Longitudinal changes in left ventricular stiffness: a community-based study

Abstract

Background: Cross-sectional studies suggest that left ventricular (LV) and arterial elastance (stiffness) increase with age, but data examining longitudinal changes within human subjects are lacking. In addition, it remains unknown whether age-related LV stiffening is merely a reaction to arterial stiffening or caused by other processes.

Methods and results: Comprehensive echo-Doppler cardiography was performed in 1402 subjects participating in a randomly selected community-based study at 2 examinations separated by 4 years. From this population, 788 subjects had adequate paired data to determine LV end-systolic elastance (Ees), end-diastolic elastance (Eed), and effective arterial elastance. Throughout 4 years, blood pressure, arterial elastance, and LV mass decreased, coupled with significantly greater use of antihypertensive medications. However, despite reductions in arterial load, Ees increased by 14% (2.10±0.67-2.26±0.70 mm Hg/mL; P<0.0001) and Eed increased by 8% (0.13±0.03-0.14±0.04 mm Hg/mL; P<0.0001). Increases in Eed were greater in women than men, whereas Ees changes were similar. Age-related increases in Ees and Eed were correlated with changes in body weight, but were similar in subjects with or without cardiovascular disease. Changes in Ees were correlated with Eed (r=0.5; P<0.0001), but not with other measures of contractility, indicating that the increase in Ees was reflective of passive stiffening rather than enhanced systolic function.

Conclusions: Despite reductions in arterial load with medical therapy, LV systolic and diastolic stiffness increase over time in humans, particularly in women. In addition to blood pressure control, therapies targeting load-independent ventricular stiffening may be effective to treat and prevent age-associated cardiovascular diseases, such as heart failure.

Keywords: aging; arterial stiffness; heart failure; hemodynamics; ventricular function.

Figure 1

Mean within subject changes (±SE) in left ventricular structure and function parameters over 4 years. *p<0.0001; †p<0.05; SBP, systolic blood pressure; LV, left ventricular; Ees, end systolic elastance; Eed, end diastolic elastance; Ea, arterial elastance.

Figure 2

Cross sectional relationships between age and end systolic elastance (Ees, A), end diastolic elastance (Eed, B) and arterial elastance (Ea, C) at Examination 2. Bar graphs show mean within subject changes (±SE) in men and women over 4 years in Ees (D), Eed (E), and Ea (F). *p<0.0001 for paired comparison within group vs Exam 1; †p<0.05 for paired comparison within group vs Exam 1.

Figure 3

[A] Stress-shortening plot of endocardial fractional shortening (FS) versus circumferential end systolic wall stress (cESS) reveals no change in chamber contractility from Exam 1 (black) to Exam 2 (gray). Dotted lines show 95% prediction bands. [B] Correlations between 4 year longitudinal changes in left ventricular end systolic elastance (Ees) and changes in end diastolic elastance (Eed, left panel) and [C] changes in preload recruitable stroke work (PRSW, right panel).

Figure 4

Schematic showing ventricular-arterial coupling at Exam 1 (solid lines) and 4 years later (dotted lines). End systolic elastance (Ees), described by the slope and intercept of the end systolic pressure-volume relationship (ESPVR) increased (steeper slope), despite lower end systolic pressure (circles) and reductions in arterial elastance (Ea). Elevations in Ees were coupled with increases in the end diastolic pressure volume relationship (EDPVR), as approximated by end diastolic elastance (Eed).