Women’s pulse pressure may begin rising up to two decades before the final menstrual period, a large Framingham Heart Study analysis found, challenging the notion that menopause-related estrogen loss is the primary driver of midlife arterial stiffening.

Pulse pressure is the difference between systolic and diastolic blood pressure. It generally falls in early adulthood, then rises from midlife as the arteries become stiffer with age. Higher pulse pressure is associated with greater cardiovascular risk. This rise is often greater in women than in men and has been attributed to the declining estrogen levels around menopause.

“To our surprise, the transition from falling to rising pulse pressure occurred at a similar age (37-39 years) in women regardless of whether they ultimately experienced early, average, or late menopause,” said study author Gary F. Mitchell, MD, president of Cardiovascular Engineering Inc., Norwood, Massachusetts, and a longtime Framingham investigator.

The findings, published in Hypertension, are based on an analysis of 6760 participants in the Framingham Heart Study, a long-running community-based study of cardiovascular health that has followed multiple generations of Massachusetts families.

Researchers classified women as persistently premenopausal or among those who reached natural menopause by age at menopause as early (< 48 years), average (48-53 years), or late (> 53 years), and examined age-related patterns in pulse pressure and other measures of pressure pulsatility across these groups and in men.

Data were collected at three visits over 14 years. At each visit, researchers measured blood pressure and used noninvasive vascular testing to assess pressure pulsatility, aortic size, and aortic wall stiffness.

Pulse pressure reached its lowest point earlier in women than in men. The nadir occurred at about age 47 in men and at approximately 39, 38, 37, and 37 years in women who were persistently premenopausal or later experienced early, average, or late menopause, respectively. The findings were similar after adjustment for cardiovascular risk factors, including body size, blood pressure, heart rate, glucose, lipids, smoking, diabetes, cardiovascular disease, and medication use.

“The similarity in the timing of the pulse-pressure nadir among women with early, average, and late menopause suggests that factors other than menopause timing may also influence vascular aging earlier in adulthood,” said Emily Lau, MD, MPH, co-director of the Women’s Heart Health Program at Mass General Brigham in Boston, who was not involved in the study.

“But that doesn’t mean menopause doesn’t play a role,” she told Medscape Medical News.“Ovarian aging and hormonal fluctuations often begin years earlier, so menopause may be part of a longer vascular trajectory rather than a single initiating event.”

The transition from falling to rising pulse pressure occurred an average of 6, 14, or 19 years before the final menstrual period in the early-, average-, and late-menopause groups, respectively. Two other measures of pressure pulsatility showed similar age-related patterns, with nadirs occurring earlier in women than in men.

Aortic Remodeling May Help Explain Earlier Shift

The researchers next examined whether differences in the way the aorta remodels with age could help explain why pressure pulsatility begins increasing earlier in women.

In the analysis, men had greater aortic wall stiffness than women across the lifespan, even after accounting for height and BMI. The age-related increase in wall stiffness was similar across men and menopause groups, although it was slightly greater among women who remained persistently premenopausal.

In contrast, aortic radius in men increased rapidly through midlife and continued to grow into their 80s, whereas in women the increase was slower and plateaued earlier across all menopause groups. The pattern is consistent with prior Framingham research showing that the aortic root enlarges with age in both sexes, but less in women.

Mitchell proposed that “the combination of continued wall stiffening and blunted diameter remodeling leads to the early transition to rapidly increasing pulse pressure in women.”

But Lau cautioned that the explanation is biologically plausible but not proven, since aortic size was derived using the same hemodynamic measures being studied.

An Earlier Window of ‘Prevention’

The findings may point to an earlier window for cardiovascular prevention, but they do not yet support a change in clinical practice.

Mitchell said that women should monitor their blood pressure and especially their pulse pressure, since elevated pulse pressure is an important risk factor for adverse cardiovascular and cognitive outcomes. “A systolic pressure of 130 mm Hg may be managed with watchful waiting, but if diastolic pressure is 60 or 50 mm Hg, pulse pressure would be 70 or 80 mm Hg, respectively, and risk will be markedly elevated,” he said.

Lau agreed that pulse pressure may provide useful information in some patients but said there is not enough evidence to recommend routine arterial-stiffness testing. 

“What this does reinforce is that cardiovascular prevention in women should start well before menopause,” she said.

The study did not measure sex hormone levels over time, so it could not determine how hormonal changes contribute to vascular aging. Future studies that follow women through the years around menopause may help clarify how hormonal changes interact with vascular aging.

The Framingham Heart Study has been supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Mitchell reported ownership of Cardiovascular Engineering Inc. and reported consulting, grant, and honoraria relationships with several companies. He also reported pending patents related to vascular aging and pulse wave velocity. The other authors, including Lau, reported having no conflicts of interest. 

Isha Ishtiaq is a health journalist based in Pakistan.