Showing papers by "Stéphane Laurent published in 2012"

Expert consensus document on the measurement of aortic stiffness in daily practice using carotid-femoral pulse wave velocity.

Abstract: Stiffness of elastic arteries like the aorta predicts cardiovascular risk. By directly reflecting arterial stiffness, having the best predictive value for cardiovascular outcome and the ease of its measurement, carotid-femoral pulse wave velocity is now considered the gold standard for arterial stiffness assessment in daily practice. Many different measurement procedures have been proposed. Therefore, standardization of its measurement is urgently needed, particularly regarding the distance measurement. This consensus document advises on the measurement procedures in general and provides arguments for the use of 80% of the direct carotid-femoral distance as the most accurate distance estimate. It also advises the use of 10 m/s as new cut-off value for carotid-femoral pulse wave velocity.

Relationship Between Short-Term Blood Pressure Variability and Large-Artery Stiffness in Human Hypertension Findings From 2 Large Databases

Abstract: Short-term blood pressure (BP) variability predicts cardiovascular complications in hypertension, but its association with large-artery stiffness is poorly understood and confounded by methodologic issues related to the assessment of BP variations over 24 hours. Carotid-femoral pulse wave velocity (cfPWV) and 24-hour ambulatory BP were measured in 911 untreated, nondiabetic patients with uncomplicated hypertension (learning population) and in 2089 mostly treated hyperten- sive patients (83% treated, 25% diabetics; test population). Short-term systolic BP (SBP) variability was calculated as the following: (1) SD of 24-hour, daytime, or nighttime SBP; (2) weighted SD of 24-hour SBP; and (3) average real variability (ARV), that is, the average of the absolute differences between consecutive SBP measurements over 24 hours. In the learning population, all of the measures of SBP variability showed a direct correlation with cfPWV (SD of 24-hour, daytime, and nighttime SBP, r0.17/0.19/0.13; weighted SD of 24-hour SBP, r0.21; ARV, r0.26; all P0.001). The relationship between cfPWV and ARV was stronger than that with 24-hour, daytime, or nighttime SBP (all P0.05) and similar to that with weighted SD of 24-hour SBP. In the test population, ARV and weighted SD of 24-hour SBP had stronger relationships with cfPWV than SD of 24-hour, daytime, or nighttime SBP. In both populations, SBP variability indices independently predicted cfPWV along with age, 24-hour SBP, and other factors. We conclude that short-term variability of 24-hour SBP shows an independent, although moderate, relation to aortic stiffness in hypertension. This relationship is stronger with measures of BP variability focusing on short-term changes, such as ARV and weighted 24-hour SD. (Hypertension. 2012; 60:369-377.) ● Online Data Supplement

Large Artery Stiffening and Remodeling Are Independently Associated With All-Cause Mortality and Cardiovascular Events in Chronic Kidney Disease

Abstract: Chronic kidney disease, even at moderate stages, is characterized by a high incidence of cardiovascular events. Subclinical damage to large arteries, such as increased arterial stiffness and outward remodeling, is a classical hallmark of patients with chronic kidney disease. Whether large artery stiffness and remodeling influence the occurrence of cardiovascular events and the mortality of patients with chronic kidney disease (stages 2–5) is still debated. This prospective study included 439 patients with chronic kidney disease (mean age, 59.8±14.5 years) with a mean measured glomerular filtration rate of 37 mL/min per 1.73 m 2 . Baseline aortic stiffness was estimated through carotid-femoral pulse wave velocity measurements; carotid stiffness, diameter, and intima-media thickness were measured with a high-resolution echotracking system. For the overall group of patients, the 5-year estimated survival and cumulative incidence of cardiovascular events were 87% and 16%, respectively. In regression analyses adjusted on classical cardiovascular and renal risk factors, aortic stiffness remained significantly associated with all-cause mortality (for 1 SD, Cox model–derived relative risk [95% CI], 1.48 [1.09–2.02]) and with fatal and nonfatal cardiovascular events (for 1 SD, Fine and Gray competing risks model–derived relative risk [95% CI], 1.35 [1.05–1.75]). Net reclassification improvement index was significant (29.0% [2.3–42.0%]). Carotid internal diameter was also independently associated with all-cause mortality. This study shows that increased aortic stiffness and carotid internal diameter are independent predictors of mortality in patients with stages 2 to 5 chronic kidney disease and that aortic stiffness improves the prediction of the risk.

Sequential nephron blockade versus sequential renin-angiotensin system blockade in resistant hypertension: a prospective, randomized, open blinded endpoint study.

Abstract: Objective:To compare two drug regimens to treat resistant hypertension.Methods:In a prospective, randomized, open blinded endpoint study, 167 patients with mean baseline daytime ambulatory blood pressure 135 mmHg or more and/or 85 mmHg or more, despite 4 weeks’ treatment with irbesartan 300 mg/day,

Arterial Stiffness as Surrogate End Point Needed Clinical Trials

Abstract: Classic risk scores may underestimate the risk of cardiovascular (CV) events in specific risk groups suitable for primary prevention, such as asymptomatic hypertensive subjects.1 Particularly, those considered as at intermediate risk may benefit the most from a reassessment of their CV risk using novel biomarkers.2 In primary prevention, some imaging biomarkers, such as arterial stiffness, enhance risk prediction to a higher extent than circulating biomarkers.3 Whether novel biomarkers are ready for routine clinical use is a matter of controversy.1–4 Particularly, whether an imaging biomarker can be substituted to clinical events in outcome trials and be considered as surrogate end point has rarely been demonstrated.1–4 The aims of the present Brief Review are to address the concepts of “imaging biomarker” and “surrogate end point”; to focus on arterial stiffness as putative surrogate end point for future CV events; and to suggest additional studies to demonstrate its value as surrogate end point. Particularly, we will discuss experimental designs of randomized clinical trials demonstrating that a therapeutic strategy that normalizes arterial stiffness is more effective in preventing CV events than usual care. ### “Circulating” Biomarkers Versus “Tissue” or “Imaging” Biomarkers Although classic risk scores, such as the Framingham risk score5 and the European Systematic Coronary Risk Evaluation,6 detect patients at high risk of CV events, they are largely influenced by aging, leading to undermanagement of CV risk in other risk groups, particularly those considered as at intermediate risk. A very large number of newer biomarkers have been proposed in the literature2,4 to increase risk prediction beyond classic risk scores. According to the Biomarkers Definition Working Group of the National Institutes of Health,7 a biomarker is “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to …

Defining vascular aging and cardiovascular risk.

Abstract: Whereas vascular aging has been identified as an emerging cardiovascular risk factor, definitions of 'normal' and 'early' vascular aging (EVA) and their precise relationship with cardiovascular risk are currently equivocal. The present review discusses the concept of vascular aging; that structural and functional changes occur in the large arteries with aging; and EVA; that such age-associated changes are accelerated in individuals at increased cardiovascular risk; and their metrics; indeed, in order to provide a definition of when EVA occurs in clinical practice, reference values of normal and accelerated vascular aging are needed. Due to the complex nature of age-associated changes in the large arteries described above, there are different parameters relating to vascular aging which can be measured. These broadly include aortic and carotid stiffening; aortic and carotid lumen dilation; endothelial dysfunction (usually measured via brachial flow-mediated dilatation); and carotid intima-media thickness.

Aortic stiffness as a tissue biomarker for predicting future cardiovascular events in asymptomatic hypertensive subjects

Abstract: Classical risk scores may underestimate the risk of cardiovascular events in specific risk groups suitable for early prevention, such as asymptomatic hypertensive subjects. Arterial stiffness and wave reflection are now well accepted as the most important determinants of increasing systolic and pulse pressures in aging societies, thus affording a major contribution to stroke and myocardial infarction. A major reason for measuring arterial stiffness in hypertensive patients comes from the demonstration that arterial stiffness has a predictive value for cardiovascular events, beyond classical cardiovascular risk factors. Aortic stiffening also gives direct evidence of target organ damage, and improves the determination of the overall cardiovascular risk of asymptomatic hypertensive subjects. In clinical practice, the measurement of aortic stiffness may avoid patients being mistakenly classified as at low or moderate risk, when they actually have an abnormally high aortic stiffness placing them within a high...

Arterial stiffness is increased in patients with inflammatory bowel disease.

Abstract: Background and aims: Recent studies have reported early atherosclerosis in patients with inflammatory bowel disease (IBD). In these patients, the chronic low-grade inflammation may predispose to vascular remodelling and arterial stiffening. We aimed at studying arterial stiffness in IBD patients. Methods: Thirty-two IBD patients without cardiovascular risk factors and 32 matched controls were enrolled (age 19–49 years). SphygmoCor device (AtCor Medical, Sydney, Australia) was used to measure carotid–femoral and carotid–radial (muscular artery) pulse wave velocity (PWV), augmentation index and central blood pressure. Results: Carotid–femoral PWV was higher in IBD patients than in controls (6.6 � 1.4 vs. 6.0 � 0.8m/s, respectively, P <0.05), as well as carotid–radial PWV (8.5 � 1.2 vs. 7.2 � 1.0m/s, P <0.001). Central pulse pressure was higher in IBD than in controls (32 � 6 vs. 28 � 7mmHg, P <0.05). Aging was an important determinant of carotid– femoral PWV in both groups and carotid–radial PWV only in IBD patients. In fully adjusted model performed in both groups of patients considered as a whole, age was positively associated with carotid–femoral PWV [R 2 ¼0.10; R0.05m/s per 1 year of aging, 95% confidence interval (CI) 0.01–0.08m/s, P <0.05], as well as IBD (R 2 ¼0.10; R0.72m/s if IBD present, 95% CI 0.19–1.26m/s, P <0.05). In IBD patients, carotid–radial PWV was positively associated with the disease duration (R 2 ¼0.20; R0.11m/s per 1 year of aging, 95% CI 0.03–0.19m/s, P <0.05).

Aortic Stiffness Predicts Functional Outcome in Patients After Ischemic Stroke

Abstract: Background and Purpose—Increased aortic stiffness (measured by carotid–femoral pulse wave velocity) and central augmentation index have been shown to independently predict cardiovascular events, including stroke. We studied whether pulse wave velocity and central augmentation index predict functional outcome after ischemic stroke. Methods—In a prospective study, we enrolled 99 patients with acute ischemic stroke (age 63.7±12.4 years, admission National Institutes of Health Stroke Scale score 6.6±6.6, mean±SD). Carotid–femoral pulse wave velocity and central augmentation index (SphygmoCor) were measured 1 week after stroke onset. Functional outcome was evaluated 90 days after stroke using the modified Rankin Scale with modified Rankin Scale score of 0 to 1 considered an excellent outcome. Results—In univariate analysis, low carotid–femoral pulse wave velocity (P=0.000001) and low central augmentation index (P=0.028) were significantly associated with excellent stroke outcome. Age, severity of stroke, prese...

Frequent and widespread vascular abnormalities in human signal transducer and activator of transcription 3 deficiency.

Abstract: Background— Signal transducer and activator of transcription 3 (STAT3) deficiency is responsible for autosomal dominant hyperimmunoglobulin E syndrome, characterized by recurrent bacterial and fungal infections, connective tissue abnormalities, hyperimmunoglobulin E, and Th17 lymphopenia. Although vascular abnormalities have been reported in some patients, the prevalence, characteristics, and etiology of these features have yet to be described. Methods and Results— We prospectively screened 21 adult STAT3-deficient patients (median age, 26 years; range, 17–44 years) for vascular abnormalities. We explored the entire arterial vasculature with whole-body magnetic resonance imaging angiography, coronary multislice computed tomography, and echo-tracking–based imaging specifically for the carotid arteries. We also assayed for serum biomarkers of inflammation and endothelial dysfunction. Finally, we studied murine models of aortic aneurysm in the presence and absence of inhibitors of STAT3-dependent signaling. Ninety-five percent of patients showed brain abnormalities (white matter hyperintensities, lacunar lesions suggestive of ischemic infarcts, and atrophy). We reported peripheral and brain artery abnormalities in 84% of the patients and detected coronary artery abnormalities in 50% of the patients. The most frequent vascular abnormalities were ectasia and aneurysm. The carotid intima-media thickness was markedly decreased, with a substantial increase in circumferential wall stress, indicating the occurrence of hypotrophic arterial remodeling in this STAT3-deficient population. Systemic inflammatory biomarker levels correlated poorly with the vascular phenotype. In vivo inhibition of STAT3 signaling or blockade of IL-17A resulted in a marked increase in aneurysm severity and fatal rupture in mouse models. Conclusions— Vascular abnormalities are highly prevalent in patients with STAT3 deficiency. This feature is consistent with the greater susceptibility to vascular aneurysm observed after inhibition of STAT3-dependent signaling in mouse models.

Association of central and peripheral pulse pressure with intermediate cardiovascular phenoytpes

Abstract: OBJECTIVE: We assessed the relationship between pulse pressure and intermediate cardiovascular phenotypes in a middle-aged cohort with high prevalence of hypertension. BACKGROUND: It has been suggested that central pulse pressure (cPP) is a better predictor of cardiovascular outcome than peripheral pulse pressure (pPP), particularly in the elderly. Yet, it is unclear if cPP provides additional prognostic information to pPP in younger individuals. METHODS: In 535 individuals we assessed cPP and pPP as well as the intermediate cardiovascular phenotypes pulse wave velocity (PWV; SphygmoCor, Complior, PulsePen), carotid intima-media thickness (C-IMT; carotid ultrasound), left-ventricular mass index (LVMI; echocardiography) and urinary albumin : creatinine ratio (ACR). cPP was derived noninvasively from brachial blood pressure by pulse wave analysis (PWA; SphygmoCor) based on radial pulse wave tonometry and a validated transfer function. RESULTS: The cohort contained 331 hypertensive participants of whom 84% were treated. The average age was 46 ± 16 years. When compared to pPP, cPP had stronger associations with PWV (r = 0.471 vs. r = 0.372; P < 0.01), C-IMT (r = 0.426 vs. r = 0.235; P < 0.01) and LVMI (r = 0.385 vs. r = 0.189; P < 0.01), but equal association with ACR (r = 0.236 vs. r = 0.226; P = n.s.). In contrast, after adjustment for age, mean arterial pressure, heart rate and hypertension status there was no significant difference between cPP and pPP for prediction of PWV (adjusted R, 0.399 vs. 0.413; P = 0.066), C-IMT (adjusted R, 0.399 vs. 0.413; P = 0.487) and LVMI (adjusted R, 0.181 vs. 0.170; P = 0.094) in multivariate analysis. CONCLUSION: In our middle-aged cohort with high prevalence of hypertension cPP is more closely correlated with cardiovascular phenotypes than pPP. When adjusted for relevant cofactors, however, cPP does not provide additional information beyond pPP. (Less)

Ambulatory arterial stiffness index does not accurately assess arterial stiffness.

Abstract: Introduction: The ambulatory arterial stiffness index (AASI), derived from ambulatory blood pressure monitoring (ABPM) recordings, has been proposed as a surrogate marker of arterial stiffness. However, there is controversy to what extent it reflects stiffness or is affected by other parameters. Using a previously validated one-dimensional computer model of the arterial circulation, the relative importance of the different determinants of the AASI was explored.

Renal artery diameter, renal function and resistant hypertension in patients with low-to-moderate renal artery stenosis.

Abstract: BACKGROUND Atherosclerotic renovascular disease is associated with resistant hypertension and chronic kidney disease, although the causal relationship is discussed. To date, the role of renal artery diameter on these pathological conditions was not clearly studied. We aimed to identify the association of reference diameter and minimal luminal renal artery diameter with glomerular filtration rate (GFR) and resistant hypertension in a high cardiovascular risk population. METHODS In this cross-sectional, single-center study, we enrolled 734 patients who underwent a renal angiography immediately after a coronary angiography indicated for a diagnosis of ischemic heart disease. RESULTS Mean age was 64 ± 10 years (men 72%). GFR was 79 ± 22 ml/min per 1.73 m(2). Five hundred and eighteen patients had no luminal narrowing and 216 patients had low-to-moderate luminal narrowing (10-70%, mean 36%). A positive significant association between reference diameter and GFR was detected in patients without luminal narrowing [beta 2.2 ml/min per 1.73 m(2) for 1 mm increase, 95% confidence interval (CI) 0.3-4.0, P < 0.05] and in those with low-to-moderate luminal narrowing (beta 7.7 ml/min per 1.73 m(2) for 1 mm increase, 95% CI 4.2-11.1, P < 0.001). The lowest quartile of reference diameter (<5.2 mm) was associated with GFR less than 60 ml/min per 1.73 m(2) [odds ratio (OR) 3.18, 95% CI 1.61-6.29, P < 0.001]. Patients with resistant hypertension had low minimal diameter and reference diameter. Reference diameter less than 5.2 mm was associated with an increased risk of resistant hypertension (OR 2.63, 95% CI 1.02-6.77, P < 0.05). CONCLUSIONS Small renal arteries, defined by a low reference diameter or minimal luminal diameter, are independently associated with low GFR and resistant hypertension, independent of the degree of stenosis and major confounders.

Long-term changes in arterial structure and function and left ventricular geometry after enzyme replacement therapy in patients affected with Fabry disease

Abstract: Aims: Fabry disease is a lysosomal storage disorder due to deficient alpha-galactosidase A activity, characterised by glycosphingolipids deposition in tissues. Patients have a common arterial involvement and contract progressive renal and cardiac disease. Although short-term effects of enzyme replacement therapy (ERT) on target organs have been established, no data are available on the long-term outcome.Methods and results: We studied the effects of ERT (agalsidase beta, 1 mg/kg/14 days) on arterial and cardiac structure and function during a longitudinal study beginning in 1999, with 4.5 ± 0.4 years follow-up (four visits) in 30 patients (age: 33 ± 12 years). In addition, we studied 16 untreated Fabry patients during 2.6 ± 1.6 years (two visits). Aortic stiffness was determined by carotid-femoral pulse wave velocity, central pulse pressure by aplanation tonometry, and carotid and radial intima-media thickness and diameter by high definition echotracking device. Left ventricular mass was determined by MRI...

Heritability of arterial stiffness and central blood pressure: the Holy Grail for detecting patients at high cardiovascular risk?

Abstract: Q uantification of arterial stiffness and central blood pressure (BP) is increasingly popular among physicians and researchers, not only because of better standardized measurement procedures and the more frequent availability of dedicated devices, but also because the spectrum of their clinical application is progressively enlarging. Particularly, evidence is available that arterial stiffness has good predictive value for cardiovascular events, independent of conventional cardiovascular risk factors. Although to a lesser extent, this applies also to estimates of central BP. As acknowledged by recent hypertension guidelines [1], an increase in arterial stiffness is regarded as a direct measure of target organ damage, indicating the occurrence of pathological changes in large artery walls under the action of cardiovascular risk factors. An increase in central BP is both an indirect and extended marker of such damage, as several parameters are known to influence the level of central BP, including arterial stiffness, pressure wave reflections (themselves also influenced by the geometry and vasomotor tone of small arteries), stroke volume, and heart rate. An important issue still under investigation is whether arterial stiffness and central BP measurements can be regarded as surrogate markers of cardiovascular events [2]. From a clinical perspective, in fact, it would be particularly important to establish whether a reduced arterial stiffness and a lower central BP may translate into a reduction in cardiovascular events. If this were the case, these measurements could be used in clinical practice to detect patients at high cardiovascular risk, to intensify

Ultrastructural scoring of skin biopsies for diagnosis of vascular Ehlers–Danlos syndrome

Abstract: Vascular Ehlers–Danlos syndrome (vEDS) results from a mutation in the gene encoding alpha-1, type III pro-collagen (COL3A1) and confers fragility to skin, ligament and vascular tissue. We tested the value of skin biopsy for diagnosis of vEDS through an ultrastructure scoring procedure. Study design was a multicentric, case–control, blinded trial consisting of two phases: phase 1 was to identify an ultra-structure score providing the best discriminative value for vEDS and phase 2 was to replicate this result in a different population. We enrolled 103 patients, 66 cases defined through the revised nosology for Ehlers–Danlos syndromes and 37 control subjects selected from patients referred for other pathologies. Ultrastructure of extracellular matrix was read by three to five experienced pathologists blinded for diagnosis. We used the receiver operating curves and logistic regression analysis for ranking ultrastructure scores. We created a detailed description of lesions observed in vEDS patients with 27 items (coded 0 or 1). In the phase 1 (17 cases and 20 controls), abnormal fibroblast shape, presence of lysosomes in the fibroblast and abnormal basal lamina were found to be independent discriminative items. Addition of these three items (defining an ultrastructure score) had the best diagnosis value (area under the curve (AUC) = 0.96). In the phase 2 (49 cases, 17 controls), ultrastructure score provided odds ratio of 9.76 (95 % CI 2.91–32.78), and AUC of 0.90. The ultrastructure score of skin biopsy has predictive value for the diagnosis of vEDS. Presence of two or more signs (either abnormal fibroblast, presence of lysosomes in the fibroblast or abnormal basal lamina) is very evocative of vEDS.

Arterial Stiffness as an Early Marker of Organ Damage

Abstract: Classical risk scores may underestimate the risk of cardiovascular events in specific risk groups suitable for early prevention, such as asymptomatic hypertensive subjects. Arterial stiffness and wave reflection are now well accepted as the most important determinants of increasing systolic and pulse pressures in aging societies, thus affording a major contribution to stroke and myocardial infarction. One of the main reasons for measuring arterial stiffness in hypertensive patients comes from the demonstration that arterial stiffness has a predictive value for cardiovascular events, beyond classical cardiovascular risk factors. Aortic stiffening also gives direct evidence of target organ damage and improves the determination of the overall cardiovascular risk of asymptomatic hypertensive subjects. In clinical practice, the measurement of aortic stiffness may avoid patients being mistakenly classified at either low or moderate risk, when they actually have an abnormally high aortic stiffness placing them within a higher risk group. This chapter successively addresses the concept of imaging biomarker, applies it to arterial stiffness, describes the methodology of its measurement, provides some pathophysiological links between arterial stiffness and organ damage, and raises the issue of whether arterial stiffness is a surrogate end point.

Hypertension 1 New drugs, procedures, and devices for hypertension

Abstract: Successful treatment of hypertension is diffi cult despite the availability of several classes of antihypertensive drug, and the value of strategies to combat the eff ect of adverse lifestyle behaviours on blood pressure. In this paper, we discuss two promising therapeutic alternatives for patients with resistant hypertension: novel drugs, including new pharmacological classes (such as vasopeptidase inhibitors and aldosterone synthase inhibitors) and new molecules from present pharmacological classes with additional properties in blood-pressure or metabolism pathways; and new procedures and devices, including stimulation of arterial baroreceptors and catheter-based renal denervation. Although several pharmacological targets have been discovered with promising preclinical results, the clinical development of novel antihypertensive drugs has been more diffi cult and less productive than expected. The eff ectiveness and safety of new devices and procedures should be carefully assessed in patients with resistant hypertension, thus leading to a new era of outcome trials and evidence-based guidelines.