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Collectively, these results indicate that cfPWV and baPWV are indices of arterial stiffness that exhibit similar extent of associations with cardiovascular disease risk factors and clinical events.

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A rterial stiffness is well-recognized as an important predictor of development of cardiovascular disease (CVD), 1,2 and meta-analyses of prospective cohort studies have revealed that increase in the carotid-femoral pulse wave velocity (cfPWV) is associated with an increase in the risk of development of CVD. 3,4 However, the cfPWV is measured by tonometry or Doppler, which requires specialized training and exposure of the inguinal region. 5,6Abstract-An individual participant data meta-analysis was conducted in the data of 14 673 Japanese participants without a history of cardiovascular disease (CVD) to examine the association of the brachial-ankle pulse wave velocity (baPWV) with the risk of development of CVD. During the average 6.4-year follow-up period, 687 participants died and 735 developed cardiovascular events. A higher baPWV was significantly associated with a higher risk of CVD, even after adjustments for conventional risk factors (P for trend <0.001). When the baPWV values were classified into quintiles, the multivariableadjusted hazard ratio for CVD increased significantly as the baPWV quintile increased. The hazard ratio in the subjects with baPWV values in quintile 5 versus that in those with the values in quintile 1 was 3.50 (2.14-5.74; P<0.001). Correspondence to Hirofumi Tomiyama, Department of Cardiology, Tokyo Medical University, 6-7-1 Nishi-Shinjuku, Tokyo, Japan. E-mail tomiyama@ tokyo-med.ac.jp In the early 2000s, a simple device for measurement of the brachial-ankle pulse wave velocity (baPWV) was launched for clinical use. Brachial-Ankle Pulse Wave Velocity and the Risk Prediction of Cardiovascular Disease An Individual Participant Data Meta-Analysis7 baPWV is automatically measured using a separate cuff for each of the 4 limbs by an oscillometric method. baPWV may be more easily applied in clinical practice than the cfPWV because of the simplicity and ease of its measurement.7,8 baPWV has been reported to be closely correlated with the directly measured aortic PWV and cfPWV. 9 A recent meta-analysis using summary data from the literature has demonstrated that higher levels of baPWV were associated with an increased risk of development of CVD.10 However, most of the studies included in the meta-analyses were conducted in patients with a high CVD risk (patients with CVD or end-stage renal disease), and thus, the usefulness of baPWV to assess the risk of development of CVD in subjects with a low to intermediate CVD risk as assessed using the Framingham risk score (FRS) had not been clearly elucidated. Furthermore, these studies did not determine the predictive ability for CVD over that of the traditional risk factors. Therefore, we conducted a meta-analysis using individual participant data (IPD) from prospective cohort studies to clarify whether baPWV could be used as an independent marker to predict the risk of development of CVD in subjects without preexisting CVD. Methods Study PopulationJ-BAVEL (Japan Brachial-Ankle Pulse Wave Velocity Individual Participant Data Meta-Analysis of Pros...

Objectives-Advanced glycation endproducts, AGEs, and its specific receptor, RAGE, are involved in diabetic vascular complications. Endogenous secretory RAGE, esRAGE, has been identified as an alternatively spliced form of RAGE, and shown to act as a decoy receptor for AGE. Here, we measured plasma esRAGE level with a recently developed enzyme-linked immunosorbent assay (ELISA) and examined its association with atherosclerosis in age-and gender-matched 203 type 2 diabetic and 134 nondiabetic subjects. Methods and Results-Plasma esRAGE was inversely associated with carotid or femoral atherosclerosis, as quantitatively measured as intimal-medial thickness (IMT) by arterial ultrasound. Stepwise regression analyses revealed that plasma esRAGE was the third strongest and independent factor associated with carotid IMT, following age and systolic blood pressure. Plasma esRAGE was significantly lower in diabetic patients (0.176Ϯ0.092 ng/mL) than nondiabetic controls (0.253Ϯ0.111). Of note, in all, diabetic or nondiabetic group, plasma esRAGE was significantly and inversely correlated with components of the metabolic syndrome including body mass index, blood pressure, triglyceride, HbA1c, or an insulin resistance index. Stepwise regression analyses showed that body mass index or insulin resistance index was the major factor determining plasma esRAGE in all, nondiabetic or diabetic population. Conclusions-esRAGE is a novel and potential protective factor for the metabolic syndrome and atherosclerosis. Key Words: pathophysiology Ⅲ risk factors Ⅲ type 2 diabetes U nder hyperglycemic conditions, endogenous nonenzymatic glycoxidation of proteins and lipids leads to the formation of heterogeneous products, collectively termed advanced glycation end products (AGEs). 1 AGE engagement of cell surface the receptor for AGE (RAGE) results in cellular signaling including activation of nuclear factor-B, increased expression of cytokines and adhesion molecules, and induction of oxidative stress. 2,3 Transgenic mice overexpressing human RAGE in vascular cells developed advanced nephropathy when they were made diabetic. 4 Thus, the AGE-RAGE system has been thought to play a pivotal role in the development of diabetic microvascular complications.Accumulating evidence suggests that RAGE is also involved in macrovascular complications in diabetes. 5,6 RAGE expression is shown to be upregulated in atherosclerotic plaques of diabetic animals. 7 Some of the human studies also implicate the involvement of RAGE in diabetic vasculopathy. 8,9 Moreover, the group of Stern and Schmidt has shown that augmentation of atherosclerosis in diabetic mice is inhibited by the competition of RAGE with its soluble truncated form termed soluble RAGE (sRAGE), lacking the transmembrane and cytoplasmic domains, produced by recombinant gene engineering. 7,10 Recently, an endogenous secretory RAGE (esRAGE) has been identified as a novel splice variant that directs the synthesis of RAGE proteins carrying all of the extracellular domains but devoid of the transmembrane...