Long-term Survival and Heart Rate Variability in Women with Ischemic Heart Disease

Abstract Background Ischemic heart disease is a leading cause of death worldwide. Although women have lower absolute mortality rates than men, prognosis in women—particularly younger women—remains insufficiently understood. Heart rate variability is an established marker of cardiac autonomic function and a predictor of mortality after myocardial infarction, but long-term prognostic data in women are scarce. Our aim was to evaluate long-term all-cause mortality over 20 years in women with ischemic heart disease compared with healthy controls, and to investigate the prognostic value of heart rate variability. Methods Survival was investigated up to 20 years after a cardiac event in 197 females with ischemic heart disease and in 141 controls. Heart rate variability was assessed at baseline in approximately 50% of individuals using frequency-domain analysis during supine position, paced breathing, and passive tilt. Results After 20 years, survival was lower in patients than in controls (59.1% vs. 72.3%). No difference in survival was observed during the first 15 years, but younger patients (≤ 60 years at baseline) showed increased mortality from 10 years onward. Patients exhibited lower total power, low frequency and high frequency components of heart rate variability compared with controls, indicating reduced parasympathetic activity. In the upright position, patients showed higher very low frequency component, which was associated with increased 15-year mortality. This increased very low frequency component reflected a slow, pronounced heart rate rise during tilt, consistent with sympathetic dominance. Conclusions Women with ischemic heart disease showed impaired cardiac autonomic function and increased long-term mortality compared with controls, particularly among younger patients. A high very low frequency component during sympathetic stimulation was associated with worse prognosis and reflected abnormal heart rate dynamics rather than protective autonomic modulation. Heart rate response to postural change is a potential risk marker after cardiac events.