on February 21, 2008
Published online before print February 21, 2008, doi: 10.1161/ATVBAHA.107.156596
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Submitted on September 23, 2007
Accepted on February 11, 2008
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 ;
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.
* To whom correspondence should be addressed. E-mail: ian.graham{at}amnch.ie.
Objective—Asymmetrical dimethylarginine (ADMA) reduces nitric oxide by inhibiting nitric oxide synthase, and it 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.
Key words: asymmetrical dimethylarginine • cardiovascular diseases • myocardial infarction • stroke • women
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