Aortic Root Diameter and Arterial Stiffness: Conjoint Relations to the Incidence of Cardiovascular Disease in the Framingham Heart Study

Higher central pulse pressure is associated with higher carotid-femoral pulse wave velocity (CFPWV) and an increased risk of cardiovascular disease (CVD). A smaller aortic root diameter (AoR) is associated with higher central pulse pressure. We hypothesized that the combination of a smaller AoR and higher CFPWV is associated with increased CVD risk (relative to a larger AoR and lower CFPWV). We tested this hypothesis in the community-based Framingham Study (N=1970, mean age 60 years, 57% women). We created sex-specific longitudinal echocardiographic AoR trajectories over 2 decades, categorizing participants into smaller versus larger AoR groups. We cross-classified participants based on their AoR trajectory and CFPWV (dichotomized at the sex-specific median). We used Cox regression to relate the cross-classified groups to CVD incidence on follow-up (median 17 years): lower CFPWV, larger AoR (referent group; 6.4/1000 person-years); lower CFPWV, smaller AoR (6.9/1000 person-years); higher CFPWV, larger AoR (23.1/1000 person-years); and higher CFPWV, smaller AoR (21.9/1000 person-years). In sex-pooled analyses, groups with higher CFPWV were associated with a multivariable-adjusted 1.8-fold risk of CVD (P<0.01) regardless of AoR size. We observed effect modification by sex (P for sex×AoR-CFPWV group interaction 0.04). In men, the group with smaller AoR and higher CFPWV was associated with a 2.5- to 2.8-fold risk of CVD (P<0.001). In women, the group with larger AoR and higher CFPWV experienced a statistically nonsignificant 70% to 80% higher CVD risk. Our observations indicate that the prognostic significance of a smaller versus larger AoR varies in men versus women. Additional studies are warranted to confirm our findings.