Asymmetric dimethyl-arginine and coronary artery calcification in young adults entering middle age: the CARDIA Study.
BACKGROUND
Normal endothelial function depends on nitric oxide (NO) release by endothelial cells. Asymmetric dimethylarginine (ADMA), by competing with L-arginine, inhibits NO production and may lead to endothelial dysfunction and atherosclerotic development. Our aim was to ascertain the association between ADMA and coronary artery calcification (CAC), a marker of atherosclerotic coronary disease burden.


METHODS
A nested case-control study within the Coronary Artery Risk Development in Young Adults (CARDIA) cohort, an observational study among young adults residing in four US cities.


METHODS
Participants were 263 white and black male and female cases with the presence of CAC and 263 sex and race-matched controls without evidence of CAC by computed tomography, 33-47 years old in 2000-2001.


RESULTS
The median level (range) of ADMA was significantly higher in cases (0.55; 0.20-2.22 micromol/l) than in controls (0.53; 0.32-1.30 micromol/l; P=0.03). In conditional logistic regression adjusting for age, field center, educational attainment, smoking status, alcohol consumption, body mass index, waist circumference, hypertension, diabetes, low-density lipoprotein and high-density lipoprotein-cholesterol, triglycerides, renal function and C-reactive protein, the highest tertile of ADMA, compared with the lowest tertile, was associated with 1.80 (95% confidence interval 1.03-3.15) increased odds of the presence of any CAC. By linear regression, a significant independent relationship was also found between ADMA and the degree of CAC.


CONCLUSIONS
These results support a role for ADMA as a biochemical marker of CAC.
Iribarren
Carlos
C
Division of Research, Kaiser Permanente, Oakland, CA, USA. cgi@dor.kaiser.org
Husson
Gail
G
Sydow
Karsten
K
Wang
Bing-Yin
BY
Sidney
Stephen
S
Cooke
John P
JP
D000328:Adult; D000704:Analysis of Variance; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002114:Calcinosis / Q000097:blood* / Q000000981:diagnostic imaging / Q000453:epidemiology; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000097:blood* / Q000000981:diagnostic imaging / Q000453:epidemiology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012107:Research Design; D012307:Risk Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D015415:Biomarkers; C018524:N,N-dimethylarginine; D001120:Arginine