Vascular Complications in Women: Why Can’t a Woman Be More Like a Man?

I have an idea that the phrase “weaker sex” was coined by some woman to disarm some man she was preparing to overwhelm. — Ogden Nash Vascular complications related to invasive and interventional procedures are disconcerting events, in part because they occur so unexpectedly and infrequently that their occurrence can seem nearly random. Clinical factors predictive of bleeding and other vascular problems are well known.^1,2 These include: age, female gender, elevated serum creatinine and decreased glomerular filtration rate, peripheral vascular disease, heart failure, acute coronary syndrome (ACS) type (ST-elevation myocardial infarction [STEMI], N-STEMI), cardiogenic shock and use of heparin and glycoprotein IIb/IIIa inhibitors. Age and female gender are the two variables that are most strongly predictive. The well-known connection between these two demographic factors in patients undergoing invasive procedures³ raises the question as to whether women are at increased risk because they are older or because they are female. Age adjustment and multivariate analysis1,^2,4–6 demonstrate that although women who undergo invasive procedures tend to be older than men, there is a robust, persistent, independent association of female gender with vascular events. Moreover, women who undergo invasive procedures more frequently present with STEMI³ and thus are exposed more often, and to more potent, combinations of antithrombotic agents. All of these factors interact and predispose women to an increased risk of vascular complications. In this issue of the Journal, Ahmed et al⁷ suggest a new variable that may be associated with vascular complications in women: the size of the femoral artery. The authors demonstrate that women with smaller femoral arteries are at significantly higher risk for bleeding and vascular complications than women with larger femoral arteries, independent of patient body size and site of arteriotomy. They also suggest that vascular devices are protective in this subgroup. Given that this is a single-center retrospective experience involving just 30 cases, the authors appropriately note that their observation is not definitive. The authors are to be congratulated on perhaps identifying a significant new factor. The proposition that smaller femoral arteries might predispose to vascular complications is provocative, but a consideration of the dimensions involved may not be sufficient to explain bleeding. The data show an average minimum lumen diameter of 4.59 mm in the complication group versus 5.43 mm in the control group, a mean difference of 0.84 mm. Thus, the relative difference in circumference is 14.4 mm vs. 17.0 mm, which in the context of a 6-French sheath with a diameter of 2.0 mm, may not be that clinically meaningful. Another consideration is the accuracy of dimensions measured by digitized angiography of the femoral vasculature: calibration is complicated by different angulations and depths of the reference catheter, especially on 9-inch magnification. An alternative way to explain their observation might be to consider the etiology of the smaller vessel size. The matching process employed evidently did not include body mass index (BMI), which was statistically significantly lower in the complication group. Further, although multivariate analysis did include BMI, this may not have adequately corrected for actual anthropometric differences in the elderly patient, whose body mass may be diminished by muscle loss, reduced body water and redistribution and reduction of fat mass with age.⁸ The mean BMI of 31.2 kg/m² in the control group suggests a rather overweight control population for this age group. Alternatively, the reduced vascular dimension in the complication group may be a reflection of peripheral vascular atherosclerosis, which may predispose to bleeding either independently, or as a consequence of the illnesses which caused it, such as diabetes, smoking and renal disease. The fact that reference-vessel diameter was similar in the two groups tends to support this explanation. Mechanical manipulation of hard plastic catheters in a diseased segment may cause vascular injury and endothelial disruption, increasing the risk of bleeding. It is not intuitively clear that the wound made by the femoral sheath in a smaller access artery would inevitably lead to more bleeding as long as the access site was in the safe zone. A consistent positional relationship between the femoral artery and the femoral head has been noted since the advent of catheterization, and fluoroscopy is recommended to help guide femoral artery access.⁹ A prospective study¹⁰ showed that access above the femoral bifurcation, but below the most inferior border of the inferior epigastric artery, was an independent predictor of fewer adverse vascular access-site complications beyond traditional risk factors. A prospective evaluation¹¹ of the use of fluoroscopy-guided femoral artery access was associated with a fourfold reduction in pseudoaneurysm formation and almost a twofold risk reduction in arterial injury, without a significant risk of bleeding or transfusion. Yet, this long-held tenet was not confirmed by the current data.⁷ Another observation made in the current study, which runs counter to prevailing thought, is that vascular closure devices (VCDs) appeared to have a favorable impact on preventing vascular complications. VCDs were highly protective (odds ratio 0.26), which may represent a selection bias in the use of vascular devices. Most large-scale studies show that VCDs either have a trend toward or a statistically increased incidence of complications compared to manual compression.^12–17 There is a higher incidence of retroperitoneal hematomas, large pseudoaneurysms, requirement for transfusion and surgical repair and late occlusion with VCD use. The opposite conclusion in this small group of patients versus matched controls in which manual compression led to a bleeding rate five times higher than that of the control group raises a question as to potential bias in the choice of closure strategies. Ascribing vascular complications in elderly women to a non-modifiable dimensional problem detracts from the very real concern of the potential role of pharmacologic adjuncts in producing bleeding in this population. Specifically, more frequent and aggressive use of anticoagulation was likely administered to the complication group. Elderly women have decreased renal function and body mass, rendering the Cockcroft-Gault equation inaccurate.³ Doses of most antithrombotic agents must be modified when creatinine clearance 18 and serum creatinine may be deceptively normal in such cases. The discrepancies between the series of Ahmed et al⁷ and prior studies regarding safe-zone arteriotomy, VCDs and selection bias to more aggressive and frequent adjunctive antithrombotic management may partially explain the findings of the study. Table 1 clearly shows that women with vascular complications had more STEMI presentations, received more glycoprotein platelet inhibitors and had lower baseline renal function. Although the authors attempted to match patients carefully, this may not have been successful, especially in light of the small sample size. In conclusion, female patients who undergo invasive procedures are different than their male counterparts, are older, smaller, more acutely ill, have worse renal function, receive more antithrombotic therapy at too-high doses and have more peripheral vascular disease. In other words, female gender is a covariate, or marker, for all of the significant factors which lead to bleeding, plus there is an independent effect as well. The nature of that effect may be that multivariate modeling cannot correct for the interaction of all of these clustering features, or there is an as-yet undetermined cause. Perhaps femoral artery dimension is an important consideration, and the study by Ahmed⁷ supports exploration of this concept in further studies. Biological differences due to gender are seldom explored vigorously by the medical community, in large part because of its political incorrectness. “Why can’t a woman be more like a man?” the Professor in Pygmalion wonders naively. But this is not the right question either for the catheterization laboratory or in life; instead, we should acknowledge the existence of such differences and ask why they exist and how they provide insights into the prevention of vascular complications. A better comprehension of what goes wrong in elderly women will guide new approaches for all patients. Knowing that there is an increased likelihood of complications of invasive procedures in women should not result in risk avoidance, but rather confirms the assertion “…that there is a pressing need to develop further therapies and adjuncts … to help fully eliminate the gender gap.”¹⁹

References

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———————————————————— From the Advocate Illinois Masonic Medical Center and Rush Medical College, Chicago, Illinois. The authors report no conflicts of interest regarding the content herein. Address for correspondence: Lloyd W Klein, MD, Cardiology Section, Advocate Illinois Medical Center, 3000 North Halsted, Suite #625, Chicago, IL 60614. E-mail: lloydklein@comcast.net