Comparison of Cardio-Ankle Vascular Index (CAVI) and CAVI0 in Large Healthy and Hypertensive Populations.

AIM: The cardio-ankle vascular index (CAVI) represents the blood pressure-independent arterial stiffness from the origin of the aorta to the ankle. CAVI0 has been proposed as a variant index. We aimed to clarify the difference between CAVI and CAVI0 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 CAVI0 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 CAVI0 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 CAVI0 showed inexplicable results in the healthy and hypertensive populations. The differences were due to the strong dependency of CAVI0 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 CAVI0 is not.

Coefficients in the CAVI Equation and the Comparison Between CAVI With and Without the Coefficients Using Clinical Data.

AIM: The Cardio-Ankle Vascular Index (CAVI) is a stiffness index of the arterial tree from the origin of the aorta to the ankle, independent of blood pressure at the time of measurement. The CAVI equation includes the coefficients "a" and "b" to adjust it to the value of Hasegawa's pulse wave velocity, which is compensated for at 80 mmHg of diastolic pressure. To verify this adjustment with the coefficients, the clinical significance of CAVI and CAVI without the coefficients (haß) were compared in both an epidemiological study and an acute clinical study. METHODS: In the epidemiological study, the significances of CAVI and haß among people with or without coronary risks such as hypertension, dyslipidemia, hyperglycemia, and abnormal electrocardiography change, were compared. In the acute clinical study, nitroglycerin was administered to subjects in a control group and to coronary artery disease patients, observing CAVI and haß values over a 20-min period. RESULTS: There was no discrepancy in terms of statistically significant differences between CAVI and haß among subjects with or without risk factors. Furthermore, there was also no discrepancy in terms of statistically significant differences between CAVI and haß during the changes of those values following nitroglycerin administration over a 20-min period. CONCLUSION: In both the epidemiologic and clinical studies, there was no discrepancy in terms of significant differences between CAVI and haß. These results suggest that both are valid as indices of stiffness of the arterial tree from the origin of the aorta to the ankle.

Awareness of the Japanese Society of Hypertension Guidelines for the Management of Hypertension and their use in clinical practices: 2009 survey results.

The objective of this study was to investigate physicians' awareness and use of the Japanese Society of Hypertension (JSH) Guidelines for the Management of Hypertension (JSH2004 and JSH2009), and determine what changes need to be implemented in the future. A questionnaire was used to survey physicians' awareness and their use of JSH2004 and JSH2009. Physicians attending educational seminars on hypertension that were held during the months after the publication of JSH2009 (January-April 2009) were asked to participate in the survey. Of the 5795 respondents, 88% were aware of the JSH2009 publication. Furthermore, physicians were also aware of JSH2004, with about 90% using JSH2004 in their practice. A hypertension blood pressure (BP) reference value of 140/90 mm Hg was used by 55% in office BP, whereas 31% used 135/85 mm Hg for home BP. Target BP levels used by physicians were 130/80 mm Hg for patients with diabetes or kidney disease (52%) and for elderly patients with diabetes or kidney disease (45%), whereas 140/90 mm Hg was used for elderly patients with low cardiovascular disease risk (44%) and for patients with chronic-phase stroke (27%). Answers to the questionnaire varied among physicians according to sex, age, workplace and specialty. The majority of the participating Japanese physicians were familiar with both JSH2004 and JSH2009, with many following the guidelines in their practice. However, some physicians use different reference values for hypertension and target BP levels. Physicians' adherence to and use of the guidelines should be regularly examined and promoted.

[Cardio-ankle vascular index (CAVI) and cardiovascular disease].

Increased arterial stiffness is closely associated with the progression of cardiovascular disease. A novel blood-pressure independent arterial stiffness parameter, the cardio-ankle vascular index (CAVI), has been developed and is used worldwide. Arterial stiffness derived using CAVI in healthy subjects increases linearly with aging, and is higher in men than in women. This is a new finding, not observed with conventional arterial stiffness indicators. In patients with risk factors such as hypertension, diabetes, hypercholesterolemia, left ventricular hypertrophy, chronic kidney disease and hyperuricemia, CAVI values are higher than in controls. Antihypertensive, antidiabetic, and antilipemic medications are effective in lowering elevated CAVI. Among the antiplatelet agents, highly purified eicosapentaenoic acid (EPA) in fish oil has the effect of lowering CAVI. It is also useful in the evaluation of the effects of lifestyle modification. It has been shown that CAVI values are elevated even with mild arteriosclerotic disease, and differences in the degree of arteriosclerosis can be estimated between patients with severe arteriosclerotic disease, for example those with ischemic cardiac disease and dialysis patients. In coronary artery disease, CAVI reflect the severity of the diseased coronary artery and latent plaque in coronary arteries using intravascular ultrasound imaging(IVUS). It is also reported that patients with higher CAVI values have a poor prognosis compared with those with lower CAVI values. Its advantage of reproducibility, with little disparity among institutions, has opened up the way for multi-center joint studies.

Cardio-ankle vascular index (CAVI) as a novel indicator of arterial stiffness: theory, evidence and perspectives.

The cardio-ankle vascular index (CAVI) is a new index of the overall stiffness of the artery from the origin of the aorta to the ankle. The most conspicuous feature of CAVI is its independence of blood pressure at the time of measurement.CAVI increases with age and in many arteriosclerotic diseases, such as coronary artery disease, carotid arteriosclerosis, chronic kidney disease and cerebrovascular disease, and is related to many coronary risk factors, such as hypertension, diabetes mellitus, dyslipidemia and smoking. Furthermore, CAVI decreases by controlling diabetes mellitus and hypertension, and also by abstaining from smoking. This suggests that CAVI is a physiological surrogate marker of athero- or arteriosclerosis, and also might be an indicator of lifestyle modification.Recently, it has been reported that CAVI and several left ventricular functions are co-related, suggesting a connection between the heart muscle and vascular function.This review covers the principles of CAVI and our current knowledge about CAVI, focusing on its roles and future outlook.

Fasudil attenuates myocardial fibrosis in association with inhibition of monocyte/macrophage infiltration in the heart of DOCA/salt hypertensive rats.

OBJECTIVE: To determine the effects of fasudil, a Rho-kinase inhibitor, on mineralocorticoid-induced myocardial remodeling, we investigated whether fasudil would suppress myocardial fibrosis and inflammation in deoxycorticosterone-acetate (DOCA)/salt hypertensive rats. METHODS: Sprague-Dawley rats treated with DOCA combined with 1% NaCl and 0.2% KCl in the drinking water after receiving left nephrectomy were given fasudil (10 mg/kg/day; n = 20) or vehicle (n = 20). Systolic blood pressure (SBP) was measured biweekly. Myocardial monocyte/macrophage infiltration and myocardial fibrosis were determined histologically. Expressions of mRNA of procollagen I (PI), procollagen III (PIII), monocyte chemoattractant protein (MCP)-1, interleukin (IL)-6, type-1 plasminogen activator inhibitor (PAI-1), transforming growth factor (TGF)-beta1, and c-fos were determined. RESULTS: SBP was significantly increased on day 14 after treatment with DOCA/salt. Extent of interstitial and perivascular fibrosis was significantly increased on day 28. Expressions of mRNA of PI, PIII, MCP-1, IL-6, PAI-1, TGF-beta1, and c-fos were significantly increased on day 14. Although SBP did not differ between the fasudil and vehicle groups, extent of monocyte/macrophage infiltration and fibrosis was attenuated in the fasudil group. Expressions of mRNA of these factors except TGF-beta1 were also attenuated. CONCLUSION: Fasudil attenuates myocardial fibrosis possibly via suppression of monocyte/macrophage infiltration of the heart in DOCA/salt hypertensive rats.

A novel blood pressure-independent arterial wall stiffness parameter; cardio-ankle vascular index (CAVI).

To measure the stiffness of the aorta, femoral artery and tibial artery noninvasively, cardio-ankle vascular index (CAVI) which is independent of blood pressure was developed. The formula for measuring this index is; CAVI=a{(2rho/DeltaP) x ln(Ps/Pd)PWV(2)} + b where, Ps and Pd are systolic and diastolic blood pressures respectively, PWV is pulse wave velocity between the heart and ankle, DeltaP is Ps - Pd, rho is blood density, and a and b are constants. This equation was derived from Bramwell-Hill's equation(1)), and stiffness parameter(2)). To elucidate the clinical utility of CAVI, the reproducibility and dependence on blood pressure were studied using VaSera (Fukuda Denshi Co., Ltd.). Furthermore, CAVI in hemodialysis patients with or without atherosclerotic diseases was measured. The average coefficient of variation for five measurements among 22 persons was 3.8%. In hemodialysis patients (n = 482), CAVI was correlated weakly with systolic and diastolic blood pressures (R = 0.175, 0.006), while brachial-ankle PWV was correlated strongly with systolic and diastolic blood pressures (R = 0.463, 0.335). CAVI in hemodialysis patients without signs of atherosclerotic diseases (NA) was 8.1 +/- 0.3 (mean +/- SD). That in patients receiving percutaneous transluminal coronary angioplasty was 8.8 +/- 0.3 (p < 0.05 vs. NA). CAVI in patients with ischemic change in their electrocardiogram (ECG) was 8.5 +/- 0.3 (p < 0.05 vs. NA). That in patients with diabetes mellitus was 8.5 +/- 0.3 (p < 0.002 vs. NA). CAVI in the patients with all three complications was 8.9 +/- 0.35 (p < 0.001 vs. NA). These results suggested that CAVI could reflect arteriosclerosis of the aorta, femoral artery and tibial artery quantitatively.

Effects of uninephrectomy on renal structural properties in spontaneously hypertensive rats.

1. To investigate effects of a reduction in nephron numbers on renal structural properties in hypertension, either unilateral nephrectomy (UNX) or sham operation (SO) was performed at 5 weeks of age in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats (n = 9 for each operation for each strain). 2. At 10-12 weeks of age, flow-pressure (F-P) and pressure-glomerular filtration rate (P-GFR) relationships were determined for maximally vasodilated, perfused kidneys. Kidneys were then perfusion fixed for histological analysis. 3. In the SO groups, the slope of F-P (minimal renal vascular resistance, reflecting overall luminal dimensions of pre- and post-glomerular vasculature) was greater in SHR than in WKY rats. The threshold pressure for beginning filtration at P-GFR (preglomerular to post-glomerular vascular resistance ratio) was higher in SHR than in WKY rats, but the slope of P-GFR (glomerular filtration capacity) did not differ between the two strains. These results suggest that vascular narrowing occurred, especially in the preglomerular resistance vessels in the kidneys of SHR, although glomerular filtration capacity was normal. 4. In UNX animals, the following results were obtained: (i) the slope of F-P was not affected in either strain; (ii) the pressure for beginning filtration at P-GFR was unchanged in WKY rats, but was decreased in SHR; (iii) the slope of P-GFR increased in WKY rats, but a compensatory adaptive increase was missing in SHR; and (iv) histologically, small increases in the luminal cross-sectional area of interlobular arteries and glomerular tuft area were observed in both strains. However, the increase in vascular lumen was more pronounced in SHR, whereas glomerular enlargement was greater in WKY rats. 5. These results suggested that UNX attenuates vascular narrowing of the preglomerular resistance vessels and glomerular structural adaptations to UNX (i.e. increased filtering capacity and glomerular enlargement) are impaired in SHR.

Tranilast attenuates myocardial fibrosis in association with suppression of monocyte/macrophage infiltration in DOCA/salt hypertensive rats.

OBJECTIVE: In order to study the association between myocardial fibrosis and inflammatory cell infiltration in the hypertensive heart, we investigated whether N(3,4-dimethoxycinnamoyl) anthranilic acid (tranilast), an anti-inflammatory drug, would suppress myocardial fibrosis via inhibition of inflammatory cell infiltration in deoxycorticosterone-acetate (DOCA) hypertensive rats. METHODS: Sprague-Dawley rats treated with DOCA combined with the addition of 1% NaCl and 0.2% KCl in the drinking water after left nephrectomy were given tranilast (100 mg/kg per day, n = 15) or vehicle (n = 15) for up to 4 weeks. Systolic blood pressure (SBP), amount of myocardial interstitial fibrosis, perivascular fibrosis and type I and III collagen, and mRNA expression of procollagen I (PI) and procollagen III (PIII), transforming growth factor (TGF)-beta1, type-1 plasminogen activator inhibitor (PAI-1), monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-6 were determined. RESULTS: SBP was increased significantly 2 weeks after treatment with DOCA and salt. Myocardial interstitial fibrosis, perivascular fibrosis and collagen accumulation increased significantly 4 weeks after the treatment. Two weeks after the treatment with DOCA and salt, mRNA expression of PI and PIII, TGF-beta1, PAI-1, MCP-1 and IL-6 increased significantly. Although the SBP was similar in animals treated with tranilast or vehicle, monocyte/macrophage infiltration was suppressed, mRNA expression of TGF-beta1, PAI-1, MCP-1, IL-6, PI and PIII was attenuated, and myocardial fibrosis and collagen accumulation were suppressed in hypertensive animals receiving tranilast. CONCLUSION: Myocardial fibrosis seen in DOCA/salt hypertensive rats might be associated with the inflammation/wound healing response. Tranilast suppresses both infiltration of monocytes/macrophages and myocardial fibrosis.

Angiotensin-converting enzyme-gene polymorphism is associated with collagen I synthesis and QT dispersion in essential hypertension.

AIM: This study tested the hypothesis that abnormal QT dispersion, an indicator of arrhythmogenic risk, is associated with angiotensin-converting enzyme (ACE) gene polymorphism and abnormalities of collagen metabolism. METHODS: A total of 132 patients with untreated essential hypertension (EHT) were recruited. QT dispersion corrected by heart rate (QTc) on a 12-lead electrocardiogram, ACE genotype, left ventricular mass index (LVMI) and E/A ratio using echocardiogram, plasma ACE activity and serum propeptide type I C-terminal procollagen (PICP) concentration, a marker of myocardial fibrosis, were determined. A normal control group (NC) of 200 normotensive subjects was used for comparison of QT dispersion. RESULTS: Number of EHT patients with ACE genotype I/I, I/D and D/D was 61, 52 and 19, respectively. LVMI and E/A ratio were similar in the three groups. Compared with subjects with I/I or I/D genotype, subjects with D/D showed higher plasma ACE activity (I/I: 13 +/- 0.6, I/D: 17 +/- 0.9, and D/D: 21 +/- 1.1 nmol/min per ml, mean +/- SE, P05) and serum PICP concentration (I/I: 106 +/- 5.4, I/D: 106 +/- 4.9, D/D: 140 +/- 12.1 ng/ml, P < 0.01). QTc dispersion was larger in the three hypertensive subgroups than in NC, and was the largest in EHT with D/D (NC: 0.037 +/- 0.001, I/I: 0.056 +/- 0.003, I/D: 0.055 +/- 0.002, D/D: 0.069 +/- 0.004 s, P < 0.05). CONCLUSION: ACE D/D genotype could be associated with an elevation of serum PICP concentration possibly leading to myocardial fibrosis and increased QT dispersion.

Relation of circulating blood volume to left ventricular geometry in essential hypertension.

To investigate whether circulating blood volume contributes to left ventricular (LV) geometry, 60 outpatients with untreated, mild to moderate essential hypertension and 45 normotensives were studied. Based on echocardiographic LV mass index and relative wall thickness, four patterns of LV geometry, i.e., normal left ventricle, concentric remodeling, eccentric hypertrophy and concentric hypertrophy, were identified. Plasma volume and blood volume were measured by the 131I labeled human serum albumin technique. LV end-diastolic volume was greater in patients with eccentric hypertrophy than in the groups of patients with normal left ventricles, concentric remodeling, or concentric hypertrophy or in normotensive subjects. No differences were found in systolic function among the five groups. Both plasma volume and blood volume were decreased in the concentric remodeling group as compared with the other four groups. However, there were no differences in plasma volume or blood volume among the normal left ventricle, eccentric hypertrophy and concentric hypertrophy groups. These data indicate that a small LV chamber in cases of "concentric remodeling" may be related to decreased plasma and blood volumes, but an enlarged LV chamber in cases of "eccentric hypertrophy" is not likely to be related to either plasma or blood volume levels in mild to moderate untreated essential hypertension.

Effects of leukocytosis and macrophage activation on anti-Thy 1.1 glomerulonephritis in the rat.

OBJECTIVE: In anti-Thy 1.1 proliferative glomerulonephritis (GN), glomerular infiltration of polymorphonuclear leukocytes (PMNs) reaches a peak level after 1 h and that of macrophages does so 24 h after induction. However, the roles of PMNs and macrophages in the pathogenesis of anti-Thy 1.1 GN remain unclear. We examined the effects on this model of leukocytosis induced by granulocyte colony-stimulating factor (G-CSF) and of macrophages stimulated by macrophage colony-stimulating factor (M-CSF). MATERIAL AND METHODS: Anti-Thy 1.1 GN was induced in male Wistar rats by intravenous injection of OX-7, a monoclonal antibody to the Thy 1 antigen. G-CSF (10 microg/kg/day), M-CSF (20 microg/kg/day) or vehicle was administered intraperitoneally for 7 days starting 24 h before the injection of OX-7. Histological examination of renal biopsy specimens was performed on Days 1, 5 and 14 after induction. RESULTS: Circulating and glomerular-infiltrating PMNs (RP-3-positive cells) were increased at Day 5 in G-CSF-treated rats compared with controls receiving vehicle, and glomerular mesangiolysis continued at Day 5. The number of proliferating cells positive for proliferating cell nuclear antigen at Day 5 and matrix scores at Day 14 were smaller in G-CSF-treated rats than in control rats. The mesangiolysis score was significantly higher in the G-CSF group than in the control group at Days 5 and 14, but not at Day 1. ED-1-positive cells were increased in number at Day 5 and matrix accumulation decreased at Day 14 in M-CSF-treated rats compared with controls. Serum creatinine level at Day 14 was lower in the M-CSF group, but not in the G-CSF group, compared with the control group. CONCLUSIONS: Activated macrophages may inhibit excess matrix accumulation and ameliorate the recovery of renal function, whereas leukocytosis inhibits the repair of mesangial cell injury in this model.