title: Lipoprotein-associated phospholipase A(2) and future risk of subclinical disease and cardiovascular events in individuals with type 2 diabetes: the Cardiovascular Health Study.
abstract: OBJECTIVE
  Type 2 diabetes is an established risk factor for cardiovascular disease (CVD). This increased risk may be due in part to the increased levels of inflammatory factors associated with diabetes. Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a risk marker for CVD and has pro-inflammatory effects in atherosclerotic plaques. We therefore sought to determine whether Lp-PLA(2) levels partially explain the greater prevalence of subclinical CVD and greater incidence of CVD outcomes associated with type 2 diabetes in the Cardiovascular Health Study.
  
  
  METHODS
  We conducted a cross-sectional and prospective study of 4,062 men and women without previous CVD from the Cardiovascular Health Study (1989 to 2007). Lp-PLA(2) mass and activity were measured in baseline plasma. Subclinical disease was determined at baseline and incident CVD was ascertained annually. We used logistic regression for cross-sectional analyses and Cox proportional hazards models for incident analyses.
  
  
  RESULTS
  At baseline, Lp-PLA(2) mass did not differ significantly by type 2 diabetes status; however, Lp-PLA(2) activity was significantly higher among type 2 diabetic individuals. Baseline subclinical disease was significantly associated with baseline diabetes and this association was similar in models unadjusted or adjusted for Lp-PLA(2) (OR 1.68 [95% CI 1.31-2.15] vs OR 1.67 [95% CI 1.30-2.13]). Baseline type 2 diabetes was also significantly associated with incident CVD events, including fatal CHD, fatal myocardial infarction (MI) and non-fatal MI in multivariable analyses. There were no differences in these estimates after further adjustment for Lp-PLA(2) activity.
  
  
  CONCLUSIONS
  In this older cohort, differences in Lp-PLA(2) activity did not explain any of the excess risk for subclinical disease or CVD outcomes related to diabetes.
authors.affiliation: Department of Health and Exercise Science, Colorado State University, 223 Moby, Fort Collins, CO 80523, USA. tnelson@cahs.colostate.edu
authors.forename: T L
authors.initials: TL
authors.lastname: Nelson
authors.forename: A
authors.initials: A
authors.lastname: Kamineni
authors.forename: B
authors.initials: B
authors.lastname: Psaty
authors.forename: M
authors.initials: M
authors.lastname: Cushman
authors.forename: N S
authors.initials: NS
authors.lastname: Jenny
authors.forename: J
authors.initials: J
authors.lastname: Hokanson
authors.forename: C
authors.initials: C
authors.lastname: Furberg
authors.forename: K J
authors.initials: KJ
authors.lastname: Mukamal
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism*; D000368:Aged; D002318:Cardiovascular Diseases / Q000201:enzymology* / Q000209:etiology / Q000378:metabolism; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000201:enzymology* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase