The effects of cinacalcet on blood pressure, mortality and cardiovascular endpoints in the EVOLVE trial.

Patients with end-stage renal disease often have derangements in calcium and phosphorus homeostasis and resultant secondary hyperparathyroidism (sHPT), which may contribute to the high prevalence of arterial stiffness and hypertension. We conducted a secondary analysis of the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial, in which patients receiving hemodialysis with sHPT were randomly assigned to receive cinacalcet or placebo. We sought to examine whether the effect of cinacalcet on death and major cardiovascular events was modified by baseline pulse pressure as a marker of arterial stiffness, and whether cinacalcet yielded any effects on blood pressure. As reported previously, an unadjusted intention-to-treat analysis failed to conclude that randomization to cinacalcet reduces the risk of the primary composite end point (all-cause mortality or non-fatal myocardial infarction, heart failure, hospitalization for unstable angina or peripheral vascular event). However, after prespecified adjustment for baseline characteristics, patients randomized to cinacalcet experienced a nominally significant 13% lower adjusted risk (95% confidence limit 4-20%) of the primary composite end point. The effect of cinacalcet was not modified by baseline pulse pressure (Pinteraction=0.44). In adjusted models, at 20 weeks cinacalcet resulted in a 2.2 mm Hg larger average decrease in systolic blood pressure (P=0.002) and a 1.3 mm Hg larger average decrease in diastolic blood pressure (P=0.002) compared with placebo. In summary, in the EVOLVE trial, the effect of cinacalcet on death and major cardiovascular events was independent of baseline pulse pressure.

Serum sclerostin: the missing link in the bone-vessel cross-talk in hemodialysis patients?

UNLABELLED: We found for the first time that in maintenance hemodialysis patients, higher sclerostin serum level was associated with severe abdominal aortic calcification (AAC). In addition, cortical bone microarchitecture (density and thickness) assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) at tibia was also independently associated with severe AAC. These results suggest that sclerostin may be involved in the association of mineral and bone disorder with vascular calcification in hemodialysis patients. INTRODUCTION: Severe abdominal aortic calcifications are predictive of high cardiovascular mortality in maintenance hemodialysis (MHD) patients. In patients with end-stage renal disease, a high aortic calcification score was associated with lower bone turnover on bone biopsies. Thus, we hypothesized that sclerostin, a Wnt pathway inhibitor mainly secreted by osteocytes and acting on osteoblasts to reduce bone formation, may be associated with vascular calcifications in MHD patients. METHODS: Fifty-three MHD patients, aged 53 years [35-63] (median [Q1-Q3]) were included. Serum was sampled before the MHD session to assay sclerostin. Framingham score was computed and the abdominal aortic calcification (AAC) score was assessed according to Kauppila method on lateral spine imaging using DEXA. Tibia bone status was evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Patients were distributed into two groups according to their AAC score: patients with mild or without AAC (score below 6) versus patients with severe AAC (score of 6 and above). RESULTS: In multivariate analysis, after adjustment on age, dialysis duration and diabetes, serum sclerostin and cortical thickness were independently associated with severe AAC (odds ratio (OR) = 1.43 for each 0.1 ng/mL increase [95 % confidence interval (CI) 1.10-1.83]; p = 0.006 and 0.16 for 1 SD increase [0.03-0.73]; p = 0.018, respectively). A second cardiovascular model adjusted on Framingham score and the above mentioned confounders showed similar results. CONCLUSIONS: Elevated sclerostin serum level and poorer tibia cortical bone structure by HR-pQCT were positively and independently associated with higher odds of severe AAC in MHD patients. Serum sclerostin may become a biomarker of mineral and bone disorder and vascular risk in MHD patients.

[Incidence of arterial hypertension in French population after 60 years]. / Incidence de l'hypertension artérielle dans la population française de plus de 60ans.

OBJECTIVE: To evaluate incidence and determinants of arterial hypertension after 60 years. METHODS: Four thousand nine hundred and forty one subjects aged 60 years or above (2505 men: 64.2±4.2 years; 2436 women: 64.8±4.3 years) were explored two times at the IPC center, Paris, between 1992 and 2007, and were normotensive at the first visit (V1): systolic BP (SBP) less than 140mmHg and diastolic BP (DBP) less than 90mmHg without treatment. The delay between the two visits was 5.8±2.2 years. At the second visit, population was analysed as normotensives and hypertensives. An age-adjusted Anova compared groups. RESULTS: In men, incidence of hypertension is 41.5% and 25.9% for isolated systolic hypertension. In women, incidences were 37.8% and 27.8% respectively. Baseline characteristics for V2-hypertensives showed higher SBP, DBP, BMI, heart rate, glycemia, ECG abnormalities thanV2-normotensives but they had lower physical activity. The determinants of hypertension were: SBP, age, BMI, DBP, glycemia, and lack of physical activity for this age class. CONCLUSION: From 60 years old, 6-year incidence of hypertension is about 40% and 26% for isolated systolic hypertension, this latter being higher in women. Regular physical activity is protective.

Arterial calcification: cardiovascular function and clinical outcome.

Arterial calcification (AC) is a common complication of CKD and ESRD, and the extents of AC are predictive of subsequent cardiovascular mortality beyond established conventional risk factors. AC develop in two distinct sites: the intima and media layers of the large and medium-sized arterial wall. These two forms are frequently associated. AC is tightly associated with aging and arterial remodeling, including intima-media thickening, but also changes of the geometry and function of aortic valves. Evidence has accumulated pointing to the active and regulated nature of the calcification process. Elevated phosphate and calcium may stimulate sodium–dependent phosphate cotransport involving osteoblast–like changes in cellular gene expression. AC is responsible for stiffening of the arteries with increased left ventricular afterload and abnormal coronary perfusion as the principal clinical consequences.

Arterial calcification: cardiovascular function and clinical outcome

Arterial calcification (AC) is a common complication of CKD and ESRD, and the extents of AC are predictive of subsequent cardiovascular mortality beyond established conventional risk factors. AC develop in two distinct sites: the intima and media layers of the large and medium-sized arterial wall. These two forms are frequently associated. AC is tightly associated with aging and arterial remodeling, including intima-media thickening, but also changes of the geometry and function of aortic valves. Evidence has accumulated pointing to the active and regulated nature of the calcification process. Elevated phosphate and calcium may stimulate sodium-dependent phosphate cotransport involving osteoblast-like changes in cellular gene expression. AC is responsible for stiffening of the arteries with increased left ventricular afterload and abnormal coronary perfusion as the principal clinical consequences (AU)

La calcificación arterial (CA) es una complicación común en la enfermedad renal crónica y la enfermedad renal en etapa terminal, y cuyo alcance es diagnóstico de una posterior mortalidad cardiovascular más allá de los factores de riesgo convencionales establecidos. La CA se desarrolla en dos ubicaciones diferentes: en las capas íntima y media de las paredes arteriales de gran y medio tamaño. Estas dos formas se encuentran frecuentemente asociadas. La CA está estrechamente relacionada con el envejecimiento y el remodelado arterial, que incluye el engrosamiento de la íntima-media y los cambios en la geometría y la función de las válvulas aórticas. Se han recogido evidencias que señalan la naturaleza activa y regulada del proceso de calcificación. Elevados niveles de fosfatos y calcio pueden estimular el cotransporte de fosfato dependiente del sodio que implique cambios osteoblásticos en la expresión genética celular. La CA es responsable del endurecimiento de las arterias, con un aumento de la poscarga ventricular izquierda y perfusión coronaria anormal como principales causas clínicas (AU)

Central artery pulse pressure in end-stage renal disease: the roles of aortic diameter, aortic stiffness and wave reflection.

In elderly subjects and patients with end-stage renal disease (ESRD), carotid pulse pressure (PP) is an independent and significant predictor of cardiovascular (CV) risk. Whereas in the elderly carotid diameter, but not carotid stiffness, is an associated CV risk factor, an opposite CV risk pattern was observed in ESRD patients that was associated with stiffness. Whether in ESRD patients arterial diameter, stiffness or both are involved in the mechanism(s) of increased carotid PP has never been investigated. Nondiabetic ESRD patients (n = 144) were compared with 57 control subjects matched for age, sex and mean blood pressure, but with higher brachial and carotid PP. Noninvasive echo-Doppler techniques and pulse wave velocity (PWV) and pulse wave analysis were used to evaluate cardiac and carotid arterial structures and functions using multiple stepwise regressions. In controls, carotid PP was associated only with stroke volume, arterial wave reflections and aortic PWV, but not aortic diameter. In ESRD patients, it was associated with wave reflections, aortic PWV, stroke volume and higher aortic diameter. In ESRD patients and controls, elevated carotid PP mainly reflected increased aortic PWV and earlier wave reflections. Aortic diameter had an impact only on ESRD patients, where it compensated for enhanced aortic stiffness and the more pronounced effect of reflected waves. This hemodynamic profile differs consistently from that in elderly subjects of the general population and selectively influences CV risk and drug treatment.

The new kidney disease: improving global outcomes (KDIGO) guidelines - expert clinical focus on bone and vascular calcification.

Chronic kidney disease-mineral and bone disorder (CKD-MBD) defines a triad of interrelated abnormalities of serum biochemistry, bone and the vasculature associated with chronic kidney disease (CKD). The new kidney disease: improving global outcomes (KDIGO) guidelines define the quality and depth of evidence supporting therapeutic intervention in CKD-MBD. They also highlight where patient management decisions lack a strong evidence base. Expert interpretation of the guidelines, along with informed opinion, where evidence is weak, may help develop effective clinical practice. The body of evidence linking poor bone health and reservoir function (the ability of bone to buffer calcium and phosphorus) with vascular calcification and cardiovascular outcomes is growing. Treating renal bone disease should be one of the primary aims of therapy for CKD. Evaluation of the biochemical parameters of CKD-MBD (primarily phosphorus, calcium, parathyroid hormone and vitamin D levels) as early as CKD Stage 3, and an assessment of bone status (by the best means available), should be used to guide treatment decisions. The adverse effects of high phosphorus intake relative to renal clearance (including stimulation of hyperparathyroidism) precede hyperphosphatemia, which presents late in CKD. Early reduction of phosphorus load may ameliorate these adverse effects. Evidence that calcium load may influence progression of vascular calcification with effects on mortality should also be considered when choosing the type and dose of phosphate binder to be used. The risks, benefits, and strength of evidence for various treatment options for the abnormalities of CKD-MBD are considered.

[Arterial hypertension, chronic renal insufficiency and dialysis]. / Hypertension arterielle, insuffisance renale chronique et dialyse.

The principal characteristic of hypertension in chronic kidney disease (CKD), especially at CKD stage 5. Is an increased systolic pressure, with normal or even low diastolic pressure. This isolated systolic hypertension is also characterized by ab abnormal increase in pulse pressure which is by itself an independent cardiovascular risk factor. The principal reason for these abnormalities is accelerated ageing of arterial system, principally the aorta and large central arteries. This ageing is characterized by stiffening of arteritis whose natural history is not clearly understood. One of the principal pathogenic factor associated with stiffening is extensive calcification of arterial walls, mainly the medial layer (media-calcinosis). Mineral metabolism disorders such as hyperphosphatemia, play a major role in pathophysiology of calcifications. Arterial stiffness is characterized by very steep volume-pressure relationship and for this reason is associated with hemodynamic instability. Small blood volume increase producing abnormally high pressure while small decrease in blood volume could be associated with deep hypotension.

Atherosclerosis versus arterial stiffness in advanced renal failure.

Epidemiological as well as clinical studies have shown that regardless of the severity of renal impairment the cardiovascular mortality in renal disease patients is very high compared to the general population. In uremia, cardiovascular disease is a combination of atherosclerosis, characterized by the presence of highly calcified plaques, and arteriosclerosis, an arterial wall alteration in response to both hemodynamic changes and humoral modifications such as inflammation or calcium-phosphate imbalance. Vascular endothelium, recognized as a large and complex endocrine organ strategically located between the wall of the blood vessel and the blood stream, could be the link between these two processes evolving during the same course.

Arterial stiffness and enlargement in mild-to-moderate chronic kidney disease.

Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular morbidity and mortality. Arterial stiffness and remodeling have been well documented in patients with end-stage renal disease, but little is known about arterial phenotype in CKD patients with moderate reduction in glomerular filtration rate (GFR). In total, 95 patients (58+/-15 years, mean+/-s.d.) with CKD and GFR measured by renal clearance of (51)Cr-ethylenediaminetetraacetate were compared to 121 hypertensive patients without CKD (59+/-11 years), and 57 normotensive subjects (56+/-6 years). Common carotid artery diameter, intima-media thickness (IMT), distensibility, and Young's elastic modulus were noninvasively determined with a high-definition echotracking system. Patients with CKD had a significantly larger carotid internal diameter than in hypertensives and normotensives (6.32+/-1.05, 5.84+/-0.74, and 5.50+/-0.64 m x 10(-3), respectively; P<0.001), resulting in 25% and 11% increases in circumferential wall stress, respectively, since no significant difference in IMT was observed. Carotid distensibility and elastic modulus did not significantly differ between CKD and hypertensives; normotensives had significantly higher distensibility and lower elastic modulus than CKD and hypertensive patients. Carotid-femoral pulse wave velocity was significantly higher in CKD patients than in hypertensives and normotensives. In multivariate analyses either involving the entire population or restricted to CKD patients, GFR was independently and strongly related to carotid diameter and elastic modulus. Arterial enlargement and increased arterial stiffness occur in parallel with the decline in renal function in patients with mild-to-moderate CKD.

Arterial structural and functional alterations in uraemia.

Epidemiological and clinical studies have shown that cardiovascular disease in patients with end-stage renal disease (ESRD) is frequently related to damage of large conduit arteries. Arterial disease is responsible for the high incidence of ischaemic heart disease, peripheral artery diseases, left ventricular hypertrophy and congestive heart failure. The vascular complications in ESRD are ascribed to two different but associated mechanisms, namely atherosclerosis and arteriosclerosis. Whereas the former principally affects the conduit function with ischaemic lesions being the most characteristic consequence, the latter primarily disturbs the dampening function of large arteries. Arteriosclerosis in ESRD patients is characterized by diffuse dilation and wall hypertrophy of large conduit arteries and stiffening of arterial walls. These changes represent a clinical form of an accelerated ageing process. The main clinical characteristics due to arterial stiffening are isolated increase in systolic blood pressure with normal or lower diastolic pressure resulting in an increased pulse pressure. The consequences of these alterations are: (i) an increased left ventricular afterload with development of left ventricular hypertrophy and increased myocardial oxygen demand; and (ii) altered coronary perfusion and subendocardial blood flow distribution. Epidemiological studies have identified arterial remodelling and stiffening as independent predictors of overall and cardiac mortality in ESRD patients.

Vascular disease and atherosclerosis in uremia.

Epidemiological and clinical studies have shown that cardiovascular disease in patients with end-stage renal disease (ESRD) is frequently related to damage of large conduit arteries. Arterial disease is responsible for the high incidence of ischemic heart disease, peripheral artery diseases, left ventricular hypertrophy and congestive heart failure. The vascular complications in ESRD are due to two different but associated mechanisms, namely atherosclerosis and arteriosclerosis. Whereas the former principally affects the conduit function with ischemic lesions being the most characteristic consequence, the latter primarily disturbs the cushioning function of large arteries. Arteriosclerosis in ESRD patients is characterized by diffuse dilation and hypertrophy of large conduit arteries and stiffening of arterial walls, and represents a clinical form of an accelerated aging process. The main clinical characteristics of arterial stiffening are changes in blood pressure with isolated increase in systolic pressure and normal or lower diastolic pressure. The consequences of these alterations are: (i) an increased LV afterload with development of LV hypertrophy and increased myocardial oxygen demand, and (ii) altered coronary perfusion and subendocardial blood flow distribution. Epidemiological studies have identified arterial remodeling and stiffening as independent predictors of overall and cardiac mortality in ESRD patients.

Vascular disease and atherosclerosis in uremia

Estudios clínicos y epidemiológicos han demostrado que la enfermedad cardiovascularen los pacientes con enfermedad renal crónica terminal (ERCT) está relacionadacon lesiones de los grandes vasos. La enfermedad arterial es responsablede cardiopatía isquémica, arteriopatía crónica periférica, hipertrofia ventricularizquierda e insuficiencia cardíaca congestiva. Las complicaciones vasculares de laECRT son secundarias a dos mecanismos distintos pero asociados; se trata de laateroesclerosis y de la arterioesclerosis. El primer mecanismo afecta la conduccióndel flujo sanguíneo siendo las lesiones isquémicas las principales consecuencias,el segundo altera la función amortiguadora del pulso por las arterias de gran tamaño.La arterioesclerosis en la ERCT se caracteriza por la dilatación difusa y lahipertrofia de arterias de gran tamaño así como por la rigidez arterial y representa funcunaforma clínica de envejecimiento acelerado. La característica clínica principalde los cambios de la rigidez arterial son los cambios de presión arterial con unapresión arterial sistólica aislada y una presión arterial diastólica normal o baja. Lasconsecuencias de estas alteraciones son las siguientes: i) aumento de la postcargadel ventrículo izquierdo (VI) y hipertrofia del VI y aumento del consumo deoxígeno, y ii) alteración de la perfusión coronaria y de la distribución del flujosanguíneo. Estudios epidemiológicos han identificado el remodelado arterial y larigidez como factores predictores de la mortalidad global y cardiáca en la ERCT

Epidemiological and clinical studies have shown that cardiovascular disease inpatients with end-stage renal disease (ESRD) is frequently related to damage oflarge conduit arteries. Arterial disease is responsible for the high incidence of ischemicheart disease, peripheral artery diseases, left ventricular hypertrophy andcongestive heart failure. The vascular complications in ESRD are due to two differentbut associated mechanisms, namely atherosclerosis and arteriosclerosis.Whereasthe former principally affects the conduit function with ischemic lesions beingthe most characteristic consequence, the latter primarily disturbs the cushioningfunction of large arteries. Arteriosclerosis in ESRD patients is characterized by diffusedilation and hypertrophy of large conduit arteries and stiffening of arterialwalls, and represents a clinical form of an accelerated aging process. The mainclinical characteristics of arterial stiffening are changes in blood pressure with isolatedincrease in systolic pressure and normal or lower diastolic pressure. The consequencesof these alterations are: i) an increased LV afterload with developmentof LV hypertrophy and increased myocardial oxygen demand, and ii) altered coronaryperfusion and subendocardial blood flow distribution. Epidemiological studieshave identified arterial remodeling and stiffening as independent predictors ofoverall and cardiac mortality in ESRD patients

Electrophysiological response to dialysis: the role of dialysate potassium content and profiling.

UNLABELLED: The task of dialysis therapy is, amongst other things, to remove excess potassium (K+) from the body. The need to achieve an adequate K+ removal with the risk of cardiac arrhythmias due to sudden intra-extracellular K+ gradient advises the distribution of the removal throughout the dialysis session instead of just in the first half. The aim of the study was to investigate the electrical behavior of two different K+ removal rates on myocardial cells (risk of arrhythmia and ECG alterations). Constant acetate-free biofiltration (AFB) and profiled K+ (decreasing during the treatment) AFB (AFBK) were used in a patient sample to understand, first of all, the effect on premature ventricular contraction (PVC) and on repolarization indices [QT dispersion (QTd) and principal component analysis (PCA)]. The study was divided into two phases: phase 1 was a pilot study to evaluate K+ kinetics and to test the effect on the electrophysiological response of the two procedures. The second phase was set up as an extended cross-over multicenter trial in patient subsets prone to arrhythmias during dialysis. Phase 1: PVC increased during both AFB and AFBK but less in the latter in the middle of dialysis (298 in AFB vs. 200 in AFBK). The PVC/h in a subset of arrhythmic patients was 404 +/- 145 in AFB and 309 +/- 116 in AFBK (p = 0.0028). QT interval (QTc) prolongation was less pronounced in AFBK than in AFB. Phase 2: The PVC again increased in both AFB and AFBK but less in the latter mid-way through dialysis (79 +/- 19 AFB vs. 53 +/- 13 AFBK). Moreover, in the most arrhythmic patients the benefit accruing from the smooth K+ removal rate was more pronounced (103 +/- 19 in AFB vs. 78 +/- 13 in AFBK). CONCLUSION: It is not the K+ dialysis removal alone that can be destabilizing from an electrophysiological standpoint, but rather its removal dynamics. This is all the more evident in patients with arrhythmias who benefit from the K+ profiling during their dialysis treatment.

Efficacy of indapamide 1.5 mg, sustained release, in the lowering of systolic blood pressure.

The relationship between the increase in blood pressure and the incidence of cardiovascular disease is well recognized today. Studies have shown that more attention should be paid to systolic blood pressure (SBP) in relation to cardiovascular risk and that therapeutic interventions should preferably focus on reducing SBP. The antihypertensive efficacy of indapamide 1.5 mg sustained release (indapamide SR), a low-dose thiazide-type diuretic, was assessed on SBP. Three randomized, double-blind, controlled studies were conducted with indapamide SR, over a period of 3 to 12 months. Elderly patients or patients with target-organ damage, hypertension and left ventricular hypertrophy (LVH) (LIVE study) or with type II diabetes with microalbuminuria (NESTOR study) showed a decrease in SBP varying from 22.7 to 31.8 mmHg. The treatment with indapamide SR resulted in a better or equivalent control of SBP than treatment with a standard dose of a true thiazide diuretic (hydrochlorothiazide), a calcium channel blocker (amlodipine), and an angiotensin-converting enzyme inhibitor (enalapril). No therapeutic escape was observed. All treatments showed good acceptability with no unexpected adverse event. In conclusion, indapamide SR is very effective in lowering SBP-a major independent cardiovascular risk factor-notably in hypertensive high-risk patients with LVH, the elderly and diabetics, when compared to major antihypertensive treatments. This SBP-lowering effect is maintained over the long term.

Cardiovascular disease in renal failure.

Cardiovascular disease is prevalent in patients with chronic kidney disease and may account for 50% of all deaths. Left ventricular hypertrophy is the most frequent cardiac alteration in end-stage renal disease (ESRD) patients. It is due to a combination of hemodynamic and humoral factors. Volume overload and pressure overload are responsible for adaptative alterations of the heart and the vessels consider as a unique functional system. These alterations are first beneficial but their persistence leads to a detrimental process, mainly cardiac dilation and failure. Treatment of the hemodynamic overload could partially stabilize or reverse this evolution.

[Cardioprotection: an essential component for predialysis chronic renal failure treatment]. / La cardioprotection: une composante essentielle du traitement de l'insuffisance rénale chronique dès le stade prédialytique.

Cardiovascular (CV) disease in uremic patients is a major concern to the nephrologist because it represents the main cause of morbidity and mortality in chronic renal failure patients, both predialysis and while on dialysis therapy. CV mortality is 3 to 20 times higher in dialysis patients than in the general population at similar age. Of note, a high prevalence of CV comorbidity is already present at start of maintenance dialysis, and is predictive of subsequent mortality on dialysis. CV disease progresses over years prior to the onset of ESRD, because risk factors develop from the early stage of chronic renal insufficiency. However, CV disease may be prevented or attenuated in patients who benefit from early, regular care of CV risk factors. Mechanisms of uremic cardiopathy, the major cause of mortality in uremic patients, are multifactorial and their effects are cumulative. Risk factors for left ventricular hypertrophy are hypertension, anemia, fluid overload and arteriosclosis, all of which are amendable by therapy. Risk factors for accelerated atherosclerosis, responsible for ischemic cardiopathy and myocardial infarction, are both common factors (e.g., hypertension, tobacco smoking and diabetes) and factors more specific for the uremic state (e.g., dyslipidemia, hyperhomocysteinemia and oxidative stress), all of which also are amendable by proper therapy. As a result, mixed hypertensive and ischemic cardiomyopathy develops, ultimately leading to cardiac failure, together with accidents resulting from valvular and arterial calcifications (favored by calcium-phosphate disorders), and from occlusion of coronary, cerebral and peripheral arteries. Cardioprotective therapy thus has become a cornerstone in the management of chronic renal failure patients, in conjunction with renoprotective therapy. Cardioprotective strategy involves optimal treatment of hypertension, anemia, fluid overload, dyslipidemia, hyperhomocysteinemia and calcium-phosphate disorders, and smoking cessation. To achieve a maximal efficacy, such treatment has to be initiated as early as possible in the course of renal failure. Because of its complexity, the integrated combined nephrotective and cardioprotective therapy requires early and sustained guidance by a nephrologist throughout the whole predialysis period.

[Combination of low-dose perindopril/indapamide versus atenolol in the hypertensive patient. Effects on systolic pressure and arterial hemodynamics. REASON Study]. / Association faiblement dosée perindopril/indapamide versus aténolol chez le patient hypertendu. Action sur la pression artérielle systolique et sur l'hémodynamique artérielle. Etude REASON.

In hypertension, consideration of systolic blood pressure (SBP) and pulse pressure (PP) is now well recognized from epidemiological and therapeutical points of view, after numerous years of interest in only diastolic blood pressure. SBP, and also PP, are tightly linked to mechanical properties of large arteries. It is now possible to investigate precisely, with very good repeatability, these mechanic properties. The REASON study is an international multicenter randomised, controlled, parallel-groups study in essential hypertensives. The very low dose perindopril/indapamide combination (Per/Ind: 2 mg/0.625 mg) was compared with atenolol (50 mg) for a 12-month active treatment period in terms of blood pressure reduction efficiency and change in large artery hemodynamics to attempt to relate changes in pressure and changes in arterial mechanics. 471 patients suffering from hypertension were included, 406 benefitted from the treatment for one year (per-protocol analysis) and 96 benefitted from arterial investigations (pulse wave velocity and aortic wave reflection with applanation tonometry). Changes in brachial and central SBP and PP were higher with Per/ind than with atenolol. The reduction in pulse wave velocity was similar with both drugs, but aortic wave reflections were more reduced with Per/Ind than with atenolol. The very low dose perindopril/indapamide decreases SBP and PP to a larger extent than does a betablocker after a 12-month treatment. Changes in arterial mechanics, non invasively measured, were the same (pulse wave velocity) or in favour of Per/Ind vs atenolol (higher reduction in aortic wave reflection, with higher reductions in central systolic and pulse pressures).

[Comparison of central pulse pressure estimated from pulse wave propagation velocity and carotid pulse pressure measured by applantation tonometry]. / Comparaison de la pression pulsée centrale estimée à partir des vitesses de propagation de l'onde du pouls et de la pression pulsée carotidienne mesurée par tonométrie d'aplanation.

BACKGROUND: Pulse pressure (PP) corresponds to the difference between arterial systolic blood pressure and diastolic blood pressure. Central PP seems to be a stronger coronary risk marker than brachial PP. Central PP can be estimated by aortic PP measured non invasively by aplanation tonometry of the carotid artery. The aim of this study was to compare 2 methods of estimation of aortic PP: estimation from Pulse Wave Velocities (PWV) and by aplanation tonometry of the carotid artery. Estimation from PWV is based on the non uniform transmission of the PP i.e. the amplification of PP from the aorta to brachial artery, through arteries of increasing impedance. METHODS: One hundred and fifty one subjects were included, 111 hemodialysis patients and 40 subjects free of cardiovascular treatment or cardiovascular organ damage, recruited in a preventive medicine setting. Central PP was measured by aplanation tonometry of the carotid artery. The following formula was used for the relationship between PP and PWV in the two arterial segments considered for pulse wave travel (waterhammer formula): [formula: see text] Where measurement of brachial PP (PPBr) and PWV at aortic (PWVAo) and brachial (PWVBr) gives an estimation of aortic PP (PPAo estimated). Carotid-femoral PWV was used for PWVAo and carotid-radial PWV was used for PWVBr. The two methods were compared by t-test and according to Bland and Altman's method. RESULTS: In the hemodialysis group (73 males, 44 +/- 12 years old), brachial PP was 56 +/- 15 mm Hg and central PP as measured at the carotid level was 47 +/- 15 mmHg. In the healthy group (29 males, 46 +/- 11 years old), these values were 46 +/- 10 mmHg and 35 +/- 10 mmHg respectively. Compared to carotid artery aplanation tonometry, PPAo estimated was larger than central PP by 2.9 +/- 6.3 mmHg in hemodialysis patients and by 5.4 +/- 6.6 mmHg in the healthy group. The difference was significantly larger in healthy subjects than in hemodialysis patients (p = 0.031). CONCLUSION: The PWV estimated PP is larger than the central PP measured at the carotid level by aplanation tonometry. The difference is larger in cardiovascular event free subjects than in patients on hemodialysis.