Mitchell Arterial Stiffness and Hypertension 211 in PP that is associated with high incidence of predominantly systolic hypertension in older people. One of the foregoing studies of relationships between arterial stiffness and incident hypertension also examined, in the same (Framingham Heart Study) cohort, relationships between initial blood pressure and progression of arterial stiffness as assessed by CFPWV. 15 The authors found that the initial value of CFPWV was strongly associated with subsequent stiffness progression. However, after accounting for the initial value of CFPWV, no blood pressure component (systolic, diastolic, or mean) entered the model for future stiffness. 15 These results provide support for the hypothesis that aortic stiffness may antedate and may contribute to the development of hypertension. Several recent longitudinal studies evaluated the correlates of progressive aortic stiffening and found mixed results with respect to relationships between initial blood pressure and progressive aortic stiffening. 15, 21–25 Wildman et al22 evaluated change in CFPWV during 2 years of follow-up in a relatively small (n= 152) and young (20–40 years old) biracial cohort and found accelerated stiffening in blacks and in association with baseline or change in various measures of adiposity. Baseline and change in blood pressures components were not, however, related to stiffness progression. Benetos et al21 examined a cohort of persistently normotensive and persistently treated hypertensive volunteers followed up for 6 years and found that baseline age, heart rate, and the presence of treated hypertension were associated with CFPWV progression in a multivariable model, whereas baseline levels of systolic blood pressure and diastolic blood pressure were not related to CFPWV progression. In contrast, Birru et al, 25 El Khoudary et al, 23 and AlGhatrif et al24 found relationships between baseline systolic blood pressure and progression of PWV in multivariable models although El Khoudary et al seem to have not included a term for baseline CFPWV in their model. The foregoing mixed results about relationships between baseline blood pressure and accelerated progression of arterial stiffness suggest that the relationship seems to be sufficiently modest that it is difficult to detect consistently. Several basic and clinical studies have demonstrated that insults that increase aortic stiffness directly, generally by disrupting elastin in the aortic wall, are associated with subsequent development of hypertension. Studies performed in mouse models of impaired elastin expression have shown that aortic stiffness is increased and diameter is reduced early, before the increase in systolic pressure and that subsequent increments in systolic pressure are inversely proportional to elastin content in the aorta. 26 Similarly, children with Williams syndrome (elastin haploinsufficiency) have increased arterial stiffness at a relatively young age, well before the development of hypertension. 27 Increasing elastin expression through introduction of an ectopic copy of the human elastin gene can rescue the arterial phenotype in elastin-deficient mice. 28 Administration of a high-dose combination of vitamin D3 and nicotine or a combination of warfarin and vitamin K produces aortic medial elastocalcinosis, stiffening of the aorta, increased PWV and PP, and isolated systolic hypertension with no antecedent increase in mean arterial pressure. 29, 30 Recently, alterations in diet alone were shown to increase aortic PWV early (1 month) after introduction of a high-fat, high-sucrose diet, before an increase in systolic blood pressure, which occurred at 6 months. 31 High-fat, high …