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(Stroke. 2006;37:332.)
© 2006 American Heart Association, Inc.

Letters to the Editor

Pathophysiology of Gender Difference in Prognosis of Asymptomatic Carotid Stenosis: Research and Future Implications

Willem E. Hellings, MD; Bart A.N. Verhoeven, MD Frans L. Moll, MD, PhD

Department of Vascular Surgery, University Medical Center, Utrecht, The Netherlands

Theo Van den Broek, MD Gerard Pasterkamp, MD, PhD

Experimental Cardiology Laboratory, University Medical Center, Utrecht, The Netherlands

To the Editor:

With great interest we read the recent article by Dick et al reporting that gender is an independent predictor of major adverse cardiovascular events in patients conservatively treated for high-grade carotid stenosis.¹ The authors discussed possible mechanisms that would explain the observed differences in outcome: eg, cardiovascular risk profile and carotid plaque burden are higher in men, and hormones could be protective for women. As appreciated by the authors, their study design did not allow inferences regarding a causal relationship between gender and outcome. Recently, we hypothesized that gender could be associated with the pathological substrate of acute cardiovascular events: a thin cap fibroatheroma. To gain insight in atherosclerotic plaque characteristics among patient groups experiencing carotid artery stenosis, we constructed a biobank containing atherosclerotic plaques.² All plaques obtained during endarterectomy are characterized. In addition, patients fill in questionnaires and undergo follow-up. Characterization of the atherosclerotic plaques pointed out that significant differences are observed between men and women. A study in 214 carotid endarterectomy plaques showed that male gender was associated with significantly higher fat content and significantly lower smooth muscle cell content.³ These factors are generally considered to be associated with plaque destabilization and subsequent cardiovascular events.⁴ More recently, a thrombectomy study in 211 patients experiencing acute myocardial infarction revealed that male sex was associated with more fresh thrombi while more organized plaque material was obtained in female patients.⁵ The value of plaque markers to predict cardiovascular events from plaque phenotype is subject of an ongoing study. Consistent with our hypothesis is that plaque area, which the authors refer to as a predictor of vascular events, is found to be related with plaque phenotype.⁶

Eventually, increasing insight in pathophysiology of the vulnerable atherosclerotic plaque and upcoming imaging technology may shift focus to plaque markers in the search for the patient at risk. The observation that risk factors for cardiovascular events, like gender, are associated with atherosclerotic plaque characteristics support this idea.

References

1. Dick P, Sherif C, Sabeti S, Amighi J, Minar E, Schillinger M. Gender differences in outcome of conservatively treated patients with asymptomatic high grade carotid stenosis. Stroke. 2005; 36: 1178–1183.[Abstract/Free Full Text]
2. Verhoeven BA, Velema E, Schoneveld AH, de Vries JP, de BP, Seldenrijk CA, de Kleijn DP, Busser E, van der GY, Moll F, Pasterkamp G. Athero-express: differential atherosclerotic plaque expression of mRNA and protein in relation to cardiovascular events and patient characteristics. Rationale and design. Eur J Epidemiol. 2004; 19: 1127–1133.[CrossRef][Medline] [Order article via Infotrieve]
3. Van den Broek T, Velema E, Schoneveld AH, Busser E, de Vries JP, de Kleijn DPV, Moll F, Pasterkamp G. Risk factors for atherosclerosis and plaque phenotype. Eur Heart J. 2004; 25(Abstract Supplement): 102.
4. Stary HC, Chandler AB, Dinsmore RE, Fuster V, Glagov S, Insull W Jr, Rosenfeld ME, Schwartz CJ, Wagner WD, Wissler RW. A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Arterioscler Thromb Vasc Biol. 1995; 15: 1512–1531.[Abstract/Free Full Text]
5. Rittersma SZ, van der Wal AC, Koch KT, Piek JJ, Henriques JP, Mulder KJ, Ploegmakers JP, Meesterman M, de Winter RJ. Plaque instability frequently occurs days or weeks before occlusive coronary thrombosis: a pathological thrombectomy study in primary percutaneous coronary intervention. Circulation. 2005; 111: 1160–1165.[Abstract/Free Full Text]
6. Pasterkamp G, Schoneveld AH, van der Wal AC, Haudenschild CC, Clarijs RJ, Becker AE, Hillen B, Borst C. Relation of arterial geometry to luminal narrowing and histologic markers for plaque vulnerability: the remodeling paradox. J Am Coll Cardiol. 1998; 32: 655–662.[Abstract/Free Full Text]

This Article Full Text (PDF) All Versions of this Article: 37/2/332    most recent 01.STR.0000199846.58077.e9v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hellings, W. E. Articles by Pasterkamp, G. Search for Related Content PubMed PubMed Citation Articles by Hellings, W. E. Articles by Pasterkamp, G.