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Iron status and its association with coronary heart disease: systematic review and meta-analysis of prospective
Sudeep Das De1, Sreedhar Krishna2, Ankeet Jethwa3
1Institute of Public Health, University of Cambridge, UK.
Insights
High transferrin saturation is linked to lower coronary heart disease (CHD) risk, while serum iron shows a negative association after study exclusion. Other iron markers had no significant link to CHD.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Epidemiology
Background:
- Previous research suggests a link between body iron status and coronary heart disease (CHD), but findings have been inconclusive.
- Epidemiological studies have not established strong positive or negative associations between iron status and CHD.
Purpose of the Study:
- To systematically investigate the association between various markers of body iron status and the risk of developing coronary heart disease (CHD).
Main Methods:
- A systematic review of prospective studies was conducted using PubMed and Cochrane Library.
- Search terms included iron, ferritin, transferrin, total iron binding capacity, coronary heart disease, and angina.
- Data extraction and analysis were performed by two independent authors using random-effects models.
Main Results:
- Analysis of 17 studies (9236 CHD cases, 156,427 participants) revealed a combined risk ratio of 0.82 for CHD/MI with high transferrin saturation.
- High transferrin saturation was associated with a lower risk of CHD/MI (Risk Ratio: 0.82, 95% CI: 0.75-0.89).
- Serum iron showed a negative association with CHD/MI (Risk Ratio: 0.80, 95% CI: 0.73-0.87) after excluding one study; other iron markers (ferritin, TIBC) showed no significant association.
Conclusions:
- Higher transferrin saturation is associated with a reduced risk of coronary heart disease (CHD) and myocardial infarction (MI).
- Serum iron also demonstrated a negative association with CHD/MI risk upon exclusion of a specific study.
- No significant associations were found for other iron status markers; causality remains difficult to infer due to potential biases.
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.
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