P292	Asymmetric dimethylarginine (ADMA): predictive power for acute coronary events in apparently healthy men depends on smoking status.
1R.Maas, 1F.Schulze, 2J.Baumert, 2H.Löwel, 1R.Böger, 3W.König
1Institute of Experimental and Clinical Pharmacology, University Hospital Hamburg-Eppendorf, Hamburg, DE; 2GSF, Research Center for Environment and Health, Institute of Epidemiology, Neuherberg, DE; 3Department of Internal Medicine II, Cardiology, University of Ulm Medical Center, Ulm, DE.

Background: An elevated plasma concentration of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) predicts adverse clinical outcome in patients with coronary artery disease or renal failure. Whether elevation of ADMA also predicts cardiovascular events and death in an initially healthy population remains to be shown. Paradoxically, smoking appears to be associated with lower ADMA levels, but how this may affect risk estimates based on ADMA is not well understood. Methods: In a nested case-control design we studied the association between plasma concentrations of ADMA and the risk of an acute coronary event (fatal and non-fatal myocardial infarction including sudden cardiac death). Subjects came from the population-based WHO MONICA/KORA Augsburg survey. ADMA was determined by GC-MS-validated ELISA (DLD, Germany) in 88 men aged 54-75 years with an incident coronary event and 254 age-matched controls with a median (IQR) follow-up of 6.2 (3.3-7.9) years. Separate analyses were performed for smokers (n=86) and non-smokers (n=256). Results: Mean (±SD) plasma ADMA levels in subjects who experienced an event and in controls were similar: 0.79±0.21 µmol/l vs. 0.80±0.22 µmol/l; p=0.721. In contrast, ADMA levels were lower in smokers as compared to non-smokers: 0.72±0.19 µmol/l vs. 0.82±0.22 µmol/l (p<0.001). In a Cox proportional hazard model adjusting for age, survey, smoking, hypertension, obesity, physical activity, education years, and alcohol consumption the relative risk of future coronary events was 1.98 (95%CI: 1.25-3.11; p=0.003) for smokers as compared to non-smokers, and 1.43 (95%CI: 0.83-2.45; p=0.335) for top vs. bottom tertile of the ADMA distribution. Analysis of ADMA-associated risk for smokers and non-smokers separately revealed striking differences: the adjusted relative risk of coronary events or death comparing the top tertile to the bottom tertile of the ADMA distribution was 0.58 (95%CI: 0.20-1.72; p=0.325) for smokers and 2.63 (95%CI: 1.25-5.51; p=0.011) for non-smokers. Conclusion: In apparently healthy men from an area of moderate absolute risk for coronary heart disease elevation of ADMA predicts risk for cardiovascular events in non smoking men but not in smoking men.

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