title: Clinical utility of lipoprotein-associated phospholipase A₂ for cardiovascular disease prediction in a multiethnic cohort of women.
abstract: BACKGROUND
  Findings regarding the association of lipoprotein-associated phospholipase A₂ (Lp-PLA2) activity and mass with incident cardiovascular disease (CVD) have been inconsistent, and their role in risk prediction is uncertain.
  
  
  METHODS
  A case-cohort sample from the Women's Health Initiative Observational Study (WHI-OS) comprised 1821 CVD cases and a reference subcohort of 1992 women. We used Cox regression models with inverse sampling weights to assess the association of Lp-PLA2 mass and activity with CVD (myocardial infarction, stroke, and CVD mortality).
  
  
  RESULTS
  Subcohort means were 184.3 mmol/min/mL for Lp-PLA2 activity and 499.2 μg/L for Lp-PLA2 mass, with 99% having mass above 200 μg/L, the clinically recommended cut point. Both activity and mass were positively associated with incident CVD in age- and race/ethnicity-adjusted analyses. Following adjustment according to CVD risk factors, the association with activity became null (hazard ratio = 1.02 for top vs bottom quartile, 95% CI = 0.79-1.33, P for trend = 0.65), but the association with mass remained (hazard ratio = 1.84, 95% CI = 1.45-2.34, P for trend < 0.0001). In contrast to blood pressure, HDL, and hsCRP, reclassification statistics for Lp-PLA2 mass did not suggest improvement for overall CVD after full adjustment.
  
  
  CONCLUSIONS
  In the WHI-OS Lp-PLA2 mass, but not activity, was independently associated with CVD. However, model fit did not significantly improve with Lp-PLA2 mass, and assay calibration remains a clinical concern.
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA. ncook@rics.bwh.harvard.edu
authors.forename: Nancy R
authors.initials: NR
authors.lastname: Cook
authors.forename: Nina P
authors.initials: NP
authors.lastname: Paynter
authors.forename: Joann E
authors.initials: JE
authors.lastname: Manson
authors.forename: Lisa W
authors.initials: LW
authors.lastname: Martin
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: Robinson
authors.forename: Sylvia
authors.initials: S
authors.lastname: Wassertheil-Smoller
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ridker
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000201:enzymology* / Q000503:physiopathology; D015331:Cohort Studies; D005006:Ethnicity; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D054467:Phospholipases A2 / Q000378:metabolism*
chemical_list: D008074:Lipoproteins; D054467:Phospholipases A2