title: Airflow Limitation and Endothelial Dysfunction. Unrelated and Independent Predictors of Atherosclerosis.
abstract: Lower FEV1 is associated with increased prevalence of atherosclerosis; however, causal mechanisms remain elusive.
  
  
  
  To determine if systemic endothelial dysfunction mediates the association between reduced FEV1 and increased atherosclerosis.
  
  
  
  Brachial artery endothelial function, pulmonary function, coronary artery calcium, and carotid plaque were assessed in 231 Pittsburgh SCCOR (Specialized Centers for Clinically Oriented Research) study participants; peripheral arterial endothelial function, pulmonary function, and coronary artery calcium were assessed in 328 HeartSCORE (Heart Strategies Concentrating on Risk Evaluation) study participants.
  
  
  
  Lower FEV1 was independently associated with increased atherosclerosis in both cohorts (per 25% lower % predicted FEV1: odds ratio [OR], 1.76; 95% confidence interval [CI], 1.30-2.40; P < 0.001 for carotid plaque in SCCOR participants) (per 25% lower % predicted FEV1: OR, 1.35; 95% CI, 1.02-1.77; P = 0.03 for coronary artery calcium in HeartSCORE participants). Similarly, reduced endothelial function was independently associated with increased atherosclerosis in both cohorts (per SD lower endothelial function: OR, 1.30; 95% CI, 1.01-1.67; P = 0.04 for carotid plaque in SCCOR participants) (per SD lower endothelial function: OR, 1.38; 95% CI, 1.09-1.76; P = 0.008 and OR, 1.41; 95% CI, 1.07-1.86; P = 0.01 for coronary artery calcium in SCCOR and HeartSCORE participants, respectively). However, there was no association between endothelial dysfunction and FEV1, FEV1/FVC, low-attenuation area/visual emphysema, and diffusing capacity in SCCOR participants, and between endothelial dysfunction and FEV1 or FEV1/FVC in HeartSCORE participants (all P > 0.05). Adjusting the association between FEV1 and atherosclerosis for endothelial dysfunction had no impact.
  
  
  
  Endothelial dysfunction does not mediate the association between airflow limitation and atherosclerosis. Instead, airflow limitation and endothelial dysfunction seem to be unrelated and mutually independent predictors of atherosclerosis.
authors.affiliation: 1 Department of Medicine.
authors.forename: Divay
authors.initials: D
authors.lastname: Chandra
authors.affiliation: 1 Department of Medicine.
authors.forename: Aman
authors.initials: A
authors.lastname: Gupta
authors.affiliation: 1 Department of Medicine.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Strollo
authors.affiliation: 2 Department of Radiology, and.
authors.forename: Carl R
authors.initials: CR
authors.lastname: Fuhrman
authors.affiliation: 2 Department of Radiology, and.
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Leader
authors.affiliation: 1 Department of Medicine.
authors.forename: Jessica
authors.initials: J
authors.lastname: Bon
authors.affiliation: 1 Department of Medicine.
authors.forename: William A
authors.initials: WA
authors.lastname: Slivka
authors.affiliation: 3 Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, Pennsylvania; and.
authors.forename: Ali Hakim
authors.initials: AH
authors.lastname: Shoushtari
authors.affiliation: 3 Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, Pennsylvania; and.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Avolio
authors.affiliation: 4 College of Nursing, University of South Florida, Tampa, Florida.
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Kip
authors.affiliation: 1 Department of Medicine.|3 Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, Pennsylvania; and.
authors.forename: Steven
authors.initials: S
authors.lastname: Reis
authors.affiliation: 1 Department of Medicine.
authors.forename: Frank C
authors.initials: FC
authors.lastname: Sciurba
mesh_terms: D000328:Adult; D000368:Aged; D000402:Airway Obstruction / Q000150:complications* / Q000503:physiopathology*; D050197:Atherosclerosis / Q000150:complications* / Q000503:physiopathology*; D001916:Brachial Artery / Q000503:physiopathology; D015331:Cohort Studies; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D008168:Lung / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D018570:Risk Assessment; D012307:Risk Factors
keywords: cardiovascular disease; chronic obstructive pulmonary disease; endothelium