Sex-Related Differences in Autonomic Modulation of Heart Rate in Middle-aged Subjects

BACKGROUND: Women have worse outcomes when they experience acute myocardial infarction (MI), but the reasons for this sex-related difference are not well understood. Because cardiovascular neural regulation plays an important role in cardiac mortality, we studied possible sex-related differences in the autonomic modulation of heart rate (HR) in middle-aged subjects without known heart disease. METHODS AND RESULTS: Baroreflex sensitivity (BRS) and HR variability were studied in randomly selected, age-matched populations of middle-aged women (n = 186; mean age, 50 +/- 6 years) and men (n = 188; mean age, 50 +/- 6 years) without hypertension, diabetes, or clinical or echocardiographic evidence of heart disease. BRS measured from the overshoot phase of the Valsalva maneuver was significantly lower in women (8.0 +/- 4.6 ms/mm Hg, n = 152) than in men (10.5 +/- 4.6 ms/mm Hg, n = 151) (P < .001), and the low-frequency component of HR variability measured from ECG recordings also was lower in women (P < .001), whereas the high-frequency component was higher in women than in men (P < .001). The ratio between the low-and high-frequency oscillations also was lower in the women (P < .001). The increase of HR and decrease of high-frequency component of HR variability in response to an upright posture were smaller in magnitude in women than in men (P < .01 for both). After adjustment for differences in the baseline-variables, such as blood pressure, HR, smoking, alcohol consumption, and psychosocial score, the sex-related differences in BRS and HR variability still remained significant (P < .001 for all). Women with estrogen replacement therapy (n = 46) had significantly higher BRS and total HR variance than the age-matched women without hormone treatment (P < .01 for both), and the BRS and HR variability of the women with estrogen therapy did not differ from those of the age-matched men. CONCLUSIONS: Baroreflex responsiveness is attenuated in middle-aged women compared with men, but the tonic vagal modulation of HR is augmented. Hormone replacement therapy appears to have favorable effects on the cardiovascular autonomic regulation in postmenopausal women.