Lipoprotein-associated phospholipase A₂ and risk of incident peripheral arterial disease in a multi-ethnic cohort: The Multi-Ethnic Study of Atherosclerosis

Abstract

Prospective studies supporting a relationship between elevated lipoprotein-associated phospholipase A (Lp-PLA) and incident peripheral arterial disease (PAD) are limited. We evaluated the association of Lp-PLA with incident PAD in a multi-ethnic cohort without clinical cardiovascular disease. A total of 4622 participants with measurement of Lp-PLA mass and Lp-PLA activity and an ankle-brachial index (ABI) between 0.9 and 1.4 were followed for the development of PAD (median follow-up = 9.3 years), defined as an ABI ⩽0.9 and decline from baseline ⩾0.15. There were 158 incident PAD events during follow-up. In adjusted logistic regression models, each higher standard deviation of both Lp-PLA activity and mass did not confer an increased risk of developing PAD [odds ratios, (95% confidence intervals)]: 0.92 (0.66-1.27) for Lp-PLA activity and 1.06 (0.85-1.34) for mass. Additionally, no significant interaction was found according to ethnicity: p=0.43 for Lp-PLA activity and p=0.55 for Lp-PLA mass. We found no evidence of an association between Lp-PLA and incident PAD.

Lipoprotein‐associated phospholipase A2 predicts lower limb ischemia in hemodialysis subjects

“…Due to its biological activity, 5,6 Lp-PLA 2 has been identified as a predictor of cardiovascular morbidity and mortality in several cohort of populations. [3][4][5][6][7][8][9]19,20 In the scientific literature, the role of Lp-PLA 2 in PAD is controversial with both some positive [14][15][16] and negative studies. 17 In about 6000 older (73 years of age) adults in the CHS Study, 11 Lp-PLA 2 mass and activity are associated with both incident low ankle-brachial index and incident PAD in a mean follow-up of 3 and 6 years.…”

“…Society of Cardiology, include the Lp-PLA 2 activity in the risk stratification, in order to optimize the lipid lowering treatment. 10 Despite these evidences, the role of Lp-PLA 2 in determining PAD remains controversial, with both positive [11][12][13] and negative 14 studies.…”

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

“…Prior investigation into the prospective relationship of Lp-PLA 2 levels with incident PAD has been conflicting. Both higher Lp-PLA 2 mass and Lp-PLA 2 activity were associated with incident PAD in the Cardiovascular Health Study (CHS) whereas neither Lp-PLA 2 mass nor Lp-PLA 2 activity were associated with incident PAD in MESA [9,10]. The rates of incident PAD in ARIC and CHS were nearly two times that reported in MESA and it is possible that the considerably lower number of events in MESA may have contributed to the lack of an association found in that cohort.…”

“…Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) is an enzyme highly expressed by macrophages in atherosclerotic lesions and is responsible for the hydrolysis of oxidized phospholipids on LDL particles [1,2]. Although the relationship of both higher Lp-PLA 2 mass and activity with greater risk of incident cardiovascular disease (CVD) is well-established [3–8], only two prospective studies have evaluated its association with incident peripheral arterial disease (PAD) [9,10]. These two studies obtained conflicting results, leaving uncertainty regarding this association.…”

Association of Lipoprotein-Associated Phospholipase A2 with the Prevalence of Nonalcoholic Fatty Liver Disease: A Result from the APAC Study

“…An increasing number of studies have indicated that NAFLD is linked to increased risk of cardiovascular disease (CVD) 4 – 6 . Meanwhile, some studies have demonstrated that lipoprotein-associated phospholipase A2 (Lp-PLA 2 ), which was named firstly as platelet-activating factor acetylhydrolase (PAF-AH), is significantly associated with CVD 7 , 8 .…”