Abstract Body (Do not enter title and authors here): Background and Research Question
Increasing pulse pressure (PP) occurs with aging and is a risk factor for CVD. PP is shown to fall to a nadir in midlife with subsequent increase with age thereafter. This increase is notably sharper in women compared to men. Sex hormones have been proposed as a vasculo-protective factor in women that is lost during menopause. Thus, we sought to evaluate the temporal patterns of age, sex, and time of menopause on age-associated PP widening in a longitudinal cohort of adults across midlife.

Methods/Approach
We evaluated participants from the Framingham Third Generation, Omni-2, and New Offspring Spouse cohorts. Participants attended up to 3 study visits over 14 years that included non-invasive hemodynamic measurements with arterial tonometry. Supine brachial PP was measured after 5 minutes of rest. Menopause age was self-reported. Women were subdivided into 4 groups based on age of menopause: persistently premenopausal, early (<25^th percentile, age <48 years), average (25^th-74^th percentile, age 48 to 52), or late-onset menopause (≥75^th percentile, age ≥53), with men as reference. Participants were excluded for missing or incomplete covariate or tonometry data. Data were analyzed using repeated-measures linear mixed models adjusted for age, age², menopause group, and CVD risk factors.

Results
Date from 6222 participants with 47.7% women (mean 1^st visit age = 47.9 years) and 52.3% men (mean 1^st visit age = 50.5 years) were analyzed. Modeled PP nadirs in women, regardless of menopause group, occurred about a decade earlier in women compared to men (Figure 1 and 2). There were minimal differences in PP nadir age (average age = 37.1 years) among post-menopausal groups. Predicted PP nadir age was unrelated to the age of menopause, with PP nadir occurring 6.1, 13.5, 18.8 years prior to menopause onset in the early, average, and late menopause groups respectively (Figure 1).

Conclusion
The estimated nadir of PP occurs nearly a decade earlier in women than men and several years prior to menopause onset in all 3 groups of postmenopausal women. While there were some marginal associations between menopause age and PP widening, it is likely other factors play a larger role in the accelerated increase in PP in women after early adulthood. Further studies are needed to establish mechanisms of the early transition and sharper increase in PP among women.