Response to Letter Regarding Article, “Metabolic Profiling of Arginine and Nitric Oxide Pathways Predicts Hemodynamic Abnormalities and Mortality in Patients With Cardiogenic Shock After Acute Myocardial Infarct”
We thank Drs Stuehlinger, Metzler, and Cooke for their interest and comments on our study. We agree that the mechanism(s) promoting increased systemic levels of asymmetric dimethylarginine (ADMA) in the setting of acute myocardial infarction complicated by cardiogenic shock may be multifactorial and remains to be fully elucidated. We agree that ADMA may be elevated as a consequence of myocardial ischemia or reperfusion and that ADMA may play a role in the pathogenesis of ischemia-reperfusion injury. It is therefore of interest that in a recent report analyzing consecutive patients admitted with myocardial infarction, plasma ADMA levels at presentation independently predicted mortality at 12 months, regardless of whether evidence existed of hemodynamic instability.1 Similarly, a prospective case-control analysis of the Population Study of Women in Gothenburg revealed that systemic ADMA levels predicted the likelihood of fatal and nonfatal myocardial infarction over a 24-year period of follow-up.2 Although data supporting the association between elevated ADMA levels and risk of mortality after myocardial infarction continue to accumulate, the challenge now is to unravel the mechanisms that underlie this relationship and determine whether they are merely an epiphenomenon or causally linked in humans.
Dr Nicholls has received honoraria from Pfizer, AstraZeneca, Merck Schering-Plough, and Takeda and consulting fees from Pfizer, Astra-Zeneca, Roche, LipoScience, and Anthera. Dr Levinson owns shares in Merck and is a consultant to Prognostix. Dr Griffith owns shares in Arginox, holds patents for the use of nitric oxide synthase inhibitors to treat hypotension, and is an employee of the Medical College of Wisconsin, which has an ownership interest in Arginox. Dr Hathway is a former employee of Arginox. Dr Dzavik has received research support from Arginox and speaking honoraria from Datascope and Arginox. Dr Panza has received research support from Arginox and Takeda and is a member of the speakers’ bureau of Pfizer and Glaxo Smith Kline. Dr Nissen has received research support from Takeda, Sanofi-Aventis, Eli Lilly, Pfizer, Sankyo, Atherogenics, Lipid Sciences, and AstraZeneca and provides consulting for a number of pharmaceutical companies but requires them to donate all honoraria or consulting fees directly to charity so that he receives neither income nor tax deductions. Dr Wang, Dr Hazen, R. Koeth, and B. DelFraino report no conflicts.
Zeller M, Korandji C, Guilland JC, Sicard P, Vergely C, Lorgis L, Beer JC, Duvillard L, Lagrost AC, Moreau D, Gambert P, Cottin Y, Rochette L. Impact of asymmetric dimethylarginine on mortality after acute myocardial infarction. Arterioscler Thromb Vasc Biol. 2008; 28: 954–960.
Leong T, Zylberstein D, Graham I, Lissner L, Ward D, Fogarty J, Bengtsson C, Bjorkelund C, Thelle D. Asymmetric dimethylarginine independently predicts fatal and nonfatal myocardial infarction and stroke in women: 24-year follow-up of the Population Study of Women in Gothenburg. Arterioscler Thromb Vasc Biol. 2008; 28: 961–967.