|Title||Lipoprotein-associated phospholipase A and risk of incident peripheral arterial disease: Findings from The Atherosclerosis Risk in Communities study (ARIC).|
|Publication Type||Journal Article|
|Year of Publication||2018|
|Authors||Garg PK, Norby FL, Polfus LM, Boerwinkle E, Gibbs RA, Grove ML, Folsom AR, Garimella PS, Matsushita K, Hoogeveen RC|
|Secondary Authors||Ballantyne CM|
|Date Published||2018 01|
|Keywords||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|
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.
|PubMed Central ID||PMC6392003|
|Grant List||HHSN268201100012C / HL / NHLBI NIH HHS / United States |
RC2 HL102419 / HL / NHLBI NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States