Showing papers by "Stéphane Laurent published in 2015"

The Structural Factor of Hypertension Large and Small Artery Alterations

Abstract: Pathophysiological studies have extensively investigated the structural factor in hypertension, including large and small artery remodeling and functional changes. Here, we review the recent literature on the alterations in small and large arteries in hypertension. We discuss the possible mechanisms underlying these abnormalities and we explain how they accompany and often precede hypertension. Finally, we propose an integrated pathophysiological approach to better understand how the cross-talk between large and small artery changes interacts in pressure wave transmission, exaggerates cardiac, brain and kidney damage, and lead to cardiovascular and renal complications. We focus on patients with essential hypertension because this is the most prevalent form of hypertension, and describe other forms of hypertension only for contrasting their characteristics with those of uncomplicated essential hypertension.

Metabolic syndrome across Europe: Different clusters of risk factors

Abstract: Background: Metabolic syndrome (MetS) remains a controversial entity. Specific clusters of MetS components - rather than MetS per se - are associated with accelerated arterial ageing and with cardiovascular (CV) events. To investigate whether the distribution of clusters of MetS components differed cross-culturally, we studied 34,821 subjects from 12 cohorts from 10 European countries and one cohort from the USA in the MARE (Metabolic syndrome and Arteries REsearch) Consortium. Methods: In accordance with the ATP III criteria, MetS was defined as an alteration three or more of the following five components: elevated glucose (G), fasting glucose >= 110 mg/dl; low HDL cholesterol, = 150 mg/dl; elevated blood pressure (B), >= 130/ >= 85 mmHg; abdominal obesity (W), waist circumference >102 cm for men or >88 cm for women. Results: MetS had a 24.3% prevalence (8468 subjects: 23.9% in men vs. 24.6% in women, p < 0.001) with an age-associated increase in its prevalence in all the cohorts. The age-adjusted prevalence of the clusters of MetS components previously associated with greater arterial and CV burden differed across countries (p < 0.0001) and in men and women (p < 0.0001). In details, the cluster TBW was observed in 12% of the subjects with MetS, but was far more common in the cohorts from the UK (32.3%), Sardinia in Italy (19.6%), and Germany (18.5%) and less prevalent in the cohorts from Sweden (1.2%), Spain (2.6%), and the USA (2.5%). The cluster GBW accounted for 12.7% of subjects with MetS with higher occurrence in Southern Europe (Italy, Spain, and Portugal: 31.4, 18.4, and 17.1% respectively) and in Belgium (20.4%), than in Northern Europe (Germany, Sweden, and Lithuania: 7.6, 9.4, and 9.6% respectively). Conclusions: The analysis of the distribution of MetS suggested that what follows under the common definition of MetS is not a unique entity rather a constellation of cluster of MetS components, likely selectively risky for CV disease, whose occurrence differs across countries. (Less)

Reference values for local arterial stiffness. Part A: carotid artery

Abstract: Objective: Non-invasive measures of common carotid artery properties, such as diameter and distension, and pulse pressure, have been widely used to determine carotid artery distensibility coefficient - a measure of carotid stiffness (stiffness ∼1/distensibility coefficient). Carotid stiffness has been associated with incident cardiovascular disease (CVD) and may therefore be a useful intermediate marker for CVD. We aimed to establish age and sex-specific reference intervals of carotid stiffness. Methods: We combined data on 22708 individuals (age range 15-99 years, 54% men) from 24 research centres worldwide. Individuals without CVD and established cardiovascular risk factors constituted a healthy sub-population (n=3601, 48% men) and were used to establish sex-specific equations for percentiles of carotid distensibility coefficient across age. Results: In the sub-population without CVD and treatment (n=12906, 52% men), carotid distensibility coefficient Z-scores based on these percentile equations were independently and negatively associated, in men and women, respectively, with diabetes {-0.28 [95% confidence interval (CI) -0.41; -0.15] and -0.27 (-0.43; -0.12)}, mean arterial pressure [-0.26 (-0.29; -0.24) and -0.32 (-0.35; -0.29)], total-to-high-density lipoprotein cholesterol ratio [-0.05 (-0.09; -0.02) and -0.05 (-0.11; 0.01)] and BMI [-0.06 (-0.09; -0.04) and -0.05 (-0.08; -0.02)], whereas these were positively associated with smoking [0.30 (0.24; 0.36) and 0.24 (0.18; 0.31)]. Conclusions: We estimated age and sex-specific percentiles of carotid stiffness in a healthy population and assessed the association between cardiovascular risk factors and carotid distensibility coefficient Z-scores, which enables comparison of carotid stiffness values between (patient) groups with different cardiovascular risk profiles, helping interpretation of such measures.

Pulse wave velocity distribution in a cohort study: from arterial stiffness to early vascular aging.

Abstract: By contrast with other southern European people, north Portuguese population registers an especially high prevalence of hypertension and stroke incidence. We designed a cohort study to identify individuals presenting accelerated and premature arterial aging in the Portuguese population.

Reference values for local arterial stiffness. Part B: femoral artery.

Abstract: OBJECTIVE: Carotid-femoral pulse wave velocity (PWV) is considered the gold standard measure of arterial stiffness, representing mainly aortic stiffness. As compared with the elastic carotid and aorta, the more muscular femoral artery may be differently associated with cardiovascular risk factors (CV-RFs), or, as shown in a recent study, provide additional predictive information beyond carotid-femoral PWV. Still, clinical application is hampered by the absence of reference values. Therefore, our aim was to establish age and sex-specific reference values for femoral stiffness in healthy individuals and to investigate the associations with CV-RFs. METHODS: Femoral artery distensibility coefficient, the inverse of stiffness, was calculated as the ratio of relative diastolic-systolic distension (obtained from ultrasound echo-tracking) and pulse pressure among 5069 individuals (49.5% men, age range: 15-87 years). Individuals without cardiovascular disease (CVD), CV-RFs and medication use (n = 1489; 43% men) constituted a healthy subpopulation used to establish sex-specific equations for percentiles of femoral artery distensibility coefficient across age. RESULTS: In the total population, femoral artery distensibility coefficient Z-scores were independently associated with BMI, mean arterial pressure (MAP) and total to high-density lipoprotein (HDL) cholesterol ratio. Standardized βs, in men and women, respectively, were -0.18 [95% confidence interval (95% CI) -0.23 to -0.13] and -0.19 (-0.23 to -0.14) for BMI; -0.13 (-0.18 to -0.08) and -0.05 (-0.10 to -0.01) for MAP; and -0.07 (-0.11 to -0.02) and -0.16 (-0.20 to -0.11) for total-to-HDL cholesterol ratio. CONCLUSION: In young and middle-aged men and women, normal femoral artery stiffness does not change substantially with age up to the sixth decade. CV-RFs related to metabolic disease are associated with femoral artery stiffness.

An update on the role of adipokines in arterial stiffness and hypertension.

Abstract: Adipokines are hormones produced by adipocytes and have been involved in multiple pathologic pathways, including inflammatory and cardiovascular complications in essential hypertension. Arterial stiffness is a frequent vascular complication that represents increased cardiovascular risk in hypertensive patients. Adipokines, such as adiponectin, leptin and resistin, might be implicated in hypertension, as well as in vascular alterations associated with this condition. Arterial stiffness has proven to be a predictor of cardiovascular events. Obesity and target-organ damage such as arterial stiffness are features associated with hypertension. This review aims to update the association between adipokines and arterial stiffness in essential and resistant hypertension (RHTN).

True antihypertensive efficacy of sequential nephron blockade in patients with resistant hypertension and confirmed medication adherence.

Abstract: Objectives:We assessed the influence of medication adherence on blood pressure (BP) control and target organ damage in a pre-specified analysis of a published trial comparing sequential nephron blockade (SNB) or sequential renin–angiotensin system blockade (SRASB) in patients with resistant hyperten

Large artery stiffness and hypertension after antiangiogenic drugs: influence on cancer progression.

Abstract: BACKGROUND Systemic hypertension is a frequent side effect of antiangiogenic drugs (AADs) and may represent a marker of efficacy on cancer. We hypothesized that large artery properties are affected by AADs, and contribute to the rise of blood pressure and may be better related to cancer progression and mortality than hypertension. METHODS AND RESULTS Participants were studied before AADs (V0), 10 days later (V1) and then every 2 weeks for 6 weeks (V1-V4). We included 57 consecutive patients in whom treatment with sorafenib (400 mg twice daily) or sunitinib (37.5-50 mg once daily) was indicated. The target dose could be adjusted according to tolerance and response. Aortic and carotid stiffness, brachial and central blood pressure and augmentation index were measured noninvasively at each visit. Data regarding cancer progression and mortality were collected at 6 months. Twenty-eight patients (49%) developed hypertension. Brachial SBP significantly increased during follow-up (V0-V1: +9.6 ± 15.2 mmHg, P < 0.001; V0-V4: +6.0 ± 17.8 mmHg, P = 0.04). Central BP, and aortic and carotid stiffness increased independently of brachial BP changes. Aortic and carotid stiffening were associated with cancer progression independently of BP changes [hazard risk 1.24 (1.01-1.51) and 1.34 (1.03-1.73), respectively; P < 0.05], but not with cancer mortality. Brachial SBP had no predictive value. CONCLUSION Large arteries stiffen during AAD treatment partly independently of BP changes. Arterial mechanical properties are associated with BP rise. Arterial stiffening is related with the effects of AAD on cancer progression independently of BP changes. Large artery properties might help monitor AAD therapy in cancer patients.

Within-visit BP variability, cardiovascular risk factors, and BP control in central and eastern Europe: findings from the BP-CARE study.

Abstract: INTRODUCTION AND OBJECTIVE Blood pressure variability (BPV) within 24 h or between visits has been found to represent an independent risk factor for cardiovascular disease. The present study was aimed at determining whether a clinical significance can be given also to the BP variations occurring within a single clinical visit. METHODS BPV was quantified as coefficient of variation and as standard deviation (SD) of the mean of three systolic SBP values within a visit in the context of a large-cross subclinical survey (BP-CARE) of treated hypertensive patients living in Eastern European countries. The study population was divided into coefficient of variation and SD quartiles and for each quartile a relationship was sought with a large number of cardiovascular risk factors based on patients' history, physical and laboratory examinations. RESULTS The 6425 hypertensive patients had an age of 59.2 ± 11 years (mean ± SD); they were equally distributed by sex and displayed an average SD and coefficient of variation amounting to 5.1 ± 6.2 mmHg and 3.5 ± 4.0%, respectively. Compared with the lowest coefficient of variation quartile (Q1), patients in the highest quartile (Q4) showed a significantly greater prevalence of several cardiovascular risk factors, such as age (Q1: 58.5 ± 11 vs. Q4: 60.3 ± 11 years, P < 0.001), serum total cholesterol (Q1: 213.0 ± 46 vs. Q4: 216.4 ± 51 mg/dl, P < 0.05), blood glucose (Q1: 106.2 ± 35 vs. Q4: 109.8 ± 39 mg/dl, P < 0.005), previous cardiovascular events (Q1: 57.4 vs. Q4: 63.9%, P < 0.001), and resistant hypertension (Q1: 26.3 vs. Q4: 34.1%, P < 0.001). They also showed higher office (Q1: 143.2 ± 18 vs. Q4: 154.3 ± 19 mmHg, P < 0.001) and 24-h ambulatory SBP values (Q1: 134.8 ± 17 vs. Q4: 141.2 ± 18 mmHg, P < 0.001). Similar results were obtained when BPV was expressed as SD. CONCLUSION Our study provides evidence that greater within-visit BP variabilities are associated with a worse cardiovascular risk profile. This suggests that even this type of BPV may have clinical significance.

A randomized and controlled study of noninvasive hemodynamic monitoring as a guide to drug treatment of uncontrolled hypertensive patients.

Abstract: Background:In the BEtter control of BP in hypertensive pAtients monitored Using the HOTMAN sYstem study, we investigated whether utilizing noninvasive monitoring of hemodynamic parameters combined with a drug selection algorithm (integrated hemodynamic management – IHM) compared with conventional dr

Contribution of Rare and Common Genetic Variants to Plasma Lipid Levels and Carotid Stiffness and Geometry A Substudy of the Paris Prospective Study 3

Abstract: Background: We assess the contribution of common and rare putatively functional genetic variants (most of them coding) present on the Illumina exome Beadchip to the variability of plasma lipids and stiffness of the common carotid artery. Methods and results: Measurements were obtained from 2283 men and 1398 women, and after filtering and exclusion of monomorphic variants, 32827 common (minor allele frequency >0.01) and 68770 rare variants were analyzed. A large fraction of the heritability of plasma lipids is attributable to variants present on the array, especially for Triglycerides (fraction of variance attributable to measured genotypes: V(G)/Vp=31.4%, P<3.1×10-11) and HDLc (V(G)/Vp=26.4%, P<4.2×10-12). Plasma lipids were associated with common variants located in known candidate genes but no implication of rare variants could be established, however this study had limited power to detect an effect of rare variants at the gene level. Gene-sets for plasma lipids, blood pressure and coronary artery disease were defined on the basis of recent meta-analyses of genome wide association studies (GWAS). We observed a strong association between the plasma lipids gene-set and plasma lipid variables but none of the 3 GWAS gene-sets was associated with the carotid parameters. Significant V(G)/Vp ratios were observed for external (14.5%, P<2.7×10-5) and internal diameter (13.4%, P<4.3×10-4), stiffness (12.5%, P< 8.0×10-4), intima-media thickness (10.6%, P<7.9×10-4) and wall cross sectional area (13.2%, P<2.4×10-5). A significant association was observed between the common rs2903692 polymorphism of the CLEC16A gene and the internal diameter (P<4.3×10-7). Conclusion: These results suggest an involvement of CLEC16A, a gene that has been reported to be associated with immune disorders, in the modulation of carotid vasodilatation.

Early vascular aging (EVA): New directions in cardiovascular protection

Abstract: Early Vascular Aging (EVA): New Directions in Cardiovascular Protection brings together the last decade of research related to the characterization of EVA, as well as the predictive power of pulse wave velocity (PWV). The book presents a novel approach to the problem of cardiovascular disease, showing it in relation to great vessels disease and revealing a comprehensive approach to the problem of increased rigidity of the great vessels, its causes, and further consequences. Information provided is accompanied by online access to a supplemental website with video clips of anatomic specimens, cardiac imaging, and surgical procedures. Key Features: Introduces the latest information on early vascular aging (EVA), complete with summaries of recent evidence and guidelines for relevant risk factor control. Ideal reference for the study of vascular aging, pulse wave velocity, arteriosclerosis, EVA, arterial stiffness, vascular, PWV biomarkers, and cardiovascular disease. Contains all the relevant information available from different fields of knowledge (from basic biology to epidemiology) in regard to EVA. Provides evidence that leads to a new target for interventions, early vascular aging (EVA) in subjects with early onset increased arterial stiffness. Includes online access to a supplemental website with video clips of anatomic specimens, cardiac imaging, and surgical procedures. (Less)

Targeting Central Blood Pressure Through the Macro- and Microcirculation Cross-Talk

Abstract: Central systolic and pulse pressures, indicative of changes in large conduit and small resistance arteries, are independent determinants of organ damage and might represent a main target of antihypertensive treatment. We superimpose here a pharmacological approach on our previous pathophysiological one. First, we review the effects of various drugs on the structural and functional properties of large and small arteries. Then we explain how some pharmacological classes can reverse the vicious circle of aggravation into a virtuous circle of improvement. We focus on antihypertensive drugs, because they have been the most studied, and we emphasize clinical pharmacology. Among antihypertensive drugs, β-blockers, and diuretics have a negligible effect on microvascular structure, while renin–angiotensin system blockers and calcium entry blockers have favorable actions: improved small artery remodeling, reduced large artery stiffness, and lowered central systolic and pulse pressures.

Foot detection and distances by different methods: implications for pulse wave velocity values.

Abstract: W e read with interest the article by Pichler et al. [1] regarding the implications for risk assessment when using two commercial pulse wave velocity (PWV) devices. Following evidences from numerous PWV morbidity–mortality studies, the European Society of Hypertension/ European Society of Cardiology guidelines [2] have established a 10m/s threshold on PWV above which there is overt target organ damage and increased cardiovascular risk. Until 2015, we counted 24 PWV mortality studies, 42% (n1⁄4 10) used Complior SP (Alam Medical, Vincennes, France) and 8% (n1⁄4 2) the SphygmoCor device (AtCor Medical, New South Wales, Australia). The question of heterogeneity in PWV measuring devices is of importance and it is of great interest to check if the 10m/s threshold is applicable to other devices than Complior. Although Pichler et al. [1] tried to answer this issue, their article is misleading on several points. Pilcher et al.’s approach to study classification according to a predetermined threshold is highly sensitive to mild differences. However, the authors did not mention which version of Complior or SphygmoCor devices was used. In a 2005 publication, with a figure very similar to Pichler et al.’s Figure 1, we have highlighted that the algorithm used to detect the foot of the waveform was of great importance [3]. Indeed, the historical Complior SP that used the second derivative algorithm provided lower PWV values than SphygmoCor CVMS that uses the intersecting tangent algorithm, especially in patients with stiff artery and hence with higher blood pressure. These results have been confirmed in several studies [3–6] and has been largely discussed and solved thanks to standardized recommendations by the Arterial Stiffness Collaboration Group for establishing PWV reference values [4]. As the ‘intersecting tangent’ algorithm has been shown to present the least variability, the Artery Society and the 2006 Expert consensus on Arterial Stiffness have advised to use this algorithm [7,8]. For these reasons, the manufacturer has implemented this algorithm in the latest Complior version. When using the same algorithm and the same distance measurement, the new Complior Analyse provided equivalent PWV values to SphygmoCor CVMS and grades ‘excellent’ on the ARTERY society protocol [9]. The second major issue is the distance measurement. When using two devices on the same arterial sites, the same distance should be used as the arterial path is identical. If different distances are used, PWV values are bound to be different [10–12]. Owing to the error that is doubled when measuring distance twice, the direct distance measurement

Aortic Stiffening, Aortic Blood Flow Reversal, and Renal Blood Flow

Abstract: See related article, pp 61–67 Normal arterial aging is characterized by arterial enlargement, wall thickening, and stiffening, which predominates at large arteries.1 Patients with chronic kidney disease (CKD) have an early vascular aging,2 characterized by an accelerated arterial enlargement and stiffening, which occurs in parallel with the decline in glomerular filtration rate (GFR).3 The relationships between central hemodynamics (either arterial stiffness or central blood pressure) and GFR decline are complex and depend mainly on both the stage of the disease—early CKD, advanced CKD or end-stage renal disease—and the level of blood pressure—optimal blood pressure, high normal, and grade 1 to 2 hypertension.3–5 O’Rourke and Safar6 suggested that the torrential flow and low resistance to flow in the kidney expose small arterial vessels of the glomerulus to the high-pressure fluctuations that exist in the renal arteries. Such fluctuations, measurable as central pulse pressure, increase 3- to 4-fold with age. For instance, the loss of renal blood flow autoregulation, because of altered myogenic tone in hypertension, can expose small glomerular vessels to higher pulsatile pressure and flow and favor higher dissipation in the microcirculation, leading to hyperfiltration and glomerulosclerosis.3 Indeed, central pulse pressure was reported to be significantly and independently associated with GFR or proteinuria in cross-sectional studies in patients with CKD.4,7 However, in the longitudinal Nephrotest study5 following prospectively CKD patients for a mean of 3.1 years, central pulse pressure was not significantly and independently associated with the decline in GFR. Thus, it is possible that an adequate autoregulatory capability of the GFR could be maintained for years. The influence of aortic stiffness on GFR is also not straightforward. Although several cross-sectional studies showed a significant and independent association between GFR and aortic stiffness measured through carotid-femoral pulse wave …

Pulse Wave Velocity and Central Blood Pressure

Abstract: An increasing number of physiological studies, as well as pathophysiological, epidemiological and pharmacological studies, have underlined the importance of measuring not only brachial systolic and pulse pressures in hypertensive patients but also central systolic and pulse pressures and pulse wave velocity. The aims of this chapter are to describe the various non-invasive methods currently available to measure pulse wave velocity (PWV) and central BP (cBP) in clinical practice, to detail the normal values in a healthy population and the reference values in a population of hypertensive patients with cardiovascular risk factors, to report the amplitude of changes under antihypertensive treatment in clinical trials and to detail the prognostic values of changes. Since PWV and cBP are two parameters strongly linked by their interdependency for the haemodynamic status of hypertensive patients, they will be addressed in parallel.

Hemodynamic and Mechanical Factors Acting on Arteries

Abstract: Arteries are permanently exposed to mechanical stress. Mechanical stress can be divided according to their nature, either tensile stress or shear stress. Tensile stress corresponds to changes in dimension according to changes in forces applied on the vessel. Shear stress is of a different nature; it corresponds to the friction of viscous fluid (here the blood) on the inner surface of the vessel (here the endothelium). It is to be noted that direct measurement of stress is difficult in vivo and that stress is most of the time deduced from stretch (elongation) and force (derived from pressure). Stress can also be derived from mechanical modelling.

Achieving Goal Blood Pressure

Abstract: Both monotherapy and combination therapy options are appropriate for antihypertensive therapy according to the 2013 European Society of Hypertension (ESH)/European Society of Cardiology (ESC) guidelines. Most patients require more than one agent to achieve blood pressure (BP) control, and adding a second agent is more effective than doubling the dose of existing therapy. The addition of a third agent may be required to achieve adequate BP reductions in some patients. Single-pill fixed-dose combinations (FDCs) allow multiple-drug regimens to be delivered without any negative impact on patient compliance or persistence with therapy. FDCs also have documented beneficial clinical effects and use of FDCs containing two or three agents is recommended by the 2013 ESH/ESC guidelines.