Asymmetrical dimethylarginine (ADMA) and risk of acute coronary events. Does statin treatment influence plasma ADMA levels?
The purpose of this study was to evaluate the hypothesis that high serum levels of ADMA, an indicator of endothelial dysfunction, are associated with an elevated risk of acute coronary events in middle-aged men. To test the hypothesis that lipid lowering medication with statins lowers circulating ADMA levels, we also investigated the effect of simvastatin and atorvastatin treatment on plasma ADMA concentration. In a prospective nested case-control study in 150 middle-aged non-smoking men from Eastern Finland, those who were in the highest quartile for serum ADMA (>0.62 micromol/l) had a 3.9-fold (95% CI: 1.25-12.3, P=0.02) increase in risk of acute coronary events compared with other quartiles. In an 8-week randomised double-blind placebo-controlled trial, plasma ADMA concentrations remained unchanged in simvastatin 80 mg/day (n=16), atorvastatin 40 mg/day (n=16) and placebo (n=16) groups over the study period. Our findings indicate that high serum levels of ADMA, a potential marker for endothelial dysfunction, may increase the risk of acute coronary syndromes. However, aggressive treatment with either simvastatin or atorvastatin did not reduce plasma ADMA levels.
Valkonen
Veli-Pekka
VP
Research Institute of Public Health, University of Kuopio, Kuopio, Finland
Laakso
Juha
J
Päivä
Hannu
H
Lehtimäki
Terho
T
Lakka
Timo A
TA
Isomustajärvi
Marja
M
Ruokonen
Inkeri
I
Salonen
Jukka T
JT
Laaksonen
Reijo
R
D000208:Acute Disease; D000328:Adult; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood* / Q000187:drug effects*; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology*; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000097:blood*; D005260:Female; D005387:Finland / Q000453:epidemiology; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use; D012307:Risk Factors; D019821:Simvastatin / Q000627:therapeutic use; D013223:Statistics as Topic; D014280:Triglycerides / Q000097:blood
D015415:Biomarkers; D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004791:Enzyme Inhibitors; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D011758:Pyrroles; D014280:Triglycerides; C018524:N,N-dimethylarginine; D001120:Arginine; D000069059:Atorvastatin; D019821:Simvastatin