The impact of circulating total homocysteine levels on long-term cardiovascular mortality in patients with acute coronary syndromes
Introduction
Previous studies have evaluated the impact of circulating total homocysteine (tHcy) on clinical outcome in patients with stable or unstable coronary artery disease [1], [2], [3], [4], [5], [6], [7]. This amino acid is the derivative of methionine demethylation. Significantly elevated circulating tHcy levels (> 100 μmol/l) observed in patients with homocystinuria, a genetically inherited enzyme defect of Hcy metabolism, have been shown to be associated with aggressive and premature vascular disease [8], [9], [10]. Thus, it has been presumed that moderately elevated circulating tHcy levels might also have some prognostic implication in several manifestations within the wide spectrum of coronary artery disease.
Yet the place and significance of circulating tHcy levels in the setting of acute coronary syndromes have not been definitively clarified. On the contrary, it seems that the limited existing data are rather controversial [3], [4], [5], [6], [7]. Since the possible pathophysiologic mechanisms remain obscure, the critical question is whether the observed relation might be accounted to the reported association of tHcy levels with known cardiovascular disease risk factors that possibly act as confounders [11], [12], [13].
The present study was designed to attempt a further elucidation of the aforementioned controversy. We prospectively evaluated the possible association of admission circulating tHcy levels with late clinical outcome during a five-year follow-up period after an acute coronary syndrome.
Section snippets
Study population
Consecutive eligible patients with ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation acute coronary syndromes (NSTE-ACS) who were admitted to our institute from September 1998 through December 2000 were recruited. Patients with STEMI were required to have: 1) continuous chest pain upon presentation, refractory to nitrates, and lasting ≥ 30 min; 2) ST-segment elevation of ≥ 2 mm in ≥ 2 contiguous precordial leads, or ≥ 1 mm in ≥ 2 contiguous limb leads; 3) presentation in
Baseline characteristics
During the recruiting period, 458 patients with STEMI and 476 with NSTE-ACS were included in the study. Baseline characteristics within the tertiles of tHcy, for each cohort, are presented in Table 1, Table 2. Patients in the upper tHcy tertile were significantly older and had more unfavorable risk profile than those in the other two tertiles; this observation was true for both cohorts. In particular, the frequency of prior angina, myocardial infarction, heart failure, peripheral artery
Discussion
The primary outcome of the present study is that circulating tHcy levels upon admission seem to lack independent value in the prediction of long-term cardiovascular mortality within a five-year follow up period after an acute coronary syndrome. Despite the significant relation demonstrated for both STEMI and NSTE-ACS patients, by means of univariate analysis, statistically non-significant results were produced when tHcy levels were included along with all other univariate predictors in the
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