Lipoprotein-associated phospholipase A 2 and risk of incident peripheral arterial disease: Findings from The Atherosclerosis Risk in Communities study (ARIC)

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


Background and aims: 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.

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-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.

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-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.

Conclusions: 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.

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

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • 1-Alkyl-2-acetylglycerophosphocholine Esterase / blood*
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase / genetics
  • Aged
  • Biomarkers / blood
  • Disease Progression
  • Female
  • Genetic Variation
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Patient Admission
  • Peripheral Arterial Disease / blood
  • Peripheral Arterial Disease / enzymology*
  • Peripheral Arterial Disease / epidemiology*
  • Peripheral Arterial Disease / genetics
  • Prevalence
  • Prognosis
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • United States / epidemiology
  • Up-Regulation


  • Biomarkers
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase
  • PLA2G7 protein, human