Abstract Body (Do not enter title and authors here): Background
Carotid-femoral pulse wave velocity (cfPWV) is a representative measure of central arterial stiffness and an independent predictor of cardiovascular disease (CVD). Femoral-ankle PWV (faPWV) represents peripheral arterial stiffness, but its association with CVD has not been specifically studied.

Aim
To compare faPWV and cfPWV regarding their associations with CVD outcomes.

Methods
We analyzed 3,402 ARIC participants without prior heart failure (HF), coronary heart disease (CHD), or stroke at visit 5 (2011-13) (mean age 74.8 [SD 4.9] years, 36.1% male, and 78.0% White). faPWV and cfPWV were measured by Omron VP-1000 Plus. The outcomes of interest were composite and individual outcomes of CVD (HF, CHD, and stroke). We ran unadjusted and multivariable Cox proportional hazards models.

Results
During a median follow-up of 9.0 years, there were 607 CVD events. Overall, faPWV showed an inverse association with CVD (Table). P-for-trend reached statistical significance in Models 1 and 2 and was borderline significant in Model 3 (p=0.077). In contrast, as anticipated, cfPWV was positively associated with CVD in all Models, although the association was somewhat attenuated in Model 3 (p-for-trend=0.045 and hazard ratio [HR] for top vs. bottom quartile 1.22 [95%CI 0.95-1.56]). Given their opposite patterns, we explored the ratio of cfPWV and faPWV (“cf/fa ratio”) and found that its association with CVD appeared stronger (p-for-trend=0.004 and HR for top vs. bottom quartile 1.37 [1.08-1.74]) than cfPWV. When each CVD subtype was examined separately, HF showed most consistent associations with our stiffness measures, and only the cf/fa ratio remained significant for HF up to Model 3 (p-for-trend=0.010 and HR for top vs. bottom quartile 1.40 [1.03-1.90]).

Conclusions
faPWV was inversely associated with CVD, and cf/fa ratio appeared more strongly associated with CVD compared to cfPWV. Our findings indicate distinct prognostic implications of central vs. peripheral arterial stiffness and suggest cf/fa ratio as a new stiffness measure predicting CVD.