Airflow Limitation and Endothelial Dysfunction. Unrelated and Independent Predictors of Atherosclerosis

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Abstract

Rationale:

Lower FEV1 is associated with increased prevalence of atherosclerosis; however, causal mechanisms remain elusive.

Objectives:

To determine if systemic endothelial dysfunction mediates the association between reduced FEV1 and increased atherosclerosis.

Methods:

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.

Measurements and Main Results:

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.

Conclusions:

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.

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