title: Lipoprotein-associated phospholipase A₂ activity predicts progression of subclinical coronary atherosclerosis.
abstract: BACKGROUND
  Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is a lipoprotein-associated enzyme that cleaves oxidized phosphatidylcholines, generating pro-atherosclerotic lysophosphatidylcholine and oxidized free fatty acids. Lp-PLA₂ is independently associated with cardiovascular disease (CVD) in a variety of populations. Coronary calcium is a measure of subclinical CVD, and progression of coronary calcification predicts future CVD events. In type 1 diabetes there is an increase in coronary calcium and CVD despite a favorable lipid profile. Levels of Lp-PLA₂ in type 1 diabetes are not known, nor is the relationship between Lp-PLA₂ and progression of coronary calcification.
  
  
  METHODS
  The Coronary Artery Calcification in Type 1 Diabetes study measured coronary calcium by electron-beam computed tomography twice over a 2.6 ± 0.3-year interval. Lp-PLA₂ mass and activity were measured at baseline (n = 1,097 subjects, 506 with and 591 without type 1 diabetes).
  
  
  RESULTS
  In type 1 diabetes Lp-PLA₂ mass was marginally higher (285 ± 79 vs. 278 ± 78 ng/mL, P = 0.1), and Lp-PLA₂ activity was significantly lower (137 ± 30 vs. 146 ± 36 nmol/min/mL, P < 0.0001) than in those without diabetes. There was a greater proportion of those with progression of coronary calcification in type 1 diabetes compared with those without diabetes (24% vs. 10%, P < 0.0001). Lp-PLA₂ activity was independently associated with progression of coronary calcification in multivariate analysis (4th quartile verses bottom three quartiles, odds ratio = 1.77 [1.08-2.91], P = 0.02). LpPLA₂ mass was not significantly associated with progression of coronary calcification in this cohort (P = 0.09).
  
  
  CONCLUSIONS
  Lp-PLA₂ activity predicts progression of subclinical atherosclerosis in individuals with and without type 1 diabetes.
authors.affiliation: The Barbara Davis Center for Childhood Diabetes, Aurora, Colorado, USA.
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Kinney
authors.forename: Janet K
authors.initials: JK
authors.lastname: Snell-Bergeon
authors.forename: David M
authors.initials: DM
authors.lastname: Maahs
authors.forename: Robert H
authors.initials: RH
authors.lastname: Eckel
authors.forename: James
authors.initials: J
authors.lastname: Ehrlich
authors.forename: Marian
authors.initials: M
authors.lastname: Rewers
authors.forename: John E
authors.initials: JE
authors.lastname: Hokanson
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism*; D000328:Adult; D000419:Albuminuria; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000502:physiology; D002097:C-Reactive Protein / Q000032:analysis; D002114:Calcinosis / Q000097:blood / Q000201:enzymology; D002784:Cholesterol / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000201:enzymology*; D055316:Cystatin C / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000201:enzymology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D014057:Tomography, X-Ray Computed; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D055316:Cystatin C; D014280:Triglycerides; D002097:C-Reactive Protein; D002784:Cholesterol; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase