Effects of age and menopause on cardiac and vascular regulation in women
Open Access
- Author:
- Moore, David
- Graduate Program:
- Physiology
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- September 25, 2014
- Committee Members:
- David Nathan Proctor, Committee Chair/Co-Chair
James Anthony Pawelczyk, Dissertation Advisor/Co-Advisor
Mary Jane De Souza, Committee Member
Urs Andreas Leuenberger, Committee Member - Keywords:
- Aging
Exercise
Women
Autonomic
Heart Rate
Blood Flow
Menopause
Baroreflex - Abstract:
- Aging is associated with an increase in cardiovascular disease risk and a decrease in physical performance capacity. These changes result predominantly from alterations in the structure and function of the heart and blood vessels. However, much of our current understanding about the aging cardiovascular system comes largely from studies performed using men. This dissertation consists of four studies that used secondary analyses to examine the influence of aging on cardiovascular function using women. The first two studies investigated the effects of age and the menopause transition on arterial baroreflex control of cardiac activity. The second two studies examined the effects of age and menopause on skeletal muscle vascular tone at rest and during acute exercise. The purpose of the first study (Chapter 2) was to determine whether cardiovagal baroreflex sensitivity (BRS) is lower across stages of the menopause transition in healthy middle-aged women. Women (41 – 59 yrs) were categorized into early perimenopausal, late perimenopausal, and early postmenopausal groups using the Stages of Reproductive Aging Workshop criteria. BRS was determined by averaging the regression coefficients of spontaneous corresponding sequences of increasing and decreasing systolic blood pressure and R-R interval (i.e., the sequence method). There was an overall influence of menopause stage on BRS (p = 0.018). Specifically, BRS values declined across menopause stage groups with a statistically significant difference observed between the early perimenopausal and early postmenopausal women (p = 0.017). In the combined sample of women, BRS was best explained by a model containing systolic blood pressure and follicle-stimulating hormone (r2= 0.57, p < 0.001). These findings suggest that the menopause transition may contribute to the decline in cardiovagal BRS with age in women. Having a higher cardiorespiratory fitness (CRF) appears to partially preserve cardiovagal BRS in older men. To what extent BRS can be modulated by CRF in older women remains unknown. Thus, the purpose of the second study (Chapter 3) was to determine the association between CRF and BRS in healthy older women, and to compare this association to that observed in older men. Healthy, older (60 – 80 yrs.) women and men were recruited from the local community and underwent CRF (graded treadmill exercise) testing. BRS was assessed using the sequence method. There was no association between peak oxygen consumption (VO2peak) normalized to either total body mass (r2 = 0.0063, p = 0.71) or lean body mass (r2 = 0.0092, p = 0.64) and BRS in older women. In older men, BRS was similarly not associated with total body mass- (r2 = 0.0085, p = 0.70) or lean body mass- (r2 = 0.029, p = 0.48) normalized VO2peak. These findings suggest that spontaneous cardiovagal BRS is not influenced by CRF in healthy older women and men. The purpose of the third study (Chapter 4) was to examine the influence of age on basal sympathetic vasoconstrictor tone in the leg muscle vasculature of women. While muscle sympathetic nerve activity (MSNA) is elevated with advancing age, correlational evidence suggests that, in contrast to men, basal MSNA is not related to resting lower-limb hemodynamics in women. To address this issue, changes in femoral artery vascular conductance (FVC) during an acute sympatho-inhibitory stimulus (-60 mm Hg neck suction, NS) were measured in groups of healthy younger (23 + 1 yrs.) and older (66 + 1 yrs) women. The percent change in FVC in response to NS was significantly augmented in the older (p = 0.006 versus young) women. Whereas NS caused no significant change (3 + 3 %, p = 0.33) in FVC in the young women, there was a robust increase in FVC (21 + 5 %, p = 0.003) in the old women. These findings provide evidence that leg sympathetic vasoconstrictor tone emerges with age in women. The purpose of the fourth study (Chapter 5) was to investigate the influence of the menopause transition on skeletal muscle vascular responses to acute exercise. Leg exercise hemodynamics during single-leg knee extensions were compared among healthy groups of early perimenopausal, late perimenopausal, and early postmenopausal women. Femoral blood flow (FBF) and vascular conductance (FVC) at rest and during very light work rates (0 and 5 Watts) were similar among all three menopause stage groups. Vascular responses at 10 Watts (FBF) and 20 Watts (FBF and FVC) were significantly higher (P < 0.05) in early perimenopausal compared with late perimenopausal women. At 15 and 25 Watts FBF and FVC were similar between late perimenopausal and early postmenopausal groups, but higher (P < 0.05) in early perimenopausal women as compared with the other two menopausal groups. In the combined sample of all three menopause stage groups, follicle-stimulating hormone was significantly correlated with vascular conductance during submaximal (15 Watts) exercise (R = -0.56, P < 0.001), even after adjustment for age, fitness, LDL cholesterol and abdominal fat (R = -0.46, P = 0.005). These findings suggest that leg vascular responsiveness during exercise may become altered as a result of the menopause transition.