title: HDL cholesterol subclasses, myocardial infarction, and mortality in secondary prevention: the Lipoprotein Investigators Collaborative.
abstract: OBJECTIVE
  High-density lipoprotein (HDL) is highly heterogeneous and the link of its subclasses to prognosis remains controversial. We aimed to rigorously examine the associations of HDL subclasses with prognosis in secondary prevention.
  
  
  RESULTS
  We collaboratively analysed data from two, complementary prospective cohorts: the TRIUMPH study of 2465 acute myocardial infarction patients, and the IHCS study of 2414 patients who underwent coronary angiography. All patients had baseline HDL subclassification by vertical-spin density gradient ultracentrifugation. Given non-linearity, we stratified by tertiles of HDL-C and its two major subclasses (HDL2-C, HDL3-C), then compared multivariable-adjusted hazard ratios for mortality and mortality/myocardial infarction. Patients were middle-aged to elderly (TRIUMPH: 58.2 ± 12.2 years; IHCS: 62.6 ± 12.6 years), and the majority were men (TRIUMPH: 68.0%; IHCS: 65.5%). IHCS had lower mean HDL-C levels (34.6 ± 10.1 mg/dL) compared with TRIUMPH (40 ± 10.6 mg/dL). HDL3-C accounted for >3/4 of HDL-C (mean HDL3-C/HDL-C 0.78 ± 0.05 in both cohorts). During 2 years of follow-up in TRIUMPH, 226 (9.2%) deaths occurred, while death/myocardial infarction occurred in 401 (16.6%) IHCS patients over 5 years. No independent associations with outcomes were observed for HDL-C or HDL2-C. In contrast, the lowest tertile of HDL3-C was independently associated with >50% higher risk in each cohort (TRIUMPH: with middle tertile as reference, fully adjusted HR for mortality of HDL3-C, 1.57; 95% CI, 1.13-2.18; IHCS: fully adjusted HR for mortality/myocardial infarction, 1.55; 95% CI, 1.20-2.00).
  
  
  CONCLUSIONS
  In secondary prevention, increased risk for long-term hard clinical events is associated with low HDL3-C, but not HDL2-C or HDL-C, highlighting the potential value of subclassifying HDL-C.
authors: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, 600 N. Wolfe St, Carnegie 565-G, Baltimore, 21287 MD, USA smart100@jhmi.edu.
authors: Seth S
authors: SS
authors: Martin
authors: St Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK.
authors: Arif A
authors: AA
authors: Khokhar
authors: Cardiovascular Department, Intermountain Medical Center, Murray, UT, USA.
authors: Heidi T
authors: HT
authors: May
authors: Atherotech Diagnostics Laboratory, Birmingham, AL, USA.
authors: Krishnaji R
authors: KR
authors: Kulkarni
authors: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, 600 N. Wolfe St, Carnegie 565-G, Baltimore, 21287 MD, USA.
authors: Michael J
authors: MJ
authors: Blaha
authors: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, 600 N. Wolfe St, Carnegie 565-G, Baltimore, 21287 MD, USA.
authors: Parag H
authors: PH
authors: Joshi
authors: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, 600 N. Wolfe St, Carnegie 565-G, Baltimore, 21287 MD, USA Department of Preventive Cardiology, CGH Medical Center, Sterling, IL, USA University of Illinois School of Medicine, Peoria, IL, USA.
authors: Peter P
authors: PP
authors: Toth
authors: Cardiovascular Department, Intermountain Medical Center, Murray, UT, USA.
authors: Joseph B
authors: JB
authors: Muhlestein
authors: Cardiovascular Department, Intermountain Medical Center, Murray, UT, USA.
authors: Jeffrey L
authors: JL
authors: Anderson
authors: Cardiovascular Department, Intermountain Medical Center, Murray, UT, USA.
authors: Stacey
authors: S
authors: Knight
authors: St Luke's Mid-America Heart Institute, University of Missouri - Kansas, Kansas City, MO, USA.
authors: Yan
authors: Y
authors: Li
authors: St Luke's Mid-America Heart Institute, University of Missouri - Kansas, Kansas City, MO, USA.
authors: John A
authors: JA
authors: Spertus
authors: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, 600 N. Wolfe St, Carnegie 565-G, Baltimore, 21287 MD, USA.
authors: Steven R
authors: SR
authors: Jones
mesh_terms: D000368:Aged; D008076:Cholesterol, HDL / Q000145:classification* / Q000302:isolation & purification / Q000502:physiology; D003327:Coronary Disease / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology* / Q000401:mortality / Q000517:prevention & control; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment / Q000379:methods; D055502:Secondary Prevention; D014461:Ultracentrifugation / Q000379:methods
chemical_list: D008076:Cholesterol, HDL
keywords: Acute myocardial infarction; Coronary heart disease; HDL subclasses; HDL2; HDL3; High-density lipoprotein cholesterol; Lipids; Mortality; Secondary prevention