Effect of rosuvastatin on plasma levels of asymmetric dimethylarginine in patients with hypercholesterolemia

Lu, Tse‐Min; Ding, Yu‐An; Leu, Hsin‐Bang; Yin, Wei-Hsian; Sheu, Wayne Huey‐Herng; Chu, Kai-Min

doi:10.1016/j.amjcard.2004.03.052

Cited by 152 publications

(96 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Third, the data related to the decline of renal function were recorded in only some individuals, although previous studies have shown that plasma ADMA might be a potential risk factor for the progression of CKD to ESRD. Finally, some studies reported that the use of statins and angiotensin-converting enzymes/angiotensin receptor blockers might reduce the plasma ADMA levels (35,36). However, in this study, no significant differences were observed in plasma ADMA levels between patients who received statins and those who did not (P ϭ 0.65) and between patients who received angiotensin-converting enzymes/angiotensin receptor blockers and those who did not (P ϭ 0.74).…”

Section: Discussioncontrasting

confidence: 69%

Asymmetric Dimethylarginine and Clinical Outcomes in Chronic Kidney Disease

Chung²,

Lin

et al. 2011

Clinical Journal of the American Society of Nephrology

Self Cite

View full text Add to dashboard Cite

SummaryBackground and objectives Elevated plasma level of asymmetric dimethylarginine (ADMA) have been reported to be associated with endothelial dysfunction and atherosclerosis risk factors, and may predict cardiovascular events in patients with ESRD. In this study, we aimed to assess the association between plasma ADMA and long-term outcome in a cohort of patients with stage 3 to 4 chronic kidney disease (CKD).Design, setting, participants, & measurements From July 2006 to June 2009, 298 consecutive patients with stage 3 to 4 CKD scheduled to undergo coronary angiography were recruited. Plasma ADMA levels were determined using HPLC. ResultsThe mean age was 73 Ϯ 10 years. Approximately half of the patients had diabetes and 88 patients had proteinuria. The baseline estimated GFR (eGFR) was 44 Ϯ 13 ml/min per 1.73 m 2 . The plasma ADMA levels of the patients with proteinuria were significantly higher than those without. The plasma ADMA levels correlated significantly with eGFR. During the median follow-up period of 2.7 years, we observed 26 all-cause deaths, 12 nonfatal myocardial infarctions, and 2 strokes. Multivariate Cox analysis revealed that an increase of 0.1 mol/L in plasma ADMA level was associated with a 37% increased risk of the composite outcomes of all-cause deaths, nonfatal myocardial infarctions, and strokes. ConclusionsIn this elder and high-risk population with stage 3 to 4 CKD, high plasma ADMA level was associated with low eGFR and macroalbuminuria. Furthermore, high plasma ADMA level appeared to be an independent predictor of long-term outcome.

show abstract

Section: Discussioncontrasting

confidence: 69%

Asymmetric Dimethylarginine and Clinical Outcomes in Chronic Kidney Disease

Chung²,

Lin

et al. 2011

Clinical Journal of the American Society of Nephrology

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the AURORA study (40), treatment with Rosuvastatin reduced CRP, but this drug had no effect on the incidence rate of death and CV events in ESRD patients. Rosuvastatin is one of the most potent ADMA modifiers, and improvement in endothelial dysfunction in patients with hypercholesterolemia goes along with the ADMA-lowering effect of this drug (41). Secondary analyses in AURORA restricted to patients with high ADMA and high CRP (that is, in the subgroup of patients in whom, as suggested by our findings, the beneficial effect of Rosuvastatin might be maximized) may allow preliminary testing the hypothesis generated by this study.…”

Section: Interaction Between Adma and Inflammationmentioning

confidence: 98%

Inflammation and Asymmetric Dimethylarginine for Predicting Death and Cardiovascular Events in ESRD Patients

Tripepi¹,

Mattace-Raso

Sijbrands

et al. 2011

Clinical Journal of the American Society of Nephrology

106

View full text Add to dashboard Cite

SummaryBackground Endothelial dysfunction as assessed by asymmetric dimethylarginine (ADMA) and inflammation has been consistently linked to atherosclerosis, death, and cardiovascular (CV) events in ESRD patients. Inflammation amplifies the effect of ADMA on the severity of atherosclerosis in ESRD patients, but it is still unknown whether inflammation and ADMA interact in the high risk of death and CV events in this population. Design, setting, participants, & measurementsIn a cohort of 225 hemodialysis patients, we investigated the interaction between inflammatory biomarkers (C-reactive protein and IL-6) and ADMA as predictors of death and CV events over an extended follow-up (13 years).Results During follow-up, 160 patients died, and 123 had CV events. With crude and multiple Cox regression analyses, an interaction was found between inflammation biomarkers and ADMA for explaining death and CV events in ESRD patients. The adjusted hazard ratios (HRs) for death (HR, 2.18; 95% confidence interval [CI], 1.34 to 3.54) and CV outcomes (HR, 2.59; 95% CI, 1.47 to 4.55) of patients with C-reactive protein and ADMA above the median were higher than expected in the absence of interaction under the additive model (1.15 and 1.97, respectively) and significantly higher than in patients with only one biomarker above the median. Data analyses carried out by stratifying patients according to IL-6 provided similar results. ConclusionsThese data support the hypothesis that inflammation amplifies the risk of death and CV events associated with high ADMA levels in ESRD. These analyses further emphasize the need for intervention studies to attenuate inflammation and high ADMA levels in this population.

show abstract

“…These have not included patients with CKD and have suffered from being small or lacking in rigorous methods. 18,19 To our knowledge, the current study is the first to show that ET receptor antagonism may reduce circulating ADMA concentrations. 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.…”

mentioning

confidence: 99%

“…14 ADMA concentrations are increased in patients with CKD, 14 and clinical data support ADMA as an independent marker of CKD progression, cardiovascular morbidity, and overall mortality. [15][16][17] Studies have shown a reduction in ADMA after therapy in patients with hypertension and hypercholesterolemia, 18,19 but not in patients with CKD.…”

mentioning

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

View full text Add to dashboard Cite

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.

show abstract

Effect of rosuvastatin on plasma levels of asymmetric dimethylarginine in patients with hypercholesterolemia

Cited by 152 publications

References 27 publications

Asymmetric Dimethylarginine and Clinical Outcomes in Chronic Kidney Disease

Asymmetric Dimethylarginine and Clinical Outcomes in Chronic Kidney Disease

Inflammation and Asymmetric Dimethylarginine for Predicting Death and Cardiovascular Events in ESRD Patients

Endothelin-A Receptor Antagonism Modifies Cardiovascular Risk Factors in CKD

Contact Info

Product

Resources

About