Title | Lipoprotein-Associated Phospholipase A2 and Incident Peripheral Arterial Disease in Older Adults: The Cardiovascular Health Study. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Garg, PK, Arnold, AM, Stukovsky, KDHinckley, Koro, C, Jenny, NS, Mukamal, KJ, Criqui, MH, Furberg, CD, Newman, AB, Cushman, M |
Journal | Arterioscler Thromb Vasc Biol |
Volume | 36 |
Issue | 4 |
Pagination | 750-6 |
Date Published | 2016 Apr |
ISSN | 1524-4636 |
Keywords | 1-Alkyl-2-acetylglycerophosphocholine Esterase, Age Factors, Aged, Aging, Ankle Brachial Index, Biomarkers, Chi-Square Distribution, Female, Humans, Incidence, Inflammation Mediators, Logistic Models, Male, Odds Ratio, Peripheral Arterial Disease, Prognosis, Proportional Hazards Models, Risk Assessment, Risk Factors, Time Factors, United States, Up-Regulation |
Abstract | <p><b>OBJECTIVE: </b>Although prior studies report a relationship between elevated lipoprotein-associated phospholipase A2 (Lp-PLA2) and incident cardiovascular disease, the prospective association of Lp-PLA2 with incident peripheral arterial disease (PAD) has not been studied. We investigated the association between Lp-PLA2 mass and activity and the risk of developing clinical PAD and low ankle-brachial index (ABI).</p><p><b>APPROACH AND RESULTS: </b>Among Cardiovascular Health Study participants, a population-based cohort of 5888 adults aged ≥65 years enrolled in 1989 to 1990, Lp-PLA2 mass and activity were measured in 4537 individuals without baseline PAD. Clinical PAD, defined as leg artery revascularization or diagnosed claudication, was ascertained through 2011. Incident low ABI, defined as ABI <0.9 and decline of ≥0.15, was assessed among 3537 individuals who had an ABI >0.9 at baseline and a second ABI measurement 3 or 6 years later. Analyses were adjusted for demographics, cholesterol, smoking, comorbidities, and C-reactive protein. Each standard deviation increment in Lp-PLA2 mass (117 ng/mL) was associated with a higher risk of developing clinical PAD (hazard ratio 1.28; 95% confidence interval 1.13, 1.45) and incident low ABI (odds ratio 1.16; 95% confidence interval 1.00, 1.33). Results per standard deviation increment in Lp-PLA2 activity (13 nmol/min per mL) were similar for clinical PAD (hazard ratio 1.24; 95% confidence interval 1.07, 1.44) and low ABI (odds ratio 1.28; 95% confidence interval 1.09, 1.50).</p><p><b>CONCLUSIONS: </b>Higher Lp-PLA2 mass and activity were associated with development of both incident clinical PAD and low ABI. Future studies are needed to determine whether pharmacological inhibition of Lp-PLA2 reduces the incidence of PAD.</p> |
DOI | 10.1161/ATVBAHA.115.306647 |
Alternate Journal | Arterioscler. Thromb. Vasc. Biol. |
PubMed ID | 26848158 |
PubMed Central ID | PMC4808367 |
Grant List | HL080295 / HL / NHLBI NIH HHS / United States K12 HL083790 / HL / NHLBI NIH HHS / United States K12-HL083790 / HL / NHLBI NIH HHS / United States N01 HC-15103 / HC / NHLBI NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States N01 HC085084 / HC / NHLBI NIH HHS / United States N01 HC085085 / HC / NHLBI NIH HHS / United States N01-HC-35129 / HC / NHLBI NIH HHS / United States N01-HC-45133 / HC / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States N01-HC-85081 / HC / NHLBI NIH HHS / United States N01-HC-85082 / HC / NHLBI NIH HHS / United States N01-HC-85083 / HC / NHLBI NIH HHS / United States N01-HC-85084 / HC / NHLBI NIH HHS / United States N01-HC-85085 / HC / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01HC85080 / HL / NHLBI NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States |