Cardio-ankle vascular index may reflect endothelial function in type 2 diabetes

To the Editor: A non-invasive arterial stiffness parameter called cardio-ankle vascular index (CAVI) has been developed recently as a marker of arteriosclerosis (1). However, factors that regulate CAVI are not fully elucidated. Endothelial dysfunction is considered to be one of the most important factors in the development of atherosclerosis. In this study, we examined whether CAVI reflects endothelial dysfunction by measuring flow mediated dilatation (FMD) and serum thrombomodulin level. A total of 206 patients with type 2 diabetes were included in this study. This study was approved by the Ethics Committee of the Toho University. All patients provided written informed consent. Cardio-ankle vascular index was measured with a VaSera CAVI instrument (Fukuda Denshi Co Ltd, Tokyo, Japan) as described previously (1). FMD is a non-invasive technique to assess endothelial function. We measured FMD according to the reported guidelines (2). Body weight and blood pressure were measured in the morning after 12 h of fasting. Blood samples were collected in the morning after 12 h of fasting, and were used for measuring glycosylated haemoglobin, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and serum thrombomodulin. Data were analysed using spss 11.01.1 (Chicago, IL, USA.) statistical package for Microsoft Windows. Table 1 shows the correlation between CAVI and several clinical parameters. CAVI correlated strongly with age (R = 0.564, p < 0.01), correlated weakly with systolic blood pressure (R = 0.314, p < 0.01), correlated with serum thrombomodulin (R = 0.332, p < 0.01) and correlated with FMD (R = −0.388, p < 0.01). Multiple regression analysis was conducted to identify clinical parameters related to CAVI (Table 2). Absolute t values for age, FMD and serum thrombomodulin were greater than 2 (age; 6.350, FMD; −5.087, serum thrombomodulin; 3.212) and were therefore identified as independent factors related to CAVI. Shirai et al. (1), Nakamura et al. (3) and Kim et al. (4) reported that CAVI may be able to detect the presence of vascular disease. On the other hand, we reported that CAVI was improved by statin, ARB and glimepiride treatment (5–7). Our studies also indicated that the improvement of CAVI correlated with the reduction of malondialdehyde-modified low-density lipoprotein or 8-hydroxy-2′-deoxyguanosimne. Oxidative stress has been reported to be a cause of endothelial dysfunction (8–10). FMD were previously described as a non-invasive technique to assess endothelial function (11). Serum thrombomodulin is considered to be a biochemical marker of endothelial dysfunction (12,13). Simple linear regression analysis showed that CAVI correlated with both FMD and serum thrombomodulin. In addition, multiple regression analysis identified FMD and serum thrombomodulin as independently related to CAVI. These results indicate that CAVI may reflect endothelial function. Endothelial dysfunction is an important abnormality for atherosclerosis (14–16), especially in the early phase of the atherosclerotic process. Perticone et al. (17) concluded that endothelial dysfunction was a marker of future cardiovascular events. Therefore, if CAVI would be validated as a marker of endothelial function, it may also be a useful predictor of future cardiovascular events. Our study had several limitations. First, the sample size was relatively small. Second, endothelial function is known to be affected by many factors, especially by dietary condition. Therefore, the effects of these factors on CAVI should be studied in the future. Moreover, prospective studies are required to validate whether CAVI predicts the progression of endothelial dysfunction and systemic atherosclerosis.