Improvement in blood pressure, arterial stiffness and wave reflections with a very-low-dose perindopril/indapamide combination in hypertensive patient: a comparison with atenolol.

International guidelines recommend that antihypertensive drug therapy should normalize not only diastolic (DBP) but also systolic blood pressure (SBP). Therapeutic trials based on cardiovascular mortality have recently shown that SBP reduction requires normalization of both large artery stiffness and wave reflections. The aim of the present study was to compare the antihypertensive effects of the very-low-dose combination indapamide (0.625 mg) and perindopril (2 mg) (Per/Ind) with the beta-blocking agent atenolol (50 mg) to determine whether Per/Ind decreases SBP and pulse pressure (PP) more than does atenolol and, if so, whether this decrease is predominantly due to reduction of aortic pulse wave velocity (PWV) (automatic measurements) and reduction of wave reflections (pulse wave analysis, applanation tonometry). In a double-blind randomized study, 471 patients with essential hypertension were followed for 12 months. For the same DBP reduction, Per/Ind decreased brachial SBP (-6.02 mm Hg; 95% confidence interval, -8.90 to -3.14) and PP (-5.57; 95% confidence interval, -7.70 to -3.44) significantly more than did atenolol. This difference was significantly more pronounced for the carotid artery than for the brachial artery. Whereas the 2 antihypertensive agents decreased PWV to a similar degree, only Per/Ind significantly attenuated carotid wave reflections, resulting in a selective decrease in SBP and PP. The very-low-dose combination Per/Ind normalizes SBP, PP, and arterial function to a significantly larger extent than does atenolol, a hemodynamic profile that is known to improve survival in hypertensive populations with high cardiovascular risk.

Comparative effects of aging in men and women on the properties of the arterial tree.

OBJECTIVES: We measured the properties of the arterial tree, seeking differences between men and women as they aged. BACKGROUND: There are many differences between men and women, besides menopause, which might account for such disparities. These include body height, heart rate, stroke volume and smaller arterial diameters. Any gender differences in arterial stiffness could influence pulse pressure (PP), now recognized as a cardiovascular risk factor. METHODS: A total of 530 patients (347 men and 183 women) were classified by age into quartiles: < or = 40, 41-47, 48-54 and > or = 55 years. The middle groups represented the menopausal years. Studies included brachial artery blood pressure (BP), aortic pulse wave velocity (PWV), B-mode ultrasonography and wave form analysis of the common carotid artery (CCA), with its conversion to the aortic wave formin. Standard echocardiography provided left ventricular dimensions and flows. Calculated values included CCA compliance and distensibility, systemic compliance, stroke volume and peripheral resistance. RESULTS: At all ages, women had higher heart rates but lower BP than men. Pulse pressure, however, was lower in young women and higher in older women. Measurements influenced by body size, such as CCA diameter, compliance and systemic compliance, were lower in women. Those related to arterial wall properties, such as CCA and aortic distensibility, were the same. Although aortic PWV rose similarly with aging, PWV had more of an influence on PP in women than did mean BP. The reverse was true in men. CONCLUSIONS: Despite lower mean BP and similar arterial distensibilitvy, women develop a higher degree of pulsatility with aging, as compared with men. This is mainly due to their smaller physical characteristics, independent of the role of menopause and its related hormonal changes.

Amelioration of arterial properties with a perindopril-indapamide very-low-dose combination.

BACKGROUND: Epidemiological studies have shown that increased arterial stiffness and wave reflections, major determinants of systolic and pulse pressure, are associated with morbidity and mortality. Therapeutic trials based on cardiovascular mortality have recently shown that reduction of systolic blood pressure (SBP) requires normalization of both large-artery stiffness and wave reflections. AIMS: To compare the antihypertensive effects of the very-low-dose combination of perindopril (2 mg) and indapamide (0.625 mg) (one or two tablets per day) with the beta-blocking agent atenolol (50 mg; one or two tablets per day) in order to determine whether the combination decreased SBP and pulse pressure more than did atenolol, and whether this decrease occurred in relation to a reduction in arterial stiffness [aortic pulse wave velocity (PWV)] or a decrease in the intensity of, or delay in, wave reflections (augmentation index, measured by applanation tonometry) or a combination of both. MATERIAL AND METHODS: This was a double-blind randomized study in 471 individuals with essential hypertension followed for 12 months. Arterial pressure was measured in the brachial artery (mercury sphygmomanometer) and in the carotid artery (applanation tonometry). RESULTS: For the same reduction in diastolic blood pressure (DBP), the combination of perindopril and indapamide decreased brachial SBP and pulse pressure significantly more than did atenolol (adjusted differences between groups -6.2 +/- 1.5 and -5.5 +/- 1.0 mmHg, respectively; P < 0.001). This difference was even more pronounced for the carotid than for the brachial artery. Whereas both antihypertensive agents similarly decreased PWV, only the combination significantly attenuated wave reflections. CONCLUSION: Normalization of SBP, pulse pressure and arterial function--a haemodynamic profile known to improve survival significantly in hypertensive populations at high cardiovascular risk--was achieved to a greater extent with a very-low-dose combination of perindopril and indapamide than with atenolol.

Noninvasive evaluation of arterial abnormalities in hypertensive patients.

Morbidity and mortality in hypertension are mainly determined by arterial lesions which may occur in different regional circulations: kidney, cerebral, coronary ..., causing respectively nephroangiosclerosis, stroke or myocardial infarction... Despite the arteries heterogeneity, structural and functional abnormalities are usually observed at an early stage of hypertension in both large and small arteries. These alterations modify arterial wall physiological and mechanical properties which can be expressed clinically by increasing arterial pulsatility or pulse pressure; they facilitate establishment and progression of atherosclerosis and arteriosclerosis. Since arteries constitute the target, site and common denominator of hypertension cardiovascular complications, several noninvasive techniques may be usefull to assess their haemodynamic: casual and ambulatory blood pressure measurements can evaluate pulse pressure which can be also directly measured in different sites of the arterial tree using the "Tonometer" device; ultrasound techniques can be applied: Doppler signal to assess the arterial flow, video-echo signal to analyse the arterial structure such as intima-media thickness, or echo-tracking systems for direct measurements of arterial wall distension and thickness; pulse wave velocity is widely used as index of arterial distensibility; its assessment, using the Complior device showed that hypertensive patients present a decrease of arterial distensibility and that antihypertensive treatment do not always reverse this abnormality. Since cardiovascular morbidity and mortality are due to arterial lesions, it is important to evaluate the effect of cardiovascular prevention on the arterial wall. Large therapeutical trials, including arterial evaluation, are necessary to assess whether this consideration may particularize patients with high cardiovascular risk and contribute to their treatment and prognostic improvement.

Racial differences in aortic stiffness in normotensive and hypertensive adults.

OBJECTIVE: To investigate whether differences exist in the mechanical properties of large arteries between white and black subjects. DESIGN: Eighty-two white (49 normotensive and 33 untreated hypertensive) and 38 black (24 normotensive and 14 untreated hypertensive) adult male volunteers were studied in a cross-sectional study. METHODS: Carotid-femoral pulse wave velocity was measured as an index of arterial stiffness, using a recently developed non-invasive automatic device, and compared between white and black subjects before and after the adjustment for age. The slope of regressions for pulse wave velocity and systolic blood pressure were also compared between racial groups. RESULTS: In the normotensive group, white subjects presented higher mean values of pulse wave velocity than blacks while the opposite behavior was found in the hypertensive group. After adjustment for age, significant differences in pulse wave velocity between whites and blacks became evident in the normotensive (whites 8.15 +/- 0.04 versus blacks 7.75 +/- 0.02 m/s; P < 0.001) and hypertensive (whites 8.88 +/- 0.02 versus blacks 9.30 +/- 0.17 m/s; P < 0.001) groups. Linear regression analysis for age-adjusted pulse wave velocity and systolic blood pressure showed that the slope was significantly greater in blacks than in whites (0.040 +/- 0.002 versus 0.019 +/- 0.001 m/s; P < 0.001). CONCLUSION: These data indicate that there is a greater pressure-dependent increase in aortic stiffness in blacks than in whites. This finding points towards major differences in mechanical properties of large arteries between these racial groups.

Large artery stiffness in hypertension.

EFFECTS OF HYPERTENSION ON LARGE ARTERIES: The mechanical properties of large arteries make a major contribution to cardiovascular haemodynamics through the buffering of stroke volume and by propagation of the pressure pulse. A sustained increase in blood pressure often leads to stiffness of the large arteries, especially when other risk factors are present. The increased stiffness, in turn, aggravates hypertension by increasing systolic blood pressure and can induce cardiac hypertrophy and arterial lesions. Epidemiological studies strongly suggest that subjects with stiffer arteries have a high pulse pressure, and that stiffening of large arteries is associated with excess morbidity and mortality independently of other cardiovascular risk factors. ENVIRONMENTAL AND GENETIC FACTORS: Apart from high blood pressure and ageing, various environmental and genetic factors that influence the composition of the extracellular matrix of the arterial wall can increase arterial stiffness. Clinical studies suggest that the presence of some genotypes may be a particularly important risk marker for arterial stiffness, and may modulate the effects of hypertension, ageing and lipids on large arteries. EFFECTS OF ANTIHYPERTENSIVE DRUGS: The development of accurate, non-invasive methods has now made it possible to detect alterations of the large arteries. Among antihypertensive drugs, angiotensin converting enzyme inhibitors and calcium channel blockers have proved to be highly effective in improving large artery compliance, and have shown no adverse effects on metabolic factors that can alter arterial structure and function such as lipids, plasma glucose and insulin tolerance. Therefore these drugs may be particularly suitable for treating patients with increased arterial stiffness. Finally, a determination of genotypes may be helpful in the future in choosing antihypertensive therapy.

Non-invasive evaluation of arterial abnormalities in hypertensive patients.

ARTERIAL ABNORMALITIES IN HYPERTENSION: Morbidity and mortality in hypertension are mainly determined by arterial lesions which may occur in different regional circulations (e.g. kidney, cerebral, coronary circulations, causing nephro-angiosclerosis, stroke or myocardial infarction, respectively). Despite arterial heterogeneity, structural and functional abnormalities are usually observed at an early stage of hypertension in both large and small arteries. These alterations modify physiological and mechanical properties of the arterial wall, which may become clinically evident by increasing arterial pulsatility or pulse pressure; the alterations facilitate the establishment and progression of atherosclerosis and arteriosclerosis. METHODS OF ASSESSING ARTERIAL ABNORMALITIES: Several non-invasive techniques can be used to assess haemodynamic properties of arteries: (1) casual and ambulatory blood pressure measurements can be used to evaluate pulse pressure; (2) pulse pressure can be measured directly in different sites of the arterial tree using the Tonometer device; (3) ultrasound techniques can be applied, including Doppler signals to assess the arterial flow, video-echo signals to analyse the arterial structure such as the intimal-medial thickness and echo-tracking systems for direct measurements of arterial wall distension and thickness; (4) pulse wave velocity is widely used as index of arterial distensibility; this parameter, assessed by the Complior device, has shown that hypertensive patients have decreased arterial distensibility and that antihypertensive treatment does not always reverse this abnormality. TREATMENT: It is important to evaluate the effect of cardiovascular risk-reduction measures on the arterial wall. Large therapeutic trials are necessary to show whether an evaluation of arterial abnormalities can identify patients with a high cardiovascular risk and contribute to their treatment and prognostic improvement.

Non-invasive ambulatory blood pressure variability and cardiac baroreflex sensitivity.

AIM: The objective of this study was to evaluate the relationship between non-invasive ambulatory blood pressure variability and cardiac baroreflex sensitivity in hypertensive patients. SUBJECTS AND METHODS: Ambulatory blood pressure measurements (15-min intervals for 24 h) and continuous blood pressure measurements (Finapres, 20 min at rest after a 10-min resting period) were performed in 123 untreated hypertensives (resting diastolic blood pressure > or = 90 mmHg; 80 males, 43 females; mean +/- SD age 49 +/- 12 years, range 19-73). Fourier series were used to model 24-h blood pressure profiles (four harmonics). Ambulatory blood pressure variability was assessed by determination of the residuals in each 24-h blood pressure profile (measured minus predicted pressures). Resting blood pressure variability was defined as the SD of the mean Finapres value. Baroreflex sensitivity was evaluated by automatic detection of blood pressure and pulse interval sequences of > or = 3 beats when systolic blood pressure and pulse interval sequences changed in the same direction (increase or decrease: 1 mmHg for systolic blood pressure and 4 ms for RR interval), and was assessed as the slope of the regression line for each sequence. RESULTS: Ambulatory systolic blood pressure variability increased with age (r = 0.28*) and systolic pressure (r = 0.44**). Baroreflex sensitivity (increasing systolic pressure/pulse interval) decreased significantly with age (r = -0.48**) and systolic pressure (r = -0.23**), and was significantly related to increased ambulatory blood pressure variability (r = -0.33**). In a multivariate stepwise analysis the relationship between ambulatory blood pressure variability and baroreflex sensitivity (increasing systolic pressure/pulse interval) was statistically independent of age and systolic pressure (R = 0.55, P<0.001); this relationship was not observed with the corresponding decreasing sequence. CONCLUSIONS: This study shows that in uncomplicated hypertension, ambulatory blood pressure variability is related to baroreflex sensitivity independently of the blood pressure level. This finding has prognostic implications for this non-invasive measurement, which needs to be confirmed by large longitudinal studies.

Distension capacity of the carotid artery and ambulatory blood pressure monitoring. Effects of age and hypertension.

In hypertension, the principal components of the mechanical stress acting on the arterial wall may be evaluated not only from the level of peak systolic and end-diastolic blood pressure but also by the level of pulse pressure and variability of blood pressure measured by ambulatory monitoring. The purpose of the present study was, in a population of 51 subjects with essential hypertension, to determine the influence of these parameters and of heart rate on the distension capacity of the common carotid artery, measured noninvasively by high-resolution echo-tracking techniques. The pulsatile change in diameter of the carotid artery diameter, estimated either in absolute or relative values, was shown to be significantly and independently correlated with four mechanical parameters deduced from daytime ambulatory blood pressure measurements: baseline diastolic blood pressure (the lower the diastolic blood pressure, the higher the distension capacity; r = -0.44; P < .001); pulse pressure (the higher the pulse pressure, the higher the distension capacity; r = 0.32; P < .024); variability of diastolic blood pressure (the higher the variability, the higher the distension capacity; r = 0.37; P < .008); and mean heart rate (the higher the heart rate, the more reduced the distension capacity; r = -0.28; P < .05). Multiple regression analysis indicated that mean diastolic blood pressure and its variability, mean heart rate, and pulse pressure acted independently on carotid artery distension, even after adjustment for age. The present study suggests for the first time that, in humans, hypertension may act on the arterial wall not only through the amplitude of peak systolic and end-diastolic blood pressure but also through several other mechanical factors involving the level of pulse pressure and heart rate and also blood pressure variability. Thus, in addition to the level of blood pressure, carotid artery distension is specifically influenced by two factors independently implicated in the epidemiologic cardiovascular risk: pulse pressure and heart rate.

Ambulatory blood pressure profile after carotid endarterectomy in patients with ischaemic arterial disease.

OBJECTIVE: To assess the circadian blood pressure profile observed 3 months after endarterectomy. DESIGN: Twenty-five patients undergoing unilateral or bilateral carotid endarterectomy were compared with a control population of 20 patients, matched for age, sex, weight and drug therapy. Casual mean blood pressure measured by mercury sphygmomanometry was similar in both groups. RESULTS: Non-invasive ambulatory blood pressure monitoring showed that, whereas mean arterial pressure was identical in both groups, the group undergoing surgery had a significant increase in pulse pressure and its variability over 24 h. Such abnormalities predominated during the nocturnal period, in which the reduction in systolic blood pressure was less pronounced in the operated group than in controls. For all parameters there was no significant difference between subjects with unilateral or bilateral endarterectomy. CONCLUSION: This study provides evidence that patients with carotid endarterectomy were characterized in the long term by an increase in the pulsatile component of blood pressure and its variability, in association with a disturbance in the physiological circadian rhythm. Such findings were not identified using casual blood pressure measurements.

Comparison of effects of felodipine versus hydrochlorothiazide on arterial diameter and pulse-wave velocity in essential hypertension.

In a double-blind cross-over study, the arterial changes produced by hydrochlorothiazide were compared with those observed after the calcium antagonist felodipine in 16 patients with mild to moderate systemic hypertension. Diameter changes at the site of the common carotid and brachial arteries were investigated using pulsed Doppler velocimetry, and pulse-wave velocities of the aortic, brachial and femorotibial areas were measured using standard noninvasive techniques. Whereas hydrochlorothiazide and felodipine similarly decreased blood pressure, hydrochlorothiazide did not change pulse-wave velocity, and the diameters of the brachial and common carotid arteries. Felodipine significantly decreased pulse-wave velocity, and increased brachial arterial diameter and compliance, with no change in carotid arterial diameter. Evidence was found that although felodipine had specific effects on the arterial system of hypertensive subjects, hydrochlorothiazide did not produce any sizable arterial change. These differential effects may influence specifically the heart afterload, with important consequences for diuretics that are known to cause minimal changes in cardiac structure and function.

Converting enzyme inhibition: dissociation between antihypertensive and arterial effects.

In this study the dose-response curves reflecting the arterial and the antihypertensive effects of converting enzyme inhibition were analysed. The BP measurement (using a random zero sphygmomanometer) and its decrease following converting enzyme inhibition were used as a marker of the arteriolar effect of the drug. The effect on conduit arteries was evaluated through determination of carotid-femoral pulse wave velocity used as an index of arterial distensibility. We compared the dose-response curves of these two parameters in a double-blind study carried out in 24 patients with essential hypertension, who were randomised between placebo and 2, 4 and 8 mg of the converting enzyme inhibitor trandolapril given for 8 days. The antihypertensive effect was observed from 2 mg, at which dose the plateau of BP reduction was already achieved. No significant correlation was found between dose and BP reduction (r = -0.34), whereas the dose was significantly related to the change in pulse wave velocity (r = -0.56, P < 0.01). No significant correlation was found between changes in BP and change of pulse wave velocity. The study provides evidence that the effect on the conduit artery was obtained for higher doses than the BP effect in patients treated for hypertension by the converting enzyme inhibitor trandolapril.

Sodium, large arteries and diuretic compounds in hypertension.

BACKGROUND: Clinical and experimental data have shown that different antihypertensive drugs do not cause similar changes in arterial compliance for an equipotent blood pressure reduction. There are no clear data on the effects of sodium and diuretics on the visco-elastic properties of the hypertensive arterial wall. DATA ANALYSIS: Cross-sectional epidemiological studies suggest that for given values of age and blood pressure, pulse wave velocity is lower in the presence than in the absence of a low sodium intake. Longitudinal studies indicate that in hypertensive subjects, a low sodium intake is associated with a larger brachial artery diameter than that seen with a high sodium intake. In hypertension in the elderly and in severe hypertension with end-stage renal disease, a sodium overload reduces arterial compliance and distensibility independently of blood pressure changes. In animal studies, the diuretic compounds cycletanine and indapamide increase systemic and carotid compliance independently of blood pressure changes. In contrast, in a crossover study in hypertensive subjects, the diuretic agent hydrochlorothiazide did not change arterial compliance and pulse wave velocity while the calcium entry-blocker felodipine did improve these hemodynamic parameters. CONCLUSION: The studies reviewed indicate that sodium may act on the arterial wall independently of blood pressure changes. the contribution made by counter-regulatory mechanisms, which may be related to the renin-angiotensin and the sympathetic nervous systems, might explain the differences between the clinical and the experimental changes observed with diuretic compounds.

Dose optimization study of arterial changes associated with angiotensin converting enzyme inhibition in hypertension.

BACKGROUND: In treating hypertension the optimal dose of angiotensin converting enzyme (ACE) inhibitor is derived from dose-response curves that relate the quantity of drug taken to the resulting fall in blood pressure; the blood pressure fall reflects a decrease in vascular resistance and hence, a degree of arteriolar vasodilation. However, ACE inhibition dilates not only the small arteries but also the larger calibre arteries, which increases compliance. Given the differences in structure and function of large and small arteries, the optimal drug dose for a given vessel may differ according to the size and structure of the vessel. DOSE-RESPONSE EFFECTS IN CLINICAL STUDIES: Clinical studies indicate that in the brachial artery territory, larger doses are required to obtain arterial dilation than to produce a decrease in vascular resistance. In the aorta, an improvement in arterial compliance and distensibility is governed both by the fall in blood pressure and the drug dose. Finally, for the femoral artery, the degree of arterial dilation is influenced markedly only by the drug dose. APPLICATION TO TREATMENT: An understanding of the drug dose required to produce a given change in the hypertensive arterial system may have important implications for the control of blood pressure. For a given mean arterial pressure, systolic blood pressure is lower and diastolic blood pressure higher when aortic compliance is increased, a haemodynamic change commonly seen following ACE inhibition. Recent double-blind studies have shown that ACE inhibitors produced a more pronounced decrease in systolic than diastolic blood pressure. CONCLUSION: These findings indicate that the optimum doses required to improve the arterial wall in large arteries must be evaluated by long-term antihypertensive therapy.

Large artery dilation produced by converting enzyme inhibition in hypertension: therapeutic aspects.

Large artery dilation is produced by angiotensin-converting enzyme inhibition in hypertensive subjects despite a significant blood pressure reduction. The resulting increase in arterial compliance may be due both to blood pressure decrease and to arterial smooth muscle relaxation. In healthy volunteers and in hypertensive subjects, dosages causing large artery dilation seem to be higher than those causing pure arteriolar dilation with resulting blood pressure reduction. Similar findings have been noted to obtain compliance enhancement. Such results may be important in considering antihypertensive therapy, particularly when remodeling of the cardiovascular system is considered in long-term treatment.

Ambulatory blood pressure measurement, smoking and abnormalities of glucose and lipid metabolism in essential hypertension.

OBJECTIVE: Casual (mercury sphygmomanometer) and ambulatory blood pressure measurements were determined in 61 subjects with sustained essential hypertension. DESIGN: Patients were classified into three subgroups: smokers or non-smokers; patients with or without hyperglycemia; and patients with or without plasma lipoprotein abnormality. Mean casual blood pressure were shown to be identical in these three subgroups. RESULTS: When ambulatory blood pressure was analyzed, smokers exhibited a significant increase in pulse pressure exclusively during the activity period, whereas diastolic blood pressure and mean arterial pressure (MAP) were not modified in comparison with controls. Patients with abnormal plasma glucose showed a significant increase in systolic and pulse pressure during both activity and non-activity periods, with a slight increase in MAP during the activity period. Patients with and without plasma lipid abnormality displayed similar ambulatory blood pressure. CONCLUSION: The study provides evidence that, in spite of similar casual blood pressure levels among smokers and non-smokers, as well as among those with elevated fasting glucose levels, smokers and patients with hyperglycemia have a higher systolic and pulse pressure during 24-h monitoring, pointing to the possible role of cyclic stress in the deterioration in the structure of the hypertensive arterial wall.

An indirect evaluation of the effect of the autonomic nervous system following converting enzyme inhibition in hypertension.

Common carotid blood flow and cold pressor test were evaluated in 16 patients with sustained essential hypertension before and after 30 days treatment with the converting enzyme inhibitor Enalapril (20 mg). Enalapril decreased blood pressure and carotid vascular resistance with no significant change in heart rate. After treatment, despite a wide range of the responses, the changes in systolic blood pressure to cold test were significantly attenuated, whereas the heart rate responses were not. Acute random and double blind administration of either Cadralazine or Nitrendipine, two vasodilating drugs which are known to cause an activation of the autonomic nervous system, were performed before and after long term treatment by Enalapril. Whereas the blood pressure and heart rate responses to cold test was unmodified by these compounds before Enalapril treatment, significant changes were observed after converting enzyme inhibition: Cadralazine reduced the heart rate response whereas Nitrendipine increased it significantly. The study provides evidence that converting enzyme inhibition causes sympatho-inhibitory influences which are principally observed in stress conditions, with heterogeneous responses depending on the nature and the type of stimulation.

[Cardiac hypertrophy and arterial compliance after antihypertensive treatment]. / Hypertrophie cardiaque et compliance artérielle après un traitement antihypertenseur.

Cardiac hypertrophy in hypertension is related to increased peripheral vascular resistance and reduced aortic compliance. Non-invasive measurement of pulse wave velocities and systolo-diastolic variations of the diameter of the aortic arch show that an increase in the elastic modulus of the aorta is closely related to the increase in cardiac mass. This relationship holds even after correction for mean arterial pressure. Therefore, it has been suggested that, in hypertension, the decreased aortic compliance leads to a disproportionate increase in systolic blood pressure and end systolic wall stress, predisposing to cardiac hypertrophy. The blood pressure, arterial haemodynamics of the forearm (by pulsed Doppler flow measurement) and echocardiographic parameters were studied in 16 patients with permanent essential hypertension, before and 3 months after treatment with perindopril, an ACE inhibitor. In a simple blinded study versus placebo, perindopril was shown to significantly reduce the blood pressure (p less than 0.01) while brachial blood flow increased (p less than 0.01) because of a simultaneous increase in blood flow velocity and arterial diameter. During 5 minutes' occlusion at the wrist, blood flow velocity decreased more in patients taking perindopril than those on placebo (p less than 0.01) whilst the reduction in arterial diameter was equivalent, indicating that the increase in arterial diameter with perindopril could not be explained by flow-dependent dilatation alone but by a direct effect of the drug on the artery. During the treatment phase, brachial arterial compliance increased (p less than 0.01) and pulse wave velocity decreased (p less than 0.01) and there was no change in arterial shear stress defined as the product of mean blood pressure and arterial diameter.(ABSTRACT TRUNCATED AT 250 WORDS)

Non-invasive evaluation of the conduit function and the buffering function of large arteries in man.

The purpose of this study was to validate a two-dimensional (2D) echography coupled range-gated Doppler system for the non-invasive measurement of internal diameter, blood flow velocity, and pulse wave velocity of peripheral arteries, such as the common carotid artery (CCA), femoral artery (FA), and brachial artery (BA) in man. The array of the ultrasonic system and the Doppler probe were attached and formed a fixed angle (38 degrees 30'). The artery was firstly visualized using the echo-graphic array probe in order to position the Doppler beam. Then, the range-gated Doppler system was used to measure both internal diameter and blood flow velocity with the sample volume position covering the internal diameter. Using a hydraulic device, there was an obvious correlation between the calculated and the measured velocities (r = 0.98). Normal values of diameter, blood flow velocity and blood flow were measured in 18 healthy volunteers. The means (+/- 1 standard deviation) was as follows: diameter, CCA = 0.636 +/- 0.027 cm, FA = 0.843 +/- 0.074 cm, BA = 0.302 +/- 0.052 cm; flow velocity, CCA = 19.5 +/- 2.1 cm s-1, FA = 11.4 +/- 1.2 cm s-1, BA = 6.7 +/- 1.0 cm s-1. Blood flows were as follows: CCA, 370.6 +/- 42.5 ml mn-1, FA 387.0 +/- 75.0 ml mn-1 and BA (wrist occlusion) 29.8 +/- 12.5 ml mn-1. The intra-observer reproducibilities for CCA, FA and BA were respectively: for diameter, 4.9%, 4.12% and 14.8%; for velocity, 8.9%, 10.6% and 10.2%. The inter-observer reproducibilities were respectively: for diameter, 5.6%, 5.4% and 11.3% for velocity, 6.5%, 5.7% and 6.3%. Simultaneous determinations of pulse wave velocity from blood flow velocity recording allowed estimations of the distensibility of these arteries. Finally, the coupled echo and range-gated Doppler system permitted non-invasive evaluation of blood flow calculated as the product of the vessel cross-sectional area and measured blood velocity and also of arterial compliance as the ratio of the cross-sectional area and the square of pulse wave velocity. Such estimations of the conduit and buffering functions of peripheral large arteries in man were shown to be more accurate for the common carotid and the femoral arteries than for the brachial artery.