Plasma asymmetric dimethylarginine predicts restenosis after coronary angioplasty

Abstract

IntroductionAsymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of endothelial nitric oxide synthase. Asymmetric dimethylarginine may influence the process of restenosis after coronary angioplasty. The aim of the study was to determine if initial plasma ADMA level could predict restenosis after coronary angioplasty and stenting.Material and methodsThe study group consisted of 60 consecutive patients (10 women and 50 men, average age 58.9 ±10.4 years old), who underwent percutaneous coronary angioplasty with bare metal stenting for stable coronary artery disease. All patients underwent follow-up coronary angiography after a 6-month period. Patients were divided into two groups, one with restenosis (n = 22), and the other one without restenosis (n = 38). In addition to measuring acknowledged restenosis risk factors, plasma ADMA level was measured before initial angiography.ResultsAsymmetric dimethylarginine plasma level was significantly higher in the group with restenosis than in the group without restenosis (1.94 ±0.94 µmol/l vs. 0.96 ±0.67 µmol/l; p < 0.05). L-arginine/ADMA ratio was also decreased in the group with restenosis, when compared with the group without restenosis (p < 0.05). Multivariate logistic regression revealed that independent restenosis risk factors were characterised by an initially high ADMA level (p < 0.01), advanced age (p < 0.05) and low level of HDL cholesterol (p < 0.05).ConclusionsPre-procedural elevated plasma ADMA level increases the risk of restenosis in patients who underwent coronary angioplasty and stenting with bare metal stents.

Could plasma asymmetric dimethylarginine level be a novel predictor beyond the classic predictors of stent restenosis?

“…In a prospective study done by Derkacz et al (9) it has been demonstrated that pre-procedural elevated plasma ADMA levels increased the risk of restenosis in patients who underwent coronary angioplasty and stenting with bare metal stents. In our study we did not analyzed the plasma ADMA levels before stenting.…”

“…In recent years few studies reveal a link between ADMA and stent restenosis due to its role on NO formation (9-11). Derkacz et al (9) concluded that pre-procedural elevated plasma ADMA levels increases the risk of restenosis in patients who underwent coronary angioplasty and stenting with bare metal stents. Khalifa et al (10) found that the patients who developed stent restenosis had an increase in ADMA levels following coronary stenting.…”

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

“…It has been shown that statins upregulate both PCSK9 mRNA levels and LDLR via activation of sterol-mediated SREBP-2, an important activator of DDAH transcription and activity 48 . Since reduced DDAH activity is linked to endothelial dysfunction, we speculate that statin therapy might decrease ADMA levels through multiple mechanisms such as activation of sterol-mediated SREBP-2, increasing of transcription of PCSK9 or by decreasing ADMA-induced inflammatory reaction, modulated by MAPK 49,50 . This meta-analysis has several limitations.…”

Increased levels of MMP-3, MMP-9 and MPO represent predictors of in-stent restenosis, while increased levels of ADMA, LCAT, ApoE and ApoD predict bare metal stent patency

“…Furthermore, by increasing VSMC proliferation and extracellular matrix formation, it may also influence the process of ISR (ref. 20,21 ). Previous reports showed an association between ISR and vasodilator dysfunction in forearm resistance vessels 18,21,22 , and several small studies have reported an association between ISR and increased plasma ADMA levels 17,18,20 .…”