Original Scientific Paper Maximal exercise oxygen pulse as a predictor of mortality among male veterans referred for exercise testing Ricardo B. Oliveira a,c , Jonathan Myers c , Claudio Gil S. Arau ´ jo a,b , Joshua Abella c , Sandra Mandic c and Victor Froelicher c a Gama Filho University, b CLINIMEX – Clı ´nica de Medicina do Exercı ´cio, Rio de Janeiro, Brazil and c Division of Cardiovascular Medicine, Stanford University and Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA Received 10 September 2008 Accepted 31 December 2008 Background Maximal oxygen pulse (O 2 pulse) mirrors the stroke volume response to exercise, and should therefore be a strong predictor of mortality. Limited and conflicting data are, however, available on this issue. Methods Nine hundred forty-eight participants, classified as those with cardiopulmonary disease (CPD) and those without (non-CPD), underwent cardiopulmonary exercise testing (CPX) for clinical reasons between 1993 and 2003. The ability of maximal O 2 pulse and maximal oxygen uptake (peak VO 2 ) to predict mortality was investigated using proportional hazards and Akaike information criterion analyses. All-cause mortality was the endpoint. Results Over a mean follow-up of 6.3 ± 3.2 years, there were 126 deaths. Maximal O 2 pulse, expressed in either absolute or relative to age-predicted terms, and peak VO 2 were significant and independent predictors of mortality in those with and without CPD (P < 0.04). Akaike information criterion analysis revealed that the model including both maximal O 2 pulse and peak VO 2 had the highest accuracy for predicting mortality. The optimal cut-points for O 2 pulse and peak VO 2 ( < 12; Z 12 ml/beat and < 16; Z 16 ml/(kg . min) respectively) were established by the area under the receiver-operating-characteristic curve. The relative risks of mortality were 3.4 and 2.2 (CPD and non-CPD, respectively) among participants with both maximal O 2 pulse and peak VO 2 responses below these cut-points compared with participants with both responses above these cut-points. Conclusion These results indicate that maximal O 2 pulse is a significant predictor of mortality in patients with and without CPD. The addition of absolute and relative O 2 pulse data provides complementary information for risk-stratifying heterogeneous participants referred for CPX and should be routinely included in the CPX report. Eur J Cardiovasc Prev Rehabil 00:000–000  c 2009 The European Society of Cardiology European Journal of Cardiovascular Prevention and Rehabilitation 2009, 00:000–000 Keywords: exercise, mortality, oxygen pulse Introduction Over the last two decades, the cardiopulmonary exercise test (CPX) has become increasingly recommended in clinical practice because of its impact on the clinical decision-making process [1]. The information obtained from CPX helps to identify unexplained exercise intolerance, determine disability, make decisions regarding therapeutic interventions, and to estimate prognosis [2,3]. Among the ventilatory expired gas variables obtained during exercise, maximal oxygen uptake (peak VO 2 ) remains the most frequently applied variable in both research and clinical settings because of its widely recognized value for clinical assessment and for estimating prognosis [4,5]. Despite the well-established value of peak VO 2 , a large body of research has been recently published regarding the prognostic value of other CPX variables. Responses such as the slope of the relationship between ventilation and carbon dioxide production (VE/VCO 2 slope) [6,7], the oxygen uptake efficiency slope [8], and maximal oxygen pulse (O 2 pulse) [9–11] have been shown to have Correspondence to Dr Ricardo B. Oliveira, PhD, VA Palo Alto Health Care System, Cardiology 111C, 3801 Miranda Avenue, Palo Alto, CA 94043, USA Tel: +1 650 493 5000 x64661; fax: +1 650 852 3473; e-mail: ricardobrandaorj@gmail.com 1741-8267  c 2009 The European Society of Cardiology DOI: 10.1097/HJR.0b013e3283292fe8 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.