It is well noted that menopause aggravates the progression of atherosclerotic cardiovascular diseases [15]. Arterial stiffness plays important roles in the development of atherosclerosis [1]. While it is logically possible that the progression of arterial stiffness with age differs in males and females, several studies reported that aging increases arterial stiffness similarly in both genders [16- 18]. However, these studies included patients with hypertension. Elevated blood pressure is an important determinant of PWV [9]. The numbers of subjects in the previous studies were also too small for chronological analysis of the influence of age on PWV. Therefore, an impeccable conclusion about the influence of age on PWV could not be arrived from these studies. On the other hand, aging increases the incidence of atherogenic metabolic disorders [19] . These disorders influence baPWV [9-12]. In the present study, a multiple regression analysis demonstrates that these influences on baPWV are weak, but significant. Consequently, to evaluate the influence of age on baPWV, we extracted a population of apparently healthy subjects who had no atherogenic and metabolic disorders.

　Our series consisted of more than 7000 healthy adult subjects and allowed a rather fine chronological classification at 5-year age intervals, spanning age 25 to over 70 years. The chronological evaluation of baPWV in males and females clearly demonstrated that age influences baPWV differently in both genders, and the augmentation of arterial stiffness with aging is more prominent in female.

　

　

　Aging induces structural and functional abnormalities such as arterial wall hypertrophy and degeneration or disorganization of the medial layer [20,21]. These changes increase PWV because of increased arterial stiffness. In the present study, multivariate analysis demonstrated that age is a more important determinant of baPWV in females than in males independent of blood pressure variables. Furthermore, baPWV is increased in a quadratic manner around age 50 to 60s in females. While we could not confirm the menopause status in each individual, these results suggest that menopause is an important factor influencing arterial stiffness in healthy female subjects. Some studies demonstrated that estrogen has beneficial effects on arterial stiffness [22]. The present study suggests that the exhaustion of estrogen augments the age-related arterial stiffing.

　In the arterial tree, atherosclerotic changes progress independently in peripheral sites and central sites [23]. Arterial stiffness reflects the changes of arterial wall degeneration [2,3]. In the arterial tree, peripheral sites contain more muscular component and central sites contain more elastic component [15,23]. Not only estrogen receptor, but androgen receptor also has been demonstrated in vascular smooth muscle cell [24,25]. Accordingly, it is possible that the influence of age on peripheral sites and central sites in the arterial tree is different in males and females. In the present study, the heart-brachial PWV assessed peripheral sites in the upper limb and baPWV assessed peripheral sites in the lower limb and central site. While the chronological change of baPWV was more marked in female, heart-brachial PWC was higher in males than in females at all ages. Thus, the augmentation of arterial stiffness with aging might be prominent in central sites (aorta) and/or peripheral sites in lower extremities in females. Using phase-contrast magnetic resonance imaging. Rogers et al [26] demonstrated that age-associated increase in aortic PWV primarily affecting the proximal sites.

　Recently, pulse pressure has been focused as an independent risk for cardiovascular diseases [27]. Left ventricular ejection and vascular component determine the pulse pressure [28]. In this vascular component, arterial stiffness and arterial wave reflection are pre-dominant factors [17,28]. In this study, baPWV reflecting arterial stiffness was lower in female than in male until age 60, and became similar in both genders after age 60. On the other hand, while pulse pressure was lower in female than in male until age 50, it was higher in female than in male over age 50. Thus, the increase of pulse pressure with age does not parallel the increase of baPWV. This phenomenon was similar to the report of Smulyan et al. [17]. They demonstrated that smaller physical characteristics are important determinants for the increase of pulsality with age in female and was independent of increasing arterial stiffness with age. In our multivariate analysis, mean blood pressure, but not pulse pressure, was significantly associated with baPWV. While PWV is an important factor for determining pulse pressure, Meaume et al. [29] demonstrated that carotid-femoral PWV is a predictor of cardiovascular death independent of pulse pressure. Thus, baPWV and pulse pressure seem to reflect different pathophysiological states in cardiovascular diseases.

　

　

　Carotid-femoral PWV has been shown to be related to atherosclerotic changes in carotid artery [4], and is a useful marker for predicting prognosis in patients with either hypertension or renal insufficiency [30,31]. Thus, several studies have demonstrated that the assessment of PWV is useful for the diagnosis and management of atherosclerotic cardiovascular diseases. While accumulated data tend to indicate that baPVW determination may be a similar marker as carotid-femoral PWV [6,7], the present study demonstrated significant influences of age and gender on baPWV. Further studies are needed to evaluate whether these influences have to be taken into account in the adoption of baPWV as a surrogate marker in assessing cardiovascular diseases.

　

　

　Aging influences baPWV, and its influence is more significant in female. In this respect, menopause seems to be the crucial phenomenon to explain the augmented increase of arterial stiffness with aging in female.

　

　

　This study was partially supported by grant in aid of Japanese Arteriosclerosis Prevention Fund and by grant in aid of St. Luke's Health Science Research Fund.