• Divay Chandra, Aman Gupta, Patrick J Strollo, Carl R Fuhrman, Joseph K Leader, Jessica Bon, William A Slivka, Ali Hakim Shoushtari, Jennifer Avolio, Kevin E Kip, Steven Reis, and Frank C Sciurba.
• 1 Department of Medicine.
• Am. J. Respir. Crit. Care Med. 2016 Jul 1; 194 (1): 38-47.

RationaleLower FEV1 is associated with increased prevalence of atherosclerosis; however, causal mechanisms remain elusive.ObjectivesTo determine if systemic endothelial dysfunction mediates the association between reduced FEV1 and increased atherosclerosis.MethodsBrachial 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.Measurements And Main ResultsLower 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.ConclusionsEndothelial 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.

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