Plasma homocysteine concentration, statin therapy, and the risk of first acute coronary events.
BACKGROUND
Elevated homocysteine levels are associated with increased coronary risk, and it has been suggested that homocysteine screening may provide a method to identify high-risk patients for aggressive primary prevention.


RESULTS
Homocysteine was measured at baseline and after 1 year among 5569 participants in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS), a randomized trial of lovastatin in the primary prevention of acute coronary events. The effects of homocysteine, LDL cholesterol, and lovastatin on risk were assessed over 5.2 years of trial follow-up. Median baseline homocysteine levels were significantly higher among study participants who subsequently had acute coronary events compared with those who did not (12.1 versus 10.9 micro;mol/L, P<0.001). The relative risks of future events from lowest (referent) to highest quartile of homocysteine were 1.0, 1.6, 1.6, and 2.2 (P<0.001). These effects were similar among those allocated to lovastatin and those allocated to placebo and were modestly attenuated after adjustment for other traditional risk factors. As predicted, the subgroup of participants with elevated LDL cholesterol and elevated homocysteine levels were at high risk and benefited greatly from statin therapy (relative risk, 0.46; 95% CI, 0.29 to 0.75; number needed to treat=26). However, in contrast to findings in this trial for C-reactive protein, homocysteine evaluation did not help to define low LDL subgroups with different responses to lovastatin therapy.


CONCLUSIONS
Although homocysteine predicted future coronary events in AFCAPS/TexCAPS, we found little evidence that homocysteine evaluation provided an improved method to target statin therapy among those with low-to-normal LDL cholesterol levels.
Ridker
Paul M
PM
Center for Cardiovascular Disease Prevention, Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass 02215, USA. pridker@partners.org
Shih
Jessie
J
Cook
Thomas J
TJ
Clearfield
Michael
M
Downs
John R
JR
Pradhan
Aruna D
AD
Weis
Stephan E
SE
Gotto
Antonio M
AM
D000208:Acute Disease; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000032:analysis; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000517:prevention & control; D003327:Coronary Disease / Q000175:diagnosis* / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008148:Lovastatin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis; D012307:Risk Factors
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D006710:Homocysteine; D002097:C-Reactive Protein; D008148:Lovastatin