title: Remnant Lipoprotein Cholesterol and Mortality After Acute Myocardial Infarction: Further Evidence for a Hypercholesterolemia Paradox From the TRIUMPH Registry.
abstract: BACKGROUND
  Remnants are partially hydrolyzed, triglyceride-rich lipoproteins that, like other apolipoprotein B-containing lipoproteins, are atherogenic. Prior observational studies suggest paradoxically better outcomes in hypercholesterolemic patients who sustain an acute myocardial infarction (AMI), one of several known recurrent risk paradoxes. To date, the association of directly measured remnant lipoprotein cholesterol (RLP-C) with survival after an AMI has not been examined.
  
  
  OBJECTIVE
  Higher RLP-C levels may be paradoxically associated with lower mortality.
  
  
  METHODS
  We examined 2465 AMI survivors in a prospective, 24-center US study of AMI outcomes. Lipoprotein cholesterol subfractions were directly measured by ultracentrifugation. RLP-C was defined as intermediate-density lipoprotein cholesterol (IDL-C) + very-low-density lipoprotein cholesterol subfraction 3 (VLDL3 -C). Given a linear relationship between RLP-C and mortality, we examined RLP-C by tertiles and continuously. Cox regression hazard ratios (HRs) were adjusted for the Global Registry of Acute Coronary Events (GRACE) score and 23 other covariates.
  
  
  RESULTS
  Participants were age 58 ± 12 years (mean ± SD), and 68% were men. After 2 years of follow-up, 226 (9%) participants died. The mortality proportion was 12.4% in the lowest tertile of RLP-C (0-15 mg/dL), 8.5% in the middle tertile (16-23 mg/dL), and 6.8% in the highest tertile (24-120 mg/dL; P < 0.001). A 1-SD increase in RLP-C (11 mg/dL) predicted a 24% lower adjusted risk of 2-year mortality (HR: 0.76, 95% confidence interval [CI]: 0.64-0.91). Similar results were found for a 1-SD increase in IDL-C (HR per 8 mg/dL: 0.80, 95% CI: 0.67-0.96), VLDL3 -C (HR per 4 mg/dL: 0.74, 95% CI: 0.61-0.89), and very-low-density lipoprotein cholesterol (VLDL-C; HR per 8 mg/dL: 0.69, 95% CI: 0.55-0.85).
  
  
  CONCLUSIONS
  Higher RLP-C levels were associated with lower mortality 2 years after AMI despite rigorous adjustment for known confounders. Unknown protective factors or a lead-time bias likely explains the paradox.
authors.affiliation: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland.
authors.forename: Seth S
authors.initials: SS
authors.lastname: Martin
authors.affiliation: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland.
authors.forename: Kamil F
authors.initials: KF
authors.lastname: Faridi
authors.affiliation: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland.
authors.forename: Parag H
authors.initials: PH
authors.lastname: Joshi
authors.affiliation: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Blaha
authors.affiliation: Atherotech Diagnostics Laboratory, Birmingham, Alabama.
authors.forename: Krishnaji R
authors.initials: KR
authors.lastname: Kulkarni
authors.affiliation: Northwest London Hospitals NHS Trust, London, United Kingdom.
authors.forename: Arif A
authors.initials: AA
authors.lastname: Khokhar
authors.affiliation: VA Eastern Colorado Health Care System, Denver, Colorado.|University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Maddox
authors.affiliation: University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Edward P
authors.initials: EP
authors.lastname: Havranek
authors.affiliation: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland.|Department of Preventive Cardiology, CGH Medical Center, Sterling, Illinois.|University of Illinois School of Medicine, Peoria, Illinois.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Toth
authors.affiliation: Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City, Kansas City, Missouri.
authors.forename: Fengming
authors.initials: F
authors.lastname: Tang
authors.affiliation: Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City, Kansas City, Missouri.
authors.forename: John A
authors.initials: JA
authors.lastname: Spertus
authors.affiliation: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Jones
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D002784:Cholesterol / Q000097:blood*; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D065840:Protective Factors; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D014280:Triglycerides / Q000097:blood*; D014481:United States / Q000453:epidemiology; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D008074:Lipoproteins; D014280:Triglycerides; C112017:remnant-like particle cholesterol; D002784:Cholesterol