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Aim: Stroke is well known to lead to hypertension; nevertheless, the role of vascular function in hypertension remains unclear. In this study, we aimed to clarify the mechanism underlying increased arterial stiffness following stroke., Methods: The cardio-ankle vascular index (CAVI) was measured in five New Zealand White rabbits. Under general anesthesia, intracranial pressure (ICP) was increased by injecting saline (15 mL) into the cisterna magna. ICP was monitored using a catheter inserted into the subarachnoid space via right frontal bone craniotomy. Blood pressure (BP), CAVI, and common carotid flow (CCF) were evaluated, and the responses of these parameters to increased ICP were analyzed., Results: Saline injection into the cisterna magna increased the ICP by over 20 mmHg. Both BP and CAVI increased from 63.2±4.84 to 128.8±14.68 mmHg and from 4.02±0.28 to 4.9±0.53, respectively. Similarly, BP and CCF increased. When hexamethonium was administered before the increase in ICP, the increase in BP (132.2±9.41 mmHg with 10 mg/kg hexamethonium vs. 105.6±11.01 mmHg with 100 mg/kg hexamethonium) and CAVI (5.02±0.64 with 10 mg/kg hexamethonium vs. 4.82±0.42 with 100 mg/kg hexamethonium) were suppressed in a dose-dependent manner., Conclusion: Increased ICP causes an increase in BP and CAVI, suggesting that enhanced stiffness of the muscular arteries contributes to high BP. Blocking the autonomic nervous system with hexamethonium suppresses the increase in BP and CAVI, indicating that these increases are mediated by activation of the autonomic nervous system.

Arterial stiffness is a good predictor of cardiovascular events. As a substitute for elastic modulus representing stiffness, pulse wave velocity (PWV) has been used for over a century as it is easy to measure; however, PWV is known to essentially depend on blood pressure at the time of measurement. The cardio-ankle vascular index (CAVI) is a relatively new index of global arterial stiffness of the origin of the aorta to the ankle arteries. The characteristic feature is its independency from blood pressure at the measuring time. Recently, a variant index CAVI 0 was proposed, which was claimed to be a more accurate arterial stiffness index than CAVI, considering independency from blood pressure. The purpose of this review is to evaluate the properties of CAVI more precisely by comparing with CAVI 0 , and to confirm the true meaning of CAVI as an index of arterial stiffness. First, the properties of PWV depending on the blood pressure and the variation of PWV values in the cardiac cycle were analyzed. Then, we attempted to clarify the point at which the PWV, adopted in CAVI or in CAVI 0 , was measured in cardiac cycle. A comprehensive comparison of the clinical data of CAVI and CAVI 0 showed that CAVI is more appropriate than CAVI 0. In conclusion, CAVI is reconfirmed to be a reliable and useful index of blood pressure-independent arterial stiffness composed of both organic and functional stiffness., Competing Interests: Koji Takahashi, Tomoyuki Yamamoto, Shinichi Tsuda and Mitsuya Maruyama are employees of Fukuda Denshi Co., Ltd., and involved in the development of CAVI. Kohji Shirai has no conflicts of interest in this work., (© 2020 Takahashi et al.)

Aim: The cardio-ankle vascular index (CAVI) represents the blood pressure-independent arterial stiffness from the origin of the aorta to the ankle. CAVI 0 has been proposed as a variant index. We aimed to clarify the difference between CAVI and CAVI 0 among large populations, and to explore reasons of the difference., Methods: The subjects were 5,293 Japanese healthy and 3,338 hypertensive people. Simple and multiple regression analyses were performed using age, sex, body mass index, systolic, and diastolic blood pressure (Pd) as variables. Sub-group analysis was performed by sex and age. The CAVI values with and without adjustment by reference pressure were also compared., Results: CAVI had a positive correlation with Pd, while CAVI 0 had a negative correlation with Pd in the healthy population. The CAVI values of the hypertensive group were higher than those of healthy group in both men and women, but the CAVI 0 values in women of the hypertensive group in the 30-39 age group was significantly lower than that of the corresponding healthy group. Differences of CAVI values with or without modification using the reference pressure were 1.09%±1.38% for the healthy group and 3.68%±1.66% for the hypertensive group., Conclusion: CAVI showed the expected values, but CAVI 0 showed inexplicable results in the healthy and hypertensive populations. The differences were due to the strong dependency of CAVI 0 on Pd. Differences of CAVI values with or without reference pressure were negligible. These results indicate that CAVI obtained by the VaSera system is appropriate, but CAVI 0 is not.

Aim: The effect of nitroglycerin on proper arterial stiffness of the arterial tree has not been fully clarified. The cardio-ankle vascular index (CAVI), which is an application of the stiffness parameter β theory on the arterial tree from the origin of the aorta to the ankle, was developed recently. Furthermore, the stiffness of the aorta (heart-thigh β (htBeta)) and of the femoral-tibial arteries (thigh to ankle β (taBeta)) could be monitored by applying the same theory. The effects of nitroglycerin on CAVI, htBeta, and taBeta were studied comparing the values of healthy people and those of arteriosclerotic patients., Methods: The subjects were healthy people (CAVI ＜7.5, n=25) and arteriosclerotic patients (CAVI ＞9, n=25). Nitroglycerin (0.3 mg) was administrated sublingually, and various arterial stiffness indices were measured at one-minute intervals for a period of 20 minutes using Vasera VS-1500 (Fukuda Denshi, Tokyo)., Results: After the administration of nitroglycerin in healthy people, CAVI decreased significantly after 5 min. [from 6.76(6.32-7.27) to 5.50(4.70-6.21), P＜0.05], and recovered after 15 min. htBeta [from 5.10(4.76-5.76) to 3.96(3.35-4.79), P＜0.05], and taBeta [from 14.41(10.80-16.33) to 10.72 (9.19-13.01), P＜0.05] also decreased significantly. In arteriosclerotic patients, CAVI decreased after 5 min. [from 10.47(9.67-11.29) to 9.71(8.74-10.57), P＜0.05] and recovered after 15 min. htBeta did not significantly change [from 12.00(11.46-13.21) to 11.81(10.14-13.83), ns], but taBeta decreased significantly [from 18.55(12.93-23.42) to 12.37(9.68-16.99), P＜0.05]., Conclusion: These results indicate that a nitroglycerin-induced decrease of arterial stiffness is more prominent in muscular arteries than in elastic arteries, and this effect was preserved much more prominently in arteriosclerotic patients than in healthy people.

Purpose: The purpose of this study was to clarify the difference between effects of nitroglycerin (NTG) on the functional stiffness in patients with and without coronary artery disease (CAD) using a newly developed stiffness index, cardio-ankle vascular index (CAVI)., Subjects and Methods: The two subject groups in this study were normal controls (n=31) and CAD patients (n=25). The normal controls had no medical history and were not on regular medications. On the other hand, the CAD patients had received various treatments like antihypertensive drugs, hypoglycemic agents, and statins. This study was conducted in CAD patients under medications. After a single sublingual administration of NTG 0.3 mg, CAVI, blood pressure (BP), and heart rate (HR) were measured every 5 minutes for 20 minutes. Comparisons of each parameter before and after taking NTG were evaluated for statistical significance using analysis of variance and post hoc tests. Tukey-Kramer test was used for post hoc comparisons., Results: In the normal controls, CAVI significantly decreased from baseline after 5, 10, and 15 minutes (from 6.5±0.9 to 5.2±0.9, 5.5±0.9, and 5.7±0.9, respectively). Systolic BP and HR were not significantly changed. Diastolic BP significantly decreased from baseline after 5 and 10 minutes (from 72±8 to 64±9 and 63±9 mmHg, respectively). On the other hand, CAVI, HR, and diastolic BP were not changed significantly in CAD patients. Systolic BP was significantly decreased from baseline after 5, 10, and 15 minutes (from 147±16 to 131±14, 129±12, and 129±13 mmHg, respectively). In the comparison of the two groups, ΔCAVI was not significantly different between the normal controls and CAD patients (-1.4±0.7 vs -1.4±0.9, -1.1±0.7 vs -1.4±1.0, -0.8±0.7 vs -1.2±1.0, and -0.5±0.7 vs -1.1±1.0 at 5, 10, 15, and 20 minutes, respectively). ΔHR was not significantly different between the two groups. ΔSystolic BP in the CAD patients was significantly higher than in the normal controls at 5, 10, 15, and 20 minutes (normal controls vs CAD; -3±7 vs -10±11, -3±5 vs -10±11, -3±6 vs -13±10, and -1±6 vs -11±10 mmHg, respectively). ΔDiastolic BP in the normal controls was significantly higher than in the CAD patients at 5 and 10 minutes (normal controls vs CAD; -8±6 vs -4±4 and -9±4 vs -6±5 mmHg, respectively)., Conclusion: After NTG administration, the stiffness of the arteries from the origin of the aorta to the ankle as measured by CAVI decreased in both the normal controls and CAD patients, indicating that the response of arterial smooth muscle cells to nitric oxide is preserved even in CAD patients under medication.

Arterial stiffness is often assessed in clinical medicine, because it is not only an important factor in the pathophysiology of blood circulation but also a marker for the diagnosis and the prognosis of cardiovascular diseases. Many parameters have so far been proposed to quantitatively represent arterial stiffness and distensibility, such as pressure-strain elastic modulus (Ep), stiffness parameter (β), pulse wave velocity (PWV), and vascular compliance (Cv). Among these, PWV has been most frequently applied to clinical medicine. However, this is dependent on blood pressure at the time of measurement, and therefore it is not appropriate as a parameter for the clinical evaluation of arterial stiffness, especially for the studies on hypertension. On the contrary, stiffness parameter β is an index reflecting arterial stiffness without the influence of blood pressure. Recently, this parameter has been applied to develop a new arterial stiffness index called cardio-ankle vascular index (CAVI). Although this index is obtained from the PWV between the heart and the ankle, it is essentially similar to the stiffness parameter β, and therefore it does not depend on blood pressure changes during the measurements. CAVI is being extensively used in clinical medicine as a measure for the evaluation of cardiovascular diseases and risk factors related to arteriosclerosis. In the present article, we will explain the theoretical background of stiffness parameter β and the process to obtain CAVI. And then, the clinical utility of CAVI will be overviewed by reference to recent studies.