Abstract 3990: Asymmetric Dimethylarginine Predicts Fatal and Non-Fatal Myocardial Infarction and Stroke in Women Independently of Homocysteine and Traditional Risk Factors: 24 Year Follow Up of the Population Study of Women in Gothenburg
Introduction Asymmetric dimethylarginine (ADMA) reduces nitric oxide production by endogenous inhibition of nitric oxide synthase and therefore may impair endothelial function. ADMA levels are raised in the presence of traditional risk factors and hyperhomocysteinaemia, and have been associated with cardiovascular disease (CVD) in renal failure, middle-aged Finnish men and post-angioplasty. We therefore examined the possible association of ADMA with CVD and homocysetine (Hcy) prospectively in a population based cohort of women.
Methods We measured ADMA in stored samples obtained from women recruited at the baseline survey of the Population Study of Women in Gothenburg, using a validated high-performance liquid chromatography assay capable of differentiating ADMA from symmetric dimethylarginine. A Cox proportional hazards model was used to examine the association of ADMA as a continuous variable with the following endpoints at 24 years: total mortality, CVD deaths, MI deaths, total CVD events and MI events. Sequential adjustments were made for:
Blood pressure, cholesterol and smoking,
Glucose, triglycerides, BMI, waist & hip circumference, and
Hcy, vitamin B12 and creatinine, all analyses stratified by age.
Results Stored serum was available in 880 of 1462 women. Risk factor distributions were similar in the other 582 in whom stored serum was not available. The respective hazard ratios for a 0.15 μM increase (1 standard deviation) of ADMA are presented in Table 1⇓.
Conclusions A 0.15 μM increase in baseline ADMA levels is associated with approximately 30% increase in risk of incident MI and stroke at 24 years in women. This association remains robust after adjusting for traditional risk factors and Hcy. It is not known whether reducing ADMA would reduce risk of CVD.