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Biomedical subjects

M E Safar

Publications and source records attributed to M E Safar.

At least 19 recordsLinked to original sources
PubMed2006

Interaction between pulse wave velocity, augmentation index, pulse pressure and left ventricular function in chronic heart failure.

Pulse wave velocity (PWV), the carotid augmentation index (AIx), and pulse pressure (PP) may be prognostic factors in heart failure, but the possible influence of the ejection fraction (EF) and other simple haemodynamic variables on them has not been investigated in this setting. Noninvasive methods were used to measure carotid-radial (CR), carotid-femoral (CF) PWV and AIx, and brachial PP, in 135 consecutive patients with stable symptomatic chronic heart failure. The patients were divided into two groups, with preserved (>or=40%) or reduced (<40%) EF. CF-PWV, AIx and PP were lower in the decreased EF group (8.85+/-2.77 versus 10.60+/-2.75 m/s, P<0.001; 121+/-21 versus 132+/-24, P=0.009 and 41+/-19 versus 67+/-17 mmHg, P<0.001), but CR-PWV values were similar regardless of the EF status. These results were not modified after adjustment for age and sex. Multiple regression analysis showed that AIx and PP were systematically related to time domain parameters (heart rate or ejection duration) and EF, whatever the group. CF-PWV was weakly related to time domain values and unrelated to mean blood pressure (BP) or EF in the preserved EF group, whereas it was related to both mean BP and EF in the low EF group. In conclusion, whatever the EF level, PP and AIx were strongly modulated in the time domain, by pressure and by the EF level. The same relationships were found with CF-PWV, but only in the reduced EF group. Whether CF-PWV is the best prognostic factor in patients with 'diastolic' heart failure must be confirmed in a prospective study.

Aged↗
PubMed2005

Age-related increase of pulse pressure and plasminogen activator inhibitor-1 I/D gene polymorphism in essential hypertension.

BACKGROUND: Pulse pressure (PP), a marker of cyclic strain on the arterial wall, is a significant predictor of cardiovascular (CV) risk, particularly regarding the incidence of coronary arterial stenosis. Genes related to haemostatic and/or fibrinolytic factors are consistently influenced in vitro by mechanical strain. OBJECTIVE: The goal of the present study was to determine, in the three genotypes of the plasminogen activator inhibitor (PAI)-1 gene polymorphism, the gender-adjusted difference in the relationships between age and PP in subjects with never treated essential hypertension. RESULTS: In the studied population, the genotype deletion (D)/D at position -675 of the PAI-1 insertion (I)/D gene polymorphism was associated with a significant increase in the adjusted slope of the curve relating age to PP by comparison with the two other genotypes. No comparable difference in age-related changes in systolic, diastolic or mean blood pressure was found. CONCLUSION: In subjects with essential hypertension, the PAI-1 I/D gene polymorphism modulates the age-mediated increase of PP, suggesting new insights on the complex interactions between genes, mechanical factors and CV risk.

Adult↗
PubMed2004

Association between pulse pressure, carotid intima-media thickness and carotid and/or iliofemoral plaque in hypertensive patients.

Increased common carotid artery intima-media thickness (CCA-IMT) and carotid and/or iliofemoral (C/IF) plaque are frequent in subjects treated for hypertension, but their association with pulse pressure (PP) has rarely been studied. Using ultrasound techniques, CCA-IMT and C/IF plaques were studied in 323 hypertensive subjects, who were classified into four groups according to the adequacy of blood pressure (BP) control (systolic BP (SBP) <140 mmHg and diastolic BP (DBP) <90 mmHg) and PP (high or low). After adjustment for confounding variables, an increase in CCA-IMT was the only factor significantly and independently associated with high PP, irrespective of the effectiveness of blood pressure control and of antihypertensive drug treatment. CCA-IMT correlated with age, PP, waist-to-hip ratio, tobacco consumption, and heart rate. C/IF plaques correlated with age, tobacco consumption, diabetes mellitus, and dyslipidaemia. To conclude, even with SBP<140 mmHg and DBP<90 mmHg on treatment, hypertensive subjects may have increased CCA-IMT values and C/IF plaque. Four cardiovascular risk factors seem to be involved in these alterations, namely tobacco consumption, dyslipidaemia, diabetes and increased PP. Only the latter factor does not have a standardized effective treatment.

Aged↗
PubMed2003

Effect of chronic heart rate reduction with ivabradine on carotid and aortic structure and function in normotensive and hypertensive rats.

BACKGROUND: A reduction of heart rate (HR) by surgical means or pharmacological agents affects the progression and/or regression of atherosclerotic lesions. Nevertheless, the effect of bradycardia per se on large artery structure and function has never been investigated in rat models of hypertension. METHODS: Four groups of Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) were treated for 28 days either by placebo or by the selective HR-reducing agent ivabradine (8.4 mg/kg/day), a novel compound devoid of inotropic or vasodilating effects and without direct action on the autonomic nervous system. At the end of the follow-up period, intra-arterial blood pressure, carotid pulsatile arterial hemodynamics (echo tracking techniques) and the medial cross-sectional area (MCSA) of the aorta and the carotid artery were determined. RESULTS: In conscious animals, chronic administration of ivabradine significantly reduced HR by 26-30% with no change in tail systolic blood pressure. In anesthetized animals, the decrease in HR and the subsequent increase in the diastolic period were responsible for a decrease in diastolic blood pressure. At the site of the large arteries, ivabradine produced a decrease in the MCSA of the thoracic but not of the abdominal aorta, as well as an increase in pulsatile change of the carotid diameter without change in the isobaric distensibility and MCSA. The changes in pulsatile diameter were significantly larger in WKY rats than in SHRs. CONCLUSION: In normotensive and mainly in SHRs, selective chronic HR reduction by ivabradine is associated with alterations in large arteries involving an aortic antihypertrophic effect.

Animals↗
PubMed2003

Influence of L-nitro-arginine methyl ester, acetylcholine, and adenosine on mean blood pressure, pulse pressure, and pulse pressure amplification in rats.

The blood pressure pattern in spontaneously hypertensive rats (SHRs) involves three main characteristics: increase in mean blood pressure (MBP); increase in thoracic aorta (proximal) and iliac (distal) pulse pressure (PP); disappearance of the normal PP amplification between the proximal and the distal arteries. Whether pharmacologic agents may reduce MBP with different or even opposite effects regarding PP and PP amplification has been poorly investigated. In SHRs and Wistar-Kyoto (WKY) anesthetized rats, the NO inhibitor l-nitro-arginine methyl ester (l-NAME) was infused at the dosage of 1 mg/kg for 30 min. Before and after infusion, 7 microg/kg/min acetylcholine (Ach) and 200 mg/kg adenosine (Ado) were perfused for 4 min. Proximal and distal intra-arterial BP was monitored throughout the procedure. In both WKYs and SHRs, l-NAME increased proximal and distal systolic (SBP), diastolic (DBP), and MBP but not PP. Before l-NAME, SBP, DBP, and MBP were significantly reduced by Ado and Ach. After l-NAME, such blood pressure reductions were abolished with Ach but not Ado. In both strains, the proximal and distal PP, when expressed in percent reduction of MBP, were significantly higher under Ado than under Ach. The Ado but not Ach changed PP amplification, causing a reduction in WKYs and an increase in SHRs independent of l-NAME. Vasodilating agents may reduce MBP with significantly different effects on PP. The Ado alters PP amplification, an effect not obtained with the nitric oxide endothelium-dependent vasorelaxing agent Ach. Tail SBP measurements cannot predict such dissociated changes.

Acetylcholine↗
PubMed2002

Effects of atorvastatin on aortic pulse wave velocity in patients with hypertension and hypercholesterolaemia: a preliminary study.

As statins may contribute to plaque stabilisation, it is important to evaluate whether these drugs may modify arterial stiffness. In 23 patients, aged 32-70 years, with hypertension and hypercholesterolaemia, a double-blind randomised study vs placebo was performed to evaluate whether atorvastatin was able to modify aortic stiffness, measured from aortic pulse wave velocity (PWV), after a 12-week treatment. The results revealed that atorvastatin did not change blood pressure, significantly lowered (P<0.003; <0.002) plasma total and LDL cholesterol, and increased aortic PWV by +8% (vs -2% under placebo) (P<or=0.05). The percentage changes in plasma total and LDL cholesterol and in PWV were significantly and negatively correlated, independent of blood pressure level. The finding of increased aortic PWV after 12-week statin treatment agrees with studies in monkeys, indicating that, at the early phase of hypolipidaemic diet but not later, aortic PWV increases transiently as a consequence of the significant reduction of lipid vascular content. In conclusion, the present results support the possibility that statins might contribute to a change in arterial stiffness independent of blood pressure level, and suggest that long-term studies in humans are needed to evaluate the contribution of arterial elasticity to statin-induced vascular remodelling.

Adult↗
PubMed2001

Impact of aortic stiffness attenuation on survival of patients in end-stage renal failure.

BACKGROUND: Aortic pulse wave velocity (PWV) is a predictor of mortality in patients with end-stage renal failure (ESRF). The PWV is partly dependent on blood pressure (BP), and a decrease in BP can attenuate the stiffness. Whether the changes in PWV in response to decreases in BP can predict mortality in ESRF patients has never been investigated. METHODS AND RESULTS: One hundred fifty ESRF patients (aged 52+/-16 years) were monitored for 51+/-38 months. From entry until the end of follow-up, the changes of PWV in response to decreased BP were measured ultrasonographically. BP was controlled by adjustment of "dry weight" and, when necessary, with ACE inhibitors, calcium antagonists, and/or beta-blockers, in combination if necessary. Fifty-nine deaths occurred, including 40 cardiovascular and 19 noncardiovascular events. Cox analyses demonstrated that independent of BP changes, the predictors of all-cause and cardiovascular mortality were as follows: absence of PWV decrease in response to BP decrease, increased left ventricular mass, age, and preexisting cardiovascular disease. Survival was positively associated with ACE inhibitor use. After adjustment for all confounding factors, the risk ratio for the absence of PWV decrease was 2.59 (95% CI 1.51 to 4.43) for all-cause mortality and 2.35 (95% CI 1.23 to 4.41) for cardiovascular mortality. The risk ratio for ACE inhibitor use was 0.19 (95% CI 0.14 to 0.43) for all-cause mortality and 0.18 (95% CI 0.06 to 0.55) for cardiovascular mortality. CONCLUSIONS: These results indicate that in ESRF patients, the insensitivity of PWV to decreased BP is an independent predictor of mortality and that use of ACE inhibitors has a favorable effect on survival that is independent of BP changes.

Adrenergic beta-Antagonists↗
PubMed2001

Should diastolic and systolic blood pressure be considered for cardiovascular risk evaluation: a study in middle-aged men and women.

OBJECTIVES: The goal of this study was to evaluate the role of diastolic blood pressure (DBP) in cardiovascular mortality for different systolic blood pressure (SBP) levels in middle-aged men and women. BACKGROUND: In middle-aged subjects it is unclear whether DBP, in addition to SBP, should be considered for risk evaluation. METHODS: Subjects (77,023 men; 48,480 women) aged 40 to 70 years old, had no major cardiovascular disease, no antihypertensive treatment and were examined at the Centre d'Investigations Preventives et Cliniques between 1972 and 1988. Mortality was assessed for an 8- to 12-year period. RESULTS: In both genders, cardiovascular mortality increased with the SBP level. In men and women with normal SBP levels, DBP did not influence cardiovascular mortality after adjustment for age and SBP. In men with systolic hypertension, a U-shaped curve relationship between cardiovascular mortality and DBP was observed, with the lowest mortality rates in the group with DBP 90 to 99 mm Hg. Compared with this group, age- and SBP-adjusted cardiovascular mortality was higher by 73% (p < 0.02) in the group with DBP <90 mm Hg and by 65% (p < 0.001) in the group with DBP > or =110 mm Hg. In women with systolic hypertension, however, DBP was positively correlated with cardiovascular mortality. CONCLUSIONS: In middle-aged subjects, classification of cardiovascular risk according to DBP levels should take into account gender, especially when SBP levels are elevated. Men with systolic hypertension are at higher risk when their DBP is "normal" than when they present a mild to moderate increase in DBP. In women of the same age, however, systolic-diastolic hypertension represents a higher risk than isolated systolic hypertension.

Adult↗
PubMed2001

Prevention of aortic and cardiac fibrosis by spironolactone in old normotensive rats.

OBJECTIVES: Because the synthesis of aldosterone is mainly modulated by angiotensin II through type I receptor stimulation and because converting enzyme inhibition (CEI) does not modify aortic extracellular matrix in old normotensive rats, the aim of the present study was to determine whether inhibition of aldosterone formation was able to prevent aortic fibrosis in old Sprague-Dawley normotensive rats. BACKGROUND: We have previously shown that long-term aldosterone antagonism prevents the age-related increase in aortic collagen accumulation in young spontaneously hypertensive rats, independent of blood pressure changes. In contrast, we reported that the positive effects of CEI in the prevention of aortic collagen accumulation were related to the inhibition of angiotensin II actions on angiotensin II type I receptors. METHODS: For this purpose, we studied the histomorphometric and stiffness (echo-tracking technique) changes of an eight-week treatment with the aldosterone antagonist spironolactone by comparison with placebo. RESULTS: At the end of treatment, spironolactone in conscious animals did not change intra-arterial blood pressure, aortic and carotid wall thickness, and cardiac weight. Cardiac collagen density and, to a lesser extent, carotid collagen and elastin densities and contents were significantly decreased in association with an increase of carotid distensibility. CONCLUSIONS: These results show that in old normotensive rats, spironolactone can markedly prevent cardiac and, to a lesser extent, arterial fibrosis and improve arterial stiffness, despite a lack of hypotensive effect.

Age Factors↗
PubMed2001

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.

Adult↗
PubMed2001

Pulse pressure and aortic pulse wave are markers of cardiovascular risk in hypertensive populations.

BACKGROUND: Pulse pressure (PP) and aortic pulse wave velocity (PWV) are significant markers of cardiovascular risk, but a similar role for central wave reflections has never been investigated. PROCEDURES: To determine the factors influencing PP, PWV, and carotid wave reflections, a cohort of 1087 patients with essential hypertension either treated or untreated was studied cross-sectionally. Atherosclerotic alterations (AA) were defined on the basis of clinical events and PWV evaluated from an automatic device. The carotid amplification index (CAI), a quantitative estimation of the magnitude of central wave reflections, was measured noninvasively from pulse wave analysis using radial and carotid aplanation tonometry. RESULTS: In the overall population, age and mean arterial pressure represented 30.4%, 32.3%, and 5.6% of the variance of, respectively PP, PWV, and CAI. For the latter, body weight and heart rate represented 22.9% of variability. On the basis of logistic regression, AA were associated, in addition to age, plasma creatinine and HDL cholesterol levels, and tobacco consumption to three mechanical factors, increased PP, increased PWV, and low diastolic blood pressure, but not by CAI (adjusted odds ratio: 1.00; 95% confidence intervals: 0.99-1.01). CONCLUSION: In cross-sectional hypertensive populations, PP and PWV, but not CAI, are significantly and independently associated with cardiovascular amplications.

Aged↗
PubMed2001

Menopause and the characteristics of the large arteries in a population study.

In previous cross-sectional and longitudinal population studies, we found that the slope of systolic pressure on age was steeper in postmenopausal than in premenopausal women. We hypothesised that this observation could be due to a specific effect of menopause on the elasticity of the large arteries. We investigated 315 randomly selected women, aged 30 to 70 years. Based on 5.2 years of follow-up, 166 women were premenopausal and 149 menopausal (44 reaching menopause and 105 postmenopausal). These women were matched on age and body mass index with 315 men. We used a wall-tracking ultrasound system to measure the diameter, compliance and distensibility of the brachial and the common carotid and femoral arteries as well as carotid-femoral pulse wave velocity. Pulse pressure was determined from 24-h blood pressure recordings. Both in menopausal women (r = 0.37; P < 0.001) and in matching male controls (r = 0.16; P = 0.04), pulse pressure widened with increasing age. The slope of the 24-h pulse pressure on age was steeper in menopausal women than in their premenopausal counterparts (0.428 vs -0.066 mm Hg per year; P = 0.003) and than in the male controls (0.428 vs 0.188 mm Hg per year; P = 0.06). After adjustment for age, 24-h mean pressure, body mass index, antihypertensive drug treatment, smoking and the use of oral contraceptives or hormonal replacement therapy, postmenopausal women showed a higher carotid-femoral pulse wave velocity (7.77 vs 6.71 m/s; P = 0.02) and had a slightly greater diameter of the common carotid artery (7.09 vs 6.79 mm; P = 0.07) than their premenopausal counterparts. After similar adjustments, menopausal class was not significantly associated with other vascular measurements in women or with any vascular measurement in control men. In conclusion, menopause per se may increase aortic stiffness. We hypothesise that this phenomenon may contribute to the rise in systolic pressure and pulse pressure in women beyond age 50 and, in turn, may lead to a slight dilatation of the common carotid artery.

Adult↗
PubMed2001

Diabetes mellitus and renal failure: effects on large artery stiffness.

Diabetes mellitus and end-stage renal disease are two pathologic entities associated with increased cardiovascular risk. Several studies have shown that arterial stiffness is increased in both cases and contributes to the increased risk. In order to determine the effect of diabetes and renal failure on arterial stiffness, we conducted a case-control study. One hundred and twenty-two diabetic patients were compared to 122 non-diabetic patients matched to the study group for sex, age, mean arterial pressure, number and localisation of the atherosclerotic alterations. Arterial stiffness was assessed by automatic measurement of the aortic pulse wave velocity (PWV) and by measuring the peripheral and carotid pulse pressure (PP) and reflected waves through analysis of the pulse wave using the principle of applanation tonometry. Aortic PWV was significantly higher in the diabetic subgroup as well as PP at the peripheral and central levels for the same age and mean arterial pressure. In addition, renal failure was independently associated with an increased aortic PWV but not PP in the general population. Independent of the degree of renal failure, a fall in the glomerular filtration rate was also associated with increased aortic PWV. No interaction was noted between renal failure and diabetes mellitus. In conclusion, this study shows that diabetic patients have higher arterial stiffness compared to non-diabetic ones having one or more cardiovascular risk factors, manifested by increased aortic PWV and PP. In addition, renal failure, irrespective of its degree and independent of diabetes mellitus, is associated with increased aortic PWV but not PP.

Adolescent↗
PubMed2001

Creatinine clearance, pulse wave velocity, carotid compliance and essential hypertension.

BACKGROUND: The vascular hallmark of subjects with end-stage renal disease is increased arterial stiffness independent of blood pressure, wall stress, and cardiovascular risk factors such as hypertension, plasma glucose and cholesterol, obesity, and tobacco consumption. Whether arterial stiffness and kidney function are statistically associated in subjects with plasma creatinine < or =130 micromol/L has not yet been determined. Material. In 1290 subjects with normal or elevated blood pressure values and plasma creatinine < or =130 micromol/L, subjects were divided into three tertiles according to the calculated creatinine clearance. Blood pressure, aortic pulse wave velocity (PWV), and standard cardiovascular risk factors were determined in parallel. In 112 of the hypertensive subjects, common carotid and radial artery structure and function (high-resolution echo-Doppler techniques) also were measured. RESULTS: From the 1290 subjects, only the low-tertile group presented a significant negative association between PWV and creatinine clearance independently of blood pressure and standard risk factors. This association was stronger in subjects < or =55 years of age. In the 112 hypertensive subjects, carotid compliance was positively correlated to creatinine clearance even after an adjustment for age, gender, and blood pressure. At less than 55 years of age, creatinine clearance represented 20% of the variance of carotid compliance. Such findings were not observed for radial artery compliance. CONCLUSION: Increased stiffness of central arteries is statistically associated with reduced creatinine clearance in subjects with mild-to-moderate renal insufficiency, indicating that kidney alterations may interact not only with small but also large arteries, and this is independent of age, blood pressure, and standard risk factors.

Adult↗
PubMed2001

Aortic pulse wave velocity as a marker of cardiovascular disease in subjects over 70 years old.

BACKGROUND: Aortic pulse wave velocity (PWV) is a significant and independent predictor of cardiovascular diseases (CVD) in hypertensive subjects and in patients with end-stage renal disease, but its contribution to cardiovascular risk in subjects between 70 and 100 years old has never been tested. PATIENTS: A cohort of 124 subjects (mean age: 87 +/- 7 years) was studied in two geriatric departments in a Paris suburb. Together with sphygmomanometric blood pressure measurements, aortic PWV was measured using a validated automatic device. RESULTS: Blood pressure, heart rate and body mass index, but not age, explained 48% of the PWV variability in this cohort. Furthermore, PWV was the major factor predicting the presence of CVD. The adjusted odds ratio was 17.44 (95% confidence intervals: 2.52-120.55). Antihypertensive drug therapy and low plasma albumin level had only an additive role. Blood pressure, particularly pulse pressure, had no predictive value. CONCLUSION: In 70-100-year-old subjects, aortic PWV is a strong independent marker of CVD, a finding that remains to be to confirmed by long-term longitudinal studies.

Aged↗