Longitudinal Hemodynamic Correlates of and Sex Differences in the Evolution of Blood Pressure Across the Adult Lifespan: The Framingham Heart Study

Abstract

Background Systolic blood pressure increases with age after midlife, particularly in women, and contributes to development of wide pulse pressure hypertension in middle-aged and older adults. Relative contributions of aortic stiffness and premature wave reflection to increases in pulse pressure remain controversial. Methods and Results We evaluated visit-specific values and change in key correlates of pulse pressure, aortic characteristic impedance, forward and backward wave amplitude, and global reflection coefficient, at 3 sequential examinations of the Framingham Generation 3 (N=4082), Omni-2 (N=410), and New Offspring Spouse (N=103) cohorts (53% women). Data were analyzed using repeated-measures linear mixed models adjusted for age, sex, and risk factor exposures. Pulse pressure increased markedly with age after midlife (age and age-squared terms, P<0.0001), particularly in women (age slope 3.1±0.2 mm Hg/decade higher in women, P<0.0001). In sex-specific models, change in pulse pressure was closely related (all P<0.0001) to baseline (6.7±0.2 and 7.3±0.2 mm Hg/SD in men and women, respectively) and change (11.8±0.1 and 11.7±0.1 mm Hg/SD) in forward wave amplitude, whereas relations with baseline (2.1±0.15 and 2.0±0.14 mm Hg/SD) and change (4.0±0.13 and 3.4±0.11 mm Hg/SD) in global reflection coefficient were weaker. Global reflection coefficient fell as aortic characteristic impedance increased (P<0.0001), consistent with the hypothesis that impedance matching reduces relative wave reflection in the arterial system. Conclusions Proximal aortic stiffening, as assessed by higher aortic characteristic impedance and larger forward wave amplitude, is strongly associated with longitudinal increase in pulse pressure, especially in women, whereas wave reflection has more modest relations.

Keywords: aging; arterial stiffness; blood pressure; pulsatile hemodynamics; sex differences.

Figure 1. Age trends and change in key hemodynamic variables across 3 examinations spanning 14 years.

Lightly colored symbols are examination 1, and lightly colored line segments represent examination 1–2 change. Darkly colored symbols and line segments represent examinations 2 and 3 and 2–3 change. Markedly nonlinear age relations and sex differences are apparent for several variables. See text for details. BWTT indicates backward wave transit time; CFPWV, carotid‐femoral pulse wave velocity; GRC, global reflection coefficient; P_b, backward wave amplitude; P_f, forward wave amplitude; and Z_c, characteristic impedance of the aorta.

Figure 2. Global reflection coefficient relations with characteristic impedance of the aorta.

Residuals from the separate risk factor models for global reflection coefficient and characteristic impedance are plotted by visit. As the aorta stiffens, characteristic impedance increases and global reflection coefficient falls, consistent with the hypothesis that stiffening of the proximal aorta flattens the impedance gradient in the arterial system, reduces global wave reflection, and therefore increases transmission of pulsatile energy into the periphery. Residuals were created by fitting separated models for characteristic impedance and global reflection coefficient using the full list of candidate covariates in both models.