Differential effects of angiotensin II receptor blocker and losartan/hydrochlorothiazide combination on central blood pressure and augmentation index.

Central systolic blood pressure (CSBP) may be a better predictor of cardiovascular risk than clinic brachial (B)SBP. The effects of dose increment from medium dose of angiotensin II receptor blockers (ARBs) to the maximum dose of ARBs (maximum) and changing from medium dose of ARBs to losartan 50 mg/hydrochlorothiazide 12.5 mg combination (combination) were compared in hypertensive patients in whom monotherapy with a medium ARB dose did not achieve goal home SBP (135 mmHg). Four weeks after treatment with a medium ARB dose monotherapy, those whose home SBP level was above 135 mmHg were randomized to receive the maximum ARB dose (n = 101) or the combination (n = 99) once daily for 8 weeks. Both regimens significantly decreased BSBP and CSBP, while a decrease in BSBP and CSBP was greater with combination. The maximum significantly decreased augmentation index (AIx), while the combination did not. The rate of a decrease in reflection to decrease in CSBP was greater in the maximum than in the combination. In the elderly subgroup, the combination more effectively lowered BSBP than the maximum, and only the combination decreased CSBP. However, in the young subgroup, the maximum decreased AIx more than combination, while both regimens lowered CSBP and BSBP to a similar extent. It is explained in part that the maximum may affect pulse wave reflection more predominantly than the combination, especially in young subjects. A weak effect on pulse wave reflection and, thus, on CSBP, of the combination may be overcome by the potent antihypertensive effect of this regimen.

Subservient relationship of the peripheral second systolic pressure peak to the central hemodynamic parameters is preserved, irrespective of atherosclerosis progression in hypercholesterolemic rabbits.

We investigated whether the subservient relationship of peripheral to central hemodynamic parameters, such as the augmentation index (AI) and the second systolic (SBP2) and pulse pressures, were preserved with the progression of atherosclerosis in the Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbit, an animal model for hypercholesterolemia and atherosclerosis. Male KHC rabbits, aged 12 and 24 months, were anesthetized with pentobarbital sodium. Two catheter-tip transducers were introduced to the central (ascending aorta) and peripheral (distal region of the right brachial artery) arteries through the left common carotid and the right radial arteries, respectively. Pressure waves were simultaneously recorded under regular atrial pacing to investigate changes in response to the intravenous infusion of angiotensin II (Ang II) (30-40 ng kg(-1) min(-1)) and sodium nitroprusside (NTP) (20-30 µg kg(-1) min(-1)). Central systolic blood pressure (cSBP) and diastolic blood pressure (DBP), peripheral systolic blood pressure (pSBP) and DBP, and peripheral second systolic blood pressure (pSBP2) showed no significant difference between the 12- and 24-month-old groups before the administration of vasoactive drugs. There was no significant difference in central AI (cAI) between the two age groups before the drug infusion, even though atherosclerosis progressed with aging. Peripheral AI (pAI) changed in parallel with cAI in response to vasopressor and depressor actions due to the infusion of Ang II and NTP, respectively. We conclude that the subservience of pSBP2 to cSBP and pAI to cAI, in addition to the regression relationship of these parameters between peripheral and central arteries, were well preserved, irrespective of the progression of atherosclerosis.

Estimation of central aortic systolic pressure using late systolic inflection of radial artery pulse and its application to vasodilator therapy.

BACKGROUND: Central blood pressure (BP) is a useful predictor of cardiovascular risk. Recently, a fully automated device that measures central SBP (cSBP) from radial late SBP (rSBP2) has been developed. METHOD: We measured cSBP using this device, compared it with aortic SBP (aSBP) measured with a high-fidelity pressure sensor, and evaluated the accuracy of cSBP before and after vasodilator administration. The data of 66 patients (mean age, 63.4 ±â€Š9.7 years; 49 men) who underwent cardiac catheterization were analyzed. The radial artery pulse waveform and brachial BP were measured sequentially and used to calculate cSBP. Brachial SBP and DBP were used for radial SBP (rSBP) and radial DBP to calculate the absolute value of rSBP2. The radial pulse waveform was recorded by an applanation tonometer (HEM-9000AI; Omron Healthcare Co. Ltd). A high-fidelity pressure sensor was placed in the ascending aorta, and aSBP was measured simultaneously by an invasive method. RESULTS: Significant positive correlations between directly measured aortic late SBP and cSBP or rSBP were observed (r = 0.93, 0.88, respectively). Changes in aSBP before and after vasodilator administration showed a trend toward higher correlation with changes in cSBP than with changes in rSBP (r = 0.84, 0.78, respectively). The slope of the linear regression line of aSBP with cSBP (slope: 0.94) was closer to unity than with rSBP (0.66). CONCLUSION: Noninvasive cSBP calculated with rSBP2 accorded well with aSBP measured by the invasive method. Vasodilator medication and four of five diseases did not affect this relation.

Increased arterial stiffness weakens the relationship between wave reflection and the central pressure indexes in men younger than 60 years of age.

BACKGROUND: Interactions among age, arterial stiffness, and pressure wave reflection affect the central blood pressure (CBP). We evaluated our hypothesis that the contribution of the wave reflection to the CBP indexes is reduced at higher levels of arterial stiffness, independent of the effect of age. METHODS: In 2,691 Japanese men aged <60 years old who are not suffering from cardiovascular disease or receiving medications for cardiovascular risk factors, the brachial-ankle pulse wave velocity (PWV), radial augmentation index (AI), and second peak of the radial pressure waveform (SBP2), a marker of CBP, were measured. RESULTS: The increase in the radial AI associated with increase of the brachial-ankle PWV became attenuated at brachial-ankle PWV values of ≥15 m/s. Stepwise multivariate linear regression analysis demonstrated that 33.6% of the total variation in the value of SBP2 and 54.0% of the total variation in the value of the SBP2 minus the diastolic blood pressure, a marker of the central pulse pressure (CPP), were accounted for by the change of the radial AI in the group with brachial-ankle PWV values of <15 m/s, with the corresponding percentages of 16.2 and 38.0% in the group with brachial-ankle PWV values of ≥15 m/s (P < 0.01). CONCLUSIONS: In non-elderly Japanese men, the contribution of the wave reflection to the CBP indexes may be reduced in subjects with higher levels of arterial stiffness, independent of the effect of age. Notwithstanding, the wave reflection may still be the major determinant of the CPP at any given level of arterial stiffness.

Significance of the second peak of systolic blood pressure for identifying both high and low cardiovascular risk states.

This study was conducted to clarify whether the second peak of the systolic blood pressure (SBP2) has significant information about cardiovascular (CV) risk state, independent of the brachial BP. SBP2 was measured by radial pressure wave analysis in 7847 Japanese subjects (50+/-10 years old), and the Framingham risk score (FRS) and general cardiovascular disease risk score were calculated (FRSgen). The results of multivariate analysis revealed that the SBP2 showed a significant correlation with the FRS (beta=0.04, t-value=3.92, P<0.01) and FRSgen (beta=0.05, t-value=6.55, P<0.01), independent of the brachial SBP. The non-standardization coefficient of SBP2 was smaller than that of brachial SBP. The logistic regression analysis showed that SBP2 (2 mm Hg per increase) had a significant odds ratio to identify not only subjects with a high risk for coronary heart disease (CHD) and general CV disease (CVDgen), but also subjects with a low risk for CHD and CVDgen, independent of the brachial SBP. However, when the analysis was limited to subjects of >or=49 years of age, SBP2 could not identify either high or low CV risk subjects. Thus, in middle-aged Japanese subjects, SBP2 may provide little, yet significant, information reflecting both high and low CV risk states, independent of the brachial BP. SBP2 seems to be more applicable for CV risk stratification in younger subjects than in older subjects.

Time for reflection predicts the progression of renal dysfunction in patients with nondiabetic chronic kidney disease.

Our previous data indicated that both home blood pressure and arterial stiffness predicted the progression of renal dysfunction in the patients with chronic kidney diseases. In the present study, we examined both home blood pressure and the parameters of arterial stiffness as the indicator to the progression of chronic kidney diseases. Forty-two nondiabetic chronic kidney disease patients were enrolled and followed for 1 year. Anti-hypertensive therapy was adjusted to achieve office blood pressure below 130/80 mmHg. Home blood pressure was examined twice a day in the morning and evening. Pulse wave velocity (PWV) and augmentation index (AI) were measured as the index of arterial stiffness. The time for reflection (TR) was also determined. The relationship of annual changes in serum creatinine (Scr) with the above parameters was assessed. Multivariate regression analysis revealed that TR inversely correlated to annual increase in Scr (beta = -0.03, p < 0.05). Home blood pressure did not correlate to annual changes in Scr in the present study. The present data indicated that arterial stiffness is elevated despite good blood pressure control in chronic kidney disease, especially among the dippings. In addition, our data suggest that PWV and AI correlated to each other, while they were influenced differently by hemodynamic factors. Finally, the present findings provide the evidence that the arterial stiffness parameter is more sensitive than home blood pressure as an indicator to the progression of chronic kidney disease.

Synergistic effect of smoking and blood pressure on augmentation index in men, but not in women.

This study was conducted in healthy Japanese subjects to examine the effects of age and gender on the relationship between the risk factors for cardiovascular disease (CVD) and augmentation index (AI), and the effects of clusters of those risk factors on AI. Radial arterial pressure wave analysis was used to obtain AI in 3675 men and 2919 women. AI was found to be higher in women than in men, and age-related increase in AI showed an attenuated curve in subjects aged >or=50 years. A step-wise multivariate linear regression analysis showed that mean blood pressure and smoking are independent significant variables related to AI in men regardless of age, and in women aged <50 years, but not in women aged >or=50 years. A general linear model univariate linear regression analysis showed that mean blood pressure and smoking had a significant interaction for their relation with AI in men, but not in women. In conclusion, among the risk factors for CVD, smoking and blood pressure were found to be independent factors related to increase in AI. Although age-related attenuation of increase in AI was confirmed in Japanese subjects, these risk factors may act to increase AI even in elderly subjects, at least in part. However, the effects of these factors on AI may differ based on gender, and these factors may act synergistically to increase AI in men. On the contrary, these factors may act independently in young women to increase AI without interaction, whereas only the blood pressure seems to increase AI in elderly women.

Effect of acute and long-term aerobic exercise on arterial stiffness in the elderly.

Arterial stiffness is an important factor for cardiovascular performance and a predictor of cardiovascular risk. We evaluated the effects of both acute and long-term aerobic exercise on arterial stiffness in community-dwelling healthy elderly subjects. In addition, we evaluated the relationship between the effects of long-term exercise and those of acute exercise. The study subjects were participants in the Shimanami Health Promoting Program study (J-SHIPP), which was designed to investigate factors relating to cardiovascular disease, dementia, and death (67+/-6 years). They performed mild-to-moderate aerobic exercise lasting for 30 min twice a week for 6 months. Arterial stiffness was assessed before and after the first 30-min acute exercise (n=99) and long-term 6-month aerobic training (n=40). The radial arterial augmentation index (AI) obtained from the radial pulse waveform by the tonometry method was used as a parameter of arterial stiffness. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly decreased after 30-min of aerobic exercise, however no significant change in AI was observed. On the other hand, there were significant decreases in AI (from 87 to 84%, p<0.01), SBP (from 136 to 129 mmHg, p<0.01), and DBP (from 75 to 70 mmHg, p<0.01) after the 6-month exercise period. Long-term exercise-induced changes in AI were significantly and inversely correlated with the pre-exercise AI (r=-0.40, p<0.01). In addition, AI changes after the 6-month exercise period were significantly related to those observed after first 30-min exercise (r=0.48, p<0.01). These findings indicate that apparently healthy and sedentary elderly subjects with higher AI may benefit from mild-to-moderate aerobic exercise to improve arterial stiffness.

Radial augmentation index: a useful and easily obtainable parameter for vascular aging.

BACKGROUND: It has been shown that the systolic augmentation index (AI) in the central arteries, including the aorta and carotid arteries, changes with age. The AI can also be obtained from the peripheral arteries. The possible usefulness of AI obtained from the radial artery as an index for vascular aging was investigated. METHODS: Radial arterial waveforms were obtained from 632 subjects with no cardiovascular disease, using radial tonometry. Radial AI was calculated as follows: (Second peak systolic blood pressure [SBP2] - diastolic blood pressure [DBP]) / (first peak SBP - DBP) x100 (%). RESULTS: Radial AI was significantly higher in women than in men (81.1% +/- 16.1% compared with 69.5% +/- 16.3%, P < .001). Radial AI was positively related to age in healthy men and women (r = 0.619, P < .001, and r = 0.644, P < .001, respectively). When comparing subjects in their 20s to those in their 70s, radial AI increased 1.56 times (from 53.2% to 83.0%) in men and 1.49 times (from 64.6% to 96.4%) in women. Multiple regression analysis showed that age is a potent predictor of radial AI in addition to gender, DBP and pulse rate. CONCLUSIONS: These findings indicate that simple and easily-obtainable radial AI is age-dependent and could be a useful index of vascular aging.

[Measurement of pulse wave "augmentation index (AI) "and its clinical application].

Hypertension, hyperlipidemia, diabetes mellitus and obesity, all of these life-style related diseases advance arteriosclerosis and cause a cardiovascular event. It is said that the event can be greatly reduced by improvement of lifestyle or medication. The device is recently developed that enables us easily to measure AI i.e. augmentation index, and the studies applying the device have been clarifying the clinical usefulness of the index. The reflected wave from the peripheral artery is superimposed on the ejection wave generated by cardiac contraction, although the blood pressure waveform is observed as the synthesized one of those two. AI is defined as the proportion of the amplitude of the reflected wave to that of the ejection wave, and it does not only express a cardiac load, but also arterial stiffness. The vessel with arteriosclerosis generates a large reflected wave, and it reaches the left ventricle at high speed. Thereby the heart receives large mechanical stress which may cause cardiac hypertrophy, and as a result, the sustained stress may cause a serious accident. Thus, it is the management for both situations of the heart and the artery that matters, and AI can be regarded as a new marker of cardiovascular disease for suitable clinical management on both heart and artery.