title: Lipoprotein-Associated Phospholipase A2 and Incident Peripheral Arterial Disease in Older Adults: The Cardiovascular Health Study.
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).
  
  
  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: 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.
authors: Parveen K
authors: PK
authors: Garg
authors: 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.).
authors: Alice M
authors: AM
authors: Arnold
authors: 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.).
authors: Karen D
authors: KD
authors: Hinckley Stukovsky
authors: 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.).
authors: Carol
authors: C
authors: Koro
authors: 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.).
authors: Nancy S
authors: NS
authors: Jenny
authors: 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.).
authors: Kenneth J
authors: KJ
authors: Mukamal
authors: 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.).
authors: Michael H
authors: MH
authors: Criqui
authors: 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.).
authors: Curt D
authors: CD
authors: Furberg
authors: 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.).
authors: Anne B
authors: AB
authors: Newman
authors: 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.).
authors: Mary
authors: M
authors: Cushman
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood*; D000367:Age Factors; D000368:Aged; D000375:Aging; D055109:Ankle Brachial Index; D015415:Biomarkers; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D015994:Incidence; D018836:Inflammation Mediators / Q000097:blood; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D058729:Peripheral Arterial Disease / Q000097:blood* / Q000175:diagnosis / Q000201:enzymology / Q000453:epidemiology* / Q000628:therapy; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C526684:PLA2G7 protein, human
keywords: ankle–brachial index; epidemiology; inflammation; lipoprotein-associated phospholipase A2; peripheral artery disease