Lipoprotein-associated phospholipase A₂ activity predicts progression of subclinical coronary atherosclerosis.

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.