Neurovascular Center, Naval Medical University Changhai Hospital, Shanghai, China.
Huamu Community Center of Pudong, Shanghai, China.
Eur Stroke J. 2024 Mar;9(1):244-250. doi: 10.1177/23969873231204420. Epub 2023 Oct 6.
Observational studies suggest that different classes of antihypertensive drugs may have different effects on the occurrence of intracranial aneurysms (IA) and subarachnoid hemorrhage (SAH). However, the reported results in previous studies are inconsistent, and randomized data are absent. We performed a two-sample Mendelian randomization (MR) analysis to study the causal effects of genetically determined blood pressure (BP) and genetic proxies for antihypertensive drug classes on the risk of IA and SAH.
Genetic instruments and outcome data were obtained from independent genome-wide association studies (GWAS) or published data, which were exclusively restricted to European ancestry. Causal relationships were identified using inverse-variance weighted MR analyses and a series of statistical sensitivity analyses. The FinnGen consortium was used for repeated analysis to verify results obtained from the above GWAS.
Two-sample MR analysis showed that genetically determined Systolic BP, Dystolic BP, and Pulse Pressure were related to a higher risk of IA and SAH. Based on identified single nucleotide polymorphisms (SNPs) that influence the effect of calcium channel blockers (CCB, 42 SNPs), beta-blockers (BB, 8 SNPs), angiotensin-converting enzyme inhibitors (ACEI, 2 SNPs), angiotensin receptor blockers (ARB, 1 SNPs), and thiazides (5 SNPs), genetically determined effect of CCBs was associated with a higher risk of IA (OR, 1.07 [95% CI, 1.03-1.10], = 5.02 × 10) and SAH (OR, 1.06 [95% CI, 1.03-1.09], = 1.84 × 10). No associations were found between other antihypertensive drugs and the risk of IA or SAH. The effect of CCBs on SAH was confirmed in FinnGenconsortium samples (OR, 1.04 [95% CI, 1.00-1.08], = 0.042).
This MR analysis supports the role of elevated blood pressure in the occurrence of intracranial aneurysms and subarachnoid hemorrhage. However, genetic proxies for calcium channel blockers were associated with an increased risk of intracranial aneurysms and subarachnoid hemorrhage. Further studies are required to confirm these findings and investigate the underlying mechanisms.
观察性研究表明，不同类别的降压药物可能对颅内动脉瘤（IA）和蛛网膜下腔出血（SAH）的发生有不同的影响。然而，先前研究的报告结果不一致，且缺乏随机数据。我们进行了两样本孟德尔随机化（MR）分析，以研究遗传决定的血压（BP）和降压药物类别的遗传代表物对 IA 和 SAH 风险的因果影响。
遗传工具和结果数据来自独立的全基因组关联研究（GWAS）或已发表的数据，这些数据仅局限于欧洲血统。使用逆方差加权 MR 分析和一系列统计敏感性分析来确定因果关系。FinnGen 联盟用于重复分析，以验证来自上述 GWAS 的结果。
两样本 MR 分析表明，遗传决定的收缩压、舒张压和脉压与 IA 和 SAH 的风险增加有关。基于影响钙通道阻滞剂（CCB，42 个 SNP）、β受体阻滞剂（BB，8 个 SNP）、血管紧张素转换酶抑制剂（ACEI，2 个 SNP）、血管紧张素受体阻滞剂（ARB，1 个 SNP）和噻嗪类药物（5 个 SNP）作用的鉴定单核苷酸多态性（SNP），CCB 的遗传决定作用与 IA 风险增加相关（OR，1.07 [95% CI，1.03-1.10]， = 5.02 × 10）和 SAH（OR，1.06 [95% CI，1.03-1.09]， = 1.84 × 10）。未发现其他降压药物与 IA 或 SAH 风险之间存在关联。在 FinnGen 联盟样本中证实了 CCB 对 SAH 的影响（OR，1.04 [95% CI，1.00-1.08]， = 0.042）。
这项 MR 分析支持血压升高在颅内动脉瘤和蛛网膜下腔出血发生中的作用。然而，钙通道阻滞剂的遗传代表物与颅内动脉瘤和蛛网膜下腔出血的风险增加相关。需要进一步的研究来证实这些发现并探讨潜在的机制。
