Blood pressure and not uraemia is the major determinant of arterial stiffness and endothelial dysfunction in patients with chronic kidney disease and minimal co-morbidity

Lilitkarntakul, Pajaree; Dhaun, Neeraj; Melville, Vanessa; Blackwell, Scott; Talwar, Dinesh; Liebman, Barbara; Asai, Takae; Pollock, Jennifer S.; Goddard, Jane; Webb, David J.

doi:10.1016/j.atherosclerosis.2011.01.045

Cited by 66 publications

(74 citation statements)

References 44 publications

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“…The kidneys and the brain are early targets for damage by elevated blood pressure. 26 Blood pressure is the major determinant of arteriosclerosis and endothelial dysfunction in patients with chronic kidney disease, 27 and endothelial dysfunction within capillaries appears to contribute to the development of CMBs. 28 Recent studies have shown that endothelial dysfunction is an important mechanism of cerebrovascular damage in patients with lacunar infarction 29 that is correlated with an increased risk of acute ischemic stroke.…”

Section: Discussionmentioning

confidence: 99%

Stroke patients with cerebral microbleeds on MRI scans have arteriolosclerosis as well as systemic atherosclerosis

et al. 2012

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Cerebral microbleeds (CMBs) are recognized as a manifestation of arteriolosclerosis in cerebral small vessels. However, little is known regarding whether stroke patients with CMBs often have systemic atherosclerosis. The aim of the present study was to elucidate this issue using the cardio-ankle vascular index (CAVI), a new index of systemic atherosclerosis, in acute ischemic stroke patients. We prospectively studied 105 patients (71 males, median age ¼ 70.0 years) with acute ischemic stroke. All of the patients were examined using T2*-weighted gradient echo magnetic resonance imaging (MRI) to look for and assess the CMBs and using fluid-attenuated inversion recovery to evaluate white matter hyperintensity (WMH). We assigned the patients into CMB and non-CMB groups and compared the clinical characteristics of these groups. The factors associated with CMBs were investigated using multivariate logistic regression analysis. T2*-weighted gradient echo MRI revealed CMBs in 47 patients (44.8%) and no CMBs in 58 patients (55.2%). The CAVI was significantly higher in the CMBs group (10.5 vs. 8.6, Po0.001).In the multivariate logistic regression analysis, CAVI per one point increase (odds ratio (OR), 1.50; 95% confidence interval (CI), 1.12-2.00; P ¼ 0.006), advanced WMH (OR, 4.78; 95% CI, 1.55-14.74; P ¼ 0.006) and impaired kidney function (OR, 3.31; 95% CI, 1.16-9.81; P ¼ 0.031) were independent factors associated with the presence of CMBs. A high CAVI was independently associated with CMBs in patients with acute ischemic stroke. Our results indicated that ischemic stroke patients with CMBs may have cerebral arteriolosclerosis as well as systemic atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Stroke patients with cerebral microbleeds on MRI scans have arteriolosclerosis as well as systemic atherosclerosis

et al. 2012

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“…We have previously shown in a cross-sectional study that ADMA concentrations directly correlate with arterial stiffness-as measured by PVW-in a similar cohort of patients with CKD. 26 The current study takes this observation further by showing for the first time that a decrease in ADMA correlates with an improvement in arterial stiffness, although we recognize this correlation to be weak. Additionally, it is not possible to separate independent effects of the ET A antagonist on arterial stiffness and ADMA in this limited number of patients.…”

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confidence: 98%

“…Many studies in patients with varying degrees of CKD have confirmed that ADMA is elevated in CKD. 14,26 Of note, data suggest that ADMA is elevated independently of renal function in CKD, 27 suggesting that mechanisms other than impaired clearance may contribute to the accumulation of ADMA in this setting. The ET system is upregulated in CKD.…”

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confidence: 99%

Endothelin-A Receptor Antagonism Modifies Cardiovascular Risk Factors in CKD

Dhaun

Melville

Blackwell

et al. 2013

Journal of the American Society of Nephrology

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Arterial stiffness and impaired nitric oxide (NO) bioavailability contribute to the high risk for cardiovascular disease in CKD. Both asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO production, and endothelin-1 (ET-1) oppose the actions of NO, suggesting that ET-1 receptor antagonists may have a role in cardiovascular protection in CKD. We conducted a randomized, double-blind, three-way crossover study in 27 patients with proteinuric CKD to compare the effects of the ET A receptor antagonist sitaxentan, nifedipine, and placebo on proteinuria, BP, arterial stiffness, and various cardiovascular biomarkers. After 6 weeks of treatment, placebo and nifedipine did not affect plasma urate, ADMA, or urine ET-1/creatinine, which reflects renal ET-1 production; in contrast, sitaxentan led to statistically significant reductions in all three of these biomarkers. No treatment affected plasma ET-1. Reductions in proteinuria and BP after sitaxentan treatment was associated with increases in urine ET-1/creatinine, whereas reduction in pulsewave velocity, a measure of arterial stiffness, was associated with a decrease in ADMA. Taken together, these data suggest that ET A receptor antagonism may modify risk factors for cardiovascular disease in CKD.

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“…Blood pressure, high sensitivity C-reactive protein, oxidized LDL (OxLDL), and interleukin (IL)-6 were determined as described previously ( 25 ). Other parameters [plasma glucose, total cholesterol, triglyceride, lipoproteins, creatinine, and glycated hemoglobin (HbA 1c )] were determined in the hospital biochemistry laboratory by assays validated to Good Laboratory Practice standard.…”

Section: Clinical and Biochemical Measurementsmentioning

confidence: 99%

“…Male CKD patients (stage 4/5) were recruited from the renal outpatient clinic at the Royal Infi rmary of Edinburgh following ethical approval by NHS Lothian Research Ethics Committee and gave informed consent as described previously ( 25 ). Renal patients were excluded on the basis of renal transplant, dialysis, systemic vasculitis or connective tissue disease, a history of established CVD, peripheral vascular disease, diabetes mellitus, respiratory disease, neurological disease, alcohol abuse, or treatment with an organic nitrate or ␤ -agonist.…”

Section: Subjects and Blood Collectionmentioning

confidence: 99%

Top-down lipidomics of low density lipoprotein reveal altered lipid profiles in advanced chronic kidney disease

Reis

Rudnitskaya

Chariyavilaskul

et al. 2015

Journal of Lipid Research

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Chronic kidney disease (CKD) is a serious and increasingly common condition ( 1 ). Patients with CKD have a greatly increased risk of CVD, which represents the most common cause of mortality and morbidity in these patients, to the extent that CKD is considered an independent risk factor for CVD ( 2, 3 ). In CKD, many conventional risk factors for CVD are prevalent, including hypertension, dyslipidemia, and insulin resistance. Underlying conditions that are typical of CVD also occur, such as heightened infl ammatory status, oxidative stress, endothelial dysfunction, and arterial stiffness ( 3, 4 ). Consequently, understanding the factors in CKD that could contribute to increased CVD risk is very important.In CVD there is a clearly established link between dyslipidemia (specifi cally hypercholesterolemia and hypertriglyceridemia) and atherosclerosis, an underlying pathology of most CVD ( 5, 6 ). In view of the clear cardiorenal relationship, there has been considerable interest in the possible contribution of hyperlipidemia to CKD-associated CVD ( 7,8 )

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Blood pressure and not uraemia is the major determinant of arterial stiffness and endothelial dysfunction in patients with chronic kidney disease and minimal co-morbidity

Cited by 66 publications

References 44 publications

Stroke patients with cerebral microbleeds on MRI scans have arteriolosclerosis as well as systemic atherosclerosis

Stroke patients with cerebral microbleeds on MRI scans have arteriolosclerosis as well as systemic atherosclerosis

Endothelin-A Receptor Antagonism Modifies Cardiovascular Risk Factors in CKD

Top-down lipidomics of low density lipoprotein reveal altered lipid profiles in advanced chronic kidney disease

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