Ageing and blood pressure modulate the relationship between metabolic syndrome and aortic stiffness in never-treated essential hypertensive patients. A comparative study.

OBJECTIVE: The aim of this study was to evaluate the impact of the metabolic syndrome (MS) and its components as defined by the National Cholesterol Education Program Adult Treatment Panel III on arterial stiffness in untreated hypertensive patients. METHODS: This was a cross sectional multi-center study performed in 46 healthcare centers, from 14 countries involved in the Complior study. Four hundred and forty patients (55% male) aged 18-73 years, with untreated essential hypertension were selected at inclusion. All patients underwent a full evaluation for all the risk factors representing the MS and an assessment of arterial stiffness using automatic measurement of carotid-femoral pulse wave velocity (PWV). RESULTS: In the overall population significant correlations were found, respectively, between PWV, MS (R=0.2, P<0.001) and gender (R=0.11, P=0.023) where PWV was higher in women. After adjustment for age and systolic blood pressure (SBP), analysis of covariance showed an independent effect of the MS on PWV, this effect increased with ageing and SBP especially after 47 years (age median, P=0.0047). Moreover, increase of mean PWV was highly associated with the number of MS factors in global population (P<0.001). These findings suggest that MS leads to early arterial wall ageing. CONCLUSIONS: Presence of MS induces an increase of arterial stiffness in untreated hypertensive patients independently from age and SBP. The increase of PWV is proportional to number of risk factors and affects principally patients after mid-age of 47 years where MS has ageing effects on arterial stiffness.

Association between arterial stiffness and atherosclerosis: the Rotterdam Study.

BACKGROUND AND PURPOSE: Studies of the association between arterial stiffness and atherosclerosis are contradictory. We studied stiffness of the aorta and the common carotid artery in relation to several indicators of atherosclerosis. METHODS: This study was conducted within the Rotterdam Study in >3000 elderly subjects aged 60 to 101 years. Aortic stiffness was assessed by measuring carotid-femoral pulse wave velocity, and common carotid artery stiffness was assessed by measuring common carotid distensibility. Atherosclerosis was assessed by common carotid intima-media thickness, plaques in the carotid artery and in the aorta, and the presence of peripheral arterial disease. Data were analyzed by ANCOVA with adjustment for age, sex, mean arterial pressure, and heart rate. RESULTS: Both aortic and common carotid artery stiffness were found to have a strong positive association with common carotid intima-media thickness, severity of plaques in the carotid artery, and severity of plaques in the aorta (P: for trend <0.01 for all associations). Subjects with peripheral arterial disease had significantly increased aortic stiffness (P:=0.001) and borderline significantly increased common carotid artery stiffness (P:=0.08) compared with subjects without peripheral arterial disease. Results were similar after additional adjustment for cardiovascular risk factors and after exclusion of subjects with prevalent cardiovascular disease. CONCLUSIONS: This population-based study shows that arterial stiffness is strongly associated with atherosclerosis at various sites in the vascular tree.

Assessment of arterial distensibility by automatic pulse wave velocity measurement. Validation and clinical application studies.

Pulse wave velocity is widely used as an index of arterial distensibility. The aim of this study was to evaluate the accuracy of a new automatic device to measure it and then to analyze the major determinants of pulse wave velocity by application of this device in a large population. We evaluated the accuracy of on-line and computerized measurement of pulse wave velocity using an algorithm based on the time-shifted and repeated linear correlation calculation between the initial rise in pressure waveforms compared with the reference method (manual calculation) in 56 subjects. The results, analyzed according to the recommendations of Bland and Altman, showed a mean difference of -0.20 +/- 0.45 m/s for the mean carotid-femoral pulse wave velocity values (reference method, 11.05 +/- 2.58 m/s; automatic device, 10.85 +/- 2.44 m/s). The interreproducibility and intrareproducibility of measurements by each method were analyzed with the use of the repeatability coefficient according to the British Standards Institution. The interobserver repeatability coefficient was 0.947 for the manual method and 0.890 for the automatic, and intraobserver repeatability coefficients were 0.938 and 0.935, respectively. We evaluated the major determinants of the carotid-femoral pulse wave velocity measured by the automatic method in a separate study performed in 418 subjects of both sexes without any cardiovascular treatment or complication (18 to 77 years of age; 98 to 222 mm Hg systolic and 62 to 130 mm Hg diastolic pressure).(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of angiotensin II type 1 receptor polymorphism on aortic stiffness in never-treated hypertensive patients.

Several clinical and experimental studies have suggested a significant role of angiotensin II in the development of alterations of small and large arteries. The present study was designed to assess the contribution of polymorphism (corresponding to an A1166-->C transversion) of the angiotensin II type 1 receptor (AT1) gene to aortic stiffness. One hundred thirty-four never-treated hypertensive patients were included in the study. Aortic distensibility was evaluated by measuring carotid-femoral pulse wave velocity. Age, systolic and diastolic pressure, and metabolic parameters were similar in the three genotypes. Pulse wave velocity was 11.4 +/- 2.5 m/s in AT1 AA homozygotes, 12.5 +/- 3.2 m/s in AC heterozygotes, and 14.7 +/- 4.0 m/s in CC homozygotes (P = .003, P < .001 after adjustment for age, blood pressure, and body mass index). Moreover, an interaction was found between AT1 genotype and the ratio of total to high-density lipoprotein cholesterol in terms of the development of aortic stiffness. Thus, a positive correlation was observed between the ratio of total to high-density lipoprotein cholesterol and pulse wave velocity in AC and CC (r = .42, P < .001) but not AA patients. These results suggest that the AT1 gene is involved in the development of aortic stiffness in hypertensive patients and could modulate the effects of lipids on large arteries.

Influence of the angiotensin II type 1 receptor gene polymorphism on the effects of perindopril and nitrendipine on arterial stiffness in hypertensive individuals.

Angiotensin-converting enzyme inhibitors improve arterial stiffness independently of blood pressure reduction. Since we have recently shown that in hypertensive individuals the A1166C polymorphism of the angiotensin II type 1 receptor (AT1-R) is an independent determinant of aortic stiffness, we designed the present study to assess the influence of this polymorphism on the changes of aortic stiffness after chronic treatment with the angiotensin-converting enzyme inhibitor perindopril and the calcium channel blocker nitrendipine. Forty perindopril- and 42 nitrendipine-treated hypertensive individuals were studied. We evaluated aortic stiffness by measuring the carotid-femoral pulse wave velocity. Carriers of the AT1-RC allele showed higher baseline values of pulse wave velocity than AA homozygotes (P < .05). In the perindopril group, a threefold greater reduction in pulse wave velocity was observed in carriers of the C allele than in AA homozygotes (-2.85 +/- 0.62 versus -0.94 +/- 0.32 m/s, respectively; P < .001), whereas in the nitrendipine group, pulse wave velocity decreased only in AA homozygotes and not in AT1-R C carriers (-1.38 +/- 0.35 versus +0.04 +/- 0.60 m/s, respectively; P < .01). These results indicate that according to the AT1-R A1166C genotype, an angiotensin-converting enzyme inhibitor and a calcium channel blocker affect pulse wave velocity in opposite ways. Since some evidence shows that increased pulse wave velocity may enhance cardiovascular risk, it might be useful for physicians to consider the AT1-R genotype when prescribing an angiotensin-converting enzyme inhibitor or calcium channel blocker to a hypertensive individual.

Differential responses of the heart and vasculature to chronic blood pressure reduction in essential hypertension.

BACKGROUND: In subjects with hypertension, converting enzyme inhibitors and calcium entry blockers may decrease arterial stiffness independently of blood pressure changes, but the heterogeneity of response of the arterial tree has never been taken into account. MATERIAL AND METHODS: In 31 subjects with hypertension, we determined through the use of Doppler echographic techniques the compliance and distensibility of the common carotid and femoral arteries and of the abdominal aorta, the radial artery wall thickness, and cardiac mass. In a double-blind randomized study, the converting enzyme inhibitor ramipril and the calcium entry blocker nitrendipine were studied and compared during 12 weeks treatment, then 4 weeks after treatment was stopped. RESULTS: The two drugs caused significantly different plasma levels of active renin, angiotensin I, and norepinephrine but the same effects on blood pressure, cardiac mass, radial artery wall thickness, and stiffness indices. In contrast, the effect of treatment differed substantially according to the site of cardiovascular measurements. Although cardiac mass decreased significantly in parallel with blood pressure reduction, no change in radial artery wall thickness occurred. Carotid compliance and distensibility increased significantly, even after drug treatment was stopped, whereas little or no change was observed for the femoral artery and the abdominal aorta. CONCLUSION: This study provides evidence that the changes in cardiovascular structure and function with ramipril and nitrendipine treatment are poorly influenced by their different mechanisms of action but highly dependent on the site of measurements. The results suggest that local autocrine-paracrine mechanisms act synergistically with blood pressure to produce cardiovascular changes.

Pulse wave velocity as endpoint in large-scale intervention trial. The Complior study. Scientific, Quality Control, Coordination and Investigation Committees of the Complior Study.

OBJECTIVE: To evaluate the ability of an antihypertensive therapy to improve arterial stiffness as assessed by aortic pulse wave velocity (PWV) in a large population of hypertensive patients. SETTING: Sixty-nine healthcare centres, private and institutional (19 countries). PATIENTS: Subjects aged 18-79 years, with essential hypertension. A total of 2,187 patients were enrolled; 1,703 (52% male) completed the study: mean age = 50 +/- 12 years; mean baseline systolic/diastolic blood pressure (S/D BP) = 158 +/- 15/98 +/- 7 mmHg; mean baseline carotid-femoral PWV = 11.6 +/- 2.4 m/s. INTERVENTIONS: Patients were treated for 6 months, starting with perindopril (angiotensin converting enzyme (ACE) inhibitor) 4 mg once daily (OD), increased to 8 mg OD, and combined to diuretic (indapamide 2.5 mg OD) if BP was uncontrolled (> 140/90 mmHg). RESULTS: It was feasible to measure carotid-femoral PWV using the automatic device Complior at inclusion, 2 and 6 months, along with conventional BP assessments in a population of 1,703 patients. Significant decreases (P < 0.001) in BP (systolic: -23.7 +/- 16.8, diastolic: -14.6 +/- 10 mmHg), and carotid-femoral PWV (-1.1 +/- 1.4 m/s) were obtained at 2 and 6 months. CONCLUSIONS: The Complior Study is the first study to show the feasibility of a large-scale intervention trial using PWV as the endpoint in hypertensive patients. Adequate results may be obtained using an automatic device and rigorous criteria for assessment. A long-term controlled intervention study is needed to confirm the results of the present uncontrolled trial.

Prevalence and circadian variations of ST-segment depression and its concomitant blood pressure changes in asymptomatic systemic hypertension.

Coronary artery disease is a major complication of hypertension; one of its manifestations is silent ischemia. The aim of this study was to assess the prevalence and circadian distribution of ST-segment depression together with concomitant blood pressure (BP) and heart rate variations. One hundred patients (male:female ratio 1:1) with a mean age (+/- SD) of 51 +/- 8 years underwent ambulatory monitoring using the combined AMP 5600 monitor which simultaneously records a continuous Holter electrocardiogram and intermittent noninvasive BP measurements at 15-minute intervals, with extra measurements triggered by detection of a horizontal or downsloping ST depression (> 1 mm and >60 seconds). Cardiovascular risk factors were fully evaluated in all patients; accurate and reliable echocardiogram enabled left ventricular mass index to be calculated in 52 patients. Twenty-three patients (15 men and 8 women) experienced a total of 72 episodes of ST depression. Duration of such episodes (mean +/- SD) was 132 +/- 65 seconds and amplitude was 1.51 +/- 0.55 mm. Circadian distribution showed 2 peaks: on awakening and in the late afternoon periods. The mean ambulatory BP load was greater in the patients with than without ST-segment depression for both systolic and diastolic BP (135 +/- 14 vs 129 +/- 15 and 84 +/- 8 vs 79 +/- 10 mm Hg, respectively; p < 0.01). Plasma glucose (5.83 +/- 0.70 vs 5.46 +/- 0.71 mmol/L; p = 0.04) and self-related work-related stress levels (22% vs 13%; p = 0.03) were also higher in patients with ST-segment depression. There were no significant differences between groups for clinical parameters, left ventricular mass index, and other cardiovascular risk factors. During ST depression episodes, systolic BP increased by 9 +/- 15 mm Hg, diastolic BP by 7 +/- 11 mm Hg, and heart rate by 5 +/- 17 beats/min. Thus, 24-hour Holter electrocardiographic monitoring showed ST depression episodes in 23 of 100 hypertensive patients (23%); ambulatory BP load was greater in these patients. BP variations, and mainly its elevation, may trigger such episodes of ST-segment depression.

Reference values for clinic pulse pressure in a nonselected population.

A wide pulse pressure (PP) may constitute an independent predictor of cardiovascular morbidity and mortality. We assessed the reference values of brachial clinic PP, according to age and gender in a nonselected population (61,724 subjects) who were undergoing a routine systematic health examination. According to mean values, 50 mm Hg is likely the reference value for clinic PP in both men and women. Diagnostic thresholds for clinic PP (> or =65 mm Hg) determined either by adding 2 SD to the means or from the 95th percentiles are in close agreement with clinic PP values previously reported to be associated with increased cardiovascular morbidity and mortality.

Assessment of the acute arterial effects of converting enzyme inhibition in essential hypertension: a double-blind, comparative and crossover study.

In subjects with essential hypertension, angiotensin-converting enzyme (ACE) inhibition increases arterial diameter, compliance and distensibility of peripheral muscular arteries in association with blood pressure reduction. Whether pulse pressure amplification is modified by ACE inhibition and whether changes in compliance and distensibility are due to a drug effect on the arterial wall, to the blood pressure reduction or to a combination of both factors, is largely ignored. In a randomised, double-blind crossover trial, we used the ACE inhibitor quinapril as a marker to evaluate the changes in: pulse pressure amplification (applanation tonometry), carotid compliance and distensibility (echo-tracking technique), and aortic distensibility (measured from pulse wave velocity). Quinapril decreased in the same extent carotid and brachial pulse pressure, thus causing a resetting of pulse pressure amplification toward normal values. Carotid compliance and distensibility as well as aortic distensibility increased significantly. Based on three-way analysis of variance, it was shown that, whereas the changes in carotid stiffness were exclusively due to blood pressure reduction and not to a drug-induced relaxation of the arterial wall, the changes in aortic distensibility were due to the combination of both factors. Thus, using an atraumatic non-invasive procedure, it was possible to show that: (i) ACE inhibition is able to maintain pulse pressure amplification, an important factor contributing to reduce the afterload of the heart; and (ii) ACE inhibition alters the hypertensive arterial wall in a very heterogeneous manner, with a maximal drug effect on muscular large arteries like the abdominal aorta, and not on elastic arteries like the carotid artery and the thoracic aorta.