The contribution of iron metabolism to heart failure: a haematological and biochemical perspective

Abstract Introduction Heart failure (HF) can be influenced by diverse modulators, such as genes involved in iron metabolism - HFE, SLC40A1 and TMPRSS6, and haematological and biochemical parameters - serum iron, ferritin, transferrin saturation, mean corpuscular volume (MCV) and Red Cell Distribution Width (RDW). Objectives To investigate the association of genetic variants in the HFE gene [C282Y (rs1800562) and H63D (rs1799945)], SLC40A1 (rs1439816 and rs2304704) and TMPRSS6 (rs855791) with haematological parameters and biochemical biomarkers of iron metabolism in HF and in its various forms of presentation [preserved Ejection Fraction-HFpEF and non-preserved Ejection Fraction-HFnpEF (middly reduced + reduced)], in each sex. Methods 301 individuals with HF were studied (141 men and 160 women), with a median age of 80 years (min=31 and max=99) and a median body mass index (BMI) of 25.90 kg/m2 (min=16.50 and max=47.30). Multiplex PCR-ARMS technique was used to analyze the HFE gene variants (C282Y and H63D) and Endpoint Genotyping was used for the remaining variants. Statistical analysis was carried out using SPSS software, version 28.0, with a statistical significance level of p<0.05. Results The presence of indicators of iron deficiency anaemia was verified in the haematological and biochemical parameters in our population of HF. Significant differences were found in serum iron values in the presence of the mutant allele for the three genes studied: 1)in the H63D (p=0.006) for females, and more particularly in females with HFnpEF (p=0.020); 2) in the rs1439816 for males (p=0.035) and more particularly in males with HFpEF (p=0.036); and 3) in the rs855791 for males (p=0.018). As for ferritin, significant differences were found in the presence of the mutant allele for the rs2304704 (p=0.001) in females. For transferrin saturation, significant differences were found in the presence of the mutant allele for the three genes studied: 1) in the H63D (p=0.013) for females, more specifically in females with HFpEF (p=0.043); 2) in the rs1439816 in males (p=0.037); and 3) in the rs855791 in females (p=0.034), particularly in females with HFpEF (p=0.023), and in males (p=0.032), particularly in males with HFpEF (p=0.037). Analyzing the MCV, there were statistically significant differences in the presence of the mutant allele for the rs2304704 (p=0.012) in females, particularly in those with HFpEF (p<0.001). Regarding RDW, significant differences were found in the presence of the mutant allele of the C282Y polymorphism in females with HFpEF (p=0.048). Conclusion Ferropenic anaemia highly prevalent in this population with HF. All the genes analyzed contribute to the modulation of the analyzed parameters/biomarkers, however, the SLC40A1 gene showed greater modulating capacity. Genetic modulation was more relevant in HFpEF women, suggesting that this sex is the most susceptible to genetic modulation.