Characterizing vascular and hormonal changes in women across the life span: a cross-sectional analysis.
Megan M Wenner, Ninette Shenouda, Leena Shoemaker, Andrew Kuczmarski, Katherine Haigh, Angelica Del Vecchio, Allyson Schwab, Shane J McGinty, David G Edwards, Ryan T Pohlig, Virginia R Nuckols, Lyndsey DuBose, Kerrie L Moreau
Author Information
Megan M Wenner: Department of Kinesiology and Applied Physiology, University of Delaware, Newark, Delaware, United States. ORCID
Ninette Shenouda: Department of Kinesiology and Applied Physiology, University of Delaware, Newark, Delaware, United States. ORCID
Leena Shoemaker: Department of Medical Biophysics, Western University, London, Ontario, Canada.
Andrew Kuczmarski: Department of Kinesiology and Applied Physiology, University of Delaware, Newark, Delaware, United States.
Katherine Haigh: School of Nursing, University of Delaware, Newark, Delaware, United States.
Angelica Del Vecchio: Department of Kinesiology and Applied Physiology, University of Delaware, Newark, Delaware, United States.
Allyson Schwab: Department of Kinesiology and Applied Physiology, University of Delaware, Newark, Delaware, United States.
Shane J McGinty: Department of Kinesiology and Applied Physiology, University of Delaware, Newark, Delaware, United States. ORCID
David G Edwards: Department of Kinesiology and Applied Physiology, University of Delaware, Newark, Delaware, United States. ORCID
Ryan T Pohlig: Department of Epidemiology, University of Delaware, Newark, Delaware, United States.
Virginia R Nuckols: Department of Kinesiology and Applied Physiology, University of Delaware, Newark, Delaware, United States. ORCID
Lyndsey DuBose: Department of Medicine, Division of Geriatric Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States. ORCID
Kerrie L Moreau: Department of Medicine, Division of Geriatric Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States. ORCID
Vascular dysfunction, marked by lower endothelial function and increased aortic stiffness, is a nontraditional risk factor that precedes the development of cardiovascular disease (CVD). However, the age at which these changes in vascular function occur in women and the degree to which reproductive hormones mediate these changes has not been characterized. Women free from major disease were enrolled across the adult life span (aged 18-70 yr, = 140). Endothelial function was assessed as flow-mediated dilation (FMD) of the brachial artery during reactive hyperemia using duplex ultrasound and expressed as percent dilation. Aortic stiffness was measured by carotid-femoral pulse wave velocity (cfPWV). Blood samples were obtained to quantify reproductive hormone concentration. Regression models determined age-related breakpoints and mediating factors between age and vascular outcomes. FMD declined with age with a breakpoint and steeper decline occurring at 47 yr of age. Thereafter, age was independently associated with lower FMD ( = -0.13, < 0.001). cfPWV was relatively stable until a breakpoint at age 48, and age was independently associated with higher cfPWV thereafter ( = 0.10, < 0.001). Path analysis revealed that the association between age and FMD was partially mediated by follicle-stimulating hormone ( = 0.051, = 0.01) and progesterone ( = 0.513, < 0.001) but not estradiol ( = -0.004, = 0.08). No mediation was present for cfPWV. Age was associated with endothelial dysfunction and aortic stiffness in women beginning at 47 and 48 yr old, respectively, 3 to 4 yr before the average age of menopause. The association between age and endothelial dysfunction was explained in part by elevations in follicle-stimulating hormone and progesterone, but not declining estradiol. We demonstrate that the age at which endothelial function declines and aortic stiffness increases in healthy women is 47 and 48, respectively. The inflection point in flow-mediated dilation (FMD) is 6 yr earlier than previously reported, and the association between age and FMD was mediated by follicle-stimulating hormone (FSH) and progesterone (P) but not estradiol (E).
