Impact of blood pressure and antihypertensive drug classes on intracranial aneurysm: a Mendelian randomization study

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. Conclusion: 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.