Arterial Stiffness and Long-Term Risk of Health Outcomes: The Framingham Heart Study

Abstract

Background: Arterial stiffness increases with age and is associated with an increased risk of adverse outcomes on short-term follow-up (typically <10 years). Data regarding associations of arterial stiffness with health outcomes on longer-term follow-up are lacking.

Methods: We evaluated 7283 Framingham Study participants (mean age 50 years, 53% women) who underwent assessment of carotid-femoral pulse wave velocity (a marker of arterial stiffness) via applanation tonometry at one or more routine examinations. We used time-dependent Cox proportional hazards regression models to relate carotid-femoral pulse wave velocity to the incidence of health outcomes (updating carotid-femoral pulse wave velocity and all covariates at serial examinations).

Results: On long-term follow-up (median 15 years; minimum-maximum, 0-20), participants developed cardiometabolic disease (hypertension [1255 events]; diabetes [381 events]), chronic kidney disease (529 events), dementia (235 events), cardiovascular disease (684 events) and its components (coronary heart disease [314 events], heart failure [191 events], transient ischemic attacks or stroke [250 events]), and death (1086 events). In multivariable-adjusted models, each SD increment in carotid-femoral pulse wave velocity was associated with increased risk of hypertension (hazard ratio [HR], 1.32 [95% CI, 1.21-1.44]), diabetes (HR, 1.32 [95% CI, 1.11-1.58]), chronic kidney disease (1.19 [95% CI, 1.05-1.34]), dementia (HR 1.27 [95% CI, 1.06-1.53]), cardiovascular disease (HR, 1.20 [95% CI, 1.06-1.36]) and its components (coronary heart disease, HR 1.37 [95% CI, 1.13-1.65]; transient ischemic attack/stroke, HR, 1.24 [95% CI, 1.00-1.53]), and death (HR, 1.29 [95% CI, 1.17-1.43]). The association with heart failure was borderline nonsignificant (HR, 1.21 [95% CI, 0.98-1.51], P=0.08).

Conclusions: Our prospective observations of a large community-based sample establish the long-term prognostic importance of arterial stiffness for multiple health outcomes.

Keywords: cardiovascular diseases; dementia; heart diseases; mortality; risk; vascular stiffness.

Figure 1.

Relations of CFPWV and incidence of outcome events dichotomized by median age (50 years for analyses combining FOS and Gen3 [incidence of hypertension, diabetes, CKD^b, CVD, CVD subtypes, and death]; 60 years for analyses limited to FOS [incidence of CKD^a and dementia]). Hazards ratios are per SD increment in CFPWV from age-stratified models adjusting for Model 3 covariates (age, sex, current smoking status, TC/HDL cholesterol, diabetes [or fasting blood glucose, for incident diabetes], systolic blood pressure, and antihypertensive treatment). Interaction P values are from models pooling age groups. CKD^a and CKD^b refer to definitions of incident disease based on reduced eGFR and increased UACR versus reduced eGFR alone, respectively.

Figure 2.

Sex-specific relations of CFPWV and incidence of outcome events. Hazards ratios are per SD increment in CFPWV from sex-stratified models adjusting for Model 3 covariates (age, sex, current smoking status, TC/HDL cholesterol, diabetes [or fasting blood glucose, for incident diabetes], systolic blood pressure, and antihypertensive treatment). Interaction P values are from pooled sex models. CKD^a and CKD^b refer to definitions of incident disease based on reduced eGFR and increased UACR versus reduced eGFR alone.

Figure 3.

Unadjusted cumulative incidence and the age- and sex-adjusted probability of outcomes according to quartiles of CFPWV. Outcomes include dementia (Panels A, B), cardiovascular disease (CVD, Panels C, D), and death (Panels E, F).

Figure 4.

Panel A. Unadjusted cumulative incidence and age- and sex-adjusted probability of CVD subtypes according to quartiles of CFPWV. Outcomes include coronary heart disease (CHD, Panels A, B), heart failure (Panels C, D), and stroke or transient ischemic attack (Panels E, F).