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Biomedical subjects

Michel E Safar

Publications and source records attributed to Michel E Safar.

At least 19 recordsLinked to original sources

Central blood pressures: do we need them in the management of cardiovascular disease? Is it a feasible therapeutic target?

It is well established that in young and healthy individuals central (aortic or carotid) systolic and pulse pressures are different from peripheral (brachial) corresponding pressures as a consequence of progressive changes in arterial stiffness and pressure wave reflections along the arterial tree. There is evidence indicating that in interventions with pharmaceutical and non-pharmaceutical agents, central pressures are subjected to greater changes than peripheral pressures, and they are more closely related to the pathophysiology of end-organ damage or cardiovascular risk. Therefore central blood pressures may be of higher clinical importance than peripheral pressures. The present review aims to provide an insight into the (patho)physiology of central blood pressures, to present the most accurate techniques for their estimation, and to discuss the available experimental and epidemiological data that support the emerging need for the evaluation of central blood pressures in clinical practice.

Aorta↗

Arterial stiffness and peripheral arterial disease.

Of the atherosclerotic diseases, peripheral arterial disease is the most characterized by its association with systolic hypertension, increased arterial stiffness and disturbed wave reflection. This disease raises the question to which extent sclerosis in 'atherosclerosis' is necessary per se to cause an increase in systolic blood pressure.

Atherosclerosis↗

Atherosclerosis, arterial stiffness and antihypertensive drug therapy.

Increased aortic stiffness is a consequence of cardiovascular (CV) aging and may be observed in the elderly with or without hypertension. Hypertension and arterial stiffness are independent risk factors for CV events, but such events may also be complicated by atherosclerosis, especially in the older population. The purpose of this chapter is to determine whether, in the presence of atherosclerosis, systolic hypertension in the elderly requires specific drug therapy. It will be shown that, in addition to the targeted drug treatment of associated hypercholesterolemia and/or hyperglycemia, the major problem nowadays is to find specific antihypertensive drugs causing a selective reduction of systolic blood pressure (SBP).

Age Factors↗

Parental longevity, carotid atherosclerosis, and aortic arterial stiffness in adult offspring.

BACKGROUND AND PURPOSE: We examined the associations of parental longevity with carotid intima-media thickness, carotid plaques, and aortic arterial stiffness in adult offspring. METHODS: A population of 1117 volunteers who participated in the SUVIMAX Vascular Study (mean age, 59.7 years; 49.0% women) were included. Carotid-femoral pulse-wave velocity (PWV) was used to assess aortic stiffness. Carotid B-mode ultrasound examination included measurements (at sites free of plaque) of intima-media thickness at the common carotid arteries and assessment of atherosclerotic plaques in the extracranial carotid arteries. RESULTS: The prevalence of carotid plaques in subjects whose fathers had died at <65 years, in those whose fathers were alive at 65 years but who had died by 80 years, and in those whose fathers were alive at 80 years was 40.4%, 30.4%, and 28.9%, respectively (P<0.001). The multivariate odds ratios of carotid plaques in the 3 groups of paternal longevity, adjusted for conventional cardiovascular risk factors, were 1, 0.68 (95% CI, 0.48 to 0.96), and 0.69 (95% CI, 0.49 to 0.98), respectively. The mean common carotid arteries intima-media thickness was higher in subjects with premature paternal death in univariate (P<0.007) but not in multivariate (P=0.39) analyses. Mean PWV decreased with increasing paternal longevity in both univariate and multivariate analyses. The multivariate-adjusted means of PWV in the 3 groups of paternal longevity were 11.9+/-0.14, 11.7+/-0.12, and 11.0+/-0.12 m/s (P<0.0001), respectively. In contrast, neither B-mode ultrasound measurements nor PWV measurements were associated with maternal longevity. CONCLUSIONS: These results may indicate that there are modifications of structure and function of large arteries according to paternal longevity.

Aged↗

Gender influence on metabolic syndrome's effects on arterial stiffness and pressure wave reflections in treated hypertensive subjects.

BACKGROUND: In hypertensive subjects, aortic stiffness, an independent predictor of cardiovascular (CV) risk, measured from pulse wave velocity (PWV), contributes to enhance augmentation index (AI), a marker of the timing and amplitude of wave reflections. Whether PWV and AI are correlated and reflect CV risk in hypertensive men and women with metabolic syndrome (MS) remains unknown. METHODS: In a cohort of 613 (364 males) treated hypertensive subjects with and without MS (41% MS) pulse wave analysis was used to determine aortic PWV and carotid AI. CV risk was estimated from standard Framingham equations. RESULTS: In females, but not in males, aortic PWV was higher in subjects with MS, when compared with those without MS (12.7+/-0.3m/s versus 11.1+/-0.4m/s, p<0.001). This result was independent of age and blood pressure. Only in females AI was independently related to the presence of MS; AI did not differ between subjects with or without MS, both males and females. AI did not correlate with PWV, except in males without MS. The overall CV risk was strongly associated to PWV independently of MS and gender, but AI was associated to CV risk only in males. CONCLUSION: In treated hypertensive subjects, the effect of MS on PWV and AI is modulated by gender. The dissociation between PWV and AI observed in women with MS was due to "blunted" wave reflections. This finding is associated with the fact that PWV, but not AI, was a constant marker of CV risk in subjects with MS, whether men and women.

Antihypertensive Agents↗

Aortic stiffness, living donors, and renal transplantation.

In subjects with renal disease, reduced renal function and increased arterial stiffness are significantly associated in cross-sectional studies. The relationship is independent of age, blood pressure (BP), and atherosclerosis. Because both variables are independent predictors of cardiovascular risk, time-dependent relationships between them are important to determine. Aortic pulse wave velocity was measured noninvasively by comparison with healthy volunteers in 101 living kidney donors and their 101 corresponding recipients. Healthy volunteers were divided into 2 groups: one was recipient related through familial links and the other was nonrecipient related. Independently of age, gender, and BP, pulse wave velocity was significantly elevated in donors and recipients by comparison with the 2 groups of healthy volunteers. Pulse wave velocity was significantly higher in the recipient-related than in the nonrecipient-related group. Whereas in healthy volunteers, pulse wave velocity was exclusively related to age, gender, and BP, in donors and recipients, it was rather associated with a cluster of cardiovascular risk factors, including smoking habits and plasma glucose. Major factors related to pulse wave velocity were renal: time since nephrectomy (donation date) in donors, in whom pulse pressure was specifically associated with proteinuria, and renal rejection in recipients. Plasma creatinine doubling secondary to chronic allograft nephropathy was significantly associated with renal rejection and donor pulse wave velocity, independent of age. Our findings strongly suggest consistent interactions (including familial factors) between kidney function and arterial stiffness. Assessment of cause-effect relationships and implication of biochemical and/or genetic factors warrant additional studies.

Adult↗

Determinants of hypertension control in a large French population of treated hypertensive subjects.

Only a minority of all hypertensives is well controlled in the population. In order to assess the proportion of well controlled hypertensives and the factors associated with hypertension control in France, we designed an observational cross-sectional epidemiological study in a population of 4702 treated adult hypertensives selected by general practitioners: EPISTRAT. This hypertensive treated population presented the following characteristics (mean+/-standard deviation): age: 60+/-12 years; blood pressure: 151+/-16/87+/-10 mmHg; men: 58%; body mass index: 27+/-5 kg/m2; diabetes mellitus: 12%; subjects in secondary cardiovascular prevention: 14%. Half of the patients presented two or more CV risk factors in addition to hypertension. Forty-eight per cent of the subjects were treated with antihypertensive monotherapy, 31% with bitherapy and 21% with more than two drugs. Patients with controlled hypertension (<140/90 mmHg) represented "only" 18% of the population. Multivariate analysis showed that male gender and advanced age were the two main variables independently associated with poor blood pressure control. Finally, the majority of patients experienced at least one antihypertensive treatment modification, mainly for insufficient therapeutic effect. In conclusion, this study has shown poor blood pressure control in a primary care-recruited population, especially in males and in the elderly.

Adult↗

Blood pressure components in clinical hypertension.

This review offers a critical evaluation of the remarkable progress in antihypertensive therapy since its inception. Despite the introduction of newer, more sophisticated drugs, treatment results have remained stable. Problems impeding further improvement include limited patient compliance, clinical inertia, incomplete adherence to guidelines, and dependence on brachial artery cuff pressures for diagnosis, risk assessment, and treatment response. Brachial artery systolic and pulse pressures do not reliably represent aortic or carotid artery pressures, which are better risk predictors for the heart and brain. Mean pressure, which is the same throughout the arterial tree, is directly measurable by cuff oscillometry, and might become the best single risk predictor. Available drugs have limited ability to decrease the aortic stiffness that is responsible for the elevated systolic blood pressure of aging. Therefore, to improve risk assessment and therapeutic benefit, we might include mean blood pressure and pulse pressure into blood pressure measurements, pursue efforts to measure central blood pressure, and search for new drugs to reduce arterial stiffness.

Antihypertensive Agents↗

Systolic hypertension in elderly patients.

Pulsatile arterial hemodynamics in cardiovascular diseases indicate that the aortic blood pressure curve may be represented by 2 different phenotypes: one in patients 64 years old and younger and the other in subjects older than 65 years. The 2 blood pressure curves may have exactly the same mean arterial pressure (ie, the same cross-sectional area under the curve) but quite different shapes. In older subjects, systolic blood pressure and pulse pressure are higher, whereas diastolic blood pressure is lower than in younger subjects.

Aged↗

Obesity, arterial stiffness, and cardiovascular risk.

Long-term follow-up studies have indicated that obesity is an independent predictor of cardiovascular risk in both genders. Increased arterial stiffness, as reflected by an increased pulse wave velocity, is significantly and independently associated with higher risk for cardiovascular morbidity and mortality. In recent years, it has been demonstrated that individuals with obesity are likely to have an increase in aortic stiffness, independent of BP level, ethnicity, and age. The pathophysiologic mechanisms that link abdominal adiposity to stiffening are not fully understood. This report focuses on the role of arterial stiffness in individuals with obesity and on the association between this hemodynamic feature and cardiovascular risk.

Arteries↗

Differences between cardiac and arterial fibrosis and stiffness in aldosterone-salt rats: effect of eplerenone.

BACKGROUND: Previous experiments have studied separately the development of either cardiac or aortic fibrosis and stiffness in aldosterone (Aldo)-salt hypertensive rats. Our aim was to determine in vivo the effects of Aldo and the Aldo receptor antagonist eplerenone (Epl) on simultaneous changes in cardiac and arterial structure and function and their interactions. METHODS AND RESULTS: Aldo was administered in uninephrectomised Sprague-Dawley rats receiving a high-salt diet from 8 to 12 weeks of age. Three groups of Aldo-salt rats were treated with 1 to 100 mg/kg-1. d-1 Epl by gavage. Arterial elasticity was measured by elastic modulus (Einc)-wall stress curves using medial cross-sectional area (MCSA). The cardiac and arterial walls were analysed by histomorphometry (elastin and collagen), immunohistochemistry (EIIIA fibronectin, Fn), and Northern blot (collagens I and III). Aldo caused increased systolic blood pressure (SBP), carotid Einc, MCSA, and EIIIA Fn with no change in wall stress or elastin and collagen densities. No difference in collagen mRNA levels was detected between groups. During the same period, cardiac mass and collagen mRNA and protein levels increased markedly in the myocardial tissue. Epl normalised collagen in the myocardium, Eincwall stress curves, MCSA, and EIIIA Fn in Aldo rats. These dose-dependent effects were not accompanied by a consistent reduction in SBP and cardiac mass. CONCLUSIONS: In exogenous hyperaldosteronism in the rat, Aldo causes independently myocardial collagen and arterial Fn accumulation, the latter being responsible for increased intrinsic carotid stiffness. Epl prevents both cardiac and arterial effects but does not reduce consistently SBP.

Animals↗