Calcium Channel Blockers Increased the Risk of Aortic Aneurysm and Dissection

Abstract Aortic aneurysm and dissection (AAD) are life-threatening conditions for which there is a lack of effective pharmacological therapies. Hypertension is a known risk factor for AAD, leading to the common prescription of antihypertensive medications for AAD patients. The impaired contractility of vascular smooth muscle cells (VSMCs) is strongly linked to AAD, yet the role of calcium channel blockers (CCBs), which directly inhibit VSMC contractility, in AAD onset of hypertensive patients remains unclear. We thus analyzed data from 501,878 initially AAD-free participants and reported that CCB use had greater risks of AAD (adjusted HR=1.31, 95% CI: 1.17-1.48), TAAD (adjusted HR=1.23, 95% CI: 1.00-1.50), and AAA (adjusted HR=1.32, 95% CI: 1.13-1.53), than hypertensive patients not receiving antihypertensive medication. during a median follow-up of 13.5 years ( P <0.001). In mouse models induced by angiotensin II, elastase, and β-aminopropionitrile (BAPN), various subtypes of CCBs significantly increased aortic stiffness and the risk of AAD. Of 95 patients with type B aortic dissection included after endovascular repair surgery in the secondary data analysis, CCBs (69 patients) limited aortic aneurysm/dissection regression compared with that associated with other antihypertensives (26 patients). Moreover, the silencing of protein kinase cGMP-dependent 1 (PRKG1) to restore VSMCs contractility significantly mitigated CCB-induced aortic stiffness and the incidence of AAD. These findings suggest that CCBs may increase AAD risk and post-stent surgery prognosis, highlighting the need for caution when prescribing CCBs to hypertensive patients at risk for AAD.