Context Observational studies have reported associations between circulating total homocysteine concentration and risk of cardiovascular disease. Oral administration of folic acid and vitamin B 12 can lower plasma total homocysteine levels.Objective To assess the effect of treatment with folic acid and vitamin B 12 and the effect of treatment with vitamin B 6 as secondary prevention in patients with coronary artery disease or aortic valve stenosis.Design, Setting, and Participants Randomized, double-blind controlled trial conducted in the 2 university hospitals in western Norway in 1999-2006. A total of 3096 adult participants undergoing coronary angiography (20.5% female; mean age, 61.7 years) were randomized. At baseline, 59.3% had double-or triple-vessel disease, 83.7% had stable angina pectoris, and 14.9% had acute coronary syndromes.Interventions Using a 2ϫ2 factorial design, participants were randomly assigned to 1 of 4 groups receiving daily oral treatment with folic acid, 0.8 mg, plus vitamin B 12 , 0.4 mg, plus vitamin B 6 , 40 mg (n=772); folic acid plus vitamin B 12 (n=772); vitamin B 6 alone (n=772); or placebo (n=780). Main Outcome MeasuresThe primary end point was a composite of all-cause death, nonfatal acute myocardial infarction, acute hospitalization for unstable angina pectoris, and nonfatal thromboembolic stroke. ResultsMean plasma total homocysteine concentration was reduced by 30% after 1 year of treatment in the groups receiving folic acid and vitamin B 12 . The trial was terminated early because of concern among participants due to preliminary results from a contemporaneous Norwegian trial suggesting adverse effects from the intervention. During a median 38 months of follow-up, the primary end point was experienced by a total of 422 participants (13.7%): 219 participants (14.2%) receiving folic acid/vitamin B 12 vs 203 (13.1%) not receiving such treatment (hazard ratio, 1.09; 95% confidence interval, 0.90-1.32; P=.36) and 200 participants (13.0%) receiving vitamin B 6 vs 222 (14.3%) not receiving vitamin B 6 (hazard ratio, 0.90; 95% confidence interval, 0.74-1.09; P=.28).Conclusions This trial did not find an effect of treatment with folic acid/vitamin B 12 or vitamin B 6 on total mortality or cardiovascular events. Our findings do not support the use of B vitamins as secondary prevention in patients with coronary artery disease.

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No clinical benefit of a high-dose concentrate of n-3 fatty acids compared with corn oil was found despite a favorable effect on serum lipids.

Objective-Enhanced tryptophan degradation, induced by the proinflammatory cytokine interferon-γ, has been related to cardiovascular disease progression and insulin resistance. We assessed downstream tryptophan metabolites of the kynurenine pathway as predictors of acute myocardial infarction in patients with suspected stable angina pectoris. Furthermore, we evaluated potential effect modifications according to diagnoses of pre-diabetes mellitus or diabetes mellitus. Approach and Results-Blood samples were obtained from 4122 patients (median age, 62 years; 72% men) who underwent elective coronary angiography. During median follow-up of 56 months, 8.3% had acute myocardial infarction. Comparing the highest quartile to the lowest, for the total cohort, multivariable adjusted hazard ratios (95% confidence intervals) were 1.68 (1.21-2.34), 1.81 (1.33-2.48), 1.68 (1.21-2.32), and 1.48 (1.10-1.99) for kynurenic acid, hydroxykynurenine, anthranilic acid, and hydroxyanthranilic acid, respectively. The kynurenines correlated with phenotypes of the metabolic syndrome, and risk associations were generally stronger in subgroups classified with pre-diabetes mellitus or diabetes mellitus at inclusion (P int ≤0.05). Evaluated in the total population, hydroxykynurenine and anthranilic acid provided statistically significant net reclassification improvements ( Experimental studies suggest that dysregulation of the Kyn pathway may be involved in the pathogenesis of both CAD 11 and DM. 12 However, Trp catabolites other than Kyn have been related only to a limited extent to clinical outcomes in humans, and there is a paucity of data from large-scale epidemiological studies. Thus, we evaluated plasma levels of kynurenic acid (KA) hydroxykynurenine (HK), anthranilic acid (AA), xanthurenic acid, and hydroxyanthranilic acid (HAA) as predictors of AMI in a prospective cohort of patients with suspected stable angina pectoris. In particular, we were interested in whether any associations with adverse prognosis were modified by evidence of impaired glucose homeostasis. Materials and MethodsMaterials and methods are available in the online-only Data Supplement. ResultsFor the 4122 patients in the current study, median (25th-75th percentile) age at inclusion was 62 (55-70) years and 2967 (72.0%) were men. According to the most recent diagnostic criteria, 1603 (38.9%) had DM, of which the vast majority (97.4%) was classified with type 2 (n=1566). However, only a subset was prescribed antidiabetic medications (Table 1). All together, 1078 (25.9%) of patients were current smokers, 1935 (46.9%) had hypertension, and 1644 (40.4%) reported a prior AMI. Compared with the total population, median age and body mass index were higher in patients with DM, as were the prevalence of hypertension at inclusion and the incidence of AMI during follow-up (Table 1). Kynurenines and Baseline CharacteristicsMedian values of all kynurenines were lower in women than in men (P<0.001). KA, HK, and AA were associated positively with age (ρ≥0.19; P<0.001), and except ...