Liu Zhekang, Fu Qingan, Cao Junda
Cardiovascular medicine, Jiujiang City Key Laboratory of Cell Therapy, JiuJiang NO.1 People's Hospital, Jiujiang, Jiangxi, China.
The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Br J Clin Pharmacol. 2025 Jul 11. doi: 10.1002/bcp.70143.
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.
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.
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.
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.
他汀类药物广泛用于管理血脂异常和预防心血管事件。关于他汀类药物使用与贫血是否相关的报道稀少且存在争议。他汀类药物与贫血之间的关系仍不明确。本研究旨在探讨他汀类药物使用与贫血之间潜在的因果联系。
我们采用两样本孟德尔随机化（MR）方法，利用与他汀类药物作用靶点HMGCR表达相关的单核苷酸多态性，评估他汀类药物使用对贫血的因果效应。使用欧洲人群特异性的全基因组关联研究数据来确定遗传关联，并分析来自美国国家健康与营养检查调查（NHANES；2005 - 2016年）的临床数据以验证MR结果。使用逻辑回归模型评估NHANES队列中他汀类药物使用与贫血风险之间的关联。
MR分析表明，HMGCR表达上调与贫血风险降低相关（比值比 = 0.72，95%置信区间0.58 - 0.88；P = 0.007）。相比之下，对NHANES数据的分析显示，使用他汀类药物与贫血风险增加显著相关（比值比 = 1.624，95%置信区间1.307，2.018；P < 0.001）。敏感性分析揭示了MR结果的可靠性，NHANES中一元和多元回归的一致性进一步支持了他汀类药物使用与贫血之间的关联。
我们的研究结果表明，虽然HMGCR的基因上调可能降低贫血风险，但他汀类药物治疗与贫血风险增加相关。这些结果凸显了对长期接受他汀类药物治疗的患者，尤其是那些已有贫血危险因素的患者，需要仔细监测血红蛋白和铁水平。有必要进行进一步研究以阐明潜在机制并在不同人群中证实这些发现。
