Dataset Information

Beneficial effects on arterial stiffness and pulse-wave reflection of combined enalapril and candesartan in chronic kidney disease--a randomized trial.

ABSTRACT:

Background

Cardiovascular disease (CVD) is highly prevalent in patients with chronic kidney disease (CKD). Inhibition of the renin-angiotensinsystem (RAS) in hypertension causes differential effects on central and brachial blood pressure (BP), which has been translated into improved outcome. The objective was to examine if a more complete inhibition of RAS by combining an angiotensin converting enzyme inhibitor (ACEI) and an angiotensin receptor antagonist (ARB) compared to monotherapy has an additive effect on central BP and pulse-wave velocity (PWV), which are known markers of CVD.

Methods

Sixty-seven CKD patients (mean GFR 30, range 13-59 ml/min/1.73 m(2)) participated in an open randomized study of 16 weeks of monotherapy with either enalapril or candesartan followed by 8 weeks of dual blockade aiming at a total dose of 16 mg candesartan and 20 mg enalapril o.d. Pulse-wave measurements were performed at week 0, 8, 16 and 24 by the SphygmoCor device.

Results

Significant additive BP independent reductions were found after dual blockade in aortic PWV (-0.3 m/s, P<0.05) and in augmentation index (-2%, P<0.01) compared to monotherapy. Furthermore pulse pressure amplification was improved (P<0.05) and central systolic BP reduced (-6 mmHg, P<0.01).

Conclusions

Dual blockade of the RAS resulted in an additive BP independent reduction in pulse-wave reflection and arterial stiffness compared to monotherapy in CKD patients.

Trial registration

Clinical trial.gov NCT00235287.

SUBMITTER: Frimodt-Moller M

PROVIDER: S-EPMC3409235 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Beneficial effects on arterial stiffness and pulse-wave reflection of combined enalapril and candesartan in chronic kidney disease--a randomized trial.

Frimodt-Møller Marie M Kamper Anne-Lise AL Strandgaard Svend S Kreiner Svend S Nielsen Arne Høj AH

PloS one 20120731 7

<h4>Background</h4>Cardiovascular disease (CVD) is highly prevalent in patients with chronic kidney disease (CKD). Inhibition of the renin-angiotensinsystem (RAS) in hypertension causes differential effects on central and brachial blood pressure (BP), which has been translated into improved outcome. The objective was to examine if a more complete inhibition of RAS by combining an angiotensin converting enzyme inhibitor (ACEI) and an angiotensin receptor antagonist (ARB) compared to monotherapy h ...[more]

PMID: 22860014

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Project description:Inflammation causes vascular dysfunction and perpetuates proatherosclerotic processes. We hypothesized that a broad panel of inflammatory biomarkers and single nucleotide polymorphisms in inflammatory genes is associated with vascular stiffness. We assessed 12 circulating inflammatory biomarkers (C-reactive protein, fibrinogen, interleukin-6, intercellular adhesion molecule-1, lipoprotein-associated phospholipase-A2 [mass and activity], monocyte chemoattractant protein-1, myeloperoxidase, CD40 ligand, osteoprotegerin, P-selectin, and tumor necrosis factor receptor-II) in relation to tonometry variables (central pulse pressure, mean arterial pressure, forward pressure wave, reflected pressure wave, carotid-femoral pulse wave velocity, and augmentation index) measured in 2409 Framingham Heart Study participants (mean age: 60 years; 55% women; 13% ethnic/racial minorities). Single nucleotide polymorphisms (n=2195) in 240 inflammatory candidate genes were related to tonometry measures in 1036 white individuals. In multivariable analyses, biomarkers explained <1% of any tonometry measure variance. Applying backward elimination, markers related to tonometry (P<0.01) were as follows: tumor necrosis factor receptor-II (inversely) with mean arterial pressure; C-reactive protein (positively) and lipoprotein-associated phospholipase-A2 (inversely) with reflected pressure wave; and interleukin-6 and osteoprotegerin (positively) with carotid-femoral pulse wave velocity. In genetic association analyses, lowest P values (false discovery rate <0.50) were observed for rs10509561 (FAS), P=6.6x10(-5) for central pulse pressure and rs11559271 (ITGB2), P=1.1x10(-4) for mean arterial pressure. These data demonstrate that, in a community-based sample, circulating inflammatory markers tumor necrosis factor receptor-II (mean arterial pressure), C-reactive protein, lipoprotein-associated phospholipase-A2 activity (reflected pressure wave), interleukin-6, and osteoprotegerin (carotid-femoral pulse wave velocity) were significantly but modestly associated with measures of arterial stiffness and wave reflection. Additional studies are needed to determine whether variation in inflammatory marker genes is associated with tonometry measures.

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Project description:ObjectivesCardiovascular disease is a major cause of morbidity and mortality in Antiphospholipid syndrome (APS). Arterial stiffness (ArS) has emerged as a predictor of future cardiovascular events in the general population. We aimed to assess ArS in patients with thrombotic APS versus diabetes mellitus (DM) and healthy controls (HC) and identify predictors of increased ArS in APS.MethodsArS was evaluated by carotid-femoral pulse wave velocity (cfPWV) and augmentation index normalized to 75 beats/min (AIx@75) using the SphygmoCor device. Participants also underwent carotid/femoral ultrasound for atherosclerotic plaque detection. We used linear regression to compare ArS measures among groups and assess ArS determinants in the APS group.ResultsWe included 110 patients with APS (70.9% female, mean age 45.4 years), 110 DM patients and 110 HC, all age/sex matched. After adjustment for age, sex, cardiovascular risk factors and plaque presence, APS patients exhibited similar cfPWV [β = -0.142 (95% CI -0.514, 0.230), p = 0.454] but increased AIx@75 [β = 4.525 (95% CI 1.372, 7.677), p = 0.005] compared with HC and lower cfPWV (p < 0.001) but similar AIx@75 (p = 0.193) versus DM patients. In the APS group, cfPWV was independently associated with age [β = 0.056 (95% CI 0.034, 0.078), p < 0.001], mean arterial pressure (MAP) [β = 0.070 (95% CI 0.043, 0.097), p < 0.001], atherosclerotic femoral plaques [β = 0.732 (95% CI 0.053, 1.411), p = 0.035] and anti-β2-glycoprotein I IgM positivity [β = 0.696 (95% CI 0.201, 1.191), p = 0.006]. AIx@75 was associated with age [β = 0.334 (95% CI 0.117, 0.551), p = 0.003], female sex [β = 7.447 (95% CI 2.312, 12.581), p = 0.005] and MAP [β = 0.425 (95% CI 0.187, 0.663), p = 0.001].ConclusionAPS patients exhibit elevated AIx@75 vs HC and similar to DM patients, indicating enhanced arterial stiffening in APS. Given its prognostic value, ArS evaluation may help to improve cardiovascular risk stratification in APS.

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Dataset Information

Beneficial effects on arterial stiffness and pulse-wave reflection of combined enalapril and candesartan in chronic kidney disease--a randomized trial.

Background

Methods

Results

Conclusions

Trial registration

Publications

Beneficial effects on arterial stiffness and pulse-wave reflection of combined enalapril and candesartan in chronic kidney disease--a randomized trial.

Similar Datasets

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