Plasma Homocysteine Concentration, Statin Therapy, and the Risk of First Acute Coronary Events

Abstract

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. Methods and 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 mol/L, PϽ0.001). The relative risks of future events from lowest (referent) to highest quartile of homocysteine were 1.0, 1.6, 1.6, and 2.2 (PϽ0.001). 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 treatϭ26). 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.

Cardiovascular/non–insulin-dependent diabetes mellitus risk factors and intramyocellular lipid in healthy subjects: a sex comparison

“…Homocysteine is thought to be an early marker of future CAD risk [29]. In our study, male subjects had higher homocysteine concentrations than female subjects.…”

Serum Homocysteine and Long-Term Risk of Myocardial Infarction and Sudden Death in Patients with Coronary Heart Disease

“…The findings of community studies and studies among healthy persons differ with regard to CHD risk and increased levels of tHcy, with some reporting a positive association [2, 4,6,7,8,9, 22, 23] but not most [10,11,12,13,14,15,16,17, 24, 25]. The summary of odds ratios of CHD associated with tHcy concentration have usually been lower in prospective than in retrospective case-control studies [26].…”

“…Cross-sectional and case-control studies have mainly reported an increased prevalence of coronary heart disease (CHD) with increasing levels of serum total homocysteine (tHcy) [2,3,4]. However, some prospective studies (mostly nested case-control studies) have found tHcy to be an independent predictor of incident CHD [5,6,7,8,9], whereas others have not [10,11,12,13,14,15]. …”

Inflammation and emerging risk factors in diabetes mellitus and atherosclerosis

“…This reduction was associated with a decrease in the risk of cardiovascular events. In the AFCAPS/ Texcaps (Air Force/Texas Coronary Atherosclerosis Prevention) study, subjects with a total cholesterol level below the median but an hs-CRP greater than the median had a reduced risk with lovastatin treatment [35]. Subjects with an hs-CRP below the median did not have such a benefit.…”