Parveen K Garg1, Alice M Arnold2, Karen D Hinckley Stukovsky2, Carol Koro2, Nancy S Jenny2, Kenneth J Mukamal2, Michael H Criqui2, Curt D Furberg2, Anne B Newman2, Mary Cushman2. 1. From the Division of Cardiology, University of Southern California Keck School of Medicine, Los Angeles (P.K.G.); Department of Biostatistics, University of Washington, Seattle (A.M.A., K.D.H.S.); Glaxo Smith Kline, Collegeville, PA (C.K.); Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington (N.S.J., M.C.); Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA (K.J.M.); Department of Family and Preventive Medicine, University of California in San Diego School of Medicine, La Jolla (M.H.C.); Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC (C.D.F.); Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA (A.B.N.); and Department of Medicine, Cardiovascular Research Institute, University of Vermont College of Medicine, Burlington (M.C.). parveeng@med.usc.edu. 2. From the Division of Cardiology, University of Southern California Keck School of Medicine, Los Angeles (P.K.G.); Department of Biostatistics, University of Washington, Seattle (A.M.A., K.D.H.S.); Glaxo Smith Kline, Collegeville, PA (C.K.); Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington (N.S.J., M.C.); Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA (K.J.M.); Department of Family and Preventive Medicine, University of California in San Diego School of Medicine, La Jolla (M.H.C.); Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC (C.D.F.); Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA (A.B.N.); and Department of Medicine, Cardiovascular Research Institute, University of Vermont College of Medicine, Burlington (M.C.).
Abstract
OBJECTIVE: 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). APPROACH AND RESULTS: 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). CONCLUSIONS: 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.
OBJECTIVE: 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). APPROACH AND RESULTS: 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). CONCLUSIONS: 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.
Authors: A R Folsom; J S Pankow; R P Tracy; D K Arnett; J M Peacock; Y Hong; L Djoussé; J H Eckfeldt Journal: Am J Cardiol Date: 2001-07-15 Impact factor: 2.778
Authors: T Häkkinen; J S Luoma; M O Hiltunen; C H Macphee; K J Milliner; L Patel; S Q Rice; D G Tew; K Karkola; S Ylä-Herttuala Journal: Arterioscler Thromb Vasc Biol Date: 1999-12 Impact factor: 8.311
Authors: A T Hirsch; M H Criqui; D Treat-Jacobson; J G Regensteiner; M A Creager; J W Olin; S H Krook; D B Hunninghake; A J Comerota; M E Walsh; M M McDermott; W R Hiatt Journal: JAMA Date: 2001-09-19 Impact factor: 56.272
Authors: C J Packard; D S O'Reilly; M J Caslake; A D McMahon; I Ford; J Cooney; C H Macphee; K E Suckling; M Krishna; F E Wilkinson; A Rumley; G D Lowe Journal: N Engl J Med Date: 2000-10-19 Impact factor: 91.245
Authors: Michelle L O'Donoghue; Eugene Braunwald; Harvey D White; Dylan P Steen; Mary Ann Lukas; Elizabeth Tarka; P Gabriel Steg; Judith S Hochman; Christoph Bode; Aldo P Maggioni; KyungAh Im; Jennifer B Shannon; Richard Y Davies; Sabina A Murphy; Sharon E Crugnale; Stephen D Wiviott; Marc P Bonaca; David F Watson; W Douglas Weaver; Patrick W Serruys; Christopher P Cannon; Dylan L Steen Journal: JAMA Date: 2014-09-10 Impact factor: 56.272
Authors: Christie M Ballantyne; Ron C Hoogeveen; Heejung Bang; Josef Coresh; Aaron R Folsom; Gerardo Heiss; A Richey Sharrett Journal: Circulation Date: 2004-02-02 Impact factor: 29.690
Authors: Parveen K Garg; Mary L Biggs; Joshua Barzilay; Luc Djousse; Calvin Hirsch; Joachim H Ix; Jorge R Kizer; Russell P Tracy; Anne B Newman; David S Siscovick; Kenneth J Mukamal Journal: Diab Vasc Dis Res Date: 2019-05-08 Impact factor: 3.291