Statins as a risk factor for anaemia: Evidence from genetic and epidemiological data

Aims: Statins are widely used for managing dyslipidaemia and preventing cardiovascular events. Reports on whether statin use and anaemia are associated are scarce and controversial. The relationship between statins and anaemia remains unclear. This study aimed to explore the potential causal link between statin use and anaemia. Methods: We employed a two-sample Mendelian randomization (MR) approach using single nucleotide polymorphisms related to HMGCR expression, the gene targeted by statins, to evaluate the causal effect of statin use on anaemia. Genome-wide association study data specific to European populations were used to identify genetic associations, and clinical data from National Health and Nutrition Examination Survey (NHANES; 2005-2016) were analysed to validate the MR findings. Logistic regression models were used to assess the association between statin use and anaemia risk in the NHANES cohort. Results: MR analysis indicated that upregulation of HMGCR expression was associated with a reduced risk of anaemia (odds ratio = 0.72, 95% confidence interval 0.58-0.88; P = .007). In contrast, the analysis of NHANES data revealed that statin use was significantly associated with an increased risk of anaemia (odds ratio = 1.624, 95% confidence interval 1.307, 2.018; P < .001). Sensitivity analyses revealed the reliability of the MR results, and the association between statin use and anaemia was further supported by the consistency of univariate and multivariate regressions in NHANES. Conclusions: Our findings suggest that while genetic up-regulation of HMGCR may reduce anaemia risk, statin therapy is associated with an increased risk of anaemia. These results highlight the need for careful monitoring of haemoglobin and iron levels in patients undergoing long-term statin treatment, especially those with pre-existing risk factors for anaemia. Further research is necessary to elucidate the underlying mechanisms and to confirm these findings in diverse populations.