Relation of Central Arterial Stiffness to Incident Heart Failure in the Community

Abstract

Background: Arterial stiffness, pressure pulsatility, and wave reflection are associated with cardiovascular disease. Left ventricular function is coupled to proximal aortic properties, but the association of central aortic stiffness and hemodynamics with incident clinical heart failure (HF) is not well described.

Methods and results: Framingham Study participants without clinical HF (n=2539, mean age 64 years, 56% women) underwent applanation tonometry to measure carotid-femoral pulse wave velocity (CFPWV), central pulse pressure, forward wave amplitude, and augmentation index. CFPWV was inverse-transformed to reduce heteroscedasticity and multiplied by -1 to restore effect direction (iCFPWV). Over 10.1 (range 0.04-12.9) years, 170 HF events developed. In multivariable-adjusted analyses, iCFPWV was associated with incident HF in a continuous, graded fashion (hazards ratio [HR] per SD unit [SDU] 1.29, 95% confidence interval [CI] 1.02-1.64, P=0.037). iCFPWV was associated with HF with reduced ejection fraction (HR=1.69/SDU, 95% CI 1.19-2.42, P=0.0037) in age- and sex-adjusted models, which was attenuated in multivariable-adjusted models (P=0.065). Central pulse pressure and forward wave amplitude were associated with HF in age- and sex-adjusted models (per SDU, HR=1.20, 95% CI 1.06-1.37, P=0.006, and HR=1.15, 95% CI 1.01-1.31, P=0.036, respectively), but not in multivariable-adjusted models (both P≥0.28). Augmentation index was not associated with HF risk (P≥0.19 in all models).

Conclusions: In our prospective investigation of a large community-based sample of middle-aged to elderly individuals, greater aortic stiffness (reflected by higher iCFPWV) was associated with increased risk of HF. Future studies may investigate the impact of modifying aortic stiffness in reducing the community burden of HF.

Keywords: aortic stiffness; epidemiology; heart failure; pressure pulsatility.

Figure 1

Plot of carotid femoral pulse wave velocity (CFPWV) with age. The variance of untransformed CFPWV increased markedly at older ages, whereas the variances of the other tonometry variables with age (Figures 2, 3, 4 through 5) were not as notable. Y axis is standardized measure of CFPWV.

Figure 2

Plot of inverse‐transformed carotid‐femoral pulse wave velocity (iCFPWV) with age. Y axis is standardized measure of iCFPWV.

Figure 3

Plot of central pulse pressure (CPP) with age. Y axis is standardized measure of CPP.

Figure 4

Plot of forward wave amplitude with age. Y axis is standardized measure of forward wave amplitude.

Figure 5

Plot of augmentation index (AI) with age. Y axis is standardized measure of AI.

Figure 6

Continuous association of iCFPWV with risk for incident HF. The risk for incident HF increased continuously with increasing standardized iCFPWV. The x‐axis represents standardized values for inverse‐transformed CFPWV: mean −104.2 s/m maps to 0 and 1 unit on x‐axis (1 SD) corresponds with 31.1 s/m. Each 1 SD increase in iCFPWV corresponds with 1.29‐fold higher hazard for incident HF. A test for non‐linearity was nonsignificant (P=0.63). iCFPWV indicates inverse‐transformed carotid femoral pulse wave velocity; HF, heart failure; HR, hazard ratio.

Figure 7

Risk of heart failure by tertile of sex‐standardized iCFPWV. The cumulative incidence of HF rose with greater tertile of iCFPWV. Sex‐standardized iCFPWV tertiles: Tertile 1: <−0.5; Tertile 2: −0.5 to 0.4; Tertile 3: >0.4. iCFPWV indicates inverse‐transformed carotid femoral pulse wave velocity; HF, heart failure.