Lipoprotein-associated phospholipase A and risk of incident peripheral arterial disease: Findings from The Atherosclerosis Risk in Communities study (ARIC).

Background And Aims: Results from prospective studies evaluating the relationship between elevated lipoprotein-associated phospholipase A (Lp-PLA) activity and incident peripheral arterial disease (PAD) have been mixed. We investigated whether higher Lp-PLA levels are associated with increased risk of incident PAD and whether PLA2G7 gene variants, which result in lower Lp-PLA levels, are associated with reduced risk of incident PAD.

Methods: Our analysis included 9922 participants (56% female; 21% African-American; mean age 63 years) without baseline PAD at ARIC Visit 4 (1996-1998), who had Lp-PLA activity measured and were subsequently followed for the development of PAD, defined by occurrence of a PAD-related hospitalization, through 2012. Cox proportional hazard models were performed to determine the association of Lp-PLA levels and PLA2G7 gene variants with incident PAD.

Results: During a median follow-up of 14.9 years, we identified 756 incident cases of PAD. In analyses adjusting for age, race, and sex, each standard deviation increment in Lp-PLA activity (62 nmol/ml/min) was associated with a higher risk of developing PAD (hazard ratio (HR) 1.17; 95% confidence interval (CI) 1.09, 1.26). This association remained significant after additional adjustment for risk factors, other cardiovascular disease, and medication use, but was strongly attenuated (HR: 1.09; 95% CI 1.00, 1.20). PLA2G7 variants were not associated with a lower risk of PAD in both white carriers (HR: 1.21; 95% CI: 0.17-8.56) and African-American carriers (HR: 0.83; 95% CI: 0.41-1.67), although statistical power was quite limited for this analysis, particularly in whites.

Conclusions: While higher Lp-PLA activity was associated with an increased risk for incident PAD, it is likely a risk marker largely represented by traditional risk factors.