Arterial stiffness is recognized mainly as an indicator of arteriosclerosis and a predictor of cardiovascular events. Cardio-ankle vascular index (CAVI), which reflects arterial stiffness from the origin of the aorta to the ankle, was developed in 2004. An important feature of this index is the independency from blood pressure at the time of measurement. A large volume of clinical evidence obtained using CAVI has been reported. CAVI is high in patients with various atherosclerotic diseases including coronary artery disease and chronic kidney disease. Most coronary risk factors increase CAVI and their improvement reduces CAVI. Many prospective studies have investigated the association between CAVI and future cardiovascular disease (CVD), and proposed CAVI of 9 as the optimal cutoff value for predicting CVD. Research also shows that CAVI reflects afterload and left ventricular diastolic dysfunction in patients with heart failure. Furthermore, relatively acute changes in CAVI are observed under various pathophysiological conditions including mental stress, septic shock and congestive heart failure, and in pharmacological studies. CAVI seems to reflect not only structural stiffness but also functional stiffness involved in acute vascular functions. In 2016, Spronck and colleagues proposed a variant index CAVI0, and claimed that CAVI0 was truly independent of blood pressure while CAVI was not. This argument was settled, and the independence of CAVI from blood pressure was reaffirmed. In this review, we summarize the recently accumulated evidence of CAVI, focusing on the proposed cutoff values for CVD events, and suggest the development of new horizons of vascular function index using CAVI. appropriate in studies that examine the effect of hypertension or the effect of antihypertensive drugs on intrinsic arterial stiffness. To overcome this problem, Hayashi 4) proposed the stiffness parameter , an index reflecting arterial stiffness of local arterial segment, which is not influenced by blood pressure at the time of measurement. Subsequently, this theory has been applied to a new arterial stiffness index called cardio-ankle vascular index (CAVI) developed in 2004 5) , and this index reflects the stiffness of the arterial tree from the origin of the aorta to the ankle. The CAVI equation was essentially derived from the stiffness parameter , and the changes of the artery caliber in the equation during the cardiac cycle were obtained Copyright©2020 Japan Atherosclerosis Society This article is distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License.

After hepatitis virus infection, plasma transforming growth factor (TGF)-β increases in either the acute or chronic inflammatory microenvironment. Although TGF-β is upregulated in patients with hepatocellular carcinoma, it is one of the most potent growth inhibitors for hepatocytes. This cytokine also upregulates extracellular matrix (ECM) production of hepatic stellate cells. Therefore, TGF-β is considered to be the major factor regulating liver carcinogenesis and accelerating liver fibrosis. Smad2 and Smad3 act as the intracellular mediators of TGF-β signal transduction pathway. We have generated numerous antibodies against individual phosphorylation sites in Smad2/3, and identified 3 types of phosphorylated forms (phospho-isoforms): COOH-terminally phosphorylated Smad2/3 (pSmad2C and pSmad3C), linker phosphorylated Smad2/3 (pSmad2L and pSmad3L) and dually phosphorylated Smad2/3 (pSmad2L/C and pSmad3L/C). These Smad phospho-isoforms are categorized into 3 groups: cytostatic pSmad3C signaling, mitogenic pSmad3L signaling and invasive/fibrogenic pSmad2L/C signaling. In this review, we describe differential regulation of TGF-β/Smad signaling after acute or chronic liver injuries. In addition, we consider how chronic inflammation associated with hepatitis virus infection promotes hepatic fibrosis and carcinogenesis (fibro-carcinogenesis), focusing on alteration of Smad phospho-isoform signaling. Finally, we show reversibility of Smad phospho-isoform signaling after therapy against hepatitis virus infection.

Measurement of arterial stiffness in routine medical practice is important to assess the progression of arteriosclerosis. So far, many parameters have been proposed to quantitatively represent arterial stiffness. Among these, pulse wave velocity (PWV) has been most frequently applied to clinical medicine because those could be measured simply and non-invasively. PWV had established the usefulness of measuring arterial wall stiffness. However, PWV essentially depends on blood pressure at the time of measurement. Therefore, PWV is not appropriate as a parameter for the evaluation of arterial stiffness, particularly for the studies involving blood pressure changes.On the other hand, stiffness parameter 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). Therefore, CAVI does not depend on blood pressure changes during the measurements; CAVI could represent the stiffness of the arterial tree from the origin of the aorta to the ankle.Many clinical studies obtained from CAVI are being accumulated. CAVI showed high value in arteriosclerotic diseases, such as coronary artery diseases, cerebral infarction, and chronic kidney diseases, and also in majority of people with various coronary risk factors. The improvement of those risk factors decreased CAVI. Furthermore, the role of CAVI as a predictor of cardio-vascular events was reported recently.We review the clinical studies on CAVI and discuss the clinical usefulness of CAVI as a candidate surrogate end-point marker for cardiovascular disease.

Aim:The three types of calcium channel blocker (CCB), L-, T-and N-type, possess heterogeneous actions on endothelial function and renal microvascular function. In the present study, we evaluated the effects of two CCBs, efonidipine and amlodipine, on renal function and arterial stiffness. Methods: Forty type 2 diabetic patients with hypertension and nephropathy receiving angiotensin receptor blockers were enrolled and randomly divided into two groups: the efonidipine group was administered efonidipine hydrochloride ethanolate 40 mg/day and the amlodipine group was administered amlodipine besilate 5 mg/day for 12 months. Arterial stiffness was evaluated by the cardioankle vascular index (CAVI). Results: Changes in blood pressure during the study were almost the same in the two groups. Significant increases in serum creatinine and urinary albumin and a significant decrease in the estimated glomerular filtration rate were observed in the amlodipine group, but not in the efonidipine group. On the other hand, significant decreases in plasma aldosterone, urinary 8-hydroxy-2'-deoxyguanosine and CAVI were observed after 12 months in the efonidipine group, but not in the amlodipine group. Conclusions: These results suggest that efonidipine, which is both a T-type and L-type calcium channel blocker, has more favorable effects on renal function, oxidative stress and arterial stiffness than amlodipine, an L-type calcium channel blocker. J Atheroscler

Aim: A novel device has been developed for measuring the cardio-ankle vascular index (CAVI) as an indicator of arterial stiffness. In this study, we evaluated the effect of pitavastatin on CAVI in type 2 diabetic patients. Methods: Forty-five type 2 diabetes mellitus patients with low-density lipoprotein cholesterolemia were enrolled and treated with pitavastatin 2 mg/day for 12 months. Before and after pitavastatin administration, HbA1c, serum lipids, serum malondialdehyde-LDL (MDA-LDL), urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and CAVI were measured.