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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:961.)
© 2008 American Heart Association, Inc.

Clinical and Population Studies

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

Tora Leong; Dimitri Zylberstein; Ian Graham; Lauren Lissner; Deirdre Ward; Jane Fogarty; Calle Bengtsson; Cecilia Björkelund; Dag Thelle for The Swedish-Irish-Norwegian (SIN) Collaboration

From the Department of Cardiology (T.L., I.G., D.W.), Adelaide & Meath Hospital, Tallaght, Dublin, Ireland; the Department of Public Health and Community Medicine (D.Z., L.L., C. Bengtsson, C. Björkelund, D.T.), Institute of Medicine at the Sahlgrenska Academy, Göteborg University, Göteborg, Sweden; the Department of Clinical Chemistry (J.F.), Adelaide & Meath Hospital, Tallaght, Dublin, Ireland; and the University of Oslo (D.T.), Oslo, Norway.

Correspondence to Prof Ian Graham, Department of Cardiology, Adelaide & Meath Hospital, Tallaght, Dublin 24, Ireland. E-mail ian.graham{at}amnch.ie

Objective— Asymmetrical dimethylarginine (ADMA) reduces nitric oxide by inhibiting nitric oxide synthase is associated with cardiovascular disease (CVD). Our study examined the association of ADMA with CVD prospectively in a healthy population-based cohort of women.

Methods and Results— We measured baseline ADMA of 880 women in the Population Study of Women in Gothenburg using high-performance liquid chromatography. After adjustment for traditional risk factors, creatinine clearance, and homocysteine using Cox models, the HR (95% CI in parentheses) of CVD end points at 24 years for a 0.15 µmol/L (1 SD) increase in ADMA were: all-cause mortality 1.12 (0.96, 1.32), fatal CVD 1.30 (1.04, 1.62), total CVD events 1.29 (1.09, 1.53). The top quintile (ADMA 0.71 µmol/L) compared with the bottom four-fifths, conferred a cumulative risk 22 versus 14%, relative risk 1.75 (95% CI 1.18, 2.59) and population attributable risk 12.7% of total CVD events, and further identified individuals who are at higher than expected risk based on the SCORE and Framingham systems.

Conclusions— A 0.15 µmol/L increase in baseline ADMA levels is associated with approximately 30% increase in incident cardiovascular risk at 24 years in women after adjustment. ADMA levels 0.71 µmol/L enhances CVD risk assessment in women.

Baseline ADMA in the Population Study of Women in Gothenburg was associated with approximately 30% increase (adjusted) in incident cardiovascular events per 0.15 µmol/L (1 SD) increase in ADMA after 24 years of follow-up. ADMA 0.71 µmol/L can enhance both the SCORE and Framingham systems of cardiovascular risk assessment.

Key Words: asymmetrical dimethylarginine • cardiovascular diseases • myocardial infarction • stroke • women

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