International Journal of Cardiology 178 (2015) 188–190
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Does elevated asymmetrical dimethylarginine predict major adverse cardiac events and mortality in patients after percutaneous coronary intervention? Yang Shao, Yichuan Fan, Jun Li, Hui Cao, Bing Liu, Junpeng Wang, Jun Yang, Qiang Zhang, Xinhua Hu ⁎ Department of Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, China
a r t i c l e
i n f o
Article history: Received 6 September 2014 Accepted 21 October 2014 Available online 22 October 2014 Keywords: Asymmetrical dimethylarginine PCI Mortality Major adverse cardiac events Meta-analysis
Percutaneous coronary interventions (PCI) have been proposed as a superior management strategy in patients with acute coronary syndrome, particularly in ST elevation myocardial infarction (MI). Despite the dramatic reduction in mortality associated with the use of PCI, cardiovascular mortality is still as high as 40% [1]. Therefore, finding predictors for future adverse events after PCI is very important. Asymmetric dimethylarginine (ADMA) is a naturally occurring oxidative substance of the human plasma. ADMA has been recognized as a cardiovascular risk factor [2,3]. Several studies [4–10] have addressed the ability of ADMA level to predict subsequent cardiovascular events and mortality in patients undergoing PCI. Considering a small number of sample sizes may be lack of power to reveal the reliable conclusion, we conducted a meta-analysis to investigate the relationship of baseline ADMA level and future MACEs and mortality event based on the prospective studies. We conducted a PubMed database and Embase search prior to May 2014. The following search keywords were used: ADMA or asymmetric dimethylarginine and mortality or death or major adverse cardiac events (MACEs) and stent or PCI or percutaneous coronary interventions. Studies were considered eligible if: 1) prospective observational studies; 2) patients undergoing PCI and follow-up at least one year; and 3) providing adjusted hazard ratio (HR) and corresponding 95% confidence interval (CI) of MACEs and cardiovascular or all-cause ⁎ Corresponding author. E-mail address: [email protected] (X. Hu).
http://dx.doi.org/10.1016/j.ijcard.2014.10.121 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
mortality comparing the highest to lowest baseline ADMA category. MACEs are defined as non-fatal myocardial infarction, in-stent thrombosis, total stroke, coronary heart disease mortality, target vessel revascularization, and cardiovascular mortality. Restenosis was defined as the diameter stenosis more than 50% both within the stent and in the adjacent segments 5 mm proximal and distal, as determined by follow-up angiography. Quality assessment was evaluated by the Meta-analysis of Observational Studies in Epidemiology guidelines [11]. HR was used for comparison of subjects with the highest ADMA versus lowest category across the studies. Heterogeneity of effect sizes across studies was assessed by using the Cochrane Q statistic and the I2 statistic. All analysis was performed using STATA software (version 12.0). A total of 88 potentially relevant citations were identified in our initial literature search. After reviewing the full texts, five studies [4–8] met the inclusion criteria. The characteristics of the included studies are listed in Table 1. Generally, these studies had a relatively high quality (data not shown). Three studies [4,6,7] reported 165 cases of MACE events among 1300 participants. Pooled HR of MACEs was 2.31 (95% CI 0.97–5.46; I2 = 85.3%; p = 0.001) compared from the highest to lowest ADMA level in a random effect model (Fig. 1.1). Three studies [5,6,8] reported 531 cases of cardiovascular mortality events among 4419 patients. Pooled HR of cardiovascular mortality was 1.65 (95% CI 1.30–2.08; I2 = 17.1%; p = 0.299) compared from the highest to lowest ADMA levels in a fixed-effect model (Fig. 1.2). Four studies [5–8] reported 856 cases of all-cause mortality among 4569 participants. Pooled HR of all-cause mortality was 1.62 (95% CI 1.17–2.25; I2 = 75.2%; p = 0.007) compared from the highest to lowest ADMA levels in a fixed-effect model (Fig. 1.3). No evidence of publication bias for studies reporting HRs of all-cause mortality was observed based on the Begg's rank correlation test (p = 0.618) and Egger's linear regression test (p = 0.308). Sensitivity analyses demonstrated that there was little influence in the pooled effect sizes when any study is omitted (data not shown). This meta-analysis indicated that the highest ADMA level was associated with 65% greater cardiovascular mortality and 62% greater risk of all-cause mortality events in patients undergoing PCI. However, highest ADMA level appears to not increase the risk of MACEs (HR 2.31; 95% CI 0.97–5.46). Elevated ADMA level and subsequent cardiovascular event risk also found in other studies which did not meet our inclusion criteria for the meta-analysis. Elevated ADMA level was independently associated with the development of restenosis (HR 5.96, 95% CI: 2.45–11.26) among patients undergoing primary PCI in a case–control study [9]. In
Y. Shao et al. / International Journal of Cardiology 178 (2015) 188–190
189
Table 1 Summary of clinical studies included in meta-analysis. Study/year
Region
Design
Lu et al. [4]
Taiwan
Cavusoglu et al. [5]
USA
Prospective study Prospective study
Lu et al. [6]
Taiwan
Prospective study
Sen et al. [7]
Turkey
Prospective study
Meinitzer et al. [8]
Subjects (% women)
Age range, mean ± SD (years)
153 (13.1) 71 ± 8 193 (0)
66.2 ± 10.4 64.1 ± 9.9
997 (37.5) 41–67
150 (30.0) 57.5 ± 9.24 (tertile 1) 57.2 ± 9.1 (tertile 2) 57.4 ± 9.0 (tertile 3) Germany Prospective 3229 (30.3) 59–91 study
ADMA comparison (μmol/L)
HR (95% CI)/event type (number)
Follow-up (years)
Adjustment for covariates
Highest vs. lowest tertile N0.62 vs. b0.50 High vs. low tertile N1.115 vs. b1.115
5.26 (2.16–12.85) MACE (51)
3
Multivariate analysis
2.45 (1.08–5.57) total death (26) 1.81 (1.01–3.25) cardiovascular death (15)
2
3.37 (1.40–8.11) total death (64) 3.61 (1.24–10.51) cardiovascular death (47) 2.48 (1.23–5.00) MACE (81) 1.20 (1.13–1.41) total death (17) 1.22 (1.12–1.44) MACE (33)
2.4
For all-cause death: age, number of diseased coronary arteries, hs-CRP, and fibrinogen. For cardiovascular death: age, LVEF, creatinine, presence of myocardial infarction, number of diseased coronary arteries, hs-CRP, and fibrinogen. Age, gender, diabetes, acute coronary syndrome and hypercholesterolemia,
1.0
TIMI risk score, LVEF, hs-CRP, abnormal TMPG
Highest vs. lowest 1.54 (1.18–2.02) tertile ≥0.89 vs. b0.72 Cardiovascular death (469) 1.61 (1.30–1.99) total death (749)
7.7
Age, sex, presence or absence of coronary heart disease on angiography, BMI, hypertension, smoking status, LDL, HDL, triglycerides, and estimated glomerular filtration rate.
Highest vs. lowest tertile N0.48 vs. b0.41
Highest vs. lowest tertile N0.78–1.60 vs. b0.72
Abbreviations: BMI, body mass index; HR, hazard ratio; MACE, major adverse cardiac event; LVEF, left ventricular ejection fraction; LDL, low-density lipoprotein; HDL, high-density lipoprotein; ADMA, asymmetric dimethylarginine; Hs-CRP, high sensitivity C-reactive protein; TMPG, TIMI myocardial perfusion grade.
another case–control study [10], high levels of ADMA were correlated with a 3.02-fold increased risk of restenosis and 2.83-fold MACEs among patients who undergo primary PCI. Elevated ADMA level and cardiovascular and all-cause mortality risk were also found in patients with coronary artery disease [12,13] and acute myocardial infarction [14].
Several mechanisms might explain by which higher ADMA levels increase risk of MACEs or mortality. ADMA is an endogenous inhibitor of endothelial NO synthase that competes with L-arginine as a substrate for NO synthase [15,16]. ADMA inhibits vascular NO production at concentrations found in pathophysiological conditions [17], leading to
Fig. 1. Hazard ratio and 95% CI of major adverse cardiac events, cardiovascular mortality and all-cause mortality comparing the highest to the lowest asymmetric dimethylarginine category.
190
Y. Shao et al. / International Journal of Cardiology 178 (2015) 188–190
disruption of the integrity of endothelium and subsequent atherosclerosis. Higher level of ADMA in acute coronary syndrome may be a result of inflammation [7]. It should be noted that renal impairment would be partly responsible for ADMA elevation in coronary heart disease [18]. Several potential limitations should be noted. First, patients in the individual study used a single value of baseline ADMA, and differential ADMA levels after PCI and during follow-up were unavailable. Second, individual studies did not adjust for potential risk factors in a consistent way; some residual confounding factors such as renal function, blood glucose, and insulin resistance could affect the results. Third, followup duration in most studies was less than 3 years. It is difficult to determine beyond the duration of follow-up with respect to long-term impact. Finally, most of the patients were male in the current metaanalysis; therefore, we could not determine if there were any differences between genders. In conclusion, this meta-analysis indicates that higher ADMA level is associated with an increase future risk of cardiovascular and all-cause mortality, but not for MACEs. Determination of ADMA might provide a simple method for assessment of prognosis in patients with undergoing PCI. However, these findings need to be further confirmed by larger and prospective studies. Conflict of interest None declared. References [1] J.M. Stolker, D.J. Cohen, J.B. Lindsey, K.F. Kennedy, N.S. Kleiman, S.P. Marso, Mode of death after contemporary percutaneous coronary intervention: a report from the Evaluation of Drug Eluting Stents and Ischemic Events registry, Am. Heart J. 162 (2011) 914–921. [2] R.H. Boger, The emerging role of asymmetric dimethylarginine as a novel cardiovascular risk factor, Cardiovasc. Res. 59 (2003) 824–833. [3] F. Schulze, H. Lenzen, C. Hanefeld, A. Bartling, K.J. Osterziel, L. Goudeva, et al., Asymmetric dimethylarginine is an independent risk factor for coronary heart disease: results from the multicenter Coronary Artery Risk Determination investigating the Influence of ADMA Concentration (CARDIAC) study, Am. Heart J. 152 (2006) 493 (e1-8). [4] T.M. Lu, Y.A. Ding, S.J. Lin, W.S. Lee, H.C. Tai, Plasma levels of asymmetrical dimethylarginine and adverse cardiovascular events after percutaneous coronary intervention, Eur. Heart J. 24 (2003) 1912–1919.
[5] E. Cavusoglu, C. Ruwende, V. Chopra, S. Yanamadala, C. Eng, D.J. Pinsky, et al., Relationship of baseline plasma ADMA levels to cardiovascular outcomes at 2 years in men with acute coronary syndrome referred for coronary angiography, Coron. Artery Dis. 20 (2009) 112–117. [6] T.M. Lu, M.Y. Chung, M.W. Lin, C.P. Hsu, S.J. Lin, Plasma asymmetric dimethylarginine predicts death and major adverse cardiovascular events in individuals referred for coronary angiography, Int. J. Cardiol. 153 (2011) 135–140. [7] N. Sen, M.F. Ozlu, E.O. Akgul, S. Kanat, T. Cayci, O. Turak, et al., Elevated plasma asymmetric dimethylarginine level in acute myocardial infarction patients as a predictor of poor prognosis and angiographic impaired reperfusion, Atherosclerosis 219 (2011) 304–310. [8] A. Meinitzer, J.T. Kielstein, S. Pilz, C. Drechsler, E. Ritz, B.O. Boehm, et al., Symmetrical and asymmetrical dimethylarginine as predictors for mortality in patients referred for coronary angiography: the Ludwigshafen Risk and Cardiovascular Health study, Clin. Chem. 57 (2011) 112–121. [9] A. Derkacz, M. Protasiewicz, R. Poreba, A. Doroszko, M. Poreba, J. AntonowiczJuchniewicz, et al., Plasma asymmetric dimethylarginine predicts restenosis after coronary angioplasty, Arch. Med. Sci. 7 (2010) 444–448. [10] H. Ari, S. Ari, E. Erdogan, O. Tiryakioglu, Y. Ustundag, K. Huysal, et al., A novel predictor of restenosis and adverse cardiac events: asymmetric dimethylarginine, Heart Vessels 25 (2010) 19–26. [11] D.F. Stroup, J.A. Berlin, S.C. Morton, I. Olkin, G.D. Williamson, D. Rennie, et al., Metaanalysis of observational studies in epidemiology: a proposal for reporting. Metaanalysis Of Observational Studies in Epidemiology (MOOSE) group, JAMA 283 (2000) 2008–2012. [12] R. Schnabel, S. Blankenberg, E. Lubos, K.J. Lackner, H.J. Rupprecht, C. Espinola-Klein, et al., Asymmetric dimethylarginine and the risk of cardiovascular events and death in patients with coronary artery disease: results from the AtheroGene study, Circ. Res. 97 (2005) e53–e59. [13] B. Siegerink, R. Maas, C.Y. Vossen, E. Schwedhelm, W. Koenig, R. Boger, et al., Asymmetric and symmetric dimethylarginine and risk of secondary cardiovascular disease events and mortality in patients with stable coronary heart disease: the KAROLA follow-up study, Clin. Res. Cardiol. 102 (2013) 193–202. [14] M. Zeller, C. Korandji, J.C. Guilland, P. Sicard, C. Vergely, L. Lorgis, et al., Impact of asymmetric dimethylarginine on mortality after acute myocardial infarction, Arterioscler. Thromb. Vasc. Biol. 28 (2008) 954–960. [15] P. Vallance, A. Leone, A. Calver, J. Collier, S. Moncada, Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure, Lancet 339 (1992) 572–575. [16] J.P. Cooke, Does ADMA cause endothelial dysfunction? Arterioscler. Thromb. Vasc. Biol. 20 (2000) 2032–2037. [17] R.H. Boger, Asymmetric dimethylarginine (ADMA) and cardiovascular disease: insights from prospective clinical trials, Vasc. Med. 10 (Suppl. 1) (2005) S19–S25. [18] J. Wang, A.S. Sim, X.L. Wang, C. Salonikas, D. Naidoo, D.E. Wilcken, Relations between plasma asymmetric dimethylarginine (ADMA) and risk factors for coronary disease, Atherosclerosis 184 (2006) 383–388.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Does elevated asymmetrical dimethylarginine predict major adverse cardiac events and mortality in patients after percutaneous coronary intervention? Yang Shao, Yichuan Fan, Jun Li, Hui Cao, Bing Liu, Junpeng Wang, Jun Yang, Qiang Zhang, Xinhua Hu ⁎ Department of Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, China
a r t i c l e
i n f o
Article history: Received 6 September 2014 Accepted 21 October 2014 Available online 22 October 2014 Keywords: Asymmetrical dimethylarginine PCI Mortality Major adverse cardiac events Meta-analysis
Percutaneous coronary interventions (PCI) have been proposed as a superior management strategy in patients with acute coronary syndrome, particularly in ST elevation myocardial infarction (MI). Despite the dramatic reduction in mortality associated with the use of PCI, cardiovascular mortality is still as high as 40% [1]. Therefore, finding predictors for future adverse events after PCI is very important. Asymmetric dimethylarginine (ADMA) is a naturally occurring oxidative substance of the human plasma. ADMA has been recognized as a cardiovascular risk factor [2,3]. Several studies [4–10] have addressed the ability of ADMA level to predict subsequent cardiovascular events and mortality in patients undergoing PCI. Considering a small number of sample sizes may be lack of power to reveal the reliable conclusion, we conducted a meta-analysis to investigate the relationship of baseline ADMA level and future MACEs and mortality event based on the prospective studies. We conducted a PubMed database and Embase search prior to May 2014. The following search keywords were used: ADMA or asymmetric dimethylarginine and mortality or death or major adverse cardiac events (MACEs) and stent or PCI or percutaneous coronary interventions. Studies were considered eligible if: 1) prospective observational studies; 2) patients undergoing PCI and follow-up at least one year; and 3) providing adjusted hazard ratio (HR) and corresponding 95% confidence interval (CI) of MACEs and cardiovascular or all-cause ⁎ Corresponding author. E-mail address: [email protected] (X. Hu).
http://dx.doi.org/10.1016/j.ijcard.2014.10.121 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
mortality comparing the highest to lowest baseline ADMA category. MACEs are defined as non-fatal myocardial infarction, in-stent thrombosis, total stroke, coronary heart disease mortality, target vessel revascularization, and cardiovascular mortality. Restenosis was defined as the diameter stenosis more than 50% both within the stent and in the adjacent segments 5 mm proximal and distal, as determined by follow-up angiography. Quality assessment was evaluated by the Meta-analysis of Observational Studies in Epidemiology guidelines [11]. HR was used for comparison of subjects with the highest ADMA versus lowest category across the studies. Heterogeneity of effect sizes across studies was assessed by using the Cochrane Q statistic and the I2 statistic. All analysis was performed using STATA software (version 12.0). A total of 88 potentially relevant citations were identified in our initial literature search. After reviewing the full texts, five studies [4–8] met the inclusion criteria. The characteristics of the included studies are listed in Table 1. Generally, these studies had a relatively high quality (data not shown). Three studies [4,6,7] reported 165 cases of MACE events among 1300 participants. Pooled HR of MACEs was 2.31 (95% CI 0.97–5.46; I2 = 85.3%; p = 0.001) compared from the highest to lowest ADMA level in a random effect model (Fig. 1.1). Three studies [5,6,8] reported 531 cases of cardiovascular mortality events among 4419 patients. Pooled HR of cardiovascular mortality was 1.65 (95% CI 1.30–2.08; I2 = 17.1%; p = 0.299) compared from the highest to lowest ADMA levels in a fixed-effect model (Fig. 1.2). Four studies [5–8] reported 856 cases of all-cause mortality among 4569 participants. Pooled HR of all-cause mortality was 1.62 (95% CI 1.17–2.25; I2 = 75.2%; p = 0.007) compared from the highest to lowest ADMA levels in a fixed-effect model (Fig. 1.3). No evidence of publication bias for studies reporting HRs of all-cause mortality was observed based on the Begg's rank correlation test (p = 0.618) and Egger's linear regression test (p = 0.308). Sensitivity analyses demonstrated that there was little influence in the pooled effect sizes when any study is omitted (data not shown). This meta-analysis indicated that the highest ADMA level was associated with 65% greater cardiovascular mortality and 62% greater risk of all-cause mortality events in patients undergoing PCI. However, highest ADMA level appears to not increase the risk of MACEs (HR 2.31; 95% CI 0.97–5.46). Elevated ADMA level and subsequent cardiovascular event risk also found in other studies which did not meet our inclusion criteria for the meta-analysis. Elevated ADMA level was independently associated with the development of restenosis (HR 5.96, 95% CI: 2.45–11.26) among patients undergoing primary PCI in a case–control study [9]. In
Y. Shao et al. / International Journal of Cardiology 178 (2015) 188–190
189
Table 1 Summary of clinical studies included in meta-analysis. Study/year
Region
Design
Lu et al. [4]
Taiwan
Cavusoglu et al. [5]
USA
Prospective study Prospective study
Lu et al. [6]
Taiwan
Prospective study
Sen et al. [7]
Turkey
Prospective study
Meinitzer et al. [8]
Subjects (% women)
Age range, mean ± SD (years)
153 (13.1) 71 ± 8 193 (0)
66.2 ± 10.4 64.1 ± 9.9
997 (37.5) 41–67
150 (30.0) 57.5 ± 9.24 (tertile 1) 57.2 ± 9.1 (tertile 2) 57.4 ± 9.0 (tertile 3) Germany Prospective 3229 (30.3) 59–91 study
ADMA comparison (μmol/L)
HR (95% CI)/event type (number)
Follow-up (years)
Adjustment for covariates
Highest vs. lowest tertile N0.62 vs. b0.50 High vs. low tertile N1.115 vs. b1.115
5.26 (2.16–12.85) MACE (51)
3
Multivariate analysis
2.45 (1.08–5.57) total death (26) 1.81 (1.01–3.25) cardiovascular death (15)
2
3.37 (1.40–8.11) total death (64) 3.61 (1.24–10.51) cardiovascular death (47) 2.48 (1.23–5.00) MACE (81) 1.20 (1.13–1.41) total death (17) 1.22 (1.12–1.44) MACE (33)
2.4
For all-cause death: age, number of diseased coronary arteries, hs-CRP, and fibrinogen. For cardiovascular death: age, LVEF, creatinine, presence of myocardial infarction, number of diseased coronary arteries, hs-CRP, and fibrinogen. Age, gender, diabetes, acute coronary syndrome and hypercholesterolemia,
1.0
TIMI risk score, LVEF, hs-CRP, abnormal TMPG
Highest vs. lowest 1.54 (1.18–2.02) tertile ≥0.89 vs. b0.72 Cardiovascular death (469) 1.61 (1.30–1.99) total death (749)
7.7
Age, sex, presence or absence of coronary heart disease on angiography, BMI, hypertension, smoking status, LDL, HDL, triglycerides, and estimated glomerular filtration rate.
Highest vs. lowest tertile N0.48 vs. b0.41
Highest vs. lowest tertile N0.78–1.60 vs. b0.72
Abbreviations: BMI, body mass index; HR, hazard ratio; MACE, major adverse cardiac event; LVEF, left ventricular ejection fraction; LDL, low-density lipoprotein; HDL, high-density lipoprotein; ADMA, asymmetric dimethylarginine; Hs-CRP, high sensitivity C-reactive protein; TMPG, TIMI myocardial perfusion grade.
another case–control study [10], high levels of ADMA were correlated with a 3.02-fold increased risk of restenosis and 2.83-fold MACEs among patients who undergo primary PCI. Elevated ADMA level and cardiovascular and all-cause mortality risk were also found in patients with coronary artery disease [12,13] and acute myocardial infarction [14].
Several mechanisms might explain by which higher ADMA levels increase risk of MACEs or mortality. ADMA is an endogenous inhibitor of endothelial NO synthase that competes with L-arginine as a substrate for NO synthase [15,16]. ADMA inhibits vascular NO production at concentrations found in pathophysiological conditions [17], leading to
Fig. 1. Hazard ratio and 95% CI of major adverse cardiac events, cardiovascular mortality and all-cause mortality comparing the highest to the lowest asymmetric dimethylarginine category.
190
Y. Shao et al. / International Journal of Cardiology 178 (2015) 188–190
disruption of the integrity of endothelium and subsequent atherosclerosis. Higher level of ADMA in acute coronary syndrome may be a result of inflammation [7]. It should be noted that renal impairment would be partly responsible for ADMA elevation in coronary heart disease [18]. Several potential limitations should be noted. First, patients in the individual study used a single value of baseline ADMA, and differential ADMA levels after PCI and during follow-up were unavailable. Second, individual studies did not adjust for potential risk factors in a consistent way; some residual confounding factors such as renal function, blood glucose, and insulin resistance could affect the results. Third, followup duration in most studies was less than 3 years. It is difficult to determine beyond the duration of follow-up with respect to long-term impact. Finally, most of the patients were male in the current metaanalysis; therefore, we could not determine if there were any differences between genders. In conclusion, this meta-analysis indicates that higher ADMA level is associated with an increase future risk of cardiovascular and all-cause mortality, but not for MACEs. Determination of ADMA might provide a simple method for assessment of prognosis in patients with undergoing PCI. However, these findings need to be further confirmed by larger and prospective studies. Conflict of interest None declared. References [1] J.M. Stolker, D.J. Cohen, J.B. Lindsey, K.F. Kennedy, N.S. Kleiman, S.P. Marso, Mode of death after contemporary percutaneous coronary intervention: a report from the Evaluation of Drug Eluting Stents and Ischemic Events registry, Am. Heart J. 162 (2011) 914–921. [2] R.H. Boger, The emerging role of asymmetric dimethylarginine as a novel cardiovascular risk factor, Cardiovasc. Res. 59 (2003) 824–833. [3] F. Schulze, H. Lenzen, C. Hanefeld, A. Bartling, K.J. Osterziel, L. Goudeva, et al., Asymmetric dimethylarginine is an independent risk factor for coronary heart disease: results from the multicenter Coronary Artery Risk Determination investigating the Influence of ADMA Concentration (CARDIAC) study, Am. Heart J. 152 (2006) 493 (e1-8). [4] T.M. Lu, Y.A. Ding, S.J. Lin, W.S. Lee, H.C. Tai, Plasma levels of asymmetrical dimethylarginine and adverse cardiovascular events after percutaneous coronary intervention, Eur. Heart J. 24 (2003) 1912–1919.
[5] E. Cavusoglu, C. Ruwende, V. Chopra, S. Yanamadala, C. Eng, D.J. Pinsky, et al., Relationship of baseline plasma ADMA levels to cardiovascular outcomes at 2 years in men with acute coronary syndrome referred for coronary angiography, Coron. Artery Dis. 20 (2009) 112–117. [6] T.M. Lu, M.Y. Chung, M.W. Lin, C.P. Hsu, S.J. Lin, Plasma asymmetric dimethylarginine predicts death and major adverse cardiovascular events in individuals referred for coronary angiography, Int. J. Cardiol. 153 (2011) 135–140. [7] N. Sen, M.F. Ozlu, E.O. Akgul, S. Kanat, T. Cayci, O. Turak, et al., Elevated plasma asymmetric dimethylarginine level in acute myocardial infarction patients as a predictor of poor prognosis and angiographic impaired reperfusion, Atherosclerosis 219 (2011) 304–310. [8] A. Meinitzer, J.T. Kielstein, S. Pilz, C. Drechsler, E. Ritz, B.O. Boehm, et al., Symmetrical and asymmetrical dimethylarginine as predictors for mortality in patients referred for coronary angiography: the Ludwigshafen Risk and Cardiovascular Health study, Clin. Chem. 57 (2011) 112–121. [9] A. Derkacz, M. Protasiewicz, R. Poreba, A. Doroszko, M. Poreba, J. AntonowiczJuchniewicz, et al., Plasma asymmetric dimethylarginine predicts restenosis after coronary angioplasty, Arch. Med. Sci. 7 (2010) 444–448. [10] H. Ari, S. Ari, E. Erdogan, O. Tiryakioglu, Y. Ustundag, K. Huysal, et al., A novel predictor of restenosis and adverse cardiac events: asymmetric dimethylarginine, Heart Vessels 25 (2010) 19–26. [11] D.F. Stroup, J.A. Berlin, S.C. Morton, I. Olkin, G.D. Williamson, D. Rennie, et al., Metaanalysis of observational studies in epidemiology: a proposal for reporting. Metaanalysis Of Observational Studies in Epidemiology (MOOSE) group, JAMA 283 (2000) 2008–2012. [12] R. Schnabel, S. Blankenberg, E. Lubos, K.J. Lackner, H.J. Rupprecht, C. Espinola-Klein, et al., Asymmetric dimethylarginine and the risk of cardiovascular events and death in patients with coronary artery disease: results from the AtheroGene study, Circ. Res. 97 (2005) e53–e59. [13] B. Siegerink, R. Maas, C.Y. Vossen, E. Schwedhelm, W. Koenig, R. Boger, et al., Asymmetric and symmetric dimethylarginine and risk of secondary cardiovascular disease events and mortality in patients with stable coronary heart disease: the KAROLA follow-up study, Clin. Res. Cardiol. 102 (2013) 193–202. [14] M. Zeller, C. Korandji, J.C. Guilland, P. Sicard, C. Vergely, L. Lorgis, et al., Impact of asymmetric dimethylarginine on mortality after acute myocardial infarction, Arterioscler. Thromb. Vasc. Biol. 28 (2008) 954–960. [15] P. Vallance, A. Leone, A. Calver, J. Collier, S. Moncada, Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure, Lancet 339 (1992) 572–575. [16] J.P. Cooke, Does ADMA cause endothelial dysfunction? Arterioscler. Thromb. Vasc. Biol. 20 (2000) 2032–2037. [17] R.H. Boger, Asymmetric dimethylarginine (ADMA) and cardiovascular disease: insights from prospective clinical trials, Vasc. Med. 10 (Suppl. 1) (2005) S19–S25. [18] J. Wang, A.S. Sim, X.L. Wang, C. Salonikas, D. Naidoo, D.E. Wilcken, Relations between plasma asymmetric dimethylarginine (ADMA) and risk factors for coronary disease, Atherosclerosis 184 (2006) 383–388.
