence interval [CI]): ApoB (HR, 1.84; 95% CI, 1.25-2.69), ApoB/ApoA-I (HR, 1.91; 95% CI, 1.32-2.76), total low-density lipoprotein-particles (LDL-P; HR, 1.77; 95% CI, 1.21-2.58), and the LDL-P/HDL-P (high-density lipoprotein-P) ratio (HR, 2.28; 95% CI, 1.54-3.37). Associations between lipoprotein particle measures and CHD were attenuated after adjustment for standard lipid panel variables. Using the American Heart Association/American College of Cardiology risk calculator as a baseline model for CHD risk assessment, significant net reclassification improvement scores were found for ApoB/ApoA-I (0.18; P=0.007) and LDL-P/high-density lipoprotein-P (0.15; P<0.001). C-statistics revealed no significant increase in CHD event discrimination for any lipoprotein measure.
  
  
  CONCLUSIONS
  Lipoprotein particle measures ApoB/ApoA-I and LDL-P/high-density lipoprotein-P marginally improved net reclassification improvement scores, but null findings for corresponding c-statistic are not supportive of lipoprotein testing. The attenuated associations of lipoprotein particle measures with CHD after the adjustment for lipids indicate that their measurement does not detect risk that is unaccounted for by the standard lipid panel. However, the possibility that lipoprotein measures may identify CHD risk in a subpopulation of individuals with normal cholesterol, but elevated lipoprotein particle numbers cannot be ruled out.
authors.affiliation: From the Department of Laboratory Medicine and Pathology (B.T.S., M.Y.T.) and Division of Biostatistics, School of Public Health (W.G.), University of Minnesota, Minneapolis; Department of Laboratory Medicine, National Institutes of Health Molecular Disease Branch, National Heart, Lung, and Blood Institute, Bethesda, MD (A.T.R.); University of Washington School of Medicine, Department of Medicine, Division of Cardiology, University of Washington Medical Center, Seattle (P.P.); Cardiovascular Health Research Unit, Department of Epidemiology, School of Public Health (S.R.H.) and Department of Biostatistics (R.L.M.), University of Washington, Seattle; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (P.G.); and Johns Hopkins School of Medicine, Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD (E.D.M.).
authors.forename: Brian T
authors.initials: BT
authors.lastname: Steffen
authors.affiliation: From the Department of Laboratory Medicine and Pathology (B.T.S., M.Y.T.) and Division of Biostatistics, School of Public Health (W.G.), University of Minnesota, Minneapolis; Department of Laboratory Medicine, National Institutes of Health Molecular Disease Branch, National Heart, Lung, and Blood Institute, Bethesda, MD (A.T.R.); University of Washington School of Medicine, Department of Medicine, Division of Cardiology, University of Washington Medical Center, Seattle (P.P.); Cardiovascular Health Research Unit, Department of Epidemiology, School of Public Health (S.R.H.) and Department of Biostatistics (R.L.M.), University of Washington, Seattle; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (P.G.); and Johns Hopkins School of Medicine, Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD (E.D.M.).
authors.forename: Weihua
authors.initials: W
authors.lastname: Guan
authors.affiliation: From the Department of Laboratory Medicine and Pathology (B.T.S., M.Y.T.) and Division of Biostatistics, School of Public Health (W.G.), University of Minnesota, Minneapolis; Department of Laboratory Medicine, National Institutes of Health Molecular Disease Branch, National Heart, Lung, and Blood Institute, Bethesda, MD (A.T.R.); University of Washington School of Medicine, Department of Medicine, Division of Cardiology, University of Washington Medical Center, Seattle (P.P.); Cardiovascular Health Research Unit, Department of Epidemiology, School of Public Health (S.R.H.) and Department of Biostatistics (R.L.M.), University of Washington, Seattle; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (P.G.); and Johns Hopkins School of Medicine, Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD (E.D.M.).
authors.forename: Alan T
authors.initials: AT
authors.lastname: Remaley
authors.affiliation: From the Department of Laboratory Medicine and Pathology (B.T.S., M.Y.T.) and Division of Biostatistics, School of Public Health (W.G.), University of Minnesota, Minneapolis; Department of Laboratory Medicine, National Institutes of Health Molecular Disease Branch, National Heart, Lung, and Blood Institute, Bethesda, MD (A.T.R.); University of Washington School of Medicine, Department of Medicine, Division of Cardiology, University of Washington Medical Center, Seattle (P.P.); Cardiovascular Health Research Unit, Department of Epidemiology, School of Public Health (S.R.H.) and Department of Biostatistics (R.L.M.), University of Washington, Seattle; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (P.G.); and Johns Hopkins School of Medicine, Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD (E.D.M.).
authors.forename: Pathmaja
authors.initials: P
authors.lastname: Paramsothy
authors.affiliation: From the Department of Laboratory Medicine and Pathology (B.T.S., M.Y.T.) and Division of Biostatistics, School of Public Health (W.G.), University of Minnesota, Minneapolis; Department of Laboratory Medicine, National Institutes of Health Molecular Disease Branch, National Heart, Lung, and Blood Institute, Bethesda, MD (A.T.R.); University of Washington School of Medicine, Department of Medicine, Division of Cardiology, University of Washington Medical Center, Seattle (P.P.); Cardiovascular Health Research Unit, Department of Epidemiology, School of Public Health (S.R.H.) and Department of Biostatistics (R.L.M.), University of Washington, Seattle; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (P.G.); and Johns Hopkins School of Medicine, Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD (E.D.M.).
authors.forename: Susan R
authors.initials: SR
authors.lastname: Heckbert
authors.affiliation: From the Department of Laboratory Medicine and Pathology (B.T.S., M.Y.T.) and Division of Biostatistics, School of Public Health (W.G.), University of Minnesota, Minneapolis; Department of Laboratory Medicine, National Institutes of Health Molecular Disease Branch, National Heart, Lung, and Blood Institute, Bethesda, MD (A.T.R.); University of Washington School of Medicine, Department of Medicine, Division of Cardiology, University of Washington Medical Center, Seattle (P.P.); Cardiovascular Health Research Unit, Department of Epidemiology, School of Public Health (S.R.H.) and Department of Biostatistics (R.L.M.), University of Washington, Seattle; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (P.G.); and Johns Hopkins School of Medicine, Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD (E.D.M.).
authors.forename: Robyn L
authors.initials: RL
authors.lastname: McClelland
authors.affiliation: From the Department of Laboratory Medicine and Pathology (B.T.S., M.Y.T.) and Division of Biostatistics, School of Public Health (W.G.), University of Minnesota, Minneapolis; Department of Laboratory Medicine, National Institutes of Health Molecular Disease Branch, National Heart, Lung, and Blood Institute, Bethesda, MD (A.T.R.); University of Washington School of Medicine, Department of Medicine, Division of Cardiology, University of Washington Medical Center, Seattle (P.P.); Cardiovascular Health Research Unit, Department of Epidemiology, School of Public Health (S.R.H.) and Department of Biostatistics (R.L.M.), University of Washington, Seattle; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (P.G.); and Johns Hopkins School of Medicine, Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD (E.D.M.).
authors.forename: Philip
authors.initials: P
authors.lastname: Greenland
authors.affiliation: From the Department of Laboratory Medicine and Pathology (B.T.S., M.Y.T.) and Division of Biostatistics, School of Public Health (W.G.), University of Minnesota, Minneapolis; Department of Laboratory Medicine, National Institutes of Health Molecular Disease Branch, National Heart, Lung, and Blood Institute, Bethesda, MD (A.T.R.); University of Washington School of Medicine, Department of Medicine, Division of Cardiology, University of Washington Medical Center, Seattle (P.P.); Cardiovascular Health Research Unit, Department of Epidemiology, School of Public Health (S.R.H.) and Department of Biostatistics (R.L.M.), University of Washington, Seattle; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (P.G.); and Johns Hopkins School of Medicine, Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD (E.D.M.).
authors.forename: Erin D
authors.initials: ED
authors.lastname: Michos
authors.affiliation: From the Department of Laboratory Medicine and Pathology (B.T.S., M.Y.T.) and Division of Biostatistics, School of Public Health (W.G.), University of Minnesota, Minneapolis; Department of Laboratory Medicine, National Institutes of Health Molecular Disease Branch, National Heart, Lung, and Blood Institute, Bethesda, MD (A.T.R.); University of Washington School of Medicine, Department of Medicine, Division of Cardiology, University of Washington Medical Center, Seattle (P.P.); Cardiovascular Health Research Unit, Department of Epidemiology, School of Public Health (S.R.H.) and Department of Biostatistics (R.L.M.), University of Washington, Seattle; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (P.G.); and Johns Hopkins School of Medicine, Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD (E.D.M.). tsaix001@umn.edu.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Tsai
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000572:American Heart Association; D015415:Biomarkers / Q000097:blood; D002309:Cardiology / Q000592:standards*; D003327:Coronary Disease / Q000097:blood* / Q000175:diagnosis* / Q000208:ethnology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008074:Lipoproteins / Q000097:blood*; D009682:Magnetic Resonance Spectroscopy / Q000592:standards; D008297:Male; D008875:Middle Aged; D017711:Nonlinear Dynamics; D017410:Practice Guidelines as Topic; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D014481:United States / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D008074:Lipoproteins
keywords: apolipoproteins; coronary disease; lipids; lipoproteins; magnetic resonance spectroscopy; risk factors