학술논문

Lipoprotein-associated phospholipase A2 and risk of incident peripheral arterial disease: Findings from The Atherosclerosis Risk in Communities study (ARIC)
Document Type
article
Source
Subject
Biomedical and Clinical Sciences
Cardiovascular Medicine and Haematology
Clinical Sciences
Cardiovascular
Prevention
Atherosclerosis
Detection
screening and diagnosis
4.2 Evaluation of markers and technologies
1-Alkyl-2-acetylglycerophosphocholine Esterase
Aged
Biomarkers
Disease Progression
Female
Genetic Variation
Humans
Incidence
Male
Middle Aged
Patient Admission
Peripheral Arterial Disease
Prevalence
Prognosis
Prospective Studies
Risk Assessment
Risk Factors
Time Factors
United States
Up-Regulation
Inflammation
Epidemiology
Peripheral artery disease
Lipoprotein-associated phospholipase A(2)
Cardiorespiratory Medicine and Haematology
Cardiovascular System & Hematology
Cardiovascular medicine and haematology
Clinical sciences
Language
Abstract
Background and aimsResults 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.MethodsOur 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.ResultsDuring 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.ConclusionsWhile 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.