血脂特征与蛛网膜下腔出血风险：一项基于英国生物样本库的系统综述和孟德尔随机化研究。
完整摘要 · 中文译文
血脂性状是动脉粥样硬化性疾病的既定危险因素；然而，其与颅内动脉瘤和蛛网膜下腔出血（SAH）的关系仍不明确。近期的孟德尔随机化（MR）研究报告了不一致的结果。本研究旨在回顾文献，并使用校正他汀类药物使用和非线性的单样本MR分析评估血脂性状与SAH之间的关联。我们对研究血脂性状与颅内动脉瘤/SAH的MR研究进行了系统综述。由于研究使用了重叠的数据集，未进行荟萃分析。同时，我们对486,603名英国生物银行参与者进行了单样本MR分析。低密度脂蛋白（LDL）、高密度脂蛋白（HDL）、总胆固醇（TC）和甘油三酯（TG）的遗传工具来自已发表的全基因组关联研究。与SAH的关联对降脂治疗进行了校正。使用三次样条和分段MR探讨了非线性关系。虽然八项MR研究符合纳入标准，但其中七项依赖于同一结局队列。尽管如此，这些研究在血脂性状之间未显示一致的效应方向，提示估计值不稳定。在英国生物银行中，没有证据表明遗传预测的血脂性状与SAH相关：LDL (HR 1.06 [0.64-1.73])、HDL (HR 2.57 [0.42-15.74])、TC (HR 1.06 [0.71-1.60])或TG (HR 1.05 [0.69-1.59)。结果在不同MR方法和敏感性分析中一致，包括对 lipid-lo 的校正。 降脂治疗。当前证据不支持血脂性状与SAH之间存在主要关联，既往孟德尔随机化研究中观察到的异质性可能反映了方法学局限性，而非一致的生物学效应。然而，无法排除降脂治疗存在较小效应及不依赖于血脂的效应。
完整摘要 · 英文原文
Lipid traits are established risk factors for atherosclerotic disease; however, their relationship with intracranial aneurysms and subarachnoid haemorrhage (SAH) remains unclear. Recent Mendelian randomisation (MR) studies have reported inconsistent findings. This study aimed to review the literature and assess the association between lipid traits and SAH using a one-sample MR analysis accounting for statin use and nonlinearity. We performed a systematic review of MR studies investigating lipid traits and intracranial aneurysms/SAH. A meta-analysis was not undertaken because studies used overlapping datasets. In parallel, we conducted a one-sample MR analysis of 486,603 UK Biobank participants. Genetic instruments for low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), and triglycerides (TG) were derived from published genome-wide association studies. Associations with SAH were adjusted for lipid-lowering therapy. Nonlinear relationships were explored using cubic splines and piecewise MR. While eight MR studies met the inclusion criteria, seven relied on the same outcome cohort. Despite this, these studies showed no consistent direction of effect across lipid traits, suggesting that the estimates were unstable. In the UK Biobank, there was no evidence of an association between genetically predicted lipid traits and SAH for LDL (HR 1.06 [0.64-1.73]), HDL (HR 2.57 [0.42-15.74]), TC (HR 1.06 [0.71-1.60]), or TG (HR 1.05 [0.69-1.59). Results were consistent across different MR methods and sensitivity analyses, including adjustment for lipid-lowering therapy. Current evidence does not support a major association between lipid traits and SAH, with the heterogeneity observed across previous MR studies likely reflecting methodological limitations rather than a consistent biological effect. However, small effects and lipid-independent effects of lipid-lowering therapies cannot be excluded.