OBJECTIVES: The aim of this study was to determine the time course of autonomic nervous system activity preceding ambulatory ischemic events. BACKGROUND: Vagal withdrawal can produce myocardial ischemia and may be involved in the genesis of ambulatory ischemic events. We analyzed trajectories of heart rate variability (HRV) 1 h before and after ischemic events, and we examined the role of exercise and mental stress in preischemic autonomic changes. METHODS: Male patients with stable coronary artery disease (n = 19; 62.1 +/- 9.3 years) underwent 48-h ambulatory electrocardiographic monitoring. Frequency domain HRV measures were assessed for 60 min before and after each of 68 ischemic events and during nonischemic heart rate-matched control periods. RESULTS: High-frequency HRV decreased from -60, -20 to -10 min before ischemic events (4.8 +/- 1.3; 4.6 +/- 1.3; 4.4 +/- 1.2 ln [ms(2)], respectively; p = 0.04) and further from -4, -2 min, until ischemia (4.4 +/- 1.3; 4.1 +/- 1.3; 3.7 +/- 1.2 ln [ms(2)]; p\'s < 0.01). Low frequency HRV decreases started at -4 min (p < 0.05). Ischemic events occurring at high mental activities were preceded by depressed high frequency HRV levels compared with events at low mental activity (p = 0.038 at -4 min, p = 0.045 at -2 min), whereas the effects of mental activities were not observed during nonischemic control periods. Heart rate variability measures remained significantly decreased for 20 min after recovery of ST-segment depression when events were triggered by high activity levels. CONCLUSIONS: Autonomic changes consistent with vagal withdrawal can act as a precipitating factor for daily life ischemia, particularly in episodes triggered by mental activities.