Previous evaluation of total aortic calcium score suggests that mutations promoting ascending aortic aneurysm development may protect against atherosclerosis. However, calcium score is a late indicator of atherosclerosis. We evaluated carotid intima-media thickness (IMT), an earlier marker, to assess the degree of atherosclerosis in ascending aortic aneurysm patients compared to controls. Images of right and left common carotid arteries were obtained in 52 patients with ascending aortic aneurysms and 29 controls using a Sonosite MicroMaxx ultrasound. IMT was measured with Sonosite Sonocalc IMT software, a computer-based algorithm with manual override. Six IMT measurements were obtained for each patient (right and left proximal, mid and distal common carotid artery) by a single observer and averaged. A multiple linear regression analysis was applied to test for an association between aneurysm and IMT. Patients with ascending aortic aneurysms had 0.131-mm lower carotid IMT values than controls (p = 0.0002), independent of risk factors for atherosclerosis (age, BMI, gender, family history, smoking, dyslipidemia, race, diabetes and hypertension). The average IMT was 0.50 ± 0.13 mm for individuals with aneurysm and 0.60 ± 0.11 mm for controls. Age increased the IMT by 0.005 mm per year (p = 0.0003). BMI, male gender, positive family history, dyslipidemia, diabetes and hypertension also increased the IMT, but did not reach statistical significance. This investigation provides further evidence that ascending aortic aneurysm provides protection against the development of atherosclerosis, supporting the hypothesis that proaneurysmal genetic mutations may also be antiatherogenic.

1.
WHO Factsheet No. 317. http://who.int/mediacentre/factsheets/fs317/en (accessed September 2011).
2.
Centers for Disease Control and Prevention, Division for Heart Disease and Stroke Prevention: Data Trends and Maps website. U.S. Department of Health and Human Services, National Center for Chronic Disease Prevention and Health Promotion, Atlanta, GA, 2010. http://www.cdc.gov/dhdsp/ (accessed January 2012).
3.
National Center for Injury Prevention and Control. WISQARS Leading Causes of Death Reports, 1999 –2007. http://webappa.cdc.gov/sasweb/ncipc/leadcaus10.html (accessed January 2012).
4.
Centers for Disease Control and Prevention, National Center for Health Statistics. CDC WONDER on-line database, compiled from Compressed Mortality File 1999–2006, series 20, No. 2L, 2009. http://wonder.cdc.gov/cmf-icd10.html (accessed January 2012).
5.
Kaschina E, Scholz H, Steckelings UM, Sommerfeld M, Kemnitz UR, Artuc M, Schmidt S, Unger T: Transition from atherosclerosis to aortic aneurysm in humans coincides with an increased expression of RAS components. Atherosclerosis 2009;205:396–403.
6.
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;14:343–349.
7.
Guo DC, Regalado ES, Minn C, Tran-Fadulu V, Coney J, Cao J, Wang M, Yu RK, Estrera AL, Safi HJ, Shete SS, Milewicz DM: Familial thoracic aortic aneurysms and dissections: identification of a novel locus for stable aneurysms with a low risk for progression to aortic dissection. Circ Cardiovasc Genet 2011;4:36–42.
8.
Milewicz DM, Regalado ES, Guo DC: Treatment guidelines for thoracic aortic aneurysms and dissections based on the underlying causative gene. J Thorac Cardiovasc Surg 2010;140:S2–S4.
9.
Wang Y, Barbacioru CC, Shiffman D, Balasubramanian S, Lakoubova O, Tranquilli M, Albornoz G, Blake J, Mehmet NN, Ngadimo D, Poulter K, Chan F, Samaha RR, Elefteriades JA: Gene expression signature in peripheral blood detects thoracic aortic aneurysm. PloS ONE 2007;2:e1050.
10.
Albornoz G, Coady MA, Roberts M, Davies RR, Rizzo J, Elefteriades JA: Familial thoracic aortic aneurysms and dissections – incidence, modes of inheritance and phenotypic patterns. Ann Thorac Surg 2006;82:1400–1405.
11.
Coady MA, Davies RR, Roberts M, Goldstein LJ, Rogalski MJ, Rizzo JA, Hammond GL, Kopf GS, Elefteriades JA: Familial patterns of thoracic aortic aneurysms. Arch Surg 1999;134:361–367.
12.
Achneck H, Modi B, Shaw C, Rizzo J, Albornoz G, Fusco D, Elefteriades J: Ascending thoracic aneurysms are associated with decreased systemic atherosclerosis. Chest 2005;128:1580–1586.
13.
Ayyash B, Tranquilli M, Elefteriades JA: Femoral artery cannulation for thoracic aortic surgery: safe under transesophageal echocardiographic control. J Thorac Cardiovasc Surg 2011;142:1478–1481.
14.
Agmon Y, Khandheria BK, Meissner I, Schwartz GL, Sicks JD, Fought AJ, O’Fallon WM, Wiebers DO, Tajik AJ: Is aortic dilatation an atherosclerosis-related process? Clinical, laboratory, and transeesophageal echocardiographic correlates of thoracic aortic dimensions in the population with implications for thoracic aortic aneurysm formation. J Am Coll Cardiol 2003;42:1076–1083.
15.
Kojima S, Suwa S, Fujiwara Y, Inoue K, Mineda Y, Ohta H, Tokano T, Nakata Y: Incidence and severity of coronary artery disease in patients with acute aortic dissection: comparison with abdominal aortic aneurysm and arteriosclerosis obliterans. J Cardiol 2001;37:165–171.
16.
Islamoglu F, Atay Y, Can L, Kara E, Ozbaran M, Yuksel M, Buket S: Diagnosis and treatment of concomitant aortic and coronary disease: a retrospective study brief review. Tex Heart Inst J 1999;26:182–188.
17.
Nakashima Y, Kurozumi T, Sueishi K, Tanaka K: Dissecting aneurysm: a clinicopathologic and histopathologic study of 111 autopsied cases. Hum Pathol 1990;21:291–296.
18.
Topol EJ, Nissen SE: Our preoccupation with coronary luminology. The dissociation between clinical and angiographic findings in ischemic heart disease. Circulation 1995;92:2333–2342.
19.
Stein JH, Fraizer MC, Aeschlimann SE, Nelson-Worel J, McBride PE, Douglas PS: Vascular age: integrating carotid intima-media thickness measurements with global coronary risk assessment. Clin Cardiol 2004;27:388–392.
20.
Stein JH, Korcarz CE, Hurst RT, Lonn E, Kendall CB, Mohler ER, Najjar SS, Rembold CM, Post WS: Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force. J Am Soc Echocardiogr 2008;21:93–111.
21.
Ali YS, Rembold KE, Weaver B, Wills MB, Tatar S, Ayers CR, Rembold CM: Prediction of major adverse cardiovascular events by age-normalized carotid intimal medial thickness. Atherosclerosis 2006;187:186–190.
22.
Gepner AD, Keevil JG, Wyman RA, Korcarz CE, Aeschlimann SE, Busse KL, Stein JH: Use of carotid intima-media thickness and vascular age to modify cardiovascular risk prediction. J Am Soc Echocardiogr 2006;19:1170–1174.
23.
Ludwig M, Petzinger-Kruthoff A, Buquoy M, Stumpe KO: Intima media thickness of the carotid arteries: early pointer to arteriosclerosis and therapeutic endpoint. Ultraschall Med 2003;24:151–152.
24.
Baldassarre D, Amato M, Bondioli A, Sirtori CR, Tremoli E: Carotid artery intima-media thickness measured by ultrasonography in normal clinical practice correlates well with atherosclerosis risk factors. Stroke 2000;31:2426–2430.
25.
Poredoš P: Intima-media thickness: indicator of cardiovascular risk and measure of the extent of atherosclerosis. Vasc Med 2004;9:46–54.
26.
Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M: Prediction of clinical cardiovascular events with carotid intima-media thickness. Circulation 2007;115:459–467.
27.
Chambless LE, Heiss G, Folsom AR, Rosamond W, Szklo M, Sharrett AR, Clegg LX: Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) Study, 1987–1993. Am J Epidemiol 1997;146:483–494.
28.
Greenland P, Alpert JS, Beller GA, Benjamin EJ, Budoff MJ, Fayad ZA, Foster E, Hlatky MA, Hodgson JM, Kushner FG, Lauer MS, Shaw LJ, Taylor AJ, Wenger NK: ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. JACC 2010;56:e50–e103.
29.
Elefteriades JA, Farkas EA: Thoracic aortic aneurysm clinically pertinent controversies and uncertainties. JACC 2010;55:841–857.
30.
Elefteriades JA, Rizzo JA: Epidemiology, prevalence, incidence, trends; in Elefteriades JA (ed): Acute Aortic Disease. New York, Informa Healthcare, 2008, pp 89–98.
31.
Kanters S, Algra A, Van Leeuwen MS, Banga J: Reproducibility of in vivo carotid intima-media thickness measurements. Stroke 1997;28:665–671.
32.
Wong M, Edelstein J, Wollman J, Bond MG: Ultrasonic-pathological comparison of the human arterial wall. Verification of intima-media thickness. Arterioscler Thromb 1993;13:482–486.
33.
Molinari F, Zeng G, Suri JS: A state of the art review on intima-media thickness (IMT) measurement and wall segmentation techniques for carotid ultrasound. Comput Methods Programs Biomed 2010;100:201–221.
34.
O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK: Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med 1999;340:14–22.
35.
Cao JJ, Arnold AM, Manolio TA, Polak JF, Psaty BM, Hirsch CH, Kuller LH, Cushman M: Association of carotid artery intima-media thickness, plaques, and C-reactive protein with future cardiovascular disease and all-cause mortality: the Cardiovascular Health Study. Circulation 2007;116:32–38.
36.
Gepner AD, Wyman RA, Korcarz CE, Aeschlimann SE, Stein JH: An abbreviated carotid intima-media thickness scanning protocol to facilitate clinical screening for subclinical atherosclerosis. J Am Soc Echocardiogr 2007;20:1269–1275.
37.
Lim TK, Lim E, Dwivedi G, Kooner J, Senior R: Normal value of carotid intima-media thickness – a surrogate marker of atherosclerosis: quantitative assessment by B-mode carotid ultrasound. J Am Soc Echocardiogr 2008;21:112–116.
38.
El-Hamamsy I, Yacoub MH: Cellular and molecular mechanisms of thoracic aortic aneurysms. Nat Rev Cardiol 2009;6:771–786.
39.
Silence J, Collen D, Lijnen HR: Reduced atherosclerotic plaque but enhanced aneurysm formation in mice with inactivation of the tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) gene. Circ Res 2002;90:897–903.
40.
Lemaitre V, O’Byrne TK, Borczuk AC, Okada Y, Tall AR, D’Armiento J: ApoE knockout mice expressing human matrix metalloproteinase-1 in macrophages have less advanced atherosclerosis. J Clin Invest 2001;107:1227–1234.
41.
Ye S, Eriksson P, Hamsten A, Kurkinen M, Humphries SE, Henney AM: Progression of coronary atherosclerosis is associated with common genetic variant of the human sromelysin-1 promoter which result in reduced gene expression. J Bio Chem 1996;271:13055–13060.
42.
Vaughan CJ, Casey M, He J, Veugelers M, Henderson K, Guo D, Campagna R, Roman MJ, Milewicz DM, Devereux RB, Basson CT: Identification of a chromosome 11q23.2-q24 locus for familial aortic aneurysm disease, a genetically heterogeneous disorder. Circulation 2001;103:2469–2475.
43.
Pendas AM, Santamaria I, Alvarez MV, Pritchard M, Lopez-Otin C: Fine physical mapping of the human matrix metalloproteinase genes clustered on chromosome 11q22.3. Genomics 1996;37:266–268.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.