03031nas a2200361 4500008004100000022001400041245018100055210006900236260001300305300001100318490000700329520192100336653005102257653000902308653002802317653002802345653003002373653001102403653001102414653000902425653003202434653002402466653001702490100001702507700001602524700001302540700001502553700001602568700001602584700001502600700001802615856003602633 2011 eng d a1432-042800aLipoprotein-associated phospholipase A(2) and future risk of subclinical disease and cardiovascular events in individuals with type 2 diabetes: the Cardiovascular Health Study.0 aLipoproteinassociated phospholipase A2 and future risk of subcli c2011 Feb a329-330 v543 a

AIMS/HYPOTHESIS: 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/INTERPRETATION: 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.

10a1-Alkyl-2-acetylglycerophosphocholine Esterase10aAged10aCardiovascular Diseases10aCross-Sectional Studies10aDiabetes Mellitus, Type 210aFemale10aHumans10aMale10aProportional Hazards Models10aProspective Studies10aRisk Factors1 aNelson, T, L1 aKamineni, A1 aPsaty, B1 aCushman, M1 aJenny, N, S1 aHokanson, J1 aFurberg, C1 aMukamal, K, J uhttps://chs-nhlbi.org/node/125003296nas a2200409 4500008004100000022001400041245013600055210006900191260001300260300001300273490000700286520212000293653005102413653000902464653002202473653002802495653003002523653001102553653001102564653001402575653002302589653000902612653001602621653003002637653001502667653002402682653000902706653001702715100001702732700001602749700001602765700001502781700001902796700001702815700001802832856003602850 2012 eng d a1945-719700aLipoprotein-associated phospholipase A2 (Lp-PLA2) and future risk of type 2 diabetes: results from the Cardiovascular Health Study.0 aLipoproteinassociated phospholipase A2 LpPLA2 and future risk of c2012 May a1695-7010 v973 a

INTRODUCTION: Lipoprotein-associated phospholipase A2 (Lp-PLA(2)) has been consistently associated with cardiovascular disease (CVD) risk factors and predictive of CVD outcomes; furthermore, it is consistently higher among type 2 diabetics than nondiabetics. However, the relationships of circulating Lp-PLA(2) mass and activity with incident type 2 diabetes mellitus have not been examined. Therefore, the purpose of this study was to determine the association of Lp-PLA(2) mass and activity with type 2 diabetes among older adults.

METHODS: We conducted analyses of Lp-PLA(2) and prevalent and incident diabetes among 5474 men and women from the Cardiovascular Health Study (1989-2007). Lp-PLA(2) mass and activity were measured in baseline plasma. Diabetes status was ascertained annually with medication inventories and repeated blood glucose measurements. Generalized linear and Cox proportional hazards models were used to adjust for confounding factors including body mass index and inflammation.

RESULTS: At baseline, the top two quintiles of Lp-PLA(2) activity were significantly associated with prevalent type 2 diabetes with a multivariable relative risk = 1.35 [95% confidence interval (CI) = 1.11-1.63] for quintile 4, and relative risk = 1.33 (95% CI = 1.07-1.66) for quintile 5. Among participants free of diabetes at baseline, we found a significant positive association with both the homeostatic model assessment for insulin resistance and β-cell function per SD increase in Lp-PLA(2) activity (P values for both <0.01). In prospective analyses, the risk of incident type 2 diabetes was significantly higher among those in the highest quintile of Lp-PLA(2) activity [multivariable hazard ratio = 1.45 (95% CI = 1.01-2.07)] compared with the lowest quintile. Lp-PLA(2) mass was not significantly associated with incident type 2 diabetes.

DISCUSSION: Lp-PLA(2) activity is positively associated with insulin resistance and predicts incident type 2 diabetes among older adults independent of multiple factors associated with diabetes pathogenesis.

10a1-Alkyl-2-acetylglycerophosphocholine Esterase10aAged10aAged, 80 and over10aCardiovascular Diseases10aDiabetes Mellitus, Type 210aFemale10aHumans10aIncidence10aInsulin Resistance10aMale10aMiddle Aged10aPredictive Value of Tests10aPrevalence10aProspective Studies10aRisk10aRisk Factors1 aNelson, T, L1 aBiggs, M, L1 aKizer, J, R1 aCushman, M1 aHokanson, J, E1 aFurberg, C D1 aMukamal, K, J uhttps://chs-nhlbi.org/node/1369