HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Carmelo A. Milano Mark F. Newman Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ti, L. K. Articles by Mathew, J. P. Search for Related Content PubMed PubMed Citation Articles by Ti, L. K. Articles by Mathew, J. P. Related Collections Cerebral protection Coronary disease Extracorporeal circulation

J Thorac Cardiovasc Surg 2003;125:211-213
© 2003 The American Association for Thoracic Surgery

Brief Communications

Apolipoprotein E4 increases aortic atheroma burden in cardiac surgical patients

From the Divisions of Cardiothoracic Anesthesiology and Critical Care, Cardiovascular and Thoracic Surgery, and Neurology, Departments of Anesthesiology, Surgery, and Medicine, Duke University Medical Center, Durham, NC.

Supported in part by grants from National Institutes of Health (NIH) grant 1R01HL54316, Clinical Research Centers Program NIH MO1-RR-30, and American Heart Association Grant-In-Aid 95010970.

Received for publication Sept 3, 2001. Accepted for publication May 22, 2002. Address for reprints: Joseph P. Mathew, MD, Box 3094, Duke University Medical Center, Durham, NC 27710 (E-mail: mathe014{at}mc.duke.edu).

The increasing numbers of elderly patients undergoing cardiac surgery emphasizes the importance of identifying risk factors associated with adverse neurologic outcomes. Although the apolipoprotein 4 allele (APOE^*E4) has been identified as a risk factor, ¹ how its presence increases neurologic risk remains uncertain. Apolipoprotein E (ApoE) plays a key role in lipoprotein metabolism and has an important influence on the pathophysiology of atherosclerosis. ApoE's 3 major alleles (APOE^*E2, APOE^*E3, and APOE^*E4) result in differing susceptibility to dyslipidemia, atherosclerosis, and coronary heart disease. Therefore we sought to determine whether the APOE^*E4 allele influences aortic atheroma burden in patients undergoing cardiac surgery.

Patients and methods

With institutional review board approval, a comprehensive transesophageal echocardiography examination was performed in 128 patients undergoing coronary artery bypass grafting surgery. For analysis, a videotaped frame displaying the most diseased area in each aortic segment was digitized. By tracing the outline of the atheroma, the area subtended by the atheroma was estimated (area of plaque). Similarly, the area of visualized aorta in the ascending aorta and aortic arch was measured by tracing the visualized segment of the aorta (Figure 1). The area of the visualized aorta in the descending aorta was measured by estimating the angle () subtended by the vessel wall and calculated as a portion of a circular or complete vessel (r² · /360°; Figure 1). Atheroma burden in each segment was then calculated as the percentage of area of the visualized aorta containing atheroma. Genomic DNA was used to determine APOE allele frequencies, as previously described. ² Differences between patients with and without the APOE^*E4 allele were compared by using the Wilcoxon rank sum test and the Fisher exact test. The association of atheroma burden and genotype was investigated with multivariable linear regression controlling for age, sex, and diabetes.

View larger version (37K): [in this window] [in a new window]   Fig. 1. Atheroma burden in each aortic segment was determined as the ratio of the atheroma area (A) to the total area of the aortic segment visualized. For the descending aorta, where the entire circumference could not always be visualized, the area of the visualized segment was adjusted according to the angle () subtended by that segment. r, Aortic radius.

The APOE^*E4 allele was present in 19% of the 128 patients enrolled. The mean percentage atheroma was greatest in the descending aorta (10.2% ± 8.9%) and least in the ascending aorta (0.9% ± 1.8%). In both the ascending aorta and the aortic arch, the atheroma burden was approximately 2 times greater in the APOE^*E4 group than in the non-APOE^*E4 group (P = .08 and P = .04, respectively; Figure 2). Multivariable analysis revealed that the APOE^*E4 allele was significantly associated with atheroma burden in the aortic arch (P = .046). The association between atheroma burden and APOE^*E4 trended toward significance in the ascending aorta (P = .085) but not in the descending aorta (P = .57). Age was also an important predictor of atherosclerosis both in the aortic arch and the descending aorta.

View larger version (18K): [in this window] [in a new window]   Fig. 2. Bar graph with SE bars showing the influence of the APOE*E4 allele on atherosclerosis in each segment of the thoracic aorta. The APOE*E4 allele was associated with a significantly greater atheroma burden in the aortic arch. It was also associated with twice the atheroma burden in the ascending aorta, although this did not reach significance.*P = .04.

The severity of aortic atherosclerosis has important ramifications on the neurologic outcome of patients undergoing cardiopulmonary bypass because atherosclerosis of the aorta has been correlated with an increased risk of stroke after cardiac surgery. ³ Aortic atherosclerosis might result in cerebral embolization of atheroma debris during cannulation, crossclamping, or decannulation and possibly as a result of a sandblasting effect from the high-velocity jet exiting the aortic cannula. Our study shows that, independent of age, sex, and diabetes, the APOE^*E4 allele is associated with a greater degree of atherosclerosis in the aortic arch. The increased atheroma burden might be a mechanism by which APOE^*E4 contributes to postoperative adverse cerebral outcomes.

Unlike the ascending aorta and aortic arch, there was no association between the descending aorta and APOE^*E4. Potential reasons for this include the fact that the progression of atherosclerosis in the aorta is influenced by the flow dynamics and wall shear stress within the segments of the aorta. ⁴ For example, the higher ejection velocity in the ascending aorta might limit formation of plaques in this region. More importantly, the influence of age on atherosclerosis is very strong, with an incidence rising steadily with age. ⁵ Because patients undergoing cardiac surgery are increasingly elderly, the effect of APOE^*E4 might be masked by the dominating influence of age on atherosclerosis, particularly in the descending aorta.

Limitations to our study include the fact that our technique uses a 2-dimensional, rather than 3-dimensional, image of a specific aortic segment. Nevertheless, the percentage of atheroma method that we used does at least account for total plaque area that can be visualized. Finally, epiaortic imaging is a more sensitive measure of assessing plaque in the ascending aorta, and it is possible that a greater degree of atherosclerosis might have been detected, with its use potentially improving the link between atheroma burden and the APOE^*E4 allele.

References

1. Tardiff BE, Newman MF, Saunders AM, et al. Preliminary report of a genetic basis for cognitive decline after cardiac operations. The Neurologic Outcome Research Group of the Duke Heart Center. Ann Thorac Surg. 1997;64:715-20.[Abstract/Free Full Text]
   
2. Saunders AM, Strittmatter WJ, Schmechel D, et al. Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease. Neurology. 1993;43:1467-72.[Abstract/Free Full Text]
   
3. Hogue CW Jr, Murphy SF, Schechtman KB, Davila-Roman VG. Risk factors for early or delayed stroke after cardiac surgery. Circulation. 1999;100:642-7.[Abstract/Free Full Text]
   
4. Stanton AV. Haemodynamics, wall mechanics and atheroma: a clinician's perspective. Proc Inst Mech Eng [H]. 1999;213:385-90.[Medline]
   
5. Marschall K, Kanchuger M, Kessler K, et al. Superiority of transesophageal echocardiography in detecting aortic arch atheromatous disease: identification of patients at increased risk of stroke during cardiac surgery. J Cardiothorac Vasc Anesth. 1994;8:5-13.[Medline]
   

This article has been cited by other articles:

				S. Sen, A. Hinderliter, P. K. Sen, J. Simmons, V. A. LeGrys, J. Beck, S. Offenbacher, K. Moss, and S. M. Oppenheimer Association of Leukocyte Count With Progression of Aortic Atheroma in Stroke/Transient Ischemic Attack Patients Stroke, November 1, 2007; 38(11): 2900 - 2905. [Abstract] [Full Text] [PDF]

				M. V. Podgoreanu and D. A. Schwinn New Paradigms in Cardiovascular Medicine: Emerging Technologies and Practices: Perioperative Genomics J. Am. Coll. Cardiol., December 6, 2005; 46(11): 1965 - 1977. [Abstract] [Full Text] [PDF]

				S. Bar-Yosef, M. Anders, G. B. Mackensen, L. K. Ti, J. P. Mathew, B. Phillips-Bute, R. H. Messier, H. P. Grocott, and the Neurological Outcome Research Group and CARE I Aortic Atheroma Burden and Cognitive Dysfunction After Coronary Artery Bypass Graft Surgery Ann. Thorac. Surg., November 1, 2004; 78(5): 1556 - 1562. [Abstract] [Full Text] [PDF]

				G. B. Mackensen, L. K. Ti, B. G. Phillips-Bute, J. P. Mathew, M. F. Newman, H. P. Grocott, and the Neurologic Outcome Research Group Cerebral embolization during cardiac surgery: impact of aortic atheroma burden Br. J. Anaesth., November 1, 2003; 91(5): 656 - 661. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Carmelo A. Milano Mark F. Newman Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ti, L. K. Articles by Mathew, J. P. Search for Related Content PubMed PubMed Citation Articles by Ti, L. K. Articles by Mathew, J. P. Related Collections Cerebral protection Coronary disease Extracorporeal circulation