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 cut-off 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 cut-off values for CVD events, and suggest the development of new horizons of vascular function index using CAVI.
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 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). 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.
Resveratrol has been reported to have potent anti-atherosclerotic effects in animal studies. However, there are few interventional studies in human patients with atherosclerogenic diseases. The ...cardio-ankle vascular index (CAVI) reflects arterial stiffness and is a clinical surrogate marker of atherosclerosis. The aim of the present study was to investigate the effect of resveratrol on arterial stiffness assessed by CAVI in patients with type 2 diabetes mellitus (T2DM).In this double-blind, randomized, placebo-controlled study, 50 patients with T2DM received supplement of a 100mg resveratrol tablet (total resveratrol: oligo-stilbene 27.97 mg/100 mg/day) or placebo daily for 12 weeks. CAVI was assessed at baseline and the end of study. Body weight (BW), blood pressure (BP), glucose and lipid metabolic parameters, and diacron-reactive oxygen metabolites (d-ROMs; an oxidative stress marker) were also measured.Resveratrol supplementation decreased systolic BP (-5.5 ± 13.0 mmHg), d-ROMs (-25.6 ± 41.8 U.CARR), and CAVI (-0.4 ± 0.7) significantly (P < 0.05) and decreased BW (-0.8 ± 2.1 kg, P = 0.083) and body mass index (-0.5 ± 0.8 kg/m2, P = 0.092) slightly compared to baseline, while there were no significant changes in the placebo group. Decreases in CAVI and d-ROMs were significantly greater in the resveratrol group than in the placebo group. Multivariate logistic regression analysis identified resveratrol supplementation as an independent predictor for a CAVI decrease of more than 0.5.In conclusion, 12-week resveratrol supplementation may improve arterial stiffness and reduce oxidative stress in patients with T2DM. Resveratrol may be beneficial in preventing the development of atherosclerosis induced by diabetes. However, a large-scale cohort study is required to validate the present findings.
Abdominal obesity as a risk factor for diagnosing metabolic syndrome (MetS) is conventionally evaluated using waist circumference (WC), although WC does not necessarily reflect visceral adiposity.
To ...examine whether replacing WC with "A Body Shape Index (ABSI)", an abdominal obesity index calculated by dividing WC by an allometric regression of weight and height, in MetS diagnosis is useful for predicting renal function decline.
In total, 5438 Japanese urban residents (median age 48 years) who participated in a public health screening program for 4 consecutive years were enrolled. Systemic arterial stiffness was assessed by cardio-ankle vascular index (CAVI). The predictability of the new-onset renal function decline (eGFR < 60 mL/min/1.73 m
) by replacing high WC with high ABSI (ABSI ≥ 0.080) was examined using three sets of MetS diagnostic criteria: Japanese, IDF and NCEP-ATPIII.
In Japanese and NCEP-ATPIII criteria, MetS diagnosed using ABSI (ABSI-MetS) was associated with significantly higher age-adjusted CAVI compared to non-MetS, whereas MetS diagnosed using WC (WC-MetS) showed no association. Kaplan-Meier analysis of the rate of new-onset renal function decline over 4 years (total 8.7%) showed remarkable higher rate in subjects with ABSI-MetS than in those without (log-rank test p < 0.001), but almost no difference between subjects with and without WC-MetS (p = 0.014-0.617). In gender-specific Cox-proportional hazards analyses including age, proteinuria, and treatments of metabolic disorders as confounders, ABSI-MetS (Japanese criteria for both sexes, IDF criteria for men) contributed independently to the new-onset renal function decline. Of these, the contribution of IDF ABSI-MetS disappeared after adjustment by high CAVI in the subsequent analysis.
In this study, replacing WC with ABSI in MetS diagnostic criteria more efficiently predicted subjects at risk of renal function decline and arterial stiffening.
This study aimed to investigate the association of cardio-ankle vascular index (CAVI), an arterial stiffness parameter, with four blood pressure (BP) indices, systolic BP (SBP), diastolic BP (DBP), ...pulse pressure (PP) and mean BP (MBP), in real-world population including untreated hypertension. We analyzed the cross-sectional data from 23,257 Japanese subjects (12,729 men and 10,528 women, aged 47.1 years) without a past history of cardiovascular disease, stroke, hypertension, diabetes or dyslipidemia. Gender differences in four BP indices were slight, but significant for SBP, DBP and MBP. All four BP indices increased linearly with age. After adjusting for confounders comprising gender, age, HDL-C and BMI identified by multiple regression analysis, CAVI was lower in normotensive subjects compared to hypertensive subjects. Trend test detected an almost linear relation of adjusted CAVI with each of four BP indices even within ideal range. Exceptionally, the increment in adjusted CAVI reached its peak over 140 mm Hg range in SBP. Logistic regression models showed that 1-SD increment in each BP index contributed independently to high CAVI (≥90th percentile), whereas that in PP showed a somewhat lower contribution. Subgroup analyses revealed that older age, dyslipidemia and hypertension were independently associated with relatively small contributions to high CAVI per 1-SD increment in SBP. PP might be less useful to assess arterial stiffness compared to other BP indices. Besides, the contribution of SBP increment to arterial stiffening was relatively large in normotensive, normolipidemic non-elderly subjects, whose individual transition of SBP should be noticed.
Aim: To investigate the associations of conventional lipid parameters with arterial stiffness assessed by cardio–ankle vascular index (CAVI).Methods: A retrospective cross-sectional study was ...conducted in 23,257 healthy Japanese subjects (12,729 men and 10,528 women, aged 47.1±12.5 years, body mass index (BMI) 22.9±3.4 kg/m2) who underwent health screening between 2004 and 2006 in Japan.Results: Male subjects had significantly higher BMI, CAVI and triglycerides (TG), and lower high-density lipoprotein cholesterol (HDL-C) compared to female subjects. After adjusting for confounders, including gender, age, systolic blood pressure and BMI identified by multiple regression analysis, adjusted CAVI was lower in normolipidemic than in dyslipidemic subjects. Among dyslipidemic subjects, those with hypertriglyceridemia had higher adjusted CAVI. A trend test detected linear relations between adjusted CAVI and all the conventional lipid parameters throughout the entire range of serum levels. After adjusting for confounders, logistic regression models showed that all lipid parameters contributed independently to high CAVI (≥90th percentile). Receiver–operating–characteristic analysis determined reliable cut-off values of 93 mg/dl for TG (area under the curve, AUC= 0.735), 114 mg/dl for low-density lipoprotein cholesterol (AUC=0.614) and 63 mg/dl for HDL-C (AUC=0.728) in predicting high CAVI. These cut-off values were confirmed to independently predict high CAVI in a bivariate logistic regression model.Conclusion: The present study demonstrated independent contribution of conventional lipid parameters to CAVI, indicating a possible association of lipid parameters with early vascular damage.
Aim: We investigated whether cardio-ankle vascular index (CAVI), an arterial stiffness marker, independently predicts future cardiovascular events in subjects with metabolic disorders. Methods: 1562 ...outpatients underwent CAVI between April 2004 and March 2006 at Toho University, Sakura Medical Center in Chiba, Japan. Patients who already had cardiovascular events at baseline, patients with low ankle brachial index (＜0.9), and patients with atrial fibrillation were excluded. After exclusion, 1080 subjects with metabolic disorders including diabetes mellitus, hypertension and dyslipidemia were screened and followed prospectively. Results: Eventually, 1003 subjects (92.9% of 1,080 subjects) followed until March 2012 (follow-up duration 6.7±1.6 years) were analyzed. During the observation period, 90 subjects had new-onset myocardial infarction or angina pectoris confirmed by angiography. All subjects were stratified into quartiles by baseline CAVI (Q1: CAVI ≤8.27, Q2: CAVI 8.28-9.19, Q3: CAVI 9.20-10.08, Q4: CAVI ≥10.09). Age, male ratio and future cardiovascular events increased as CAVI quartile became higher. In Cox proportional hazards regression analysis, the factors independently associated with higher risk of future cardiovascular events were every 1.0 increment of CAVI hazard ratio (HR) 1.126, p= 0.039, male gender (HR 2.276, p=0.001), smoking (HR 1.846, p=0.007), diabetes mellitus (HR 1.702,p=0.020), and hypertension (HR 1.682, p=0.023). Conclusion: In individuals with metabolic disorders, CAVI was a predictor of future cardiovascular events, independent of traditional coronary risk factors. CAVI is a potentially valuable tool to identify persons likely to benefit from more intensive therapeutic approaches.
Aim: To clarify the mechanism by which pitavastatin reduced cardiovascular (CV) events more effectively than atorvastatin in the TOHO Lipid Intervention Trial Using Pitavastatin (TOHO-LIP), the ...changes in (Δ) non-heparinized serum level of lipoprotein lipase mass (LPL mass) during administration of the respective statins were investigated. Methods: From TOHO-LIP data, 223 hypercholesterolemic patients with any CV risks followed at Toho University Sakura Medical Center were analyzed. The patients were randomized to pitavastatin (2 mg/day) group (n=107) or atorvastatin (10 mg/day) group (n=116), and followed for 240 weeks. In this subgroup study, the primary and secondary end points were the same as those in TOHO-LIP, and 3-point major adverse cardiovascular events (3P-MACE) was added. The relationship between ΔLPL mass during the first year and the incidences of each end point was analyzed. Results: The lipid-lowering effect was not different between the two statins. Cumulative 240-week incidence of each end point was significantly lower in pitavastatin group (primary: 1.9% vs. 10.3%, secondary: 4.7% vs. 18.1%, 3P-MACE: 0.9% vs. 6.9%). Mean LPL mass (64.9 to 69.0 ng/mL) and eGFR (70.1 to 73.6 ml/min/1.73m 2) increased in pitavastatin group, but not in atorvastatin group during the first year. Cox proportional-hazards model revealed that ΔLPL mass (1 ng/mL or 1SD) contributed to almost all end points. Conclusions: Pitavastatin administration reduced CV events more efficaciously than atorvastatin despite similar LDL cholesterol-lowering effect of the two statins. Increased LPL mass during the first year by pitavastatin treatment may be associated with this efficacy.
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