Prognostic implications of exercise induced and ambulatory ischemia in patients with stable angina pectoris

Sammanfattning: Results from exercise testing and ambulatory ECG registration were studied in 809 patients with stable angina pectoris; special attention was paid to signs of ischemia during both tests. Autonomic nervous system activity was investigated by measurements of heart rate variability (HRV) and catecholamines in plasma and urine. At baseline, the patients were compared with 50 age and sex matched controls. Prognostic implications of HRV, catecholamine levels, signs of ischemia during exercise testing and ambulatory ECG registration were performed. We investigated relationships between laboratory markers of poor prognosis and signs of ischemia during exercise and ambulatory monitoring. Clinical outcome [cardiovascular (CV) death, nonfatal MI, revascularization] after a median follow-up of 3.4 years in terms of cardiovascular events and effects of treatment with metoprolol or verapamil was evaluated. More men reported chest pain during exercise compared to women, but signs of ischemia were equally common. Thus, females were more prone toward silent ischemia during exercise. Plasma adrenaline levels after exercise were the same, indicating similar relative effort. ST-segment depression during ambulatory ECG registration was equally common among men and women. Women excreted more noradrenaline both during the day and at night. During exercise or recovery, signs of ischemia, especially if marked (> 3 min) carried prognostic information for CV death and non-fatal MI. Prolonged ST-segment depression duration (> 30 min) on ambulatory ECG, showed prognostic importance mainly for CV death. Exercise duration showed prognostic importance among men. Chest pain was not related to prognosis. Verapamil reduced ST-segment depression during exercise more than metoprolol, whereas metoprolol had a better effect on signs of ischemia during ambulatory ECG registration. These treatment effects were slight but significant. Treatment effects on ischemia did not, however, show any significant prognostic importance. HRV in the frequency domain [total power, high (HF) and low frequency (LF) components] was closely related to CV death. Catecholamine levels in plasma and urine, and the LF/HR ratio had no prognostic importance. This and other results indicate that vagal activity is more important than sympathetic nerve activity for prognosis. Metoprolol treatment increased HRV in all frequency domains, but verapamil treatment had no influences on HRV. Plasma adrenaline and noradrenaline after exercise increased with metoprolol treatment, probably due to reduced plasma clearance. Verapamil treatment reduced the urinary excretion of noradrenaline. Treatment effects on catecholamines or HRV did not have any prognostic impact. Signs of ischemia and laboratory markers of increased risk were largely independent of one another. Thus, laboratory risk indicators and signs of ischemia during exercise testing provide complementary information regarding prognosis in patients with stable angina pectoris. Ischemia during exercise testing and ambulatory ECG registration carry important prognostic information. HRV is also related to adverse events, and might become a valuable tool in predicting prognosis in patients with stable angina pectoris, but more research is needed before it is useful in the clinical routine.