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Interaction between systemic iron parameters and left ventricular structure and function in the preserved ejection
Xiong-Bin Ma1, Yong-Ming Liu2, Yan-Lin Lv1
1The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu, China.
Insights
This study found a causal link between transferrin saturation (TSAT) and left ventricular (LV) remodeling in people with preserved ejection fraction heart failure. Higher TSAT was associated with reduced LV mass-to-volume ratio, suggesting iron status impacts heart structure.
Area of Science:
- Cardiovascular Medicine
- Genetics
- Iron Metabolism
Background:
- Left ventricular (LV) remodeling and diastolic dysfunction in heart failure (HF) are linked to iron status, but causality remains unclear.
- Investigating the bidirectional causal relationship between systemic iron parameters and LV structure/function in preserved ejection fraction (PEF) is crucial.
Purpose of the Study:
- To determine the causal effect of systemic iron parameters on LV structure and function in a PEF population.
- To explore the reverse causality: the impact of LV structure and function on iron parameters.
Main Methods:
- A two-sample Mendelian randomization (MR) study utilizing UK Biobank data (n=16,923) for LV parameters.
- Instrumental variables for iron parameters (TSAT, TIBC, serum iron, ferritin) derived from public GWAS meta-analyses.
- Inverse variance weighting (IVW) as the primary analysis, with robust estimation methods and Bonferroni correction.
Main Results:
- Increased transferrin saturation (TSAT) causally correlated with decreased LV mass-to-end-diastolic volume ratio (LVMVR) (P=0.0002).
- Reverse MR analysis revealed increased LV ejection fraction (LVEF) causally correlated with decreased TSAT (P=0.0004).
- No significant causal links were found for other iron parameters with LV structure/function, and no heterogeneity or pleiotropy was detected.
Conclusions:
- A causal relationship exists between TSAT and LV remodeling/function in individuals with PEF.
- Findings suggest that iron status, specifically TSAT, plays a role in the cardiac remodeling process in PEF.
Background:
Left ventricular (LV) remodeling and diastolic function in people with heart failure (HF) are correlated with iron status; however, the causality is uncertain. This Mendelian randomization (MR) study investigated the bidirectional causal relationship between systemic iron parameters and LV structure and function in a preserved ejection fraction population.
Methods:
Transferrin saturation (TSAT), total iron binding capacity (TIBC), and serum iron and ferritin levels were extracted as instrumental variables for iron parameters from meta-analyses of public genome-wide association studies. Individuals without myocardial infarction history, HF, or LV ejection fraction (LVEF) < 50% (n = 16,923) in the UK Biobank Cardiovascular Magnetic Resonance Imaging Study constituted the outcome dataset. The dataset included LV end-diastolic volume, LV end-systolic volume, LV mass (LVM), and LVM-to-end-diastolic volume ratio (LVMVR). We used a two-sample bidirectional MR study with inverse variance weighting (IVW) as the primary analysis method and estimation methods using different algorithms to improve the robustness of the results.
Results:
In the IVW analysis, one standard deviation (SD) increased in TSAT significantly correlated with decreased LVMVR (β = -0.1365; 95% confidence interval [CI]: -0.2092 to -0.0638; P = 0.0002) after Bonferroni adjustment. Conversely, no significant relationships were observed between other iron and LV parameters. After Bonferroni correction, reverse MR analysis showed that one SD increase in LVEF significantly correlated with decreased TSAT (β = -0.0699; 95% CI: -0.1087 to -0.0311; P = 0.0004). No heterogeneity or pleiotropic effects evidence was observed in the analysis.
Conclusions:
We demonstrated a causal relationship between TSAT and LV remodeling and function in a preserved ejection fraction population.
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