Roland Asmar

Aortic Stiffness Is an Independent Predictor of All-Cause and Cardiovascular Mortality in Hypertensive Patients

Abstract—Although various studies reported that pulse pressure, an indirect index of arterial stiffening, was an independent risk factor for mortality, a direct relationship between arterial stiffness and all-cause and cardiovascular mortality remained to be established in patients with essential hypertension. A cohort of 1980 essential hypertensive patients who attended the outpatient hypertension clinic of Broussais Hospital between 1980 and 1996 and who had a measurement of arterial stiffness was studied. At entry, aortic stiffness was assessed from the measurement of carotid-femoral pulse-wave velocity (PWV). A logistic regression model was used to estimate the relative risk of all-cause and cardiovascular deaths. Selection of classic risk factors for adjustment of PWV was based on their influence on mortality in this cohort in univariate analysis. Mean age at entry was 50±13 years (mean±SD). During an average follow-up of 112±53 months, 107 fatal events occurred. Among them, 46 were of cardiovascular origin. PWV was significantly associated with all-cause and cardiovascular mortality in a univariate model of logistic regression analysis (odds ratio for 5 m/s PWV was 2.14 [95% confidence interval, 1.71 to 2.67, P <0.0001] and 2.35 [95% confidence interval, 1.76 to 3.14, P <0.0001], respectively). In multivariate models of logistic regression analysis, PWV was significantly associated with all-cause and cardiovascular mortality, independent of previous cardiovascular diseases, age, and diabetes. By contrast, pulse pressure was not significantly and independently associated to mortality. This study provides the first direct evidence that aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in patients with essential hypertension.

Aortic Pulse Wave Velocity as a Marker of Cardiovascular Risk in Hypertensive Patients

Large artery damage is a major contributory factor to cardiovascular morbidity and mortality of patients with hypertension. Pulse wave velocity (PWV), a classic evaluation of arterial distensibility, has never been ascertained as a cardiovascular risk marker. To determine the factors influencing aortic PWV and the potential predictor role of this measurement, we studied a cohort of 710 patients with essential hypertension. Atherosclerosis alterations (AA) were defined on the basis of clinical events. Calculation of cardiovascular risks, by use of Framingham equations, was performed in subjects without AA. PWV was higher in the presence of AA (14.9+/-4.0 versus 12.4+/-2.6 m/s, P<0.0001), even after adjustments on confounding factors and was the first determinant (P<0.0001) of the extent of atherosclerosis assessed as the sum of the atherosclerotic sites. In patients without AA, all cardiovascular risks increased constantly with PWV. Furthermore, at a given age, aortic PWV was the best predictor of cardiovascular mortality. The odds ratio of being in a high cardiovascular mortality risk group (>5% for 10 years) for patients in the upper quartile of PWV was 7.1 (95% confidence intervals 4.5 to 11.3). The presence of a PWV >13 m/s, taken alone, appeared as a strong predictor of cardiovascular mortality with high performance values. This study shows that aortic PWV is strongly associated with the presence and extent of atherosclerosis and constitutes a forceful marker and predictor of cardiovascular risk in hypertensive patients.

Plasma Homocysteine, Aortic Stiffness, and Renal Function in Hypertensive Patients

Hyperhomocysteinemia has been associated with both vascular structure alterations and vascular clinical end points. To assess the relation between plasma homocysteine, structure and function of large arteries, and the presence of clinical vascular disease, we investigated a population of 236 hypertensive patients. We estimated arterial stiffness by measuring the carotid-femoral pulse wave velocity. Total plasma homocysteine was determined by fluorometric high-performance liquid chromatography. The presence of cardiovascular disease was defined on the basis of clinical events, including coronary heart disease, cerebrovascular disease, and peripheral vascular disease. In this population, pulse wave velocity was positively correlated with homocysteine, even after adjustments for age, mean blood pressure, extent of atherosclerosis, and creatinine clearance (P=0.016). Analysis of variance showed statistically significant differences between the mean values of homocysteine, creatinine clearance, and pulse wave velocity according to the extent of atherosclerosis, with an increase in these 3 parameters concomitant with an increase in the number of vascular sites involved with atherosclerosis. In conclusion, in hypertensive patients the levels of homocysteine are strongly and independently correlated to arterial stiffness measured by aortic pulse wave velocity. Plasma homocysteine, creatinine clearance, and aortic pulse wave velocity are higher in patients presenting with clinical vascular disease. These results suggest that the evaluation of aortic distensibility and homocysteine levels can help in cardiovascular risk assessment in hypertensive populations.

Aortic Distensibility in Normotensive, Untreated and Treated Hypertensive Patients

BACKGROUND Compared with normotensive subjects, untreated hypertensive patients show a decrease of their aortic distensibility. Whether antihypertensive treatment, by reducing blood pressure and changing functional and/or structural abnormalities of the arterial wall, may prevent or reverse the arterial damage due to the accelerated ageing process remains unclear. The objective of the present study was to determine, using a cross-sectional approach, whether aortic distensibility as measured by pulse wave velocity, in treated hypertensive patients whose diastolic blood pressure had been normalised for several months, was significantly improved over that of untreated hypertensive patients. METHODS Carotid femoral pulse wave velocity was measured in 124 normotensive subjects and 388 hypertensive patients. The latter group included 164 treated patients with well controlled diastolic blood pressure and 224 untreated hypertensive subjects. The three groups did not differ in other cardiovascular risk factors. RESULTS In each group there was a significant relationship between age and pulse wave velocity. When compared with untreated hypertensives, treated hypertensives with well controlled diastolic blood pressure had significantly lower blood pressure and pulse wave velocity according to age. However, although diastolic blood pressure of well controlled hypertensives was not significantly different from that of normotensive subjects, the aortic distensibility of the controlled hypertensives remained reduced showing two characteristics: a faster increase in pulse wave velocity with age and a negative relationship with HDL-cholesterol. CONCLUSION These results suggest that long-term antihypertensive treatment and control of blood pressure using only diastolic blood pressure criteria may not fully reverse arterial alteration associated with hypertensive vascular disease.

Arterial distensibility and left ventricular hypertrophy in patients with sustained essential hypertension

Reduced aortic distensibility and compliance may participate in the genesis of cardiac hypertrophy in patients with hypertension. In these patients the increase in end-systolic stress, a determinant factor contributing to the development of cardiac hypertrophy, is influenced not only by the geometric properties of the ventricle but also by the level of systolic pressure. In patients with sustained essential hypertension, the degree of cardiac hypertrophy correlates significantly with the increase in aortic rigidity, which is assessed by the calculation of the characteristic impedance, by the measurement of carotid-femoral pulse-wave velocity, or by the calculation of the Peterson elastic modulus at the level of the aortic arch. Dihydralazine-like substances are unable to modify arterial stiffness, whereas calcium-entry blockers and converting-enzyme inhibitors improve arterial stiffness when achieving the same degree of blood pressure reduction. Modifications in the stiffness of the aorta and other large arteries must be considered to understand reversion of cardiac hypertrophy as a result of antihypertensive treatment.

Arterial distensibility and ambulatory blood pressure monitoring in essential hypertension

Arterial distensibility estimated by carotid femoral pulse wave velocity was evaluated in 22 patients with sustained essential hypertension, together with 3 different methods of blood pressure (BP) measurement: mercury sphygmomanometer, semiautomatic BP recording using the Dinamap apparatus and 24-hour ambulatory BP monitoring using a Spacelabs monitor. Although pulse wave velocity did not correlate with BP measured by mercury sphygmomanometer, it strongly and positively correlated with BP measurements using the other 2 procedures. The best correlation was observed with ambulatory BP with respect to systolic BP only (r = 0.685, p less than 0.001). Since cardiovascular morbidity and mortality in hypertensive patients is mainly related to lesions of the large arteries, the determination of pulse wave velocity together with ambulatory BP measurements is proposed for the evaluation of cardiovascular risk.

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.

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.

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.