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(Circulation. 2005;112:1959-1964.)
© 2005 American Heart Association, Inc.

Coronary Heart Disease

Rapid Heart Rate Increase at Onset of Exercise Predicts Adverse Cardiac Events in Patients With Coronary Artery Disease

Colomba Falcone, MD; Maria Paola Buzzi, MD; Catherine Klersy, MD; Peter J. Schwartz, MD

From the Department of Lung, Blood, and Heart (C.F., M.P.B., P.J.S.), University of Pavia, Pavia, Italy; Department of Cardiology (C.F., M.P.B., P.J.S.), IRCCS Policlinico S. Matteo, Pavia, Italy; and Biometry and Clinical Epidemiology Unit (C.K.), IRCCS Policlinico S. Matteo, Pavia, Italy.

Correspondence to Peter J. Schwartz, MD, Professor & Chairman, Department of Cardiology, Policlinico S. Matteo IRCCS, Via le Golgi, 19-27100 Pavia, Italy. E-mail PJQT{at}compuserve.com

Received February 23, 2005; revision received July 7, 2005; accepted July 8, 2005.

Background— We previously demonstrated that reduced vagal activity and/or increased sympathetic activity identify post–myocardial infarction patients at high risk for cardiac mortality. Simple and inexpensive autonomic markers are necessary to perform autonomic screening in large populations. We tested our hypothesis that abnormally elevated heart rate (HR) responses at the onset of an exercise stress test, which imply rapid vagal withdrawal immediately preceding sympathetic activation, might predict adverse cardiac events in patients with documented coronary artery disease.

Methods and Results— The HR increase during the first minute (HR_{1 minute}) of a symptom-limited exercise stress test was quantified in 458 patients with documented coronary artery disease. During a 6-year (interquartile range 3.7 to 9.0 years) follow-up, 71 patients experienced adverse cardiac events (21 cardiac deaths, 56 nonfatal myocardial infarctions). In univariate analysis, HR_{1 minute} 12 bpm (above the median value of its distribution) predicted both adverse outcome and cardiac death with a hazard ratio of 5.0 (95% CI 2.7 to 9.1; P<0.0001) and of 15.6 (95% CI 2.0 to 118.7; P<0.001), respectively. After adjustment for potential confounders, HR_{1 minute} remained predictive for both combined end points and for cardiac death.

Conclusions— A marked HR increase at the onset of a standard exercise stress test is a novel and easily available parameter that could be clinically useful as an independent predictor of adverse cardiac events, including death, among patients with documented coronary artery disease.

Key Words: exercise • heart rate • mortality • nervous system, autonomic • risk factors

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