Lipoprotein-Associated Phospholipase A 2 and Incident Peripheral Arterial Disease in Older Adults

Abstract

Objective— Although prior studies report a relationship between elevated lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) and incident cardiovascular disease, the prospective association of Lp-PLA 2 with incident peripheral arterial disease (PAD) has not been studied. We investigated the association between Lp-PLA 2 mass and activity and the risk of developing clinical PAD and low ankle–brachial index (ABI). Approach and Results— Among Cardiovascular Health Study participants, a population-based cohort of 5888 adults aged ≥65 years enrolled in 1989 to 1990, Lp-PLA 2 mass and activity were measured in 4537 individuals without baseline PAD. Clinical PAD, defined as leg artery revascularization or diagnosed claudication, was ascertained through 2011. Incident low ABI, defined as ABI <0.9 and decline of ≥0.15, was assessed among 3537 individuals who had an ABI >0.9 at baseline and a second ABI measurement 3 or 6 years later. Analyses were adjusted for demographics, cholesterol, smoking, comorbidities, and C-reactive protein. Each standard deviation increment in Lp-PLA 2 mass (117 ng/mL) was associated with a higher risk of developing clinical PAD (hazard ratio 1.28; 95% confidence interval 1.13, 1.45) and incident low ABI (odds ratio 1.16; 95% confidence interval 1.00, 1.33). Results per standard deviation increment in Lp-PLA 2 activity (13 nmol/min per mL) were similar for clinical PAD (hazard ratio 1.24; 95% confidence interval 1.07, 1.44) and low ABI (odds ratio 1.28; 95% confidence interval 1.09, 1.50). Conclusions— Higher Lp-PLA 2 mass and activity were associated with development of both incident clinical PAD and low ABI. Future studies are needed to determine whether pharmacological inhibition of Lp-PLA 2 reduces the incidence of PAD.