Contradicting conventional wisdom, a new study published in Hypertension suggests that menopause may not be the driving force behind an increase in aortic stiffness in women after midlife. The research, an analysis from the large and multi-generation Framingham Heart Study, found that pulse pressure—the gap between the upper and lower numbers in blood pressure readings—begins to rise about two decades before women enter menopause, challenging the long-held belief that falling estrogen levels are responsible.
Pulse pressure is influenced by the stiffness and width of the aorta, the body's largest blood vessel. A wider pulse pressure means the heart is working harder and can cause damage to small vessels in organs such as the brain and kidneys. The study found that pulse pressure reached its lowest point and began to rise about a decade earlier in women than in men—in their late 30s among women rather than late 40s in men. Whether menopause occurred early, late, or at a typical time had no influence on the age when women had the lowest point in pulse pressure, which occurred up to two decades before menopause.
"To our huge surprise, our results suggest that factors other than the timing of the final menstrual period were likely involved in the accelerated increase in pulse pressure in women after midlife," said study senior author Gary F. Mitchell, M.D., a longstanding NIH-funded investigator with the Framingham Heart Study and president of Cardiovascular Engineering, Inc., in Needham, Mass.
The study analyzed data from 6,760 adult women and 3,248 adult men in the Framingham Heart Study, which has collected health information for up to three generations of families. Women were divided into groups based on self-reported age at menopause. The research highlights that wide pulse pressure is a major risk factor for cardiovascular disease, dementia, and kidney disease, and may make high blood pressure less responsive to some medication treatments.
Despite strong evidence that wide pulse pressure is an independent risk factor, it is currently not included in clinical guidelines for managing blood pressure. "Healthcare professionals should definitely consider pulse pressure in middle-aged and older patients – especially women – with high blood pressure," Mitchell said. "Because women's overall heart disease risk is lower, they are often told that a blood pressure that is 'borderline' - for example an upper number of 130 mm Hg - can just be watched. However, women and their doctors should sound the alarm if pulse pressure is higher than 60 mm Hg [such as 130/70 mm Hg] and track it over time to see if pulse pressure is rising."
Greater attention to pulse pressure may also help guide individual treatment approaches, as high blood pressure with a wide pulse pressure is less likely to respond to usual treatments. Samar R. El Khoudary, Ph.D., M.P.H., FAHA, who chaired the writing group for a 2020 American Heart Association scientific statement on the menopause transition, noted that vascular aging may begin years before menopause. "We shouldn't wait until menopause to start thinking about cardiovascular health," said El Khoudary, who was not involved in the current study and is chair and professor of epidemiology at the School of Public Health and director of Women's Public Health Research Initiatives at the Institute of Women's Health at Virginia Commonwealth University in Richmond, Va. "By the time a woman reaches her final menstrual period, vascular changes may already have been underway for years. Midlife is an opportunity to identify cardiovascular risk early and intervene before disease develops."
The study's limitations include its observational design, which cannot prove cause and effect, and its reliance on self-reported age at menopause rather than measurements of estrogen levels. Most participants were of white European descent, so results might not apply to other racial or ethnic groups. The Framingham Heart Study has been supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health since just after its 1948 beginning and has been led by Boston University since 1971.
The findings suggest that healthcare professionals should pay greater attention to pulse pressure in middle-aged and older women, as it may signal early vascular aging and increased risk for serious health conditions. More research is needed to understand the mechanisms behind these sex differences and to develop tailored prevention strategies.
