Effect of Renin-Angiotensin-Aldosterone System Inhibitors on the Rupture Risk Among Hypertensive Patients With Intracranial Aneurysms

Abstract

Background: Mounting experimental evidence supports the concept that the RAAS (renin-angiotensin-aldosterone system) is involved in the pathogenesis of intracranial aneurysm rupture. However, whether RAAS inhibitors could reduce the rupture risk of intracranial aneurysms remains unclear. Methods: We performed a chart review of a multicenter, prospectively maintained database of 3044 hypertensive patients with intracranial aneurysms from 20 medical centers in China. The patients were separated into ruptured and unruptured groups. Univariable and multivariable logistical regression analyses were performed to determine the association between the use of RAAS inhibitors and the rupture risk. Sensitivity analyses and subgroup analyses were performed to verify the robustness of the results. Results: In multivariable analyses, female sex, passive smoking, uncontrolled, or unmonitored hypertension, use of over 2 antihypertensive medications, RAAS inhibitors use, antihyperglycemic agents use, hyperlipidemia, ischemic stroke, and aneurysmal location were independently associated with the rupture risk. The use of RAAS inhibitors was significantly associated with a reduced rupture risk compared with the use of non-RAAS inhibitors (odds ratio, 0.490 [95% CI, 0.402–0.597]; P =0.000). Compared with the use of non-RAAS inhibitors, the use of ACE (angiotensin-converting enzyme) inhibitors (odds ratio, 0.559 [95% CI, 0.442–0.709]; P =0.000) and use of ARBs (angiotensin receptor blockers; odds ratio, 0.414 [95% CI, 0.315–0.542]; P =0.000) were both significantly associated with a reduced rupture risk. The negative association of the rupture risk with RAAS inhibitors was consistent across 3 analyzed data and the predefined subgroups (including controlled hypertension). Conclusions: The use of RAAS inhibitors was significantly associated with a decreased rupture risk independent of blood pressure control among hypertensive patients with intracranial aneurysms.

Genetically Determined Blood Pressure, Antihypertensive Medications, and Risk of Intracranial Aneurysms and Aneurysmal Subarachnoid Hemorrhage: A Mendelian Randomization Study

“…Despite numerous observational studies showing that ARB and ACEI may be protective for aneurysm rupture, 4 our study failed to confirm these associations. However, our results cannot completely rule out their effect on IA/SAH because the limited number of SNPs in this study may not provide sufficient statistical power.…”

“…However, the literature is inconclusive in this regard. For example, while some studies suggest that ARBs and ACEI are effective in preventing aneurysm rupture, 4 others found no such effect. 5 One cross-sectional study even found CCBs were independently associated with the presence of IAs.…”

Genetically determined blood pressure, antihypertensive medications, and risk of intracranial aneurysms and aneurysmal subarachnoid hemorrhage: A Mendelian randomization study

“…Despite numerous observational studies showing that ARB and ACEI may be protective against aneurysm rupture, 29 our study failed to confirm these associations. However, our results cannot completely rule out their effect on IA/SAH because the limited number of SNPs in this study may not provide sufficient statistical power.…”

A web-based dynamic nomogram for rupture risk of posterior communicating artery aneurysms utilizing clinical, morphological, and hemodynamic characteristics

“…Our results also suggest that a history of hypertension and higher AR increase the rupture risk of PcomA aneurysms. Previous studies suggested that hypertension may be involved in aneurysm rupture through the renin–angiotensin–aldosterone system, and the latest multicenter study demonstrated that the risk of aneurysm rupture due to hypertension could be significantly reduced using renin–angiotensin–aldosterone system inhibitors ( 44 ). A large cohort study also showed recently that higher AR was an independent predictor of aneurysm rupture ( 45 ).…”