Showing papers by "Stéphane Laurent published in 2019"
1,396 citations
TL;DR: The concept of supernormal vascular aging (SUPERNOVA) was proposed in this article, which refers to the life of a supernova, a large explosion that takes place at the end of a star's life cycle.
Abstract: With advancing age, changes in the arterial wall contribute to what has been called vascular aging, and in some prematurely affected subjects even early vascular aging (EVA).1–5 Several years ago,1 we listed various components of EVA, including arteriosclerosis, atherosclerosis, and excess vasoconstriction, with their clinical expression: arterial stiffening and increased central pulse pressure, carotid intima media thickening and endothelial dysfunction, and increased total peripheral resistance, respectively. In this review, we focus on arteriosclerosis, ie, arterial stiffening, for several reasons: this is the most characteristic clinical feature of the aging process of the arterial system,6 its measurement has been well standardized and referenced,7,8 and an increasing number of epidemiological studies have analyzed its independent determinants.9–11 Increased pulse wave velocity (PWV) is the established hallmark of arterial stiffening and is suggested to be one of the best biomarkers available to calculate the prospective cardiovascular risk and mortality risk of an individual.9,10,12,13 EVA can be diagnosed in subjects who present an abnormally high arterial stiffness for their age and sex.In the present review, we propose the concept of supernormal vascular aging (SUPERNOVA). SUPERNOVA can be diagnosed in subjects who present an exceptionally low arterial stiffness for their age and sex. We address the issue of the metrics and definition of EVA and SUPERNOVA as 2 extremes of the distribution of vascular aging. We discuss the concept of extremes in cardiometabolic research. Further, we review the molecular basis and mechanobiology of EVA and SUPERNOVA, in parallel with their epidemiological, genetic, and epigenetic determinants. Finally, we suggest therapeutic options and insist on the need for discovering novel molecular targets for slowing arterial aging and protecting against cardiovascular complications. By choosing the wording SUPERNOVA, we referred to the life of a supernova—a large explosion that takes place at the end of a star’s life cycle. The relationship between supernova and black hole is not firmly established, but physics theory states that in a black hole, time is slowed…like aging of arteries in SUPERNOVA subjects.
113 citations
02 Oct 2019
TL;DR: The results of this post hoc analysis of the randomized Systolic Blood Pressure Intervention Trial (SPRINT) support an incremental predictive role of estimated pulse wave velocity with outcomes beyond Framingham Risk Score.
Abstract: Importance Aortic stiffness, as assessed by carotid-femoral pulse wave velocity, is an independent predictor of future events in individuals with hypertension. Recent data suggest a predictive role of estimated pulse wave velocity (ePWV) calculated by previously published equations using age and blood pressure in future events in individuals with hypertension. Objective To investigate whether ePWV and its response to treatment predict survival in the Systolic Blood Pressure Intervention Trial (SPRINT). Design, Setting, and Participants This exploratory, hypothesis-generating, post hoc secondary analysis conducted from October 1, 2018, to August 31, 2019, examined data from 9361 participants in SPRINT and calculated ePWV at baseline and at 12 months. Adjusted hazard ratios (HRs) with 95% CIs of ePWV per 1 SD were estimated using Cox proportional hazards regression models. A total of 8450 patients were assigned to 4 groups according to their treatment allocation and their response in ePWV after 12 months. Interventions Participants were assigned a systolic blood pressure target of less than 120 mm Hg (intensive treatment) or less than 140 mm Hg (standard treatment). Main Outcomes and Measures The primary composite cardiovascular outcome was myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. Results In the SPRINT population (3332 women and 6029 men; mean [SD] age, 67.9 [9.4] years), ePWV predicted the primary outcome (HR, 1.30 [95% CI, 1.17-1.43];P Conclusions and Relevance These results suggest that, in the SPRINT trial, ePWV predicted outcomes independent of the Framingham Risk Score, indicating an incremental role of markers of aortic stiffness on cardiovascular risk. Better survival of individuals whose ePWV responded to antihypertensive treatment independently of systolic blood pressure reduction suggests a role of markers of aortic stiffness as effective treatment targets in individuals with hypertension.
86 citations
TL;DR: Shear wave speed in the carotid anterior appeared to be the best candidate to evaluate arterial stiffness from ultrafast imaging and increased with blood pressure throughout the cardiac cycle and did not differ between normotensive participants and patients with essential hypertension when compared at similar blood pressures.
Abstract: Shear wave elastography and ultrafast imaging of the carotid artery pulse wave were performed in 27 normotensive participants and 29 age- and sex-matched patients with essential hypertension, and compared with reference techniques: carotid–femoral pulse wave velocity (cfPWV) determined via arterial tonometry and carotid stiffness (carPWV) determined via echotracking. Shear wave speed in the carotid anterior (a–SWS) and posterior (p-SWS) walls were assessed throughout the cardiac cycle. Ultrafast PWV was measured in early systole (ufPWV–FW) and in end-systole (dicrotic notch, ufPWV-DN). Shear wave speed in the carotid anterior appeared to be the best candidate to evaluate arterial stiffness from ultrafast imaging. In univariate analysis, a-SWS was associated with carPWV (r = 0.56, p = 0.003) and carotid-to-femoral PWV (r = 0.66, p
52 citations
TL;DR: A low prevalence of traditional risk factors, an increased aortic pulse wave velocity (aPWV), and an excess of cardiovascular events are associated with inflammatory bowel disease (IBD) as mentioned in this paper.
Abstract: Background Inflammatory bowel disease (IBD) is characterized by a low prevalence of traditional risk factors, an increased aortic pulse‐wave velocity (aPWV), and an excess of cardiovascular events....
34 citations
TL;DR: The large arterial stiffening starts early during CKD, even in participants with a very mild reduction in renal function, as tested in the Paris Prospective Study 3.
Abstract: OBJECTIVE Increased carotid stiffness and remodelling is reported in patients with moderate and advanced chronic kidney disease (CKD) and is associated with cardiovascular events. Here, we tested the hypothesis that carotid artery alterations start earlier, during mild CKD. METHODS Within the Paris Prospective Study 3, a large prospective observational survey of nonreferred people aged 50-75 who received an extensive health check-up, there were 294 participants with glomerular filtration rate (GFR) of at least 45 and less than 60 ml/min per 1.73 m (Stage 3A CKD), 840 participants with GFR 60-89 ml/min per 1.73 m with proteinuria (Stage 2 CKD), 4666 participants with GFR 60-89 ml/min per 1.73 m without proteinuria and 3317 individuals with GFR at least 90 ml/min per 1.73 m at study recruitment. Carotid artery measurements were performed using a high-resolution echotracking device. RESULTS Compared with patients with GFR at least 90 ml/min per 1.73 m, the carotid distensibility and strain progressively decreased (P for trend <0.0001), whereas carotid stiffness progressively increased (P for trend <0.0001) across GFR categories starting at early stage from GFR 60-89 ml/min per 1.73 m without proteinuria. Higher Young's elastic modulus was observed only for Stage 3A CKD, whereas carotid internal diastolic diameter did not differ between groups. CONCLUSION The large arterial stiffening starts early during CKD, even in participants with a very mild reduction in renal function.
23 citations
TL;DR: Nonclinically affected large- and medium-sized arteries in patients with multifocal renal fibromuscular dysplasia exhibit a cluster of diffuse alterations in smooth muscle cell function, arterial geometry, wall characteristics, and mechanical properties.
Abstract: Arterial fibromuscular dysplasia is a nonatherosclerotic, noninflammatory vascular disease, whose pathophysiology is still unknown. We performed deep image-based vascular phenotyping of nonaffected...
14 citations
TL;DR: In this article, a cross-sectional analysis of 8649 adults aged 50 to 75 years was conducted to determine the association between occupational, sport, leisure, and total PA with baroreflex sensitivity (BRS), distinguishing between neural and mechanical BRS.
Abstract: Physical activity (PA) is a preventative behavior for noncommunicable disease. However, little consideration is given as to whether different domains of PA have differing associations with health outcomes. We sought to determine the association between occupational, sport, leisure, and total PA with baroreflex sensitivity (BRS), distinguishing between neural (nBRS) and mechanical (mBRS) BRS. In a cross-sectional analysis of 8649 adults aged 50 to 75 years, resting nBRS (estimated by low-frequency gain, from carotid distension rate and heart rate) and mBRS (carotid stiffness) were measured by high-precision carotid echo-tracking. PA was self-reported using the validated Baecke questionnaire. The associations between PA and nBRS and mBRS were quantified using multivariate linear regression analysis, separately in the working and nonworking population. In working adults (n=5039), occupational PA was associated with worse nBRS (unstandardized β=-0.02; [95% CI, -0.04 to -0.003]; P=0.022) whereas sport PA was associated with better nBRS (β=0.04; [95% CI, 0.02-0.07]; P=0.003) and mBRS (β=-0.05; [95% CI, -0.09 to -0.00001]; P=0.049). Neither leisure PA nor total PA was associated with nBRS or mBRS. In nonworking adults (n=3610), sport PA and total PA were associated with better mBRS (β=-0.08; [95% CI, -0.15 to 0.02]; P=0.012 and β=-0.05; [95% CI, -0.10 to 0.009]; P=0.018) but not nBRS. These findings suggest differential associations between domains of PA and BRS and may provide insights into the mechanisms underlying the association between occupational PA and cardiovascular disease.
8 citations
TL;DR: In this paper, the authors evaluated the feasibility of assessment of central pulse pressure (cPP) with a specific device fitted with a 6-m long hose and looked at the influence of using such cPP within the magnet instead of bPP on aortic distensibility in a control population.
Abstract: OBJECTIVES Aortic distensibility estimation of local aortic stiffness is based on local aortic strains and central pulse pressure (cPP) measurements. Most MRI studies used either brachial PP (bPP) despite differences with cPP, or direct cPP estimates obtained after MRI examination, assuming no major pressure variations. We evaluated the feasibility of assessment of cPP with a specific device fitted with a 6 m long hose (study1) and looked at the influence of using such cPP within the magnet instead of bPP on aortic distensibility in a control population (study 2). METHODS Brachial and central pressures values were recorded with the SphygmoCor XCEL system fitted with 2 and 6 m long tubing randomly assigned on arms. A 6 m long tubing was used in the second study to measure aortic distensibility with MRI. Aortic distensibility was calculated using either bPP (bAD) or cPP (cAD). RESULTS Study1, performed on 38 patients (mean age: 43 ± 17 years), showed no statistical difference between bPP and cPP measured with 2 or 6 m long tubing (0.41 ± 4.45 and 0.78 ± 3.18 mmHg, respectively, both P = ns). In study 2, cAD provided statistically higher values than bAD (1.87 ± 1.43 10 · mmHg, P < 0.001) especially in younger individuals (3.28 ± 0.86 10 · mmHg). The correlation between age and aortic distensibility was stronger with cAD (r = -0.92; P < 0,001) than with bAD (r = -0.88; P < 0.001). CONCLUSION cPP can be estimated with reasonable accuracy during MRI acquisition using a 6 m long tube. Using either cPP or bPP greatly influences aortic distensibility values, especially in young individuals in whom an accurate detection of early or accelerated vascular aging can be of major importance.
6 citations
01 Jan 2019
TL;DR: This chapter details the haemodynamic characteristics of the arterial circulation and describes the various non-invasive methods currently available to measure arterial stiffness and central BP to discuss how these measurements can help understanding the relationship between hypertension and heart failure.
Abstract: Two concepts have gained a growing audience these last years: the pressure amplification between central and peripheral arteries in response to arterial stiffening and pressure wave reflection and the left ventricle (LV)-arterial system coupling in heart failure (notably with preserved ejection fraction also referred to as diastolic heart failure) as arterial stiffening can result in impaired active ventricular relaxation and passive ventricular compliance. The aims of this chapter are (1) to detail the haemodynamic characteristics of the arterial circulation in order to explain why it is important to measure arterial stiffness and central BP in hypertensive patients, (2) to describe the various non-invasive methods currently available to measure arterial stiffness and central BP and (3) to discuss how arterial stiffness and central BP measurements can help understanding the relationship between hypertension and heart failure.
4 citations
01 Jan 2019
TL;DR: It is of crucial importance to increase physical activity and reduce obesity in children in order to reduce arterial stiffness, and thus, decrease the prevalence of high BP in childhood.
Abstract: Children and adolescents with high normal blood pressure and/or high arterial stiffness have a high risk for developing hypertension. Modifiable cardiovascular risk factors, such as dietary salt intake, fructose, and lifestyles including food sources—processed and fast foods—, sleep patterns, stress, and reductions in physical activity, play a crucial role in the transition between high-normal BP and hypertension. In this review, we will analyze the epidemiological and hemodynamic evidence that increased arterial stiffness is a determinant of incident hypertension. We will also address the complexity of this relationship by discussing the hemodynamic and biomechanical pathways involved in the bidirectional influence between arterial stiffness and blood pressure. And then, we will discuss how the concept of early vascular ageing—EVA—can help in understanding the relationship between arterial stiffness and high-normal BP. Finally, we will apply these concepts to the relationship between metabolic syndrome, arterial stiffness and high-normal BP in children. We will demonstrate that it is of crucial importance to increase physical activity and reduce obesity in children in order to reduce arterial stiffness, and thus, decrease the prevalence of high BP in childhood.
01 Jan 2019
TL;DR: A review of the epidemiological and hemodynamic evidences that increased arterial stiffness is a determinant of incident hypertension, and how the concept of Early Vascular Ageing can help understanding the relationship between arterIAL stiffness and prehypertension, is discussed.
Abstract: Children, adolescent, and adults with prehypertension have a high risk for developing hypertension. Modifiable cardiovascular risk factors, such as prediabetes and diabetes mellitus, overweight and obesity, high lipid diet, high salt intake, and lack of regular physical activity play a crucial role in the transition between prehypertension and hypertension. Because these cardiovascular risk factors are key determinants of increased arterial stiffness, and because increased arterial stiffness is a determinant of incident hypertension, the question arises as to whether arterial stiffness plays a crucial role in the transition between early phases of prehypertension and hypertension. In this review, we will analyze the epidemiological and hemodynamic evidences that increased arterial stiffness is a determinant of incident hypertension. We will also address the complexity of this relationship by discussing the hemodynamic and biomechanical pathways involved in the bidirectional influence between arterial stiffness and blood pressure. And then, we will discuss (a) the predictive value of arterial stiffness not only for incident hypertension, but also for cardiovascular events, (b) the influence of low-grade inflammation associated with chronic diseases in the development of arterial stiffness and subsequently hypertension, (c) how the concept of Early Vascular Ageing can help understanding the relationship between arterial stiffness and prehypertension, and (d) the relationships between metabolic syndrome, arterial stiffness, and prehypertension in children.
06 Jun 2019
TL;DR: In 2007, aliskiren was approved as first-in-class direct renin inhibitor, thus introducing a new method of pharmacological interference with the RAAS into the clinics as discussed by the authors.
Abstract: The renin—angiotensin—aldosterone system (RAAS) is one of the oldest hormonal systems—regardless of whether ‘old’ is defined as phylogenetically old, or in the sense of being discovered a long time ago. Originally, the RAAS has been described as a circulating endocrine system, with angiotensinogen being released by the liver, and renin secreted from the juxtaglomerular apparatus of the kidney, both ‘joining’ in the circulation for processing of angiotensin I. For some forms of secondary hypertension, the activation of the RAAS is an obvious and well-examined pathophysiological mechanism. In 2007, aliskiren was approved as first-in-class direct renin inhibitor, thus introducing a new method of pharmacological interference with the RAAS into the clinics. The gene encoding the renin precursor preprorenin is localized on chromosome Iq32. Renin is primarily released by the juxtaglomerular apparatus of the kidney. Renin secretion is under tight control of several parameters, such as blood pressure and blood volume, plasma sodium content, and sympathetic activation.