Tohru Nunokawa

Utility of automated brachial ankle pulse wave velocity measurements in hypertensive patients

BACKGROUND We examined whether pulse wave velocity (PWV), determined by brachial ankle arterial pressure wave measurements, using a newly developed, fully automated device could be a surrogate measure for carotid femoral PWV. METHODS & RESULTS This device (AT-form PWV/ABI, Nippon Colin, Komaki, Japan) can simultaneously monitor bilateral brachial and ankle pressure wave forms using the volume plethysmographic method, with two optional tonometry sensors for carotid and femoral arterial wave measurements. We examined the right brachial-right ankle PWV and left carotid-left femoral PWV in 89 normotensive and untreated hypertensive patients. The brachial ankle PWV correlated well with carotid femoral PWV (r = 0.755, P <.00001). The Bland-Altman plots of the two variables, however, showed a significant difference exists between the two techniques over the range of measurement. The within-observer and between-observer coefficients of variation of the brachial ankle PWV were 6.5% +/- 4.1% and 3.6% +/- 3.9%, respectively. To determine the factors affecting brachial ankle PWV, we studied treated and untreated hypertensive patients with World Health Organization stage I (n = 146), stage II (n = 74), or stage III (n = 54). In multiple regression analysis, age, brachial ankle PWV, and the presence of diabetes were significant predictors of the severity of hypertensive organ damage. Age, systolic blood pressure, and the stage of hypertensive organ damage were major determinants of brachial ankle PWV. CONCLUSIONS Although the brachial ankle PWV does not agree with the carotid femoral PWV, this parameter may yet become a new, useful measure for arterial stiffness. Further longitudinal studies are necessary to confirm the clinical significance of the brachial ankle PWV.

Higher Brachial-Ankle Pulse Wave Velocity Is Associated with More Advanced Carotid Atherosclerosis in End-Stage Renal Disease

Brachial-ankle pulse wave velocity is a new measure of arterial stiffness. We examined whether higher brachial-ankle pulse wave velocity is associated with more advanced carotid atherosclerosis and left ventricular hypertrophy in patients with end-stage renal disease, and whether this effect would be mediated by the influence of wave reflection on central arterial pressure. In 68 patients with end stage renal disease, we examined blood pressures, brachial-ankle pulse wave velocity and the augmentation index of the left common carotid artery, a measure of the impact of wave reflection on the systolic peak in central arteries. The degree of carotid atherosclerosis was quantified by a plaque score and maximum intimal-medial thickness. Echocardiography was used to determine the left ventricular mass index. In simple regression analysis, brachial-ankle pulse wave velocity was correlated with both plaque score and maximum intimal-medial thickness (r=0.420, p<0.001 and r=0.452, p<0.0005, respectively) but not with left ventricular mass index. Multiple regression analysis was performed with the plaque score or maximum intimal-medial thickness as the dependent variable and brachial-ankle pulse wave velocity and known clinical risk factors as the independent variables. The brachial-ankle pulse wave velocity was an independent risk factor for both plaque score (β=0.006, p=0.004) and maximum intimal-medial thickness (β=0.008, p=0.04). Independent risk factors for left ventricular mass index were left ventricular diastolic dimension (β=3.509, p=0.000007) and augmentation index (β=0.580, p=0.04). The brachial-ankle pulse wave velocity was unrelated to augmentation index in patients with end stage renal disease. In conclusion, higher brachial-ankle pulse wave velocity was found to be a risk factor for carotid atherosclerosis in patients with end-stage renal disease; this effect was independent of the influence of wave reflection on central arterial pressure. The brachial-ankle pulse wave velocity was unrelated to left ventricular structure.

Circadian blood pressure rhythm in patients with higher and lower spinal cord injury : simultaneous evaluation of autonomic nervous activity and physical activity

Objective To examine the relationships among the circadian rhythms of blood pressure, autonomic nervous function, and physical activity of patients with varying levels of spinal cord injury. Design and methods We studied 19 patients with spinal cord injury [10 tetraplegic patients with cervical cord injury (C4–C7), and nine paraplegic patients with thoracic cord injury (Th6–Th12)] compared with 16 control subjects. A new multibiomedical recorder was used to measure blood pressure (every 30 min), cardiac vagal activity (hourly frequency of R-R50), and physical activity (integrated acceleration/min) for 24 h under hospital conditions. Systemic sympathetic nervous activity and sympathoadrenal functioning were assessed by examination of hormone levels in the blood. Results Daytime and night-time values were compared; the variations in systolic and diastolic blood pressures and heart rate were slight in members of the tetraplegia group, but almost normal differences were observed in members of the paraplegia group. The circadian profile of cardiac vagal activity was normal for both patient groups, suggesting that an alteration in the sympathetic nervous rhythm had occurred in the tetraplegic patients. The plasma norepinephrine level was lower in members of the tetraplegia group than it was in members of the control group (P < 0.001), but was normal in members of the paraplegia group. The plasma level of epinephrine was lower in members of the tetraplegia (P < 0.05) and the paraplegia (P < 0.1) groups than it was in members of the control group. Daytime physical activity of members of both groups of patients was lower than that of subjects in the control group (P < 0.001 for both). Conclusion The central sympathoexcitatory pathway to the upper thoracic cord plays a critical role in the maintenance of normal circadian blood pressure rhythm in humans. Motor nerve functioning and sympathoadrenal secretion are not essential to this regulation.

Brachial-Ankle Pulse Wave Velocity Is an Independent Risk Factor for Microalbuminuria in Patients with Essential Hypertension—A Japanese Trial on the Prognostic Implication of Pulse Wave Velocity (J-TOPP)

Brachial-ankle pulse wave velocity is a new measure of arterial stiffness. The clinical significance of brachial-ankle pulse wave velocity as a measure of early vascular damage remains unclear. We examined the hypothesis that higher brachial-ankle pulse wave velocity is associated with a much greater risk of albuminuria by employing a cohort of 718 never-treated hypertensive patients registered in a prospective study. The 718 patients consisted of 500 patients with normoalbuminuria (69.6%), 191 patients with microalbuminuria (26.6%) and 27 patients with macroalbuminuria (3.8%). The prevalence of microalbuminuria increased with a graded increase in brachial-ankle pulse wave velocity (17.6, 22.8, 28.2 and 39.6%, p<0.0001). The prevalence of macroalbuminuria remained constant until the third grade group of the brachial-ankle pulse wave velocity but increased significantly in the highest grade group compared with the lower grade groups (2.3, 3.2, 2.3, 9.9%, p<0.0001). Age, systolic and diastolic blood pressure, pulse pressure, heart rate, and fasting glucose concentration were also significantly increased with an increase in brachial-ankle pulse wave velocity (p<0.0001 for all). Multiple logistic regression analysis has shown that systolic blood pressure, fasting blood glucose, and brachial-ankle pulse wave velocity are significant risk factors for microalbuminuria. After adjusting for other risk factors, the odds ratio for an increase of 200 cm/s in brachial-ankle pulse wave velocity was 1.192 (95% confidence interval: 1.022–1.365; p<0.05). These data suggest that brachial-ankle pulse wave velocity is an independent risk factor for microalbuminuria and could be used as a marker for early vascular damage in never-treated hypertensive patients.

Altered Mayer wave and baroreflex profiles in high spinal cord injury

Spinal sympathetic neurons are distributed in cord segments from Th1 to L3. High spinal cord injury demonstrates severe orthostatic hypotension, but not lower cord injury. It remains to be clarified as to where is the critical spinal level disturbing neural cardiovascular regulations in response to orthostatic stress. To address this issue, beat-to-beat blood pressure (BP) (measured using a Finapres device) and RR interval (measured electrocardiographically) were recorded at rest and in a 60 degree head-up position in 26 patients with varying levels of spinal cord injury (C4 to Th12) and in 15 healthy (control) subjects. Sympathetic vascular tone was examined by the Mayer wave power spectrum of systolic blood pressure (SBP) variability. Baroreflex sensitivity was examined by transfer function analysis of SBP and RR interval variabilities. The Mayer wave power spectrum increased in response to postural shift in most patients injured at Th4 or below, whereas this parameter either remained unchanged or decreased in patients with higher-level injury. Baroreflex sensitivity tended to decrease with postural shift in patients injured at Th3 or below, whereas this parameter increased in all patients with higher-level injury. We divided spinal patients into high-level injury (Th3 or above, n = 14) and low-level injury (Th4 or below, n = 12) groups. Systolic blood pressure significantly fell (-10 +/- 4 mm Hg, P < .05) with postural shift in high-level injury group but did not change in low-level injury group or in control subjects. The low-level injury group and the control group demonstrated essentially similar autonomic nervous responses to postural shift, ie, a significant increase in Mayer wave power and an insignificant decrease in baroreflex sensitivity. On the contrary, the high-level injury group showed opposite responses, ie, an insignificant decrease in Mayer wave power and a significant increase in baroreflex sensitivity in response to postural shift. We conclude that spinal cord injury at Th3 or above eliminates normal neural cardiovascular responses to mild orthostatic stress in humans.

Type A behavior is associated with an increased risk of left ventricular hypertrophy in male patients with essential hypertension.

OBJECTIVE To determine whether type A behavior, which is associated with a risk of coronary heart disease, affects left ventricular hypertrophy in patients with essential hypertension. DESIGN Cross-sectional study of 88 untreated patients with mild to moderate essential hypertension (33 men, mean +/- SEM age 54 +/- 1 years). METHODS We measured the type A behavior score using a standardized questionnaire, left ventricular mass index using M-mode echocardiography and 24 h mean ambulatory blood pressure (recorded every 30 min). Beat-to-beat blood pressure was also measured using a Finapres device in patients at rest and during mental stress (counting backward) to determine the blood pressure response to stress. RESULTS The left ventricular mass index was correlated with the type A behavior score (r = 0.214, P < 0.05), age (r = 0.266, P < 0.05), 24 h mean systolic and diastolic blood pressures (r = 0.391, P < 0.001, and r = 0.382, P < 0.001, respectively), systolic blood pressure both at rest and during stress (r = 0.255, P < 0.05, and r = 0.215, P < 0.05, respectively), and the variability of both systolic and diastolic blood pressures at rest (r = 0.253, P < 0.05, and r = 0.321, P < 0.01, respectively). Stepwise multiple linear regression analysis demonstrated that age was associated with an increase in the left ventricular mass index for both sexes (P = 0.004 for males, P = 0.003 for females). The type A behavior score predicted a greater increase in left ventricular mass index in men (P = 0.018) but not in women. The 24 h mean systolic blood pressure was associated with a greater increase in left ventricular mass index in women (P < 0.001) but not in men. CONCLUSION Type A behavior is an independent risk factor for left ventricular hypertrophy in male patients with essential hypertension.

Brachial-Ankle Pulse Wave Velocity as a Novel Measure of Arterial Stiffness: Present Evidences and Perspectives

Atherosclerotic cardiovascular disease is a leading cause of death in most developed countries. Cardiovascular risk factors such as hypertension, diabetes, and dyslipidemia initiate structural and functional abnormalities in the arterial wall, leading to the development of atherosclerosis. Atherosclerosis is characterized by the stiffening and/or thickening of the arterial wall. Aortic pulse wave velocity as evaluated by carotid and femoral arterial waves is the most established measure for arterial stiffness. Recently, a new arterial stiffness measure using brachial and tibial arterial waves has been developed. The measurement of the brachial-ankle wave velocity is fully automatic, needs no skill and is reproducible. Age and blood pressure are robust independent predictors for the brachial-ankle pulse wave velocity. Recent studies have shown that higher brachial ankle pulse wave velocity is associated with more advanced atherosclerotic changes of the arterial wall not only in the clinical patients but also in subclinical individuals. Thus, brachial-ankle pulse wave velocity may be a useful measure of vascular damage, which predisposes individuals to cardiovascular events. A multicenter trial examining the prognostic significance of the brachial-ankle pulse wave velocity is presently in progress.

The influence of one-year treatment by angiotensin converting enzyme inhibitor on baroreflex sensitivity and flow-mediated vasodilation of the brachial artery in essential hypertension--comparison with calcium channel blockers.

Background. Both baroreflex sensitivity and flow‐mediated vasodilator function have been recognized to have prognostic significance in cardiovascular diseases. Long‐term antihypertensive treatment effects on these parameters, however, remain unclear. Subjects and Methods. We examined the effects of long‐term treatment by angiotensin converting enzyme inhibitors (ACEI) or calcium channel blockers (CCB) on baroreflex and flow‐mediated vasodilator function in patients with essential hypertension (EH). We recruited 36 patients aged 56 ± 11 years, with systolic blood pressure ≧160 mmHg and/or diastolic blood pressure ≧95 mmHg. Patients were assigned either to treatment by long‐acting ACEI (n = 12) or CCB (n = 24). All patients were followed for 12 months. Optimal BP was achieved by two optional increases in treatment: dose‐doubling of the primary drug during the first three months and the addition of diuretics or β‐blockers thereafter. Target blood pressure was 140/90 mmHg or a fall ≧20/10 mmHg. Baroreflex sensitivity was examined by spectral analysis of blood pressure and RR interval variabilities before treatment and after 3 and 12 months of treatment. The flow‐mediated vasodilator function was determined before and 12 months after treatment by measuring the change in brachial artery diameter during increases in flow induced by reactive hyperemia. Results. Baseline blood pressures were similar between the ACEI and CCB groups (172 ± 5/103 ± 2 vs. 172 ± 4/101 ± 3 mmHg). Blood pressures after 3 and 12 months of treatment also did not differ between the ACEI and CCB groups (149 ± 4/91 ± 2 vs. 145 ± 2/ 85 ± 2 mmHg, and 133 ± 5/84 ± 2 vs. 133 ± 2/81 ± 2 mmHg, respectively). Baseline baroreflex sensitivity was similar between the groups (6.7 ± 0.8 vs. 5.9 ± 0.6 msec/mmHg). This parameter remained unchanged at three months but increased after 12 months of treatment in both the ACEI (9.5 ± 1.6 msec/mmHg, p = 0.05) and CCB (9.1 ± 1.2 msec/mmHg, p = 0.006) groups. Percent increases in brachial arterial diameter and flow during reactive hyperemia increased in the group treated with ACEI (12.4 ± 3.5 vs. 25.8 ± 6.3% and 618 ± 72 vs. 953 ± 166, p < 0.05 for both) but both parameters remained unchanged in the group treated with CCB. Conclusion. These data suggest that long‐term blood pressure control with modern antihypertensive drugs improves baroreflex function. Treatment with ACEI may be more favorable for flow‐mediated vasodilator function than treatment with CCB.

Psychobehavioral factors involved in the isolated office hypertension : comparison with stress-induced hypertension

Objective To investigate the psychobehavioral factors involved in the isolated clinic blood pressure elevation and hypertension induced by mental stress. Design and methods We studied 73 untreated patients with essential hypertension defined as World Health Organization stage I or II (28 men and 45 women, mean age 55 ± 11 years). The amount of isolated clinic blood pressure elevation was examined in terms of the difference between clinic and daytime ambulatory blood pressures. Blood pressure (measured using a Finapres device) and R–R interval (measured electrocardiographically) were continuously monitored with subjects at rest and under mental stress (counting backward) to examine the cardiovascular response to the stress. Psychobehavioral characteristics such as anger, anxiety, tension, type A behavior pattern, and nervousness were evaluated and scored using structured interviews and self-reporting questionnaires. Results The anger score was inversely correlated to the clinic–ambulatory blood pressure difference for the systolic (r = −0.308, P < 0.01) and diastolic (r = −0.233, P < 0.05) blood pressures. The score for type A behavior pattern tended to be inversely correlated to the clinic-ambulatory blood pressure difference for diastolic blood pressure (r = −0.209, P < 0.1). The nervousness score was positively correlated to stress-induced increase in the systolic (r = 0.249, P < 0.05) and diastolic (r = 0.232, P < 0.05) blood pressures. The clinic-ambulatory blood pressure difference was not related to the blood pressure rise induced by mental stress (r = 0.170 for systolic blood pressure; r = 0.112 for diastolic blood pressure). Conclusion The isolated clinic blood pressure elevation and hypertension due to mental stress were related to different psychobehavioral factors.