Showing papers by "Stéphane Laurent published in 2008"

The early life origins of vascular ageing and cardiovascular risk: the EVA syndrome.

Abstract: Early vascular ageing is common in patients with hypertension and increased burden of cardiovascular risk factors, often influenced by chronic inflammation. One aspect of this vascular ageing is arterial stiffening, as measured by increased pulse wave velocity or augmentation index and central pressure. Several studies have indicated that this process starts early in life and that arterial function and ageing properties could be programmed during foetal life or influenced by adverse growth patterns in early postnatal life. This could explain the repeated findings in observational epidemiology that an inverse association exists between birth weight, adjusted for gestational age, and systolic blood pressure elevation in childhood, adolescence and adulthood, as well as for increased cardiovascular risk. One new marker of increased pulse pressure and arterial ageing is telomere length, as regulated by telomerase enzymatic activity. Future studies will hopefully shed light on the possibilities to halt or even reverse vascular ageing, and thereby also influence telomere biology and its different expressions.

The metabolic syndrome in hypertension: European society of hypertension position statement.

Abstract: The metabolic syndrome considerably increases the risk of cardiovascular and renal events in hypertension. It has been associated with a wide range of classical and new cardiovascular risk factors as well as with early signs of subclinical cardiovascular and renal damage. Obesity and insulin resistance, beside a constellation of independent factors, which include molecules of hepatic, vascular, and immunologic origin with proinflammatory properties, have been implicated in the pathogenesis. The close relationships among the different components of the syndrome and their associated disturbances make it difficult to understand what the underlying causes and consequences are. At each of these key points, insulin resistance and obesity/proinflammatory molecules, interaction of demographics, lifestyle, genetic factors, and environmental fetal programming results in the final phenotype. High prevalence of end-organ damage and poor prognosis has been demonstrated in a large number of cross-sectional and a few number of prospective studies. The objective of treatment is both to reduce the high risk of a cardiovascular or a renal event and to prevent the much greater chance that metabolic syndrome patients have to develop type 2 diabetes or hypertension. Treatment consists in the opposition to the underlying mechanisms of the metabolic syndrome, adopting lifestyle interventions that effectively reduce visceral obesity with or without the use of drugs that oppose the development of insulin resistance or body weight gain. Treatment of the individual components of the syndrome is also necessary. Concerning blood pressure control, it should be based on lifestyle changes, diet, and physical exercise, which allows for weight reduction and improves muscular blood flow. When antihypertensive drugs are necessary, angiotensin-converting enzyme inhibitors, angiotensin II-AT1 receptor blockers, or even calcium channel blockers are preferable over diuretics and classical beta-blockers in monotherapy, if no compelling indications are present for its use. If a combination of drugs is required, low-dose diuretics can be used. A combination of thiazide diuretics and beta-blockers should be avoided.

Carotid Plaque, Arterial Stiffness Gradient, and Remodeling in Hypertension

Abstract: The analysis of plaque mechanics along the longitudinal axis (bending strain) may provide useful information because repetitive bending strain of an atherosclerotic plaque can fatigue the wall material and result in plaque rupture. Whether essential hypertension is associated with a specific pattern of bending strain has not yet been determined. The study included 92 patients with an atherosclerotic plaque on the common carotid artery: 66 patients with essential hypertension, either treated or not, and 26 normotensive patients. A novel noninvasive echotracking system (ArtLab; Esaote, The Netherlands) was used to measure intima-media thickness, diameter, and distensibility at 128 sites on a 4-cm-long carotid segment. Carotid plaque was either less elastic than adjacent carotid artery (inward strain) or more elastic (outward strain). Inward strain was more frequently associated with an inward plaque remodeling, whereas an outward strain was more frequently associated with an outer remodeling. In multivariate logistic regression analysis, patients with essential hypertension were more likely to exhibit an inward strain of carotid plaque (odds ratio=6.9 [1.4 to 34.9]; P<0.02), independently of 2 factors favoring inward strain: an outer remodeling (odds ratio=4.6 [1.7 to 13.4]; P<0.005) and the absence of renin-angiotensin system blockers (odds ratio=4.8 [1.1 to 20.4]; P<0.05). In conclusion, arterial wall material of hypertensive patients was less elastic at the site of the plaque than upstream, and carotid was inwardly strained in the zone affected by plaque. This may generate a high level of stress concentrations and fatigue, exposing the plaque to a greater risk of rupture.

Importance of arterial stiffness as cardiovascular risk factor for future development of new type of drugs.

Abstract: Cardiovascular risk prediction relies on classical risk factors such as age, gender, lipids, hypertension, smoking and diabetes. Although the value of such scales of risk is high for populations, its value for individual is reduced and too much influenced by non-modifiable risk factors (age and gender). Biomarkers of risk have been deceiving and genome wide scan approach is too recent. Target organ damage may help in selecting patients at high risk and in determining intervention. Aortic pulse wave velocity, an index of aortic stiffness, has been widely validated as providing additional risk predictions beyond and above classical risk factors, and has now entered into official guidelines. Many interventions (dietary, behaviour, drug treatment) were shown to influence arterial stiffness positively, but little evidence of a direct effect of intervention on arterial stiffness independent of blood pressure is available. New pharmacological targets and new drugs need to be identified. To become a surrogate endpoint for drug development, there is a need to demonstrate that regression arterial stiffness is associated with improved outcome. In parallel to this demonstration, points to be improved are the homogenization and spreading of the technique of measurement, the establishment of a reference value database.

Accelerated arterial stiffening and gene expression profile of the aorta in patients with coronary artery disease.

Abstract: Background Hypertension and chronic renal failure (CRF) are considered models of accelerated arterial stiffening. Arterial stiffness increases further when CRF is associated with hypertension. We hypothesized that, in patients with mild CRF, aortic gene expression profile would include genes involved in arterial calcifications and enlargement. Method We analysed human aorta with the ‘GeneChip Microarray’ technology, in patients with or without CRF, scheduled for a coronary artery bypass graft. Results Nine of 25 patients had high-quality RNA and were included in the study. Among the 101 transcripts differentially expressed between CRF patients and controls, 97 transcripts were overexpressed in CRF patients. Two genes had the highest overexpression in CRF patients: lumican (LUM), involved in the regulation of collagen fibrillogenesis; and ornithine decarboxylase (ODC1), involved in polyamine biosynthesis, smooth muscle cell growth and proliferation. Immunohistochemical staining revealed an increased amount of LUM and ODC1 in the vascular smooth muscle cells (VSMCs) of CRF compared to non-CRF aortic sections. Eight genes were implicated in the regulation of the cytoskeleton (including capping protein muscle Z-line 1 α and moesin) and cell migration, and five genes were implicated in extracellular matrix function and apoptosis. A trend towards an upregulation of candidate genes involved in arterial calcifications was observed in CRF patients, but did not reach statistical significance. Carotid-femoral pulse wave velocity was not correlated with gene expression level. Conclusion In conclusion, these results show that patients at an early stage of CRF have a specific gene expression profile of aortic tissue and suggest that genes implicated in collagen fibrillogenesis, and VSMCs migration and proliferation, particularly LUM and ODC1, may play a role.

Cardiovascular risk assessment through target organ damage: role of carotid to femoral pulse wave velocity.

Abstract: 1. Cardiovascular risk prediction relies on classical risk factors such as age, gender, lipids, hypertension, smoking and diabetes. Although the value of such scales of risk is high for populations, its value for individuals is reduced and much influenced by non-modifiable risk factors (age and sex). 2. Biomarkers of risk have been deceiving and the genome-wide scan approach is too recent to have been useful. Target-organ damage may help in selecting patients at high risk and determine the necessity of intervention. 3. Aortic pulse wave velocity, an index of aortic stiffness, has been widely validated as providing additional risk prediction above and beyond classical risk factors and has now entered the 2007 guidelines for hypertension of the European Society of Hypertension. 4. We aim to show that individual prediction of cardiovascular-related death can be improved by taking aortic stiffness into account in a cohort of patients during a longitudinal follow-up. 5. Points to be improved are the homogenization and spreading of the technique of measurement, the establishment of a reference value database and the demonstration of the added value of aortic stiffness screening and stratification in interventional trials.

Efficacy of manidipine/delapril versus losartan/hydrochlorothiazide fixed combinations in patients with hypertension and diabetes.

Abstract: BACKGROUND Hypertension markedly increases the already high risk for cardiovascular complications in patients with diabetes mellitus. Less than one in eight patients with hypertension and type 2 diabetes have adequately controlled blood pressure. As a result, antihypertensive combinations are now widely used in management of hypertension associated with diabetes. METHODS This double-blind study investigated efficacy of a new fixed dose combination of a calcium antagonist, manidipine 10 mg, and an angiotensin-converting enzyme inhibitor, delapril 30 mg, compared with a combination of an angiotensin receptor blocker, losartan 50 mg, and a diuretic, hydrochlorothiazide 12.5 mg. Patients with hypertension (blood pressure > or = 130/80 mmHg) with controlled type 2 diabetes (HbA1c < or = 7.5%) were randomized to manidipine/delapril (n = 153) or losartan/hydrochlorothiazide (n = 161), administered once daily for 12 weeks. Patients underwent ambulatory blood pressure monitor evaluation at baseline and end of treatment. RESULTS Mean decreases in 24-h systolic blood pressure were seen with both manidipine/delapril (-9.3 mmHg) and losartan/hydrochlorothiazide (-10.7 mmHg) combinations. The mean (95% confidence interval) treatment difference was -1.4 (-4.5/1.8) mmHg, demonstrating noninferiority of the manidipine/delapril combination. Reduction in 24-h diastolic blood pressure (-4.6 versus -4.5 mmHg) and daytime (systolic blood pressure -10.5 versus -11.1 mmHg) and night-time (systolic blood pressure -7.1 versus -9.3 mmHg) blood pressure were also not significantly different between treatments. Compliance and adverse events were comparable for both groups. CONCLUSION The study demonstrated that the combination of manidipine and delapril is as effective as losartan and hydrochlorothiazide in treatment of hypertension in type 2 diabetes.

The management of the type 2 diabetic patient with hypertension - too late and too little: suggested improvements.

Abstract: Patients with comorbid hypertension and type 2 diabetes are common, have a greatly increased risk of premature cardiovascular and renal morbidity and mortality, and are likely to increase substantially in number over the next 10-15 years. We suggest the need for more aggressive management strategies for these patients, regardless of their baseline blood pressure, including the early use of combination therapy with blockers of the renin-angiotensin system.

Aortic, carotid and femoral stiffness: how do they relate? Towards reference values.

Abstract: The determination of aortic stiffness, through the measurement of carotid–femoral pulse wave velocity (PWV), has been recommended by the 2007 European Society of Hypertension (ESH)/International Society of Hypertension (ISH) Guidelines for the Management of Hypertension [1] in order to assess arterial damage, evaluate the level of cardiovascular risk and adapt the therapeutic strategy. Aortic stiffness was introduced into the list of subclinical organ damage [1] of these recommendations because of the large number of epidemiological studies showing its independent predictive value for cardiovascular events [2].

Lowering of brachial pulse pressure in 9379 hypertensives with type 2 diabetes and reduction of cardiovascular events

Abstract: Objectives. Pulse pressure (PP) is a major risk factor for cardiovascular (CV) events, mainly in diabetic hypertensives. The objectives of the study were to determine which clinical characteristics could predict the fall in PP and the reduction of CV events under treatment. Design and methods. Type 2 diabetic hypertensives (n59379) with PPw60 mmHg (mean age 64 years) were included in a cohort study. During the 9 months follow-up, the physician in charge was asked to reinforce treatment in order to lower PP, using preferentially a fixed low-dose perindopril/indapamide combination. Results. After 9 months, PP had fallen by 9.1i0.2 mmHg (pv0.001). Multivariate analysis of the determinants of PP reduction showed a significant positive association with administration of fixed ACEI/diuretic combination (pv0.001) and a negative association with glycated hemoglobin (pv0.01). During the 9 months follow-up, 632 CV events occurred. In multivariate analysis, the administration of fixed perindopril/indapamide combination was associated with a lower incidence of CV events (OR50.64 [0.48–0.86], pv0.01), independently of CV risk factors. Conclusions. The reinforcement of therapeutic measures made possible the reduction of PP in type 2 diabetic hypertensives, under conditions of usual care. Administration of a fixed perindopril/indapamide combination therapy was associated with an independent reduction of CV events.

European guidelines on cardiovascular disease prevention in clinical practice: past, present, and future: a need for joint forces.

Abstract: Abbreviations: BP, blood pressure; CHD, coronary heart disease; CV, cardiovascular; CVD, cardiovascular disease; EASD, European Association for the Study of Diabetes; ECG, electrocardiogram; MONICA, MONitoring of trends and determinants in Cardiovascular diseases; SCORE, Systematic COronary Risk Evaluation; WONCA, World Organisation of National Colleges, Associations and Academies of General Practitioners

Valeur prédictive de l’épaisseur intima-média de l’artère carotide commune sur le risque de survenue d’événements cardiovasculaires

Abstract: Le remodelage arteriel correspond a toute modification de la structure (epaisseur intima-media et diametre arteriel) et de la fonction (i.e. rigidite) arterielle au cours de processus physiologiques et pathologiques. Au cours de l’hypertension, l’atteinte des arteres de gros calibre est caracterisee par une atteinte hypertrophique et une augmentation de la rigidite. Cette atteinte differe le long de l’arbre arteriel : elle est importante pour l’aorte, plus moderee pour les arteres elastiques comme l’artere carotide et paradoxalement diminuee pour les arteres musculaires de plus faible calibre. Il est bien demontre que la rigidite aortique est un facteur de risque independant de survenue d’evenements primaires. La valeur pronostique de l’hypertrophie et de l’augmentation de la rigidite pour le risque de survenue d’un evenement cardiovasculaire est maintenant bien etablie et l’hypertrophie parietale est reconnue comme un facteur d’atherosclerose. De meme, les plaques d’atherosclerose carotidienne sont plus frequentes chez les sujets dont l’epaisseur parietale est augmentee. Il s’avere donc que l’exploration fonctionnelle non invasive des gros troncs arteriels s’impose comme une methode d’identification des patients a haut risque cardiovasculaire. Les techniques actuelles d’exploration reposent sur l’echotracking haute definition, la tonometrie d’aplanation et la velocite de l’onde de pouls, permettant l’evaluation du risque a partir de methodes de mesure non invasives, peu contraignantes pour le patient.

Anévrismes artériels multiples chez un adolescent de 15 ans

Abstract: Auteur(s) : Kim-Thanh Ong1, Anne-Laure Fauret2, Laurence Bal-Theoleyre3, Erwan Bozec1, Stephane Laurent1, Pierre Boutouyrie1 1Service de pharmacologie clinique et Inserm U872, AP-HP, hopital europeen Georges-Pompidou, 20, rue Leblanc, 75908 Paris cedex 15, France 2Service de genetique, AP-HP, hopital europeen Georges-Pompidou, 20, rue Leblanc, 75908 Paris cedex 15, France 3Service de medecine vasculaire, AP-HP, hopital europeen Georges-Pompidou, 20, rue Leblanc, [...]