Aortic–Brachial Arterial Stiffness Gradient and Cardiovascular Risk in the Community

Under physiological conditions, the arterial vasculature is characterized by a progressive increase in stiffness from the aorta and large elastic arteries toward the peripheral muscular conduit arteries, often labeled as the arterial stiffness gradient. However, this gradient is not by any means invariable as stiffness of the aorta tends to increase with age, whereas the relationship between peripheral muscular arteries and advancing age is not as pronounced. In fact, upper-limb muscular artery compliance may even decrease with age in women and in individuals with diabetes mellitus. Age-related changes in vasculature thereby result in a reduction, or even a reversal of the physiological arterial stiffness gradient in most individuals. Increased aortic stiffness, most commonly measured as the carotid–femoral pulse wave velocity (CFPWV), is a strong predictor of cardiovascular disease (CVD) both in patient and population-based cohorts. In contrast, it is unclear whether muscular conduit artery stiffness, often measured in the arm as the carotid–radial pulse wave velocity (CRPWV), is associated with cardiovascular morbidity. Although CRPWV has been largely overshadowed in research and clinical practice by CFPWV because of its limited prognostic value, recent research suggests that CRPWV may, after all, also have an important role in CVD risk prediction. Specifically, a recent study by Fortier et al reported that an increased aortic–brachial arterial stiffness gradient (defined as the ratio of CFPWV and CRPWV) was a better predictor of all-cause mortality than CFPWV per se. Fortier et al and Covic and Siriopol of an accompanying editorial speculated that the finding of a clinically significant Abstract—A recent study reported that the aortic–brachial arterial stiffness gradient, defined as carotid–radial/carotid– femoral pulse wave velocity (PWV ratio), predicts all-cause mortality better than carotid–femoral pulse wave velocity (CFPWV) alone in dialysis patients. However, the prognostic significance of PWV ratio for cardiovascular disease (CVD) in the community remains unclear. Accordingly, we assessed the correlates and prognostic value of the PWV ratio in 2114 Framingham Heart Study participants (60±10 years; 56% women) free of overt CVD. Mean PWV ratio decreased from 1.36±0.19 in participants aged <40 years to 0.73±0.21 in those aged ≥80 years. In multivariable linear regression, older age, male sex, higher body mass index, diabetes mellitus, lower high-density lipoprotein cholesterol, higher mean arterial pressure, and higher heart rate were associated with lower PWV ratio (P<0.001 for all). During a median follow-up of 12.6 years, 248 first CVD events occurred. In Cox regression models adjusted for standard CVD risk factors, 1-SD changes in CFPWV (hazard ratio, 1.33; 95% confidence interval, 1.10–1.61) and PWV ratio (hazard ratio, 1.32; 95% confidence interval, 1.09–1.59) were associated with similar CVD risks. Models that included conventional CVD risk factors plus CFPWV or PWV ratio gave the same C statistics (C=0.783). Although PWV ratio has been reported to provide incremental predictive value over CFPWV in dialysis patients, we could not replicate these findings in our communitybased sample. Our findings suggest that the prognostic significance of PWV ratio may vary based on baseline CVD risk, and CFPWV should remain the criterion standard for assessing vascular stiffness in the community. (Hypertension. 2017;69:1022-1028. DOI: 10.1161/HYPERTENSIONAHA.116.08917.) • Online Data Supplement