背景:血压是颅内动脉瘤(IA)的危险因素。然而,目前尚不清楚各种抗高血压药物类别在降低IA风险方面是否有区别.
方法:全基因组关联研究收缩压(SBP)汇总统计,舒张压(DBP),IA(未破裂),并下载了IA[蛛网膜下腔出血(SAH)]。为了替代抗高血压药物的作用,选择了与不同降压药编码区相邻的SBP相关的遗传变异.采用逆方差加权(IVW)方法作为因果估计的主要方法。此外,我们采用了另外3种MR方法和敏感性试验来评估可靠性.
结果:升高的血压显着增加了IA的风险:(i)SBP-IA(未破裂):比值比(OR)=1.046,95%置信区间(CI):1.032-1.061,P=1.05E-10;(ii)SBP-IA(SAH):OR=1.040,95%CI:1.030-1.050BP(iv)1.5665-1.此外,在钙通道阻滞剂(CCB)中,β受体阻滞剂(BBs),和噻嗪类利尿剂(TD),仅TDs靶基因介导的SBP显著增加IA(非破裂)(OR=1.164,95%CI:1.060-1.279,P=0.001)和IA(SAH)(OR=1.136,95%CI:1.063-1.214,P=1.58E-04)的风险,而由BBs或CCBs的靶基因介导的SBP与IA无因果关系。
结论:血压升高显著增加IA风险,而TDs可能是降低IA风险的有前途的抗高血压药物。对更大队列的进一步研究对于验证至关重要。
BACKGROUND: Blood pressure is a risk factor for intracranial aneurysms (IA). Nevertheless, whether various antihypertensive drug classes discriminate in reducing IA risk is unclear.
METHODS: Genome-wide association
study summary statistics for systolic blood pressure (SBP), diastolic blood pressure (DBP), IA (non-ruptured), and IA [subarachnoid hemorrhage (SAH)] were downloaded. To proxy the effects of antihypertensive drugs, genetic variants associated with SBP adjacent to the coding regions of different antihypertensive drugs were selected. The inverse-variance-weighted (IVW) method was employed as the primary method for causal estimation. In addition, three additional MR methods and sensitivity tests were utilized to assess the reliability.
RESULTS: Elevated blood pressure significantly increases the risk of IA: (i) SBP-IA (non-ruptured): odds ratio (OR) = 1.046, 95 % confidence interval (CI): 1.032-1.061, P = 1.05E-10; (ii) SBP-IA (SAH): OR = 1.040, 95 % CI: 1.030-1.050, P = 2.56E-15; (iii) DBP-IA (non-ruptured): OR = 1.082, 95 % CI: 1.056-1.110, P = 3.15E-10; (iv) DBP-IA (SAH): OR = 1.066, 95 % CI: 1.047-1.085, P = 1.25E-12. In addition, among calcium channel blockers (CCBs), beta-blockers (BBs), and thiazide diuretics (TDs), only SBP mediated by TDs target genes significantly increased the risk of IA (non-rupture) (OR = 1.164, 95 % CI: 1.060-1.279, P = 0.001) and IA (SAH) (OR = 1.136, 95 % CI: 1.063-1.214, P = 1.58E-04), while SBP mediated by target genes of BBs or CCBs did not causally associate with IA.
CONCLUSIONS: Elevated blood pressure significantly increases IA risk, while TDs may be a promising antihypertensive medication for reducing IA risk. Further research with larger cohorts is essential for validation.