Contradicting conventional wisdom, menopause may not be the driving force behind an increase in aortic stiffness in women after midlife, according to new research published today in Hypertension, a peer-reviewed scientific journal published by the American Heart Association. The study, an analysis from the large and multi-generation Framingham Heart Study, found that increasing pulse pressure, long attributed to falling estrogen levels caused by menopause, begins about two decades before women enter menopause.
Pulse pressure is the difference between the upper (systolic) and lower (diastolic) numbers in a blood pressure reading. A wider pulse pressure (higher number) indicates that the aorta, the body’s largest blood vessel, is becoming stiffer and less flexible, increasing the risk of heart disease, dementia, and kidney disease. It may also make high blood pressure less responsive to some medication treatments.
“Many people believe that the change in pulse pressure is linked to the hormonal shifts caused by menopause. Here, we are evaluating whether the timing of this change, from falling to rising pulse pressure, is connected to menopause timing in a long-term study,” 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.
Researchers analyzed data from 6,760 adult women and 3,248 adult men in the Framingham Heart Study, which has conducted health exams and collected information for up to three generations of families living in Massachusetts. They found that pulse pressure reached its lowest point and changed from a falling to a rising profile about a decade earlier in women than 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 the onset of menopause.
After midlife, pulse pressure increased faster in women, resulting in average pulse pressure that was higher in women than in men after age 60. “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,” Mitchell said.
While high blood pressure is the most modifiable risk factor for cardiovascular disease, there is strong evidence that wide pulse pressure is an independent risk factor for various cardiovascular conditions, as well as dementia and kidney disease. However, pulse pressure 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. High blood pressure with a wide pulse pressure is less likely to respond to the usual treatments, so tailored treatment is important, Mitchell added.
“Vascular aging may begin years before menopause, but that doesn't mean menopause is irrelevant. The trajectory may accelerate as women enter perimenopause,” said 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. El Khoudary 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. She added that women and healthcare professionals should be thinking about heart health long before menopause.
“We shouldn’t wait until menopause to start thinking about cardiovascular health. 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 estrogen measurements. 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 (NHLBI) of the National Institutes of Health since just after its 1948 beginning and has been led by Boston University since 1971.
