Angiographic Predictors of Vascular Complications Among Women Undergoing Cardiac Catheterization and Intervention


Bina Ahmed, MD, Stefan Lischke, MD, Leigh Ann Holterman BS, Faye Straight, RN, Harold L. Dauerman, MD

512 - 516

ABSTRACT: Background. Bleeding and vascular complications remain more common in women than men undergoing invasive cardiovascular procedures. We determined the role of femoral angiographic variables in risk-stratifying women for vascular complications. Methods. Between 2004–2009, all major bleeding and vascular complications among women undergoing diagnostic or interventional cardiovascular procedures were identified at a single center. Thirty consecutive female patients (major bleeding or vascular complication) were then age- and procedure-matched to 90 controls (no vascular complications). Quantitative femoral angiography was performed on all cases and controls. Results. Smaller minimum luminal diameter was a strong univariate predictor of vascular complications in women (odds ratio [OR] 0.65; 95% confidence interval [CI] 0.47–0.90; p = 0.009), while site of arteriotomy was not predictive of complications. The prognostic significance of smaller femoral lumen diameter was mildly attenuated after adjusting for the predictive factor of smaller patient body size, even after adjusting for the predictive factor of smaller patient body size. Finally, multivariable modeling suggests that utilization of vascular closure devices (OR 0.26, 95% CI 0.07–0.96; p = 0.04) may be protective in women. Conclusions. Women with smaller femoral arteries are at significantly higher risk for bleeding and vascular complications than women with larger femoral arteries. Risk stratification for bleeding complications among women should account for clinical, pharmacologic and femoral angiographic factors.

J INVASIVE CARDIOL 2010;22:512–516

Key words: women, bleeding complications, femoral artery

Over the last decade there have been significant improvements in bleeding and vascular complications (VC) among women undergoing cardiac catheterization.1 Several observational reports show that procedure-related improvements such as use of smaller sheaths, fluoroscopy-guided access to obtain “safe-zone” arteriotomy, and improved antithrombotic therapies have been associated with a 50% reduction in VC rates.2–5 However, when VC do occur, they continue to be associated with significant morbidity and mortality; procedure-related bleeding is among the strongest predictors of subsequent adverse cardiac events.6–9 A recent analysis of over 37,000 patients from the Northern New England Cardiovascular Database Registry continues to show a disturbing, and largely unexplained, adjusted 2.5 fold increase risk of VC in women compared to men undergoing percutaneous coronary intervention.1 One explanation for this persistent disparity in bleeding complications is a possible difference in femoral artery anatomy and access site suitability between the genders. While prior studies have demonstrated a difference in common femoral artery (CFA) diameters between men and women,10,11 the role of femoral angiographic variables in predicting bleeding and vascular complications specifically among women has not been studied. Accordingly, we sought to define angiographic predictors of bleeding and vascular complications in women undergoing cardiac catheterization and coronary intervention.


A case-control study was performed utilizing age and procedure (diagnostic only or percutaneous coronary intervention [PCI]) to match 30 women with VC (cases) to 90 women without VC (controls) and analyze the association of femoral angiographic variables with VC. Data were obtained from the University of Vermont’s interventional cardiology database for all women undergoing cardiac catheterization over a 5-year period (2004–2009). In addition to detailed data on demographics, medical history, laboratory, pharmacotherapy and procedure-related information, quantitative femoral angiographic analysis was performed by a single reviewer blinded to outcomes using an automated edge-detection software program (Philips Medical). VC was defined according to the Northern New England Cardiovascular Disease Study Group 1): hematoma > 6 cm, any access site related bleeding requiring transfusion or any injury requiring mechanical intervention. All VCs were confirmed using chart review to identify associated complications occurring during the index hospitalization. All patients underwent femoral angiography in an approximately 30-degree ipsilateral view. Quantitative femoral angiography was performed to determine the following variables: common femoral artery (CFA) reference vessel diameter; CFA minimum luminal diameter (MLD); CFA maximum stenosis; CFA length defined as distance from ostium of the inferior epigastric artery (IEA) to CFA bifurcation; anatomic site of arteriotomy (CFA, external iliac artery, profunda or superficial femoral artery). For patients with no visible femoral plaque, MLD and reference vessel diameter are the same. Safe-zone arteriotomy was defined angiographically as sheath insertion between the inferior border of the inferior epigastric artery and above the CFA bifurcation (Figure 1).12,13 Safe-zone length was defined as the distance between inferior border of IEA and the CFA bifurcation. High bifurcation was defined as CFA bifurcation above the inferior border of the femoral head.

Statistical analysis. Continuous variables are expressed as mean ± standard deviation and frequencies are expressed as percentages. Due to the multiple case-control matching ratio of 1 to 3, univariate and multivariate comparisons between cases and controls used conditional logistic regression methods. These univariate and multivariate methods were used to determine univariate predictors of VC as well as predictors for VC after adjusting for significant clinical differences between the cases and controls. To assess whether CFA minimum luminal diameter was an independent predictor of VC among women, multivariate analysis was performed incorporating clinical variables known to be associated with femoral dimensions (body mass index [BMI],11 as well as potentially confounding angiographic variables shown to be univariate predictors (high bifurcation anatomy). Given the prior description of safezone arteriotomy as protective against VC,12 safe-zone arteriotomy was also controlled for in this model. The multivariate analysis was then repeated incorporating vascular closure devices in order to understand the interaction between vessel size, closure devices and complications among women. All analyses were generated using SAS software, version 9.2 for Windows (SAS, Inc., Chicago, Illinois).


The mean age of the entire group was 66.5 ± 12.1 years. Approximately 30% of all patients had a high bifurcation of the CFA, and the mean CFA length was 37.86 ± 9.36 mm. VC in cases were clinically severe: 50% of cases had retroperitoneal bleeds, 50% required blood transfusion and 43% required mechanical intervention due to bleeding/vascular complications. When comparing cases and controls, women with VC had a significantly lower BMI compared to women without a VC (26.6 ± 6.7 vs. 31.2 ± 6.8; p = 0.002) and were more likely to present with ST-elevation myocardial infarction (STEMI) (24% vs. 8%; p = 0.05) (Table 1).

Creatinine clearance tended to be lower in women with complications. Women with VC were also more likely to receive glycoprotein IIb/IIIa inhibitors during PCI, whereas women without VC were more likely to receive bivalirudin during PCI. In addition, vascular closure devices were used more frequently in women without VC compared to women with VC (92% vs. 70%; p

Quantitative femoral angiography showed that women with VC had a smaller CFA reference vessel diameter (5.4 ± 1.2 mm vs. 5.9 ± 1.1 mm; p

The overall distribution of arteriotomy site location was similar between cases and controls: women with VCs were just as likely to have a safe-zone arteriotomy as women without VCs (77% vs. 77%; p = NS). Furthermore, among female cases specifically identified for retroperitoneal bleeding, three-quarters of those patients had a documented safe-zone arteriotomy.

In order to understand the potential interaction of patient size (BMI) on femoral angiographic variables, we performed a multivariate conditional logistic regression to analyze the influence of MLD on VC while controlling for BMI and two other potential angiographic predictors of VC (high bifurcation and lack of safe-zone arteriotomy). CFA MLD impact on risk of VC was mildly attenuated in this model (OR 0.69, C.I. 0.45–1.02; p = 0.06), while higher BMI remained a protective factor (OR. 0.90, 95% C.I 0.83–0.98; p = 0.03). High bifurcation and absence of a safe-zone arteriotomy were not independent predictors of VC in this model (Table 3). Finally, we explored the potential interaction of closure devices on VC among women. In a multivariate analysis controlling for both BMI and potential angiographic risk factors (MLD, high bifurcation and non-safe-zone arteriotomy), closure device utilization remained highly protective (OR 0.26, 95% CI 0.07–0.96; p = 0.04). In this model, higher BMI remained protective (0.91, 95% CI 0.84–0.99; p = 0.03), MLD impact was attenuated (OR 0.72, 95% CI 0.47–1.1; p = 0.17) and once again, safe-zone arteriotomy did not prove protective against VC (p = 0.44).


Our case-control study confirms that among women undergoing cardiac catheterization or coronary intervention, common femoral artery vessel size is inversely associated with a significant increased risk of VC: women with the smallest femoral artery MLD are three times more likely to have a VC than those with the largest femoral arteries. On the other hand, we found no clear relationship between site of arteriotomy and a propensity for VC in women.

To our knowledge, this is the first study to specifically evaluate the role of femoral anatomy as it relates to the incidence of bleeding and VCs among women. There is ample evidence of associations between clinical factors (gender, BMI, renal failure, diabetes, cardiogenic shock, peripheral vascular disease)4,5,12,14 and vascular/bleeding complications. Whether femoral artery anatomy contributes to the higher incidence of vascular complications in women remains understudied. With changes in contemporary practice resulting in overall reduction in vascular complication rates, we expected to see a narrowing of the gender gap; however this has not been observed and women remain at an increased risk of VC despite rigorous adjustment for clinical co-morbidities.1

Given that pharmacologic and procedural developments have been likely uniformly applied to men and women over the past decade, this persistent disparity leads to the hypothesis that there are intrinsic physiologic or anatomic differences that predispose women to bleeding and vascular complications.

Women and femoral artery size. One explanation for this enhanced risk is the smaller femoral artery size of women as compared to men.10,11 Our results confirm that women with VCs do indeed have smaller femoral arteries compared to women without VCs. Furthermore, CFA size is strongly inversely associated with the incidence of vascular complications among women. Although the relationship between CFA size and VCs was attenuated after adjusting for patient size, there remained a 31% decreased likelihood of vascular complications for every increase in 1 mm of femoral arterial size among women (p = 0.06).

Recently, Mehran et al devised a risk model utilizing seven clinical and procedural variables to categorize overall bleeding risk among patients undergoing cardiac catheterization.5 Angiographic variables may further enhance the ability to predict the risk of bleeding and VCs among women.

Safe-zone arteriotomy in women. Meticulous attention to femoral access technique has been hypothesized to decrease vascular complications: specifically, prior studies have associated arterial puncture within the common femoral artery safe zone as a strong predictor of reduced risk of VCs.10,12,15 In a quantitative angiographic study, arteriotomy outside of the safe zone led to 28-fold increased risk of VC and a strong association with the devastating complication of retroperitoneal bleeding.12 These prior studies were done predominantly in men: our data specifically derived from a female cohort do not support these conclusions. Approximately three-quarters of women with any VC, including retroperitoneal bleeding, had a safe-zone arteriotomy (exactly the same rate of safe puncture as for controls). Our findings suggest that a woman with back pain and hypotension after cardiac catheterization should be considered at risk for retroperitoneal bleeding, even if the femoral angiogram shows a good puncture; instead, a greater suspicion of a VC should be based upon presence of small femoral size, smaller BMI, potentially high bifurcation of the common femoral artery and known clinical risk factors for bleeding. These disparate findings with prior non-gender-specific registries may also highlight the need for specific analyses and trials in women.16

Women and vascular closure devices. Recent studies have suggested that vascular closure devices may be protective against VCs.2,3,14,17 In the Northern New England Registry study on women and VCs, closure devices were protective and associated with an independent 28% reduction in VCs.1 Our current data are concordant with those findings. All non-randomized data on vascular closure devices are limited by patient selection bias where patients with unsuitable femoral anatomy are less likely to receive a closure device. Unlike other registries that did not incorporate detailed femoral angiographic measurements, we were able to adjust for angiographic factors that may have resulted in a selection bias against closure device utilization (such as smaller femoral artery lumen diameters and site of arteriotomy), and still found closure device use to be strongly protective. Thus, suitability for a vascular closure device may be a protective factor for women and could be measured against other proven methods for reduction of bleeding complications in women (radial artery approach, bivalirudin).5,14,18

Study limitations. This case-control study is limited by its analysis of only 30 cases and 90 control patients, and thus is exploratory; it is not specifically powered to demonstrate a reduction of bleeding complications with safe-zone arteriotomy or other angiographic variables. Multivariate analysis was used to control for differences between cases and controls, but data may be confounded by persistent unmeasured differences, and thus our findings should be considered hypothesis-generating. On the other hand, the case-control design amplifies and extends findings from previous registries5,14 by providing detailed quantitative femoral angiographic information specific to women.


Among women undergoing cardiac catheterization and coronary intervention, angiographic variables play an important part in mediating the risk of bleeding and vascular complications. Femoral artery MLD is inversely related to access-site VCs; on the other hand, there was no relationship between site of arteriotomy and incidence of bleeding and VCs. These findings have important clinical implications regarding the further risk stratification of women for bleeding and VCs according to specific femoral angiographic findings.


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From the Division of Cardiology, University of Vermont, Burlington, Vermont.
Disclosures: Dr. Dauerman is a consultant to The Medicines Company, Abbott Vascular and Medtronic. Dr. Dauerman has received research grants from Abbott Vascular and Medtronic. All other authors have no relevant disclosures.
Manuscript submitted July 28, 2010, provisional acceptance given August 24, 2010, final version accepted August 27, 2010.
Address for correspondence: Harold L. Dauerman, MD, Division of Cardiology, McClure 1, University of Vermont/Fletcher Allen Health Care, 111 Colchester Avenue, Burlington VT 05401. E-mail:

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