Estrogen linked to more efficient regulation of a woman’s heartbeat

Age is the ’equalizer,’ according to a study that provides new insights into why women live longer than men

Men die earlier than women. This fact leads scientists and medical researchers to conclude that gender and age are two basic factors continuously affecting body functions, disease categories and even life expectancy. Previous research has determined that gender influences brain structure and functions; however, in considering the cardiac pacemaker, there is still debate as to whether heart rate dynamics differ between women and men.

Electrocardiogram (ECG) findings offer interesting arguments for both sides of the issue. There is a similarity in the sexes regarding the mean and standard deviation of the R-R interval portion of electrocardiogram (intervals between positive deflection of the QRS complex, which involves the depolarization of ventricular cardiac cells). On the other hand, women have been reported to have lower, similar, and higher high-frequency power (HF) and similar low-frequency power (LF) of heart rate variability (HRV). (HRV is a strong predictor of mortality adversely affected by such problems as anxiety, depression, and trauma.)

A team of researchers has speculated whether confusing findings in heart activity of the sexes could be attributed to the nonlinear characteristics of pacemaker activity, which may cause large variations when analyzed by traditional linear methods. Such variations might lead to severe interference if there are gender differences in the discharge from the heart’s natural pacemaker, the sinus (SA) node. Accordingly, they set out to determine whether the complexity or chaos of cardiac pacemaker activity differs between women and men. Because aging may be a major determinate of heart rate dynamics, the researchers systemically studied the effect of aging on nonlinear properties and on gender-related differences. The results were then compared with standard frequency-domain methods to measure the nervous system’s parasympathetic and sympathetic regulation of heart rate.

The authors of “Sexual Dimorphism in the Complexity of Cardiac Pacemaker Activity,” are Terry B. J. Kuo from Tzu Chi University and Tzu Chi Buddhist General Hospital, Hualien, Taiwan, and Cheryl C. H. Yang, also from Tzu Chi University. Their findings appeared in the October 2002 edition of the American Journal of Physiology–Heart and Circulatory Physiology.

Methodology

The study entailed the participation of 480 volunteers (240 women and 240 men), age 40–79, similar to overall distribution of males and females. They were distributed into eight groupings based on five-year age intervals, with each age stratum containing 30 women and 30 men. Subjects excluded had cardiovascular fluctuations: hypotension, hypertension, diabetic neuropathy, an implanted cardiac pacemaker, frequent occurrence of atrial fibrillation, premature atrial or ventricular contractions, or other forms of arrhythmia. Nonlinear analysis of short-term resting R-R intervals was performed using the correlation dimension (CD), approximate entropy (ApEn), and largest Lyapunov exponent (LLE). Evidence of nonlinear structure was obtained by the surrogate data test. CD, ApEn, and LLE were negatively correlated with age.

Results

The short-term heart rate variability analyses reveal that a woman’s heart rate is characterized by a higher CD, ApEn, and LLE when compared with that of a man in the middle age, indicating a more complex signal broadcasting from a woman’s cardiac pacemaker.

In assessing the brain, a more complex neural signal is always accompanied with a more involved neural network. On the other hand, a very simple firing pattern can only be observed in an isolated neuron. Thus the higher complexity of women’s heart rate dynamics implies that the female heart is modulated more comprehensively by the autonomic nervous system (ANS), especially the rapid vagal influence, although such modulation is not strong enough to produce an evident change in the mean and standard deviation of R-R intervals. With the effect of age, previous studies have revealed that aging is accompanied with a decrease of complexity in either cardiac pacemaker activity or midbrain neural activity. Older subjects, regardless of gender, had a lower CD, ApEn, and LLE, indicating a lower degree of neural modulation to the cardiac pacemaker.

The researchers conclude that this lower complexity in the elderly may be due to a decrease in the ANS potency resulting from the normal aging process. The higher complexity of heart rate dynamics observed in women before the age of menopause may be related to the lower cardiac mortality and longer life expectancy of women. Previous studies regarding the nonlinear analysis of HR dynamics chiefly focused on its capability to discriminate pathological states or senile changes from normal conditions. Because illness and aging may lead to a prominent change in ANS function, which in turn leads to a prominent change in HR dynamics, such alterations can usually be detected by traditional linear methods.

Conclusions

In almost every country, women have a longer life expectancy than men, generally attributed to gender-related differences in cardiovascular function. The exact mechanism underlying these differences remains unclear; however, the data in this study indicate that changes in the nonlinear properties may reflect effects of gender and aging on cardiac parasympathetic regulation. The gender-related difference in autonomic regulation function is key: women before menopause have a lower risk of heart diseases than do men. The “cardioprotective” effect of estrogen has been proposed for this trend but the linkage between the sex hormone and the heart is ambiguous. Because a potentiated vagal function may protect the heart from tachyarrhythmias after ischemic heart disease and decrease the mortality rate, the dominance of vagal function in middle-aged women may produce a protective effect against lethal tachyarrhythmias.

The study revealed 71 percent of women were postmenopausal; the mean age of menopause was 47.7, and only six percent of postmenopausal women received hormone replacement therapy. Thus the loss of gender-related differences in the nonlinear indexes after age 50 supports the hypothesis that estrogen has a facilitating effect on cardiac parasympathetic regulation as revealed by the nonlinear content of heart rate dynamics. Nonlinear analysis techniques may reveal new aspects of HR dynamics. Mechanisms underlying the effects of gender and aging on nonlinear properties of cardiac pacemaker activity and related clinical applications warrant further investigations. Because the algorithms may be directly incorporated into current HRV analysis protocols, CD, ApEn, and LLE have a high potential for studying gender-related differences in cardiac pacemaker activity and related autonomic regulation.

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Source: October 2002 edition of the American Journal of Physiology–Heart and Circulatory Physiology.

The American Physiological Society (APS) was founded in 1887 to foster basic and applied science, much of it relating to human health. The Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals every year.