EDITORIAL COMMENT
What's Good for the Gander Is Now Good for the Goose*
Robert F. Wilson, MD* and
Ganesh Raveendran, MD, FACC
Cardiovascular Division of the University of Minnesota, Minneapolis, Minnesota.
* Reprint requests and correspondence: Dr. Robert F. Wilson, MMC 508, 420 Delaware Street SE, Minneapolis, Minnesota 55455. (Email: wilso008{at}umn.edu).
Gender differences in the application of revascularization were noted soon after bypass surgery and percutaneous coronary intervention (PCI) were developed. In the early experience, revascularization of either type appeared to be less frequently applied to women. Furthermore, when used, the results generally were not as good in women as those found in men. Two questions surround these empirical observations. First, is the gender gap real or a product of differences in comorbidities and age? Second, if there is a true gender-based difference in the application and results of revascularization, is it rooted in irrational bias or good medicine?
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Is There a Gender Difference in the Application of PCI?
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Lower utilization of PCI in women has been well-documented and persists to the current era. Women with acute coronary syndromes enrolled in the Swiss National registry from 1999 to 2006, after adjusting for other covariables, were 30% less likely to undergo PCI than their male counterparts (1). In 1999, French women presenting with ST-segment elevation myocardial infarction were 35% less likely to undergo PCI (2).
Maybe that difference in use of PCI was justified by a worse outcome from PCI in women. In the National Heart, Lung, and Blood Institute (NHLBI) registry 2 decades ago, women had 6-fold higher procedure-related mortality, and, if they needed emergency coronary artery bypass grafting, the death risk was 5-fold. Coronary dissection and acute in-procedure coronary closure was more common in women (3). Older age and additional comorbid conditions were identified as the contributing factors for these poor outcomes (4–6). A report from the Swiss National registry also concluded that female patients had higher unadjusted in-hospital mortality (3.0% vs. 4.2%) after PCI. In subgroup analysis, women <50 years of age have much worse outcomes compared with men (odds ratio 2.94), whereas female patients over age 70 years had similar outcomes (1).
Thus, there does appear to be a gender-based difference in the application of PCI and its outcome, at least in younger women, and the problem lay, in part, on procedure-based complications.
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Has the Revascularization Gap Narrowed?
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The study by Singh et al. (7) in this issue of the Journal describes an interesting reversal of the gender gap at the Mayo Clinic. There, the gender gap narrowed significantly in the last 25 years, primarily because the results in women have gotten much better.
Procedural success was similar between genders in both the early and recent era groups. Mortality in women for the 30 days after PCI, however, fell from 4.4% in the early period to 2.9% in the recent era. In men, the corresponding reduction in mortality was much less (2.8% to 2.2%). As in the NHLBI registry, women undergoing PCI at Mayo were older, had more severe symptoms of coronary artery disease, more heart failure, and more frequent presentation with acute coronary syndrome. Like the data presented from the Swiss National registry, the gender gap at Mayo narrowed with advancing age.
Similar reductions in the complications of PCI in women have been reported. In contrast to the 1985 to 1986 NHLBI registry, the PCI mortality was the same between men and women during the recent Dynamic NHLBI registry. Likewise, in northern New England, the incidence of emergency bypass surgery and myocardial infarction after PCI fell in the decade of the 1990s (8). Combined with the present study from Mayo, the data suggest that men and women now have fairly similar adjusted outcome from PCI.
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Why Was There a Gender Gap in Revascularization Outcome?
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Patient selection has been suggested as a reason for worse PCI outcomes in women, and the incidence of PCI in Olmsted County Minnesota, home to the Mayo Clinic, is markedly lower in women than in men (469.5 vs. 211.1 of 100,000 population) (9). The Mayo group, however, did an excellent job in analyzing the influence of patient selection on outcome and found that it did not account for the relative change in mortality in women.
One may be tempted to ascribe the last decade's improvement in PCI mortality for women to the recent improvements in preventative drug therapy such as early statin use and more effective platelet antagonists. Although this might account for a portion of the improvement, men appear to be beneficiaries of the same treatment, yet their mortality has not changed as much.
A number of procedural-based explanations for inferior PCI results in women have been set forth. The first is that women have smaller arteries (10). Coronary dimension is an important predictor of restenosis after PCI and outcome after bypass surgery. In one study, women undergoing bypass surgery had a higher rate of mortality (3.3% vs. 7.1%) compared with that seen in men, and the odds ratio for mortality by midleft anterior descending coronary artery luminal diameter (<2.5 vs. >2.5 mm) was 8.59 (11).
Stenting produces a more consistent acute result with a larger lumen and is an effective treatment of PCI-related coronary dissection, reducing the need for emergency bypass surgery. For women, who had a higher incidence of PCI-related coronary dissection in the early balloon angioplasty era (NHLBI), stenting might be particularly important. Moreover, it is noteworthy that the improvements in women's outcome in the Mayo report, the New England registry, and the NHLBI registry were coincident with the introduction of stenting as the primary PCI method. This suggests that stenting might be the primary reason for outcome improvement in women.
Better procedural management of anticoagulation might also have improved outcome for women. Women are at higher risk for hemorrhage after PCI, and the use of periprocedural anticoagulation has improved significantly over that last decade. It is possible that a portion of the risk reduction for women is also related, in part, to less periprocedural bleeding. Bleeding confers a significantly higher risk of death after PCI (12).
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Is the Gender Gap Bad (for Women)?
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Finally, it is ironic that in the current era of questioning the effect of PCI on overall patient outcome we still discuss the relative underutilization of PCI in women as something to be overcome. In the majority of reports, women more often undergo PCI for unstable angina and class 3 or 4 angina. These are "harder" indications where the available data suggest better efficacy of the procedure. Maybe we are focusing too much on how women are treated and not enough on overtreatment in men.
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Footnotes
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* Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology. 
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References
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1. Radovanovic D, Erne P, Urban P, Bertel O, Rickli H, Gaspoz JM, AMIS Plus Investigators Gender differences in management and outcomes in patients with acute coronary syndromes: results on 20,290 patients from the AMIS Plus registry Heart 2007;93:1369-1375.[Abstract/Free Full Text]2. Milcent C, Dormont B, Durand-Zaleski I, Steg PG. Gender differences in hospital mortality and use of percutaneous coronary intervention in acute myocardial infarction: microsimulation analysis of the 1999 nationwide French hospitals database Circulation 2007;115:833-839.[Abstract/Free Full Text] 3. Cowley MJ, Mullin SM, Kelsey SF, et al. Sex differences in early and long-term results of coronary angioplasty in the NHLBI PTCA registry Circulation 1985;71:90-97.[Abstract/Free Full Text] 4. Jacobs AK, Johnston JM, Haviland A, et al. Improved outcomes for women undergoing contemporary percutaneous coronary intervention: a report from the National Heart, Lung, and Blood Institute Dynamic registry J Am Coll Cardiol 2002;39:1608-1614.[Abstract/Free Full Text] 5. Kelsey SF, James M, Holubkov AL, Holubkov R, Cowley MJ, Detre KM. Results of percutaneous transluminal coronary angioplasty in women. 1985–1986 National Heart, Lung, and Blood Institute's Coronary Angioplasty registry. Circulation 1993;87:720-727.[Abstract/Free Full Text] 6. Maynard C, Every NR, Martin JS, Kudenchuk PJ, Weaver WD. Association of gender and survival in patients with acute myocardial infarction Arch Intern Med 1997;157:1379-1384.[Abstract/Free Full Text] 7. Singh M, Rihal CS, Gersh BJ, et al. Mortality differences between men and women after percutaneous coronary interventions: 25-year, single-center experience J Am Coll Cardiol 2008;51:2313-2320.[Abstract/Free Full Text] 8. Malenka DJ, Wennberg DE, Quinton HA, et al. Gender-related changes in the practice and outcomes of percutaneous coronary interventions in northern New England from 1994 to 1999 J Am Coll Cardiol 2002;40:2092-2101.[Abstract/Free Full Text] 9. Gerber Y, Rihal CS, Sundt 3rd TM, et al. Coronary revascularization in the community: a population-based study, 1990 to 2004 J Am Coll Cardiol 2007;50:1223-1229.[Abstract/Free Full Text] 10. Dodge JT, Brown BG, Bolson EL, Dodge HT. Lumen diameter of normal human coronary arteries: influence of age, sex, anatomic variation, and left ventricular hypertrophy or dilation Circulation 1992;86:232-246.[Abstract/Free Full Text] 11. O'Connor GT, Morton JR, Diehl MJ, et al. Differences between men and women in hospital mortality associated with coronary artery bypass graft surgery Circulation 1993;88:2104-2110.[Abstract/Free Full Text] 12. Kinnaird TD, Stabile E, Mintz GS, et al. Incidence, predictors, and prognostic implications of bleeding and blood transfusion following percutaneous coronary interventions Am J Cardiol 2003;92:930-935.[CrossRef][Web of Science][Medline]
Related Article
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Mortality Differences Between Men and Women After Percutaneous Coronary Interventions: A 25-Year, Single-Center Experience
- Mandeep Singh, Charanjit S. Rihal, Bernard J. Gersh, Veronique L. Roger, Malcolm R. Bell, Ryan J. Lennon, Amir Lerman, and David R. Holmes, Jr
J. Am. Coll. Cardiol. 2008 51: 2313-2320.
[Abstract]
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