Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Athanase Benetos is active.

Publication


Featured researches published by Athanase Benetos.


Hypertension | 2001

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

Stéphane Laurent; Pierre Boutouyrie; Roland Asmar; Isabelle Gautier; Brigitte Laloux; Louis Guize; Pierre Ducimetière; Athanase Benetos

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.


Hypertension | 1995

Assessment of Arterial Distensibility by Automatic Pulse Wave Velocity Measurement: Validation and Clinical Application Studies

Roland Asmar; Athanase Benetos; Jirar Topouchian; Pierre Laurent; Bruno Pannier; Anne-Marie Brisac; Ralph Target; Bernard I. Levy

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)


Hypertension | 1997

Pulse Pressure A Predictor of Long-term Cardiovascular Mortality in a French Male Population

Athanase Benetos; Michel E. Safar; Annie Rudnichi; Harold Smulyan; J. L. Richard; Pierre Ducimetière; Louis Guize

Studies on the usefulness of blood pressure as a prognostic factor in cardiovascular disease have more often involved investigations of the levels of diastolic or systolic blood pressure. However, blood pressure may be divided into two other components: steady (mean pressure) and pulsatile (pulse pressure). In this study, the relationship of pulse pressure to cardiovascular mortality was investigated in 19 083 men 40 to 69 years old who were undergoing a routine systematic health examination and were being followed up after a mean period of 19.5 years. Subjects were divided into four groups according to age (40 to 54 and 55 to 69 years) and mean arterial pressure (<107 and > or =107 mm Hg). Each group was further divided into four subgroups according to the pulse pressure level. A wide pulse pressure (evaluated according to the quartile group or as a continuous quantitative variable) was an independent and significant predictor of all-cause, total cardiovascular, and, especially, coronary mortality in all age and mean pressure groups. No significant association between pulse pressure and cerebrovascular mortality was observed. In conclusion, in a large population of men with a relatively low cardiovascular risk, a wide pulse pressure is a significant independent predictor of all-cause, cardiovascular, and, especially, coronary mortality.


European Heart Journal | 2010

Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors: 'Establishing normal and reference values'

Francesco Mattace-Raso; Albert Hofman; Germaine C. Verwoert; Jacqueline C. M. Witteman; Ian B. Wilkinson; John R. Cockcroft; Carmel M. McEniery; Yasmin; Stéphane Laurent; Pierre Boutouyrie; Erwan Bozec; Tine W. Hansen; Christian Torp-Pedersen; Hans Ibsen; Jørgen Jeppesen; Sebastian Vermeersch; Ernst Rietzschel; Marc De Buyzere; Thierry C. Gillebert; Luc M. Van Bortel; Patrick Segers; Charalambos Vlachopoulos; Constantinos Aznaouridis; Christodoulos Stefanadis; Athanase Benetos; Carlos Labat; Patrick Lacolley; Coen D. A. Stehouwer; Giel Nijpels; Jacqueline M. Dekker

Aims Carotid–femoral pulse wave velocity (PWV), a direct measure of aortic stiffness, has become increasingly important for total cardiovascular (CV) risk estimation. Its application as a routine tool for clinical patient evaluation has been hampered by the absence of reference values. The aim of the present study is to establish reference and normal values for PWV based on a large European population. Methods and results We gathered data from 16 867 subjects and patients from 13 different centres across eight European countries, in which PWV and basic clinical parameters were measured. Of these, 11 092 individuals were free from overt CV disease, non-diabetic and untreated by either anti-hypertensive or lipid-lowering drugs and constituted the reference value population, of which the subset with optimal/normal blood pressures (BPs) (n = 1455) is the normal value population. Prior to data pooling, PWV values were converted to a common standard using established conversion formulae. Subjects were categorized by age decade and further subdivided according to BP categories. Pulse wave velocity increased with age and BP category; the increase with age being more pronounced for higher BP categories and the increase with BP being more important for older subjects. The distribution of PWV with age and BP category is described and reference values for PWV are established. Normal values are proposed based on the PWV values observed in the non-hypertensive subpopulation who had no additional CV risk factors. Conclusion The present study is the first to establish reference and normal values for PWV, combining a sizeable European population after standardizing results for different methods of PWV measurement.


Annals of Internal Medicine | 2006

Dogma Disputed: Can Aggressively Lowering Blood Pressure in Hypertensive Patients with Coronary Artery Disease Be Dangerous?

Franz H. Messerli; Giuseppe Mancia; C. R. Conti; Ann C. Hewkin; Stuart Kupfer; Annette Champion; Rainer Kolloch; Athanase Benetos; Carl J. Pepine

Context Experts debate the consequences of excessive lowering of diastolic pressure in patients with hypertension and coronary artery disease. Contribution This report is a secondary analysis of data from a large trial of 2 antihypertensive drug regimens in patients with known coronary artery disease. The authors found a J-shaped relationship between diastolic blood pressure and all-cause death and myocardial infarction, with the increased risk occurring at diastolic blood pressures below 70 to 80 mm Hg, that is, the lower the diastolic pressure, the higher the risk. Cautions The study examined associations between blood pressure and outcomes; it could not prove that the antihypertensive therapy that lowered diastolic pressure too much caused the adverse outcomes. The Editors For 2 decades, the hypertension literature has been haunted by the phenomenon of a paradoxical increase in morbidity and mortality with an excessive decrease in blood pressure (J-curve). Indeed, several reports have shown that low diastolic pressure is associated with an increased risk for coronary heart disease and related mortality in older adults and in patients taking antihypertensive medications (1-13). After doing a review and meta-analysis of pertinent studies, Farnett and colleagues (14) concluded that although there was no consistent J-shaped relationship between stroke and systolic or diastolic pressure, there was a consistent J-shaped relationship for cardiac events and diastolic pressure. These authors stated that this dichotomy in the relationship between diastolic pressure and target organ disease may leave a clinician with the uncomfortable choice of whether to prevent stroke or renal disease at the expense of coronary heart disease. These findings were at variance with the generally accepted dogma formulated by the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) (15), which stated that the relationship between pressure and risk was strong, continuous, independent, predictive and etiologically significant. Within the past decade, the phenomenon of a J-curve has been studied in several large trials of normotensive and hypertensive patients (16-30). Not surprisingly, arguments regarding whether a J-curve could be clinically significant have become somewhat contentious. That is, some rely on evidence that on-treatment diastolic pressure below 70 mm Hg does not increase risk for cardiovascular disease and thus deny an impairment of vital organ perfusion within the usual values achievable by antihypertensive treatment. Others, however, consider the J-curve a more real possibility, particularly for the heart. In contrast to other organs, the heart is perfused mostly during diastole and thus could be more vulnerable to diastolic pressure reduction. If a J-curve did exist, it should be most evident in patients with limited coronary perfusion, in other words, in those with manifest coronary artery disease (CAD). Optimal blood pressure in patients with hypertension and CAD remains controversial because few randomized clinical trials have been done in this population (31, 32). The International Verapamil-Trandolapril Study (INVEST) (33), a randomized trial, evaluated more than 22000 patients with CAD and hypertension. This patient profile, together with unprecedented levels of blood pressure control, provided a unique opportunity to critically investigate the hypothesis that the risk for CAD would increase with an excessive decrease in diastolic pressure. Methods Study Design and Intervention The INVEST design, methods, and principal results have been previously published (33). The trial used an open design with blinded end point assessment. In brief, clinically stable patients with CAD and hypertension were randomly assigned to a verapamil sustained-releasebased or atenolol-based strategy. Patients with previous myocardial infarction (MI) within 3 months of enrollment or class IV or V congestive heart failure were excluded. Blood pressure goals were based on JNC VI (systolic pressure <140 mm Hg and diastolic pressure <90 mm Hg or systolic pressure <130 mm Hg and diastolic pressure <85 mm Hg in patients with diabetes or renal impairment) (15). The addition of trandolapril or hydrochlorothiazide was recommended when necessary to achieve blood pressure goals. Trandolapril was also recommended for patients with heart failure, diabetes, or renal impairment. Documented CAD was defined as any of the following: remote (3 months before enrollment) confirmed MI, coronary angiography showing more than 50% narrowing of at least 1 major coronary artery, diagnosis of classic angina pectoris, or concordant abnormalities on 2 different signals (electrocardiography, echocardiography, or radionuclide scans) from stress test findings concordant for ischemia (for example, ST-segment depression or perfusion defects on radionuclide scanning or wall-motion abnormalities on echocardiography or radionuclide scanning). Patient Monitoring and Follow-up Protocol visits were scheduled every 6 weeks for the first 6 months and then biannually until 2 years after the last patient was enrolled. Patients were assessed for response to treatment, symptoms, treatment adherence, and adverse effects at each visit and at the end of the study as detailed elsewhere (33). Patient follow-up was complete when we received a final assessment form through the online data system or a death report. The Internet-based electronic data collection method used in INVEST did not accept the entry until all required fields were complete. Blood pressure was measured by using a standard mercury sphygmomanometer with an appropriately sized cuff applied to the upper nondominant arm at heart level. By auscultation at the brachial artery, systolic pressure was recorded at the first Korotkoff sound and diastolic pressure was recorded at the disappearance of the fifth Korotkoff sound. Blood pressure was measured twice, at least 2 minutes apart, and the measurements were averaged. Study Outcomes The primary outcome was the first occurrence of all-cause death, nonfatal MI, or nonfatal stroke by intention-to-treat analysis. The MI and stroke definitions are detailed elsewhere (34). These 3 components individually were the main secondary outcomes. For this analysis, additional outcomes included fatal and nonfatal MI, fatal and nonfatal stroke, and average on-treatment blood pressure before outcome or censoring. Ascertainment and blinded adjudication of outcomes were described previously (32). Follow-up data were available for 22008 (97.5%) patients. Statistical Analysis The main conclusions of INVEST were that the 2 treatment strategies were equivalent with respect to the primary outcome, main secondary outcomes, and on-treatment systolic and diastolic pressures. Thus, data for all enrolled patients were combined and included in these analyses following the intention-to-treat principle. A P value of 0.05 or less was considered statistically significant. Patients without a primary outcome event were censored at their latest follow-up visit. Average follow-up systolic and diastolic pressures were calculated for each patient by using all post-baseline results, up to the date of primary outcome or censoring. The baseline value was substituted for patients with no post-baseline data (n= 1154). In this exploratory analysis, the proportions of patients were pooled by 10mm Hg strata of average follow-up systolic pressure, and the distribution of primary outcome event rate was evaluated to determine whether the relationship was linear. A similar presentation was prepared for diastolic pressure. Because the frequency distributions seemed consistent with a quadratic curve, a quadratic Cox proportional hazards model was formed for the time to primary outcome for each blood pressure variable, with factors for blood pressure and blood pressure squared. Similarly, the relationship between each 10mm Hg stratum of average systolic pressure and diastolic pressure and all-cause death, fatal and nonfatal MI, and fatal and nonfatal stroke was evaluated. For the time to primary outcome, a second model was fitted, adjusting for the following baseline covariates: age (10-year increments), sex, race and ethnicity (white, Asian, black, Hispanic, multiracial, or other), previous MI, heart failure (classes I to III), body mass index in increments of 5 kg/m2, U.S. residency, renal impairment, peripheral vascular disease, left ventricular hypertrophy, smoking history, coronary revascularization, dyslipidemia, stroke or transient ischemic attack, angina pectoris, arrhythmia, diabetes, cancer, aspirin use, and average systolic pressure or diastolic pressure and systolic pressure squared or diastolic pressure squared. To identify clinically relevant interactions between the J-shaped curve and baseline diastolic pressure, demographic characteristics, and comorbid conditions for the primary outcome, a 2-step procedure was used. First, baseline covariates were tested individually by adding the variable and 2 interaction terms (variablediastolic pressure and variable[diastolic pressure squared]) to the Cox proportional hazards model. Variables included were age older than 70 years, sex, previous MI, heart failure (classes I to III), previous stroke or transient ischemic attack, diabetes, cancer, renal impairment, hypercholesterolemia, peripheral vascular disease, smoking history, U.S. residency, body mass index greater than 29 kg/m2 (mean baseline body mass index), and diastolic pressure greater than 86 mm Hg (mean baseline diastolic pressure). The change in log likelihood was used to assess the significance of simultaneously adding the 2 interaction terms. The second step in identifying clinically relevant interactions between the J-shaped curve and baseline covariates was to plot the hazard ratios for the primary outcome versus diastolic pressure in the pr


Circulation | 1996

Influence of Angiotensin-Converting Enzyme and Angiotensin II Type 1 Receptor Gene Polymorphisms on Aortic Stiffness in Normotensive and Hypertensive Patients

Athanase Benetos; Sylvie Gautier; Sylvain Ricard; Jirar Topouchian; Roland Asmar; Odette Poirier; Emile Larosa; Louis Guize; Michel E. Safar; Florent Soubrier; Franc¸ois Cambien

BACKGROUND Clinical and experimental studies have demonstrated a major role of the renin-angiotensin system in the functional and structural changes of the large arteries in hypertension. Because genetic studies may help us to understand the mechanisms underlying the involvement of this system in arterial regulation, the present study was designed to assess the contribution of polymorphisms of the ACE insertion/deletion (I/D) and angiotensin II type 1 receptor (AGTR1 A 1166C) genes on aortic stiffness regulation. METHODS AND RESULTS This study included 311 untreated hypertensive and 128 normotensive subjects. Aortic stiffness was evaluated by measurement of the carotid-femoral pulse-wave velocity (PWV). In normotensive subjects, the two polymorphisms did not influence any of the studied parameters. In hypertensive subjects, there was a decreasing trend of mean PWV with the number of ACE D alleles, but this association became significant only after adjustment for blood pressure (P < .05). Conversely, the AGTR1 A 1166C polymorphism was independently associated with aortic stiffness. Mean values of PWV were 11.6 +/- 2.7 m/s in AGTR1 AA homozygotes, 13.3 +/- 3.3 m/s in AC heterozygotes, and 15.3 +/- 4.3 m/s in CC homozygotes (P < .0001 and P < .00001 after adjustment for age and mean blood pressure, respectively). The percentage of variance of PWV explained by AGTR1 A 1166C polymorphism (11.6%) was much larger than that of ACE I/D polymorphism (1.7%). CONCLUSIONS These results suggest that in hypertensive but not normotensive subjects, the AGTR1 and ACE genotypes are involved in the regulation of aortic rigidity. The presence of the AGTR1 C allele is a strong independent determinant of aortic stiffness, whereas presence of the ACE 1 allele is weakly associated with increased stiffness.


Hypertension | 2004

Short Telomeres Are Associated With Increased Carotid Atherosclerosis in Hypertensive Subjects

Athanase Benetos; Jeffrey P. Gardner; Mahmoud Zureik; Carlos Labat; Lu Xiaobin; Chris Adamopoulos; M. Temmar; Kathryn Bean; Frédérique Thomas; Abraham Aviv

Abstract—Recent studies have shown that individuals with shorter telomeres present a higher prevalence of arterial lesions and higher risk of cardiovascular disease mortality. As a group, patients with high blood pressure are at an increased risk for cardiovascular diseases. However, some hypertensive patients are more prone than others to atherosclerotic lesions. The main objective of this study was to examine the relationship between telomere length, as expressed in white blood cells, and carotid artery atherosclerotic plaques in hypertensive males. Data from 163 treated hypertensive men who were volunteers for a free medical examination were analyzed. Extracranial carotid plaques were assessed with B-mode ultrasound. Telomere length was measured from DNA samples extracted from white blood cells. The results of this study show that telomere length was shorter in hypertensive men with carotid artery plaques versus hypertensive men without plaques (8.17±0.07 kb versus 8.46±0.07 kb; P <0.01). Multivariate analysis showed that in addition to age, telomere length was a significant predictor of the presence of carotid artery plaques. The findings from this study suggest that in the presence of chronic hypertension, which is a major risk factor for atherosclerotic lesions, shorter telomere length in white blood cells is associated with an increased predilection to carotid artery atherosclerosis.


Nature Communications | 2013

Telomeres shorten at equivalent rates in somatic tissues of adults

Lily N. Daniali; Athanase Benetos; Ezra Susser; Jeremy D. Kark; Carlos Labat; Masayuki Kimura; Kunj K. Desai; Mark S. Granick; Abraham Aviv

Telomere shortening in somatic tissues largely reflects stem cell replication. Previous human studies of telomere attrition were predominantly conducted on leukocytes. However, findings in leukocytes cannot be generalized to other tissues. Here we measure telomere length in leukocytes, skeletal muscle, skin and subcutaneous fat of 87 adults (aged 19–77 years). Telomeres are longest in muscle and shortest in leukocytes, yet are strongly correlated between tissues. Notably, the rates of telomere shortening are similar in the four tissues. We infer from these findings that differences in telomere length between proliferative (blood and skin) and minimally proliferative tissues (muscle and fat) are established during early life, and that in adulthood, stem cells of the four tissues replicate at a similar rate.


Journal of Hypertension | 1997

Association between high heart rate and high arterial rigidity in normotensive and hypertensive subjects.

Roberto de Sá Cunha; Bruno Pannier; Athanase Benetos; J. P. Siche; Gérard M. London; Jean Michel Mallion; Michel E. Safar

Background The dynamic elastic modulus of central arteries is very frequency-dependent. Although resting heart rate is a potent independent risk factor for morbidity and mortality both from cardiovascular and from noncardiovascular disease, no link between tachycardia and arterial stiffness has ever been established. Objective To relate arterial stiffness to heart rate in a population with relatively low cardiovascular risk. Methods Pulse-wave velocity measurements and highresolution echo-tracking techniques were used to determine the degree of arterial distension (of carotid and femoral arteries, and terminal aorta) and the velocity of the pulse wave (aorta and upper and lower limbs) at the same time as heart rate, in members of a large population of normotensive and hypertensive subjects in a multicenter study in Paris, Fleury-Merogis and Grenoble (France). Results A high heart rate was strongly associated with reduced distension and elevated pulse-wave velocity, even after adjustment for age and blood pressure. A high aortic pulse-wave velocity was also negatively associated with a low baroreflex sensitivity. The most significant associations between high heart rate and high arterial rigidity were found for the carotid artery, the thoracic aorta, and the lower limbs, but there was no significant result for the terminal aorta and the arm arteries. Conclusion This study demonstrates that there is a statistically significant positive link between high heart rate and high arterial stiffness measured at the site of central and lower limb arteries. Since an elevated heart rate has been shown to be associated with cardiovascular risk, such findings may be relevant for future cardiovascular studies in epidemiology.


Hypertension | 1999

Genotype-Phenotype Relationships for the Renin-Angiotensin-Aldosterone System in a Normal Population

Françoise Paillard; Dominique Chansel; Eva Brand; Athanase Benetos; Frédérique Thomas; Stanislaw Czekalski; Raymond Ardaillou; Florent Soubrier

The renin-angiotensin-aldosterone system plays an important role in blood pressure regulation by influencing salt-water homeostasis and vascular tone. The purpose of the present study was to search for associations of single nucleotide polymorphisms on 3 major candidate genes of this system with the plasma concentrations of the corresponding renin-angiotensin-aldosterone system components considered as quantitative phenotypes. Genotyping was performed in 114 normotensive subjects for different variants of the angiotensinogen (AGT) gene (C-532T, G-6A, M235T), the angiotensin I-converting enzyme (ACE) gene [4656(CT)(2/3)], the aldosterone synthase (CYP11B2), and the type 1 angiotensin II receptor (AT1R) gene (A1166C) by hybridization with allele-specific oligonucleotides (ASO) or enzymatic digestion of polymerase chain reaction products. Plasma levels of AGT, ACE, angiotensin II (Ang II), aldosterone, and immunoreactive active renin were measured according to standard techniques. Platelet binding sites for Ang II were analyzed by the binding of radioiodinated Ang II to purified platelets. B(max) and K(D) values of the Ang II binding sites on platelets of each individual were calculated to examine a possible relationship between these parameters and the AT1R genotype. A highly significant association of the ACE 4656(CT)(2/3) variant with plasma ACE levels was observed (P<0.0001). ANOVA showed a significant effect of the AGT C-532T polymorphism on AGT plasma levels (P=0.017), but no significant effect was detectable with the other AGT polymorphisms tested, such as the G-6A or the M235T. A significant effect association was also found between the C-344T polymorphism of the CYP11B2 gene and plasma aldosterone levels, with the T allele associated with higher levels (P=0.02). No genotype effect of the AT1R A1166C polymorphism was detected either on the B(max) or the K(D) value of the Ang II receptors on platelets.

Collaboration


Dive into the Athanase Benetos's collaboration.

Top Co-Authors

Avatar

Michel E. Safar

Paris Descartes University

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Louis Guize

Paris Descartes University

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Roland Asmar

Cardiovascular Institute of the South

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Laure Joly

University of Lorraine

View shared research outputs
Top Co-Authors

Avatar

Olivier Hanon

Paris Descartes University

View shared research outputs
Top Co-Authors

Avatar

Stéphane Laurent

Paris Descartes University

View shared research outputs
Top Co-Authors

Avatar
Researchain Logo
Decentralizing Knowledge