Iron status and its association with coronary heart disease: Systematic review and meta-analysis of prospective studies

Background: Observations in the past have hypothesized an association between body iron status and coronary heart disease (CHD). Epidemiological studies to date have however been inconclusive without the existence of strongly positive or strongly negative associations between iron status and coronary heart disease. Objectives: To investigate the association between iron status and coronary heart disease. Data sources: A systematic review was performed using the databases PubMed and Cochrane Library. Search terms included iron, ferritin, transferrin, total iron binding capacity, coronary heart disease and angina. Study selection: Only prospective studies investigating the association of body iron status and coronary heart disease were included. All participants were free from coronary heart disease at baseline. There were no language or geographic restrictions imposed on the search strategy. Data extraction: Independent extraction of articles by 2 authors using predefined data fields. Data synthesis: All pooled analyses were based on random-effects models. A total of 17 studies were identified for analysis, involving a total of 9236 cases of coronary heart disease and 156,427 participants. Several studies reported more than 1 marker of iron status. For serum ferritin, comparison of individuals in the top third versus the bottom third of baseline measurements yielded a combined risk ratio of 1.03 (95%CI, 0.87-1.23) for CHD/MI. For transferrin saturation, the combined risk ratio for CHD/MI was 0.82 (95% CI, 0.75-0.89) for individuals in the top third versus the bottom third of baseline measurements. Comparison of individuals in top and bottom thirds of baseline measurements yielded non-significant risk ratios of studies involving total iron-binding capacity (combined risk ratio, 0.99; 95% CI 0.86-1.13) and serum iron (combined risk ratio, 0.87; 95% CI 0.73-1.04). For serum iron, the combined risk ratio for CHD/MI after excluding the study by Morrisson et al. [1] was 0.80 (95% CI, 0.73-0.87). Conclusions: The results suggest that there is a negative association of transferrin levels and coronary heart disease with high transferrin saturations being associated with a lower risk of CHD/MI. There was also a negative association of serum iron and CHD/MI after one study [1] was excluded. There is no significant association between the other markers of iron status and CHD. It is however difficult to infer causality from these findings due to limitations in terms of reverse causality bias and residual confounding.