Modulation of the renin-angiotensin-aldosterone system for the secondary prevention of stroke.

Recurrent stroke is a major public health concern and new treatment strategies are needed. While modulation of the renin angiotensin aldosterone system (RAAS) has proven effective in reducing recurrent cardiac events, its role in preventing recurrent cerebrovascular events remains unclear. RAAS is both a circulating and tissue based hormonal system that regulates homeostasis and tissue responses to injury in both the CNS and the periphery, via the activity of angiotensin II (Ang II). Vascular and hematologic effects induced by Ang II including endothelial dysfunction, vascular structural changes, inflammation, hemostasis, and fibrinolysis are increasingly linked to the occurrence of cerebrovascular events. Animal models have shown that RAAS modulation may be protective in cerebrovascular disease. The HOPE and LIFE trials support the role of blood pressure independent mechanisms of RAAS modulation for improving outcomes in a broad range of patients with cardiovascular disease but do not specifically address recurrent stroke prevention. PROGRESS, a trial of secondary stroke prevention, demonstrates that blood pressure reduction with a combination strategy including the routine use of ACE inhibitors prevents recurrent stroke. Current evidence suggests that the RAAS plays an important role in the development and progression of cerebrovascular disease. Modulation of the RAAS holds promise for the secondary prevention of stroke, however, ongoing clinical trials will better define the exact role of ACE inhibitor and angiotensin II Type 1 receptor blocker therapy in stroke survivors.

Abdominal aortic aneurysms and thoracic aortic atheromas.

BACKGROUND: Abdominal aortic aneurysm (AAA) is associated with atherosclerosis elsewhere. Thoracic aortic atheromas (ATHs) seen on transesophageal echocardiography (TEE) are an important cause of stroke and peripheral embolization. The purposes of this study were to determine whether an association exists between AAA and ATHs and to assess the importance of screening patients with ATHs for AAA. METHODS: For the retrospective analysis, 109 patients with AAA and 109 matched controls were compared for the prevalence of ATHs on TEE and for historical variables. For the prospective analysis, screening for AAA on ultrasonography was performed in 364 patients at the time of TEE. RESULTS: Results of the retrospective analysis showed that ATHs were present in 52% of patients with AAA and in 25% of controls (odds ratio [OR] = 3.3; P =.00003). There was a significantly higher prevalence of hypertension, myocardial infarction, heart failure, smoking, and carotid or peripheral arterial disease in patients with AAA. However, only ATHs were independently associated with AAA on multivariate analysis (P =.001). Results of the prospective analysis showed that screening at the time of TEE in 364 patients revealed AAA in 13.9% of those with ATHs and in 1.4% of those without ATHs (P <.0001; OR = 11.4). CONCLUSIONS: (1) There is a strong, highly significant association between abdominal aneurysm and thoracic atheromas. (2) Patients with AAA may be at high risk for stroke because of the concomitance of thoracic aortic atheromas. (3) The high prevalence of abdominal aneurysm in patients with thoracic atheromas suggests that screening for abdominal aneurysm should be carried out in all patients with thoracic atheromas identified by TEE.