This study was conducted in healthy Japanese subjects to examine the effects of age and gender on the relationship between the risk factors for cardiovascular disease (CVD) and augmentation index (AI), and the effects of clusters of those risk factors on AI. Radial arterial pressure wave analysis was used to obtain AI in 3675 men and 2919 women. AI was found to be higher in women than in men, and age-related increase in AI showed an attenuated curve in subjects aged X50 years. A step-wise multivariate linear regression analysis showed that mean blood pressure and smoking are independent significant variables related to AI in men regardless of age, and in women aged o50 years, but not in women aged X50 years. A general linear model univariate linear regression analysis showed that mean blood pressure and smoking had a significant interaction for their relation with AI in men, but not in women. In conclusion, among the risk factors for CVD, smoking and blood pressure were found to be independent factors related to increase in AI. Although age-related attenuation of increase in AI was confirmed in Japanese subjects, these risk factors may act to increase AI even in elderly subjects, at least in part. However, the effects of these factors on AI may differ based on gender, and these factors may act synergistically to increase AI in men. On the contrary, these factors may act independently in young women to increase AI without interaction, whereas only the blood pressure seems to increase AI in elderly women. Keywords: age; augmentation index; gender; risk factors INTRODUCTION Accumulating evidence suggest that increased arterial stiffness is an independent risk for cardiovascular disease (CVD). 1-3 The augmentation index (AI) is a marker related to systemic arterial stiffness, and some studies reported that increased AI or central blood pressure estimated by AI predicts future cardiovascular events. [4][5][6] Some studies reported that CVD risk factors affect AI. 7-11 The age-related increase in AI shows an attenuated curve in subjects aged 450 years, and AI is thought to be less sensitive in reflecting arterial stiffness in elderly subjects. 12 Although AI increases predominantly in women, the Second Australian National Blood Pressure Study (ANBP 2 study) showed that it cannot be used as a marker for predicting future CVD events in elderly women with hypertension. 13 Matsui et al. 14 examined the effects of age and gender on AI in subjects with hypertension under anti-hypertensive medication. However, their study could not avoid the influence of anti-hypertensive medication on the results. Thus, the effects of both age and gender on the relationship between the risk factors for CVD and AI in healthy individuals have not been fully clarified. Furthermore, although it is noted that a cluster of those risk factors additively or synergistically augments the progression of

This study was conducted to clarify whether the second peak of the systolic blood pressure (SBP2) has significant information about cardiovascular (CV) risk state, independent of the brachial BP. SBP2 was measured by radial pressure wave analysis in 7847 Japanese subjects (50 ± 10 years old), and the Framingham risk score (FRS) and general cardiovascular disease risk score were calculated (FRSgen). The results of multivariate analysis revealed that the SBP2 showed a significant correlation with the FRS (b¼0.04, t-value¼3.92, Po0.01) and FRSgen (b¼0.05, Po0.01), independent of the brachial SBP. The non-standardization coefficient of SBP2 was smaller than that of brachial SBP. The logistic regression analysis showed that SBP2 (2 mm Hg per increase) had a significant odds ratio to identify not only subjects with a high risk for coronary heart disease (CHD) and general CV disease (CVDgen), but also subjects with a low risk for CHD and CVDgen, independent of the brachial SBP. However, when the analysis was limited to subjects of X49 years of age, SBP2 could not identify either high or low CV risk subjects. Thus, in middle-aged Japanese subjects, SBP2 may provide little, yet significant, information reflecting both high and low CV risk states, independent of the brachial BP. SBP2 seems to be more applicable for CV risk stratification in younger subjects than in older subjects. INTRODUCTIONPressure wave reflection in the aorta is an independent marker of cardiovascular (CV) risk, 1,2 and the blood pressure measured in the aorta by non-invasive pressure wave analysis, the so-called central blood pressure (central BP), has been proposed to be a predictor of future CV events, independent of brachial blood pressure (brachial BP). [3][4][5][6] The second peak of radial systolic blood pressure (SBP2) is a non-invasive surrogate marker of central BP, and this value is closely correlated with the aortic systolic BP values obtained by invasive methods in both high-and low-aortic systolic BP ranges. 7 Brachial BP is a continuous variable reflecting the CV risk state, with CV risk increasing with increasing brachial BP. 8,9 Furthermore, even in normal brachial BP ranges, low brachial BP reflects a low CV risk state. 10 However, it is not yet clear whether low SBP2 would provide a significant additive predictive value of a low CV risk state, independent of brachial BP.We have recently succeeded in measuring SBP2 in a large number of Japanese subjects undergoing health screenings. 11 This cross-sectional study was conducted to clarify whether SBP2 might provide significant information for CV risk stratification not only for high CV risk state,