Abstract 3606: LpPLA2 Predicts Progression of Coronary Calcification
Lipoprotein Associated Phospholipase A2 (LpPLA2), a marker of vascular inflammation, is related to stroke, clinical, and subclinical CAD. Persons with type 1 diabetes have excess CAD and rapid progression of subclinical CAD (measured as coronary calcium) despite a favorable lipid profile. Progression of coronary calcium is a strong predictor of CAD. Levels of LpPLA2 in type 1 diabetes are not known, nor is the relationship between LpPLA2 and progression of subclinical CAD. The Coronary Artery Calcium in Type 1 Diabetes (CACTI) study measured coronary calcium by electron beam CT twice (2.7 ± 0.3 yr interval) in 1184 subjects with (n = 544 , 37.1 ± 9.1 yrs old) and without (n = 640, 39.9 ± 8.9 yrs old) type 1 diabetes. Significant coronary calcium progression was defined as a difference of ≥ 2.5 in the square root of the two coronary calcium volume scores (CVS) (Hokanson et al. 2004). Baseline LpPLA2 mass by sandwich ELISA (ng/mL), and activity as phospholipase activity on an artificial substrate (nmol/min/mL) were assayed. A greater proportion diabetic patients had coronary calcium progression than non-diabetics (25.4% vs. 10.5%, p<0.0001). In type 1 diabetes, LpPLA2 activity was significantly lower (137 ± 30 vs. 145 ± 36 , p<0.0001) than in non-diabetics and this difference was fully accounted for by lower LDL-C (101 ± 29 vs. 114 ± 33 mg/dL, p<0.0001) . LpPLA2 mass was marginally higher in type 1 diabetes. In those with coronary calcium progression, LpPLA2 activity was significantly higher (150 ± 35 vs. 140 ± 33, p<0.001) and mass was marginally higher (290 ± 82 vs. 278 ± 78, p=0.07) than those without progression. LpPLA2 activity predicted coronary calcium progression (Odds Ratio = 2.12, 95% CI = 1.01– 4.45, p=0.01, upper vs. lower quartile) in logistic regression with backward selection of demographic, diabetes specific, inflammatory, lipid, and common CAD risk factors (final model included baseline CVS [p<0.0001], age [p<0.0001], sex [p=0.01], followup time [p=0.02], diabetes [p<0.0001], BMI [p<0.0001], apo B [p=0.04], and cystatin C [p=0.01]). This relationship was similar in those with and without type 1 diabetes. In this study of individuals with and without type 1 diabetes, LpPLA2 activity was a significant and independent predictor of progression of subclinical CAD.