Thalassemia trait and arterial thromboembolic events: A systematic review and a meta-analysis of the literature

Background: An increased risk of venous thromboembolic events has been reported in thalassemic patients, in particular in patients with thalassemia intermedia. The association between β-thalassemia trait and atherothrombotic cardiovascular events is not well established. Methods: In a systematic review and meta-analysis of the literature, we evaluated the association between β-thalassemia trait and arterial cardiovascular disease. Studies were identified from the MEDLINE and EMBASE (until July 2010) electronic databases. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with a random-effects model. Statistical heterogeneity was evaluated with the I² statistic. Results: Of the 354 identified articles, eight case-control studies were eligible for the analysis. β-Thalassemia trait was associated with a reduced risk of arterial cardiovascular disease (OR 0.45; 95% CI 0.45-0.60). Heterogeneity among studies was low (I²=13%). The protective effect of β-thalassemia trait was confined to male patients (OR 0.39; 95% CI 0.24-0.62), and was not observed in female subjects (OR 0.89; 95% CI 0.52-1.53). Conclusions: β-Thalassemia trait may act as a protective factor against the development of arterial cardiovascular and cerebrovascular disease in male subjects. Larger prospective studies are necessary to confirm these preliminary findings and to further investigate the mechanisms underlying this protective effect.