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Atherosclerosis. 2018 Jan;268:12-18. doi: 10.1016/j.atherosclerosis.2017.11.007. Epub 2017 Nov 14.

Lipoprotein-associated phospholipase A2 and risk of incident peripheral arterial disease: Findings from The Atherosclerosis Risk in Communities study (ARIC).

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Division of Cardiology, University of Southern California Keck School of Medicine, Los Angeles, CA, USA. Electronic address:
Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
University of Texas Health Sciences Center at Houston, Houston, TX, USA.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Division of Nephrology-Hypertension, University of California San Diego, La Jolla, CA, USA.
Department of Epidemiology, The Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Section of Atherosclerosis and Vascular Medicine, Baylor College of Medicine, Houston, TX, USA; The Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart Center, Houston, TX, USA.



Results from prospective studies evaluating the relationship between elevated lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and incident peripheral arterial disease (PAD) have been mixed. We investigated whether higher Lp-PLA2 levels are associated with increased risk of incident PAD and whether PLA2G7 gene variants, which result in lower Lp-PLA2 levels, are associated with reduced risk of incident PAD.


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-PLA2 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-PLA2 levels and PLA2G7 gene variants with incident PAD.


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-PLA2 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.


While higher Lp-PLA2 activity was associated with an increased risk for incident PAD, it is likely a risk marker largely represented by traditional risk factors.


Epidemiology; Inflammation; Lipoprotein-associated phospholipase A(2); Peripheral artery disease

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