Postexercise ischemia is associated with increased neuropeptide Y in patients with coronary artery disease

Abstract

Background - Neurohormones may influence vascular tone both during and after exercise. Neuropeptide Y (NPY), which is costored and released with norepinephrine (NE) during sympathetic activity, is a potent vasoconstrictor with a relatively long half-life. We therefore examined its possible association with the ischemic response to exercise in patients with coronary artery disease. Methods and Results - Twenty-nine male patients with effort-induced angina pectoris underwent a symptom-limited exercise test. In addition to conventional ST-segment analysis, we examined ischemia on the basis of heart rate (HR)-adjusted ST-segment changes through calculation of the ST/HR slope during the final 4 minutes of exercise and of the ST/HR recovery loop after exercise. Blood samples were taken before, during, and after exercise for an analysis of several neurohormones. Mean ST-segment depression was -223±20.2 μV (P<0.0001) just before the termination of exercise, followed by a gradual normalization, but it remained significant after 10 minutes (-49±8.9 μV, P<0.0001). At the end of exercise, the ST/HR slope, which reflects myocardial ischemia, was -6.0±0.77 μV/HR. In most patients, ST-segment levels at a given HR were lower during recovery than during exercise, here referred to as ST 'deficit.' Exercise increased the plasma levels of NPY, NE, epinephrine, and N-terminal proatrial natriuretic peptide, but big endothelin remained unchanged. Although NE and epinephrine peaked at maximal exercise, the highest levels of NPY and N-terminal proatrial natriuretic peptide were observed 4 minutes after exercise. The maximal increase in the NPY correlated significantly with ST-segment depression at 3 minutes after exercise (r= -0.61, P=0.0005), the ST deficit at the corresponding time point (r=-0.66, P=0.0001), and the duration of ST-segment depression after exercise (r=0.42, P=0.02). In contrast, no such correlations were found for NE. Conclusions - The present study has for the first time demonstrated a correlation between plasma NPY levels and the degree and duration of ST-segment depression after exercise in patients with coronary artery disease, which suggests that NPY may contribute to myocardial ischemia in these patients.