The association between normal lung function and peak oxygen uptake in patients with exercise intolerance and coronary artery disease.

Øystein Rasch-Halvorsen,Erlend Hassel,Sigurd Steinshamn,Martijn A Spruit,Haldor Jenssen,Arnulf Langhammer,Ben M Brumpton

doi:10.1371/journal.pone.0232693

Abstract

In coronary artery disease (CAD), exercise intolerance with reduced oxygen uptake at peak exercise (VO2peak) is assumed to primarily reflect cardiovascular limitation. However, oxygen transport and utilization depends on an integrated organ response, to which the normal pulmonary system may influence overall capacity. This study aimed to investigate the associations between normal values of lung function measures and VO2peak in patients with exercise intolerance and CAD. We hypothesized that forced expiratory lung volume in one second (FEV1), transfer factor of the lung for carbon monoxide (TLCO) and TLCO/alveolar volume (TLCO/VA) above lower limits of normal (LLN) are associated with VO2peak in these patients. We assessed patients with established CAD (n = 93; 21 women) referred for evaluation due to exercise intolerance from primary care to a private specialist clinic in Norway. Lung function tests and cardiopulmonary exercise testing (CPET) were performed. Z-scores of FEV1, FEV1/forced vital capacity (FVC), TLCO and TLCO/VA were calculated using the Global Lung Function Initiative (GLI) software and LLN was defined as the fifth percentile (z = -1.645). Non-obstructive patients, defined by both FEV1 and FEV1/FVC above LLN, were assessed. The associations of FEV1Z-score, TLCOZ-score and TLCO/VAZ-score above LLN with VO2peak were investigated using linear regression models. Mean VO2peak ± standard deviation (SD) was 23.8 ± 6.4 ml/kg/min in men and 19.7 ± 4.4 ml/kg/min in women. On average, one SD increase in FEV1, TLCO and TLCO/VA were associated with 1.4 (95% CI 0.2, 2.6), 2.6 (95% CI 1.2, 4.0) and 1.3 (95% CI 0.2, 2.5) ml/kg/min higher VO2peak, respectively. In non-obstructive patients with exercise intolerance and CAD, FEV1, TLCO and TLCO/VA above LLN are positively associated with VO2peak. This may imply a clinically significant influence of normal lung function on exercise capacity in these patients.

Highlights

Exercise intolerance is a major manifestation of cardiopulmonary disease
In order to reduce confounding by concurrent chronic obstructive pulmonary disease (COPD), we excluded 89 patients with potential obstructive ventilatory defect defined as both FEV1 and FEV1/forced vital capacity (FVC) less than lower limits of normal (LLN)
In this study we found dynamic lung volume, measured by FEV1 and lung diffusing capacity, measured by both the lung for carbon monoxide (TLCO) and TLCO/alveolar volume (TLCO/VA), above LLN to be positively associated with VO2peak in non-obstructive patients with coronary artery disease (CAD) and exercise intolerance from cardiovascular limitation

Summary

Introduction

Exercise intolerance is a major manifestation of cardiopulmonary disease. The gold standard for assessment of exercise capacity is cardiopulmonary exercise testing (CPET) with direct measurement of oxygen uptake at peak exercise (VO2peak). In patients with coronary artery disease (CAD), regional myocardial dysfunction may affect cardiac stroke volume (SV) [5]. At submaximal levels of exercise, reduced SV can be compensated for by increased heart rate (HR), but the maximal cardiac output (CO) is reduced. This implies impaired capacity for oxygen transport during exercise [6] with reduced VO2peak and functional impairment from cardiovascular limitation in CAD

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