XX and Risky Business

There is extensive literature demonstrating a disturbingly higher mortality rate, intraprocedural coronary artery injury rate and periprocedural vascular complication rate in women versus men. The disparity has been partially explained by more comorbid disease, older age, smaller size and higher prevalence of hypertension, diabetes, peripheral vascular disease and more severe angina at presentation. Furthermore, it has been suggested that smaller vessel diameters associated with smaller body size have been a driving force for the observed higher rates of both coronary and entry-site vascular complications.^1,2 Data from our own institution have substantiated a gender difference in outcomes in terms of coronary vascular injury and bleeding complications for both the pre-stent era and more recently in a contemporary patient cohort.^3,4 However, it appears that the higher complication rates seen in women are not consistently accounted for by coronary artery size and other patient characteristics previously thought to represent risk factors for complications. ^2,5–7 The persistence of gender differences in bleeding risk and vascular complications after adjustment for historically identified risk-factors suggests that this excess is the result of inherent sex differences and a yet unidentified gender-related biologic factor.^8–10

In this issue of the Journal, Applegate et al report their experience of vascular complications following cardiac catheterization (cath) and percutaneous coronary intervention (PCI) procedures in women and men.¹¹ In this large, single-center experience spanning 8 years, overall vascular complication rates were low, but once again rates were higher in women. The trend was observed for both diagnostic cath and PCI, suggesting that the disparity is not explained by anticoagulant dosing miscalculation or inaccuracy. While intuitive and historically recognized predictors of vascular complications were indeed independently associated with increased risk of vascular complications in both groups, these were present at similar frequency in both genders. The authors meticulously adjusted for baseline and procedural confounders, and once again implicate gender as a powerful predictor of vascular complications. Body surface area did not have an association with a higher risk of complications as the literature would lead one to believe. Even more interesting is the observation that overall rates of vascular complications more than halved during the 8 years of the study, with the largest decline occurring during the first 2 years of the study and a more gradual decline thereafter. While this makes one wonder if this represents the departure of a technically challenged operator, it is unlikely since the overall rates of complications are low and in keeping with prior studies. The authors do identify three variables that potentially account for the overall decrease in vascular complications in women during the course of the study: less frequent closure device failure, smaller sheath size and increase in body surface area (BSA) over the study period. It is not clear whether these variables applied to men to explain their similar decrease in vascular complications over the course of the study period. The decline in vascular complications with the particularly abrupt early change raises the question of whether awareness of the fact that data for this study were prospectively being collected impacted operator attention to pre- and postprocedural access site management. Nevertheless, the significantly higher incidence of vascular complications for women relative to men persisted except for the years 2002 and 2005, with rates being lower (although not significantly so) for women in the final year. One might wonder if knowledge of the fact that the study group of particular interest was women caused exceptionally meticulous attention to groin management in this group, leading to fewer complications as the study progressed.

A prospectively collected database of this size is an invaluable tool for identification of trends and further hypothesis generation. There are a few points not mentioned in this article that would be essential tools for this purpose. While not part of the study design, this information might be particularly useful in pursuing the elusive entity of increased complications in women. For instance, the authors mention that vascular closure devices were used in about one-third of patients in both groups, and that the decision to use one was at the discretion of the cardiologist and based on a preclosure femoral angiogram. What is not mentioned is whether there was a temporal trend in the use of vascular closure devices that may have paralleled the trend in a decreased incidence of vascular complications. While not the focus of this analysis, data on such a large group of patients may provide some insight as to whether closure devices are playing a role in reducing complications. Conceivably, there could have been less vascular closure device use at their center (perhaps after the introduction of closure patches in 2003 for manual compression) with a parallel decrease in vascular complications. This certainly would be data worthy of analyzing retrospectively.

While we are provided with data regarding the odds ratios for any major and minor vascular complications, we are not given the breakdown of each category of complication. Based on historical data, it is reasonable to assume that the majority of complications, and therefore the complication that most dramatically declined over the study period, was bleeding. However, it would be helpful to be able to associate specific complications with those variables presumed to reduce the incidence of complications. For example, is the only benefit of smaller sheath size and larger BSA that of less bleeding, or was the largest impact that of fewer femoral artery dissections or occlusions? Is a larger BSA associated with fewer vascular occlusive complications suggesting a protective role of larger habitus, or does larger BSA lead to more bleeding, suggesting difficulty with hemostasis in larger individuals? Furthermore, in addition to BSA, data related to body mass index (BMI) would allow for further hypothesis generation. BSA may be a surrogate of vessel size, but BMI gives the reader a better idea of the body habitus of patients encountering complications. This, combined with type of complication, may even tell us that obesity is protective from occlusion or loss of pulse, but predictive of bleeding. For now, we are left to speculate.

A last piece of data that would be useful, but may not have been collected in this study design, is information on late complications during the week or two following cath/PCI. Vascular access-site evaluation was performed prior to discharge. It would be intriguing to see if the lower rates of complications in both groups held true with longer follow up. In a contemporary experience such as this, earlier discharge following such procedures may have allowed some complications to go unrecorded. While one would expect the vast majority of vascular complications to be evident within the first 24 hours following the procedure, there may be an undetected incidence known only to the primary care doctors or other care-givers not associated with the study.

Overall, this study confirms what we know about increased vascular complications in women relative to men, but demonstrates it in a contemporary population. As the authors point out, this lends support to the concept of an intrinsic biologic risk for such complications. Perhaps the additional information suggested above would unmask some other contributor, but the underlying mechanism for this phenomenon remains elusive. In this study, the general trend towards lower rates of vascular complications in both men and women with a closure of the gender gap as time went on may be the best take-home lesson. Perhaps we all should adopt standard practices of vascular access management (as in the authors’ institution) for similar results and worry about the mechanism of disparity after the disparity has been resolved.

References

1. Peterson ED, Lansky AJ, Kramer J, et al. Effect of gender on the outcomes of contemporary percutaneous coronary intervention. Am J Cardiol 2001;88:359–364.

2. Schunkert H, Harrell L, Palacios IF. Implications of small reference vessel diameter in patients undergoing percutaneous coronary revascularization. J Am Coll Cardiol 1999;34:40-48.

3. Weintraub WS, Wenger NK, Kosinski AS, et al. Percutaneous transluminal coronary angioplasty in women compared with men. J Am Coll Cardiol 1994;24:81–90.

4. Argulian E, Patel AD, Abramson JL, et al. Gender differences in short-term cardiovascular outcomes after percutaneous coronary interventions. Am J Cardiol 2006;98:48–53.

5. Arnold AM, Mick MJ, Piedmonte MR, Simpfendorfer C. Gender differences for coronary angioplasty. Am J Cardiol 1994;74:18–21.

6. Watanabe CT, Maynard C, Ritchie JL. Comparison of short-term outcomes following coronary artery stenting in men versus women. Am J Cardiol 2001;88:848–852.

7. Cho L, Topol EJ, Balog C, et al. Clinical benefit of glycoprotein IIb/IIIa blockade with abciximab is independent of gender: Pooled analysis from EPIC, EPILOG and EPISTENT Trials. J Am Coll Cardiol 2000;36:381–386.

8. Jacobs AK. Coronary revascularization in women in 2003: Sex revisited. Circulation 2003;107:375–377.

9. Tavris DR, Gallauresi B, Lin B, et al. Risk of local adverse events following cardiac catheterization by hemostasis device use and gender. J Invasive Cardiol 2004;16:459–464.

10. Glaser R, Herrmann HC. Safety of vascular closure devices-are women different? J Invasive Cardiol 2004;16:464–465.

11. Applegate RJ, Sacrinty MT, Kutcher MA, et al. Vascular complications in women after cath and percutaneous coronary intervention 1998–2005. J Invasive Cardiol 2007;19:369–374.