Asymmetrical dimethylarginine (ADMA) and risk of acute coronary events

Valkonen, Veli-Pekka; Laakso, Juha; Päivä, Hannu; Lehtimäki, Terho; Lakka, Timo A.; Isomustajärvi, Marja; Ruókonen, Inkeri; Salonen, Jukka J.T.; Laaksonen, Reijo

doi:10.1016/s1567-5688(03)00029-1

Cited by 57 publications

(39 citation statements)

References 16 publications

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“…It seems that our meta-analysis provides the answer to the question on the role of statins on ADMA levels (mainly hydrophilic), irrespective of the statins doses and therapy duration. These results also show the marginal or lack of effect of simvastatin and atorvastatin (hydrophobic statins) on plasma ADMA levels 43 . There are few hypotheses on how statins influence ADMA levels.…”

Section: Discussionmentioning

confidence: 72%

A systematic review and meta-analysis on the effect of statins on plasma asymmetric dimethylarginine concentrations

et al. 2015

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Section: Discussionmentioning

confidence: 72%

A systematic review and meta-analysis on the effect of statins on plasma asymmetric dimethylarginine concentrations

et al. 2015

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“…However, the results of human studies have been contradictory. Some randomized trials have demonstrated that shortterm statin treatment lowers circulating ADMA levels in humans (61, 76, 112), while other studies have failed to find such an effect (36,74,85,109,121). These discordant results could possibly be attributed to differences in the characteristics of the populations examined.…”

Section: Effects Of Statins On Enosmentioning

confidence: 99%

Statins as Regulators of Redox State in the Vascular Endothelium: Beyond Lipid Lowering

Margaritis

Channon

Antoniades

2014

Antioxidants & Redox Signaling

117

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Significance: Endothelial dysfunction and the imbalance between nitric oxide (NO) and reactive oxygen species production in the vascular endothelium are important early steps in atherogenesis, a major socioeconomic health problem. Statins have well-established roles in primary and secondary prevention of cardiovascular disease (CVD), due to both their lipid-lowering capacity and their pleiotropic properties. It is therefore important to understand the mechanisms by which statins can modify endothelial function and affect atherogenesis. Recent Advances: In the last decade, the concept of statin pleiotropy has been reinforced by a large number of cell culture, animal, and translational studies. Statins have been shown to suppress the activity of pro-oxidant enzymes (such as NADPH oxidase) and pro-inflammatory transcriptional pathways in the endothelium. At the same time, they enhance endothelial NO synthase expression and activity while they also improve its enzymatic coupling. This leads to increased NO bioavailability and improved endothelial function. Critical Issues: Despite significant recent advances, the exact mechanisms of statin pleitropy are still only partially understood. The vast majority of the published literature relies on animal studies, while the actual mechanistic studies in humans are limited. Future Directions: The success of statins as endothelium redox-modifying agents with a direct impact on clinical outcome highlights the importance of the endothelium as a therapeutic target in CVD. Better understanding of the mechanisms that underlie endothelial dysfunction could lead to the design of novel therapeutic strategies that target the vascular endothelium for the prevention and treatment of CVD. Antioxid. Redox Signal. 20, 1198Signal. 20, -1215

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“…In addition, clinical studies indicated that intervention with metformin, ACE inhibitors, angiotensin receptor blockers or alpha-lipoic acid would be able to reduce the levels of circulating ADMA [49][50][51][52][53][54][55] . The bibliography on the efficacy of statins on ADMA is contentious [20,[56][57][58][59][60][61] . Meanwhile, one clinical study demonstrated an ADMA decrease during intervention with rosiglitazone, and this was not recognized in a discrete age group [62,63] .…”

Section: Our Experience With Admamentioning

confidence: 99%

Asymmetric dimethylarginine, a biomarker of cardiovascular complications in diabetes mellitus

Konya

Miuchi

Satani

et al. 2015

WJEM

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Cardiovascular (CV) complications are an essential causal element of prospect in diabetes mellitus (DM), with carotid atherosclerosis being a common risk factor for prospective crisis of coronary artery diseases and/or cerebral infarction in DM subjects. From another point of view, asymmetric dimethylarginine (ADMA) has been established as an inhibitor of endogenous nitric oxide synthesis and the relationship between ADMA and arteriosclerosis has been reported. In our study with 87 type 2 DM (T2DM) patients, we have examined whether ADMA and other CV risk factors are the useful predictors of DMCV complications. After the measurement of the respective CV risk factors, we have followed the enrolled T2DM patients for 5 years. We have finally analyzed 77 patients. DMCV complications developed in 15 cases newly within 5 years, and 4 cases recurred. The concentrations of ADMA in plasma were markedly more elevated in 19 DM patients with CV complications than in 58 DM patients without CV complications. Urinary albumin (U-Alb), mean intimal-medial thickness (IMT) and ankle brachial index (ABI) were also higher in patients with CV complications. Multiple regression analyses showed that U-Alb had an influence on the high level of ADMA (standardized β = 6.59, P = 0.00014) independently of age, systolic BP, fibrinogen, mean IMT, plaque score, and ABI. The review indicates what is presently known regarding plasma ADMA that might be a new and meaningful biomarker of CV complications in DM subjects. Core tip: Asymmetric dimethylarginine (ADMA) is an emerging independent biomarker for prospective cardiovascular (CV) complications. In our study, the results show that the cases with a high level of ADMA could have diabetes mellitus CV (DMCV) complications in the future within five years. Furthermore, not only ADMA but also urinary albumin was associated with DMCV complications in the multiple regression analyses. The clinical acceptation of this parameter will rely on the availability of therapies to immediately reduce ADMA such as incretin-based drugs, which could support the part of ADMA as an etiologic risk factor.

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Asymmetrical dimethylarginine (ADMA) and risk of acute coronary events

Cited by 57 publications

References 16 publications

A systematic review and meta-analysis on the effect of statins on plasma asymmetric dimethylarginine concentrations

A systematic review and meta-analysis on the effect of statins on plasma asymmetric dimethylarginine concentrations

Statins as Regulators of Redox State in the Vascular Endothelium: Beyond Lipid Lowering

Asymmetric dimethylarginine, a biomarker of cardiovascular complications in diabetes mellitus

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