- Email: [email protected]
ACE inhibitors and abdominal aortic aneurysm
Comment
in women. The odds ratios were higher in younger than older individuals, perhaps indicating the lower underlying risk of myocardial infarction in younger persons apart from the risk from smoking, and perhaps also showing some survivor-cohort effect in the older smokers. The latest findings from INTERHEART should stimulate a redoubling of our efforts to rid the planet of the scourge of smoking. Sarah A Rosner, *Meir J Stampfer Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA [email protected]
We declare that we have no conflict of interest. 1
2
3
4
5
6
Peto R, Lopez A. The future worldwide health effects of current smoking patterns. In: Koop CE, Pearson CE, Schwarz MR, eds. Critical issues in global health. San Francisco: Jossey-Bass, 2000: 151–61. Teo KK, Ounpuu S, Hawken S, on behalf of the INTERHEART Study Investigators. Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case-control study. Lancet 2006; 368: 647–58. US Department of Health and Human Services. The health consequences of smoking: a report of the United States Surgeon General. 2004: http:// www.cdc.gov/tobacco/sgr/sgr_2004/index.htm (accessed Aug 2, 2006). Rastogi T, Jha P, Reddy KS, et al. Bidi and cigarette smoking and risk of acute myocardial infarction among males in urban India. Tob Control 2005; 14: 356–58. Willett WC, Green A, Stampfer MJ, et al. Relative and absolute excess risks of coronary heart disease among women who smoke cigarettes. N Engl J Med 1987; 317: 1303–09. US Department of Health and Human Services. The health consequences of involuntary exposure to tobacco smoke: a report of the United States Surgeon General. June 27, 2006: http://www.cdc.gov/tobacco/sgr/sgr_2006/ index.htm (accessed Aug 2, 2006).
ACE inhibitors and abdominal aortic aneurysm See Articles page 659
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Abdominal aortic aneurysm is a potentially fatal disorder, defined as a focal dilatation exceeding 150% of the normal arterial diameter, with the risk for rupture increasing as maximum diameter increases. The prevalence of the disorder is estimated at 3% in individuals over the age of 50 years, with male dominance. 2·1% of all men over 65 years of age die from aortic aneurysm rupture, the tenth leading cause of death in this group. However, no drug treatments are effective in prevention. It seems that patients and doctors are still waiting for aneurysms to rupture or to become large enough to justify surgical or endovascular repair.1 Abdominal aortic aneurysm and atherosclerotic disease manifestations are characterised by acute and chronic inflammation of the vessel wall, matrix degradation, and vascular tissue remodelling.2 Angiotensin II (ATII), the major effector peptide of the renin-angiotensin-aldosterone system, plays an important part in the perpetuation of the inflammatory response, and in animal studies consistently promotes the formation of aneurysms. Mechanisms have not been clearly defined.3 In animal models an attenuated degradation of medial elastin and prevention of aneurysmal degeneration was seen with angiotensinconverting-enzyme (ACE) inhibitors but not with blockers of ATII receptor.4,5 So, although the reninangiotensin-aldosterone system is associated with a range of key events in vascular inflammation, mechanisms underlying inflammation-associated
evolution of abdominal aortic aneurysm seem to be distinct from events directly mediated via ATII receptors.4 In today’s Lancet, Daniel Hackam and colleagues6 present clinically relevant data from a large populationbased case-control study about the influence of ACE inhibitors on the risk of aortic rupture. Analysing 15 326 patients hospitalised with a primary diagnosis of abdominal aortic aneurysm in Canada, the researchers found that patients receiving ACE inhibitors before admission were significantly less likely to present with aortic rupture. The beneficial effect of such drugs is independent from their antihypertensive properties, the study indirectly concludes, because intake of other antihypertensive agents was not associated with a lower risk of abdominal aortic aneurysm rupture. Furthermore, and in accordance with work in animal models,4 the beneficial effect of ACE inhibitors was not seen in patients treated with ATII-receptor blockers. Biological explanations for this finding might be that ACE inhibitors specifically bind zinc, an essential cofactor for some of the matrix metalloproteinases implicated in the metabolism of elastin and collagen,7 or that collagen metabolism is affected differentially by ACE inhibitors and ATII-receptor blockers.8 Abdominal aortic aneurysm is considered to be a coronary heart disease risk equivalent, ie, 20 of 100 individuals with aneurysm will develop a coronary event within 10 years. In Hackam’s series, despite the fact that a third of patients admitted for www.thelancet.com Vol 368 August 19, 2006
Comment
Science Photo Library
We do not have the rights to reproduce this image on the web.
and progression of abdominal aortic aneurysm.13 Consequently, smoking habits drastically and considerably influence the prognosis of patients with abdominal aortic aneurysm, and we recommended them to stop smoking first. On the basis of insight from animal models and results from this study, we also favour ACE inhibitor treatment. Hackam and colleagues’ study is the first to show beneficial effects of ACE inhibitors compared with ATII-receptor blockers in a large series of patients with abdominal aortic aneurysm. Observations from this series should help to make way for randomised studies on the potential of ACE inhibitors in the prevention of aneurysmal degeneration. But the study also highlights suboptimum secondary prevention of patients with a primary diagnosis of abdominal aortic aneurysm. Nicolas Diehm, *Iris Baumgartner
Angiogram showing abdominal aortic aneurysm
a primary diagnosis of aneurysm had already had symptomatic coronary artery disease, and although the prevalence of polyvascular disease is particularly high in patients with abdominal aortic aneurysm, use of beneficial medical therapies for prevention of atherothrombotic events was less than optimum and achievement of prevention goals seems to be considerably poorer as compared with patients with coronary artery disease.9,10 Not surprisingly, the proportion of patients with abdominal imaging before admission for abdominal aortic aneurysm was substantially lower in the group of patients presenting with rupture. Recommendations differ as to patients in whom an ultrasound screening is regarded as effective.11 The US Preventive Services Task Force12 found good evidence that screening for abdominal aortic aneurysm and surgical repair of large aneurysms (≥5·5 cm) in men aged 65–75 years who have never smoked leads to decreased mortality from the aneurysm. Ultrasound screening for such aneurysms is not routine and remains optional in clinical practice throughout Europe. The main shortcoming of Hackam and colleagues’ study is that no information on the smoking status of patients is given. Cigarette smoking is the main avoidable risk factor for the development www.thelancet.com Vol 368 August 19, 2006
Clinical and Interventional Angiology, University Hospital Bern, Swiss Cardiovascular Centre, CH-3010 Bern, Switzerland [email protected] We declare that we have no conflict of interest. 1
2
3 4
5
6
7 8
9
10
11 12
13
Diehm N, Schmidli J, Dai-Do D, Baumgartner I. Current evidence and prospects for medical treatment of abdominal aortic aneurysms. Vasa 2005; 34: 217–23. Van Vickle-Chavez SJ, Tung WS, Absi TS, et al. Temporal changes in mouse aortic wall gene expression during the development of elastase-induced abdominal aortic aneurysms. J Vasc Surg 2006; 43: 1010–20. Daugherty A, Cassis L. Angiotensin II and abdominal aortic aneurysms. Curr Hypertens Rep 2004; 6: 442–46. Liao S, Miralles M, Kelley BJ, Curci JA, Borhani M, Thompson RW. Suppression of experimental abdominal aortic aneurysms in the rat by treatment with angiotensin-converting enzyme inhibitors. J Vasc Surg 2001; 33: 1057–64. da Cunha V, Tham DM, Martin-McNulty B, et al. Enalapril attenuates angiotensin II-induced atherosclerosis and vascular inflammation. Atherosclerosis 2005; 178: 9–17. Hackam D, Thiruchelvam D, Redelmeier DA. Angiotensin-converting enzyme inhibitors and aortic rupture: a population-based case-control study. Lancet 2006; 368: 659–65. Klevay LM. Trace elements, atherosclerosis, and abdominal aneurysms. Ann NY Acad Sci 1996; 800: 239–42. Claridge MW, Hobbs SD, Quick C, Day N, Bradbury A, Wilmink A. ACE inhibitors increase type III collagen synthesis: a potential explanation for reduction in acute vascular events by ACE inhibitors. Eur J Vasc Endovasc Surg 2004; 28: 67–70. Cornuz J, Sidoti Pinto C, Tevaearai H, Egger M. Risk factors for asymptomatic abdominal aortic aneurysm: systematic review and meta-analysis of population-based screening studies. Eur J Public Health 2004; 14: 343–49. Barba A, Estallo L, Rodríguez L, Baquer M, Vega de Céniga M. Detection of abdominal aortic aneurysm in patients with peripheral artery disease. Eur J Vasc Endovasc Surg 2005; 30: 504–08. Kent KC, Zwolak RM, Jaff MR, et al. Screening for abdominal aortic aneurysm: a consensus statement. J Vasc Surg 2004; 39: 267–69. US Preventive Services Task Force. Screening for abdominal aortic aneurysm: recommendation statement. Ann Intern Med 2005; 142: 198–202. Lederle FA, Johnson GR, Wilson SE, et al. The aneurysm detection and management study screening program: validation cohort and final results. Aneurysm Detection and Management Veterans Affairs Cooperative Study Investigators. Arch Intern Med 2000; 160: 1425–30.
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in women. The odds ratios were higher in younger than older individuals, perhaps indicating the lower underlying risk of myocardial infarction in younger persons apart from the risk from smoking, and perhaps also showing some survivor-cohort effect in the older smokers. The latest findings from INTERHEART should stimulate a redoubling of our efforts to rid the planet of the scourge of smoking. Sarah A Rosner, *Meir J Stampfer Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA [email protected]
We declare that we have no conflict of interest. 1
2
3
4
5
6
Peto R, Lopez A. The future worldwide health effects of current smoking patterns. In: Koop CE, Pearson CE, Schwarz MR, eds. Critical issues in global health. San Francisco: Jossey-Bass, 2000: 151–61. Teo KK, Ounpuu S, Hawken S, on behalf of the INTERHEART Study Investigators. Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case-control study. Lancet 2006; 368: 647–58. US Department of Health and Human Services. The health consequences of smoking: a report of the United States Surgeon General. 2004: http:// www.cdc.gov/tobacco/sgr/sgr_2004/index.htm (accessed Aug 2, 2006). Rastogi T, Jha P, Reddy KS, et al. Bidi and cigarette smoking and risk of acute myocardial infarction among males in urban India. Tob Control 2005; 14: 356–58. Willett WC, Green A, Stampfer MJ, et al. Relative and absolute excess risks of coronary heart disease among women who smoke cigarettes. N Engl J Med 1987; 317: 1303–09. US Department of Health and Human Services. The health consequences of involuntary exposure to tobacco smoke: a report of the United States Surgeon General. June 27, 2006: http://www.cdc.gov/tobacco/sgr/sgr_2006/ index.htm (accessed Aug 2, 2006).
ACE inhibitors and abdominal aortic aneurysm See Articles page 659
622
Abdominal aortic aneurysm is a potentially fatal disorder, defined as a focal dilatation exceeding 150% of the normal arterial diameter, with the risk for rupture increasing as maximum diameter increases. The prevalence of the disorder is estimated at 3% in individuals over the age of 50 years, with male dominance. 2·1% of all men over 65 years of age die from aortic aneurysm rupture, the tenth leading cause of death in this group. However, no drug treatments are effective in prevention. It seems that patients and doctors are still waiting for aneurysms to rupture or to become large enough to justify surgical or endovascular repair.1 Abdominal aortic aneurysm and atherosclerotic disease manifestations are characterised by acute and chronic inflammation of the vessel wall, matrix degradation, and vascular tissue remodelling.2 Angiotensin II (ATII), the major effector peptide of the renin-angiotensin-aldosterone system, plays an important part in the perpetuation of the inflammatory response, and in animal studies consistently promotes the formation of aneurysms. Mechanisms have not been clearly defined.3 In animal models an attenuated degradation of medial elastin and prevention of aneurysmal degeneration was seen with angiotensinconverting-enzyme (ACE) inhibitors but not with blockers of ATII receptor.4,5 So, although the reninangiotensin-aldosterone system is associated with a range of key events in vascular inflammation, mechanisms underlying inflammation-associated
evolution of abdominal aortic aneurysm seem to be distinct from events directly mediated via ATII receptors.4 In today’s Lancet, Daniel Hackam and colleagues6 present clinically relevant data from a large populationbased case-control study about the influence of ACE inhibitors on the risk of aortic rupture. Analysing 15 326 patients hospitalised with a primary diagnosis of abdominal aortic aneurysm in Canada, the researchers found that patients receiving ACE inhibitors before admission were significantly less likely to present with aortic rupture. The beneficial effect of such drugs is independent from their antihypertensive properties, the study indirectly concludes, because intake of other antihypertensive agents was not associated with a lower risk of abdominal aortic aneurysm rupture. Furthermore, and in accordance with work in animal models,4 the beneficial effect of ACE inhibitors was not seen in patients treated with ATII-receptor blockers. Biological explanations for this finding might be that ACE inhibitors specifically bind zinc, an essential cofactor for some of the matrix metalloproteinases implicated in the metabolism of elastin and collagen,7 or that collagen metabolism is affected differentially by ACE inhibitors and ATII-receptor blockers.8 Abdominal aortic aneurysm is considered to be a coronary heart disease risk equivalent, ie, 20 of 100 individuals with aneurysm will develop a coronary event within 10 years. In Hackam’s series, despite the fact that a third of patients admitted for www.thelancet.com Vol 368 August 19, 2006
Comment
Science Photo Library
We do not have the rights to reproduce this image on the web.
and progression of abdominal aortic aneurysm.13 Consequently, smoking habits drastically and considerably influence the prognosis of patients with abdominal aortic aneurysm, and we recommended them to stop smoking first. On the basis of insight from animal models and results from this study, we also favour ACE inhibitor treatment. Hackam and colleagues’ study is the first to show beneficial effects of ACE inhibitors compared with ATII-receptor blockers in a large series of patients with abdominal aortic aneurysm. Observations from this series should help to make way for randomised studies on the potential of ACE inhibitors in the prevention of aneurysmal degeneration. But the study also highlights suboptimum secondary prevention of patients with a primary diagnosis of abdominal aortic aneurysm. Nicolas Diehm, *Iris Baumgartner
Angiogram showing abdominal aortic aneurysm
a primary diagnosis of aneurysm had already had symptomatic coronary artery disease, and although the prevalence of polyvascular disease is particularly high in patients with abdominal aortic aneurysm, use of beneficial medical therapies for prevention of atherothrombotic events was less than optimum and achievement of prevention goals seems to be considerably poorer as compared with patients with coronary artery disease.9,10 Not surprisingly, the proportion of patients with abdominal imaging before admission for abdominal aortic aneurysm was substantially lower in the group of patients presenting with rupture. Recommendations differ as to patients in whom an ultrasound screening is regarded as effective.11 The US Preventive Services Task Force12 found good evidence that screening for abdominal aortic aneurysm and surgical repair of large aneurysms (≥5·5 cm) in men aged 65–75 years who have never smoked leads to decreased mortality from the aneurysm. Ultrasound screening for such aneurysms is not routine and remains optional in clinical practice throughout Europe. The main shortcoming of Hackam and colleagues’ study is that no information on the smoking status of patients is given. Cigarette smoking is the main avoidable risk factor for the development www.thelancet.com Vol 368 August 19, 2006
Clinical and Interventional Angiology, University Hospital Bern, Swiss Cardiovascular Centre, CH-3010 Bern, Switzerland [email protected] We declare that we have no conflict of interest. 1
2
3 4
5
6
7 8
9
10
11 12
13
Diehm N, Schmidli J, Dai-Do D, Baumgartner I. Current evidence and prospects for medical treatment of abdominal aortic aneurysms. Vasa 2005; 34: 217–23. Van Vickle-Chavez SJ, Tung WS, Absi TS, et al. Temporal changes in mouse aortic wall gene expression during the development of elastase-induced abdominal aortic aneurysms. J Vasc Surg 2006; 43: 1010–20. Daugherty A, Cassis L. Angiotensin II and abdominal aortic aneurysms. Curr Hypertens Rep 2004; 6: 442–46. Liao S, Miralles M, Kelley BJ, Curci JA, Borhani M, Thompson RW. Suppression of experimental abdominal aortic aneurysms in the rat by treatment with angiotensin-converting enzyme inhibitors. J Vasc Surg 2001; 33: 1057–64. da Cunha V, Tham DM, Martin-McNulty B, et al. Enalapril attenuates angiotensin II-induced atherosclerosis and vascular inflammation. Atherosclerosis 2005; 178: 9–17. Hackam D, Thiruchelvam D, Redelmeier DA. Angiotensin-converting enzyme inhibitors and aortic rupture: a population-based case-control study. Lancet 2006; 368: 659–65. Klevay LM. Trace elements, atherosclerosis, and abdominal aneurysms. Ann NY Acad Sci 1996; 800: 239–42. Claridge MW, Hobbs SD, Quick C, Day N, Bradbury A, Wilmink A. ACE inhibitors increase type III collagen synthesis: a potential explanation for reduction in acute vascular events by ACE inhibitors. Eur J Vasc Endovasc Surg 2004; 28: 67–70. Cornuz J, Sidoti Pinto C, Tevaearai H, Egger M. Risk factors for asymptomatic abdominal aortic aneurysm: systematic review and meta-analysis of population-based screening studies. Eur J Public Health 2004; 14: 343–49. Barba A, Estallo L, Rodríguez L, Baquer M, Vega de Céniga M. Detection of abdominal aortic aneurysm in patients with peripheral artery disease. Eur J Vasc Endovasc Surg 2005; 30: 504–08. Kent KC, Zwolak RM, Jaff MR, et al. Screening for abdominal aortic aneurysm: a consensus statement. J Vasc Surg 2004; 39: 267–69. US Preventive Services Task Force. Screening for abdominal aortic aneurysm: recommendation statement. Ann Intern Med 2005; 142: 198–202. Lederle FA, Johnson GR, Wilson SE, et al. The aneurysm detection and management study screening program: validation cohort and final results. Aneurysm Detection and Management Veterans Affairs Cooperative Study Investigators. Arch Intern Med 2000; 160: 1425–30.
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