Published online before print July 3, 2008, doi: 10.1161/STROKEAHA.107.522011
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(Stroke. 2008;39:e135.)
© 2008 American Heart Association, Inc.
Letters to the Editor |
Response to Letter by Paraskevas
Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
Response:
We have recently demonstrated that simvastatin suppresses the progression of experimentally induced rat cerebral aneurysms (CA). Stains are used in the prevention and treatment of various cardiovascular and cerebrovascular diseases. Large clinical trials demonstrated the efficacy of statins in preventing cardiovascular and cerebrovascular events,1–4 whereas there are no randomized controlled trials proving statins’ beneficial effects on aortic abdominal aneurysm and CA so far.
A clinical trial investigating the preventive effect on CA rupture is difficult because of a low incidence of CA rupture. Only <1% of unruptured CA lead to subarachnoid hemorrhage in 1 year.5 If CA rupture would be set as a primary end point, a tremendous number of patients would need to be enrolled in a study. Such a clinical trial encompasses an ethical problem. Subarachnoid hemorrhage has a high mortality, and surgical clipping and endovascular coiling can prevent CA rupture. To overcome the difficulties described above, we must identify a predictive factor for the stability of CA walls.
Positive results obtained from an animal experiment cannot be directly applied to human disease. However, a series of our studies using an experimentally induced CA model provide evidences that vascular inflammation and resultant endothelial dysfunction contribute to degenerative changes in CA walls.6,7 We hope our results will be a clue to the development of a less invasive treatment for preventing subarachoid hemorrhage.
Acknowledgments
Disclosures
None.
References
1. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002; 360: 7–22.[CrossRef][Medline] [Order article via Infotrieve]
2. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994; 344: 1383–1389.[CrossRef][Medline] [Order article via Infotrieve]
3. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998; 339: 1349–1357.
4. Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, Brown L, Warnica JW, Arnold JM, Wun CC, Davis BR, Braunwald E; Cholesterol and Recurrent Events Trial investigators. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med. 1996; 335: 1001–1009.
5. International Study of Unruptured Intracranial Aneurysms Investigators. Unruptured intracranial aneurysms–risk of rupture and risks of surgical intervention. N Engl J Med. 1998; 339: 1725–1733.
6. Aoki T, Kataoka H, Morimoto M, Nozaki K, Hashimoto N. Macrophage-derived matrix metalloproteinase-2 and -9 promote the progression of cerebral aneurysms in rats. Stroke. 2007; 38: 162–169.
7. Aoki T, Kataoka H, Shimamura M, Nakagami H, Wakayama K, Moriwaki T, Ishibashi R, Nozaki K, Morishita R, Hashimoto N. NF-kappaB is a key mediator of cerebral aneurysm formation. Circulation. 2007; 116: 2830–2840.
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