The risk of recurrent cardiovascular events in patients with increased plasma homocysteine levels is reduced by short but not long-term therapy with folate and B vitamins.

Hyperhomocysteinemia is considered an independent risk factor for atherosclerosis, atherothrombosis and Venous ThromboEmbolism (VTE) [1], [2] and [3]. Normal total plasma homocysteine concentrations range from 5 to 15 μmol/L in the fasting state. Hyperhomocysteinemia is classified as moderate (homocysteine concentration, 15 to 30 μmol/L), intermediate (> 30 to 100 μmol/L), and severe (> 100 μmol/L) on the basis of concentrations measured during fasting. Although severe hyperhomocysteinemia is rare, mild hyperhomocysteinemia occurs in approximately 5% to 7% of the general population. In this case, patients are typically asymptomatic until the third or fourth decade of life when premature Coronary Artery Disease (CAD) develops, as well as recurrent arterial and venous thrombosis [1] and [2]. Vitamin supplementation (Folic Acid and B Vitamins) usually decreases or even normalizes plasma homocysteine concentrations in most cases [1]; however, the advantages of such approach is not always evident [3]. Recently, the results of the Norwegian Vitamin (NORVIT) trial and the Heart Outcomes Prevention Evaluation (HOPE) 2 trial have shown that, after a median follow-up of 40 months, despite a 27% lowering of the mean total homocysteine concentration from the baseline value among patients treated with folic acid and vitamin B12, there was no significant effect on the risk of the composite primary end points (recurrent myocardial infarction, stroke, or sudden death CAD) [4] and [5].....