Vascular Complications in Women after Catheterization and Percutaneous Coronary Intervention 1998–2005

Women have been shown historically to have a greater risk of complications than men following invasive procedures.^1–5 The increased incidence of complications in women appears to occur independently of other factors known to influence the incidence of complications after invasive procedures.^6–8 Moreover, in the past several years, multiple reports have indicated that women also experience a higher incidence of vascular complications after cardiac catheterization (CATH) and percutaneous coronary interventional (PCI) procedures.^9–14 Whether heightened awareness of the increased risk of invasive cardiac procedures in women or practice changes such as smaller sheath size have affected the gender risk of vascular complications is unknown. We hypothesized that the increased risk of vascular complication in women previously observed would be eliminated in an analysis of more contemporary outcomes. Accordingly, we evaluated the riskadjusted rate of vascular complications after CATH and PCI procedures in men and women in a large cohort of patients spanning the past 8 years.

Methods

All patients at our institution undergoing percutaneous CATH and coronary revascularization using the femoral artery approach were evaluated for this study, which was approved by our institutional review board. Only patients with missing data were excluded. A total of 20,654 patients undergoing 31,035 CATH and PCI procedures using the femoral approach between January 1998 and December 2005 form the basis for this study.

Diagnostic CATH was performed using 4–6 Fr catheters using standard techniques. Anticoagulation after sheath insertion for PCI patients was obtained using unfractionated heparin or bivalirudin following standard guidelines for use. The intensity of anticoagulation with heparin was similar throughout the entire study period. Patients in the study received glycoprotein (GP) IIb/IIIa receptor inhibition also according to usual protocol with abciximab or eptifibatide.¹⁵ Post-PCI patients were treated with aspirin (81–325 mg/day) and clopidogrel (300–600 mg as a loading dose followed by 75 mg/day) if stents were placed.

Femoral artery access management. The method of arterial access management was chosen by the cardiologist performing the procedure. Manual compression was performed by standard techniques. Beginning in 2003, closure patches were introduced and used in conjunction with all manual compressions.¹⁶ Access-site closure was performed using a variety of vascular closure devices at the discretion of the cardiologist performing the procedure after reviewing a femoral angiogram to determine suitability for closure. Ambulation was initiated 2–3 hours after a vascular closure device or closure patch was placed and 6 hours following manual compression.¹⁷

Femoral access site evaluation was routinely made postprocedure and prior to discharge by the medical team caring for the patient. The presence of vascular complications was recorded in the chart. Prior to hospital discharge, the patient’s chart was evaluated by a clinical research nurse.¹⁷ Data collection and outcomes measures conformed to the ACC database definitions for vascular complications.¹⁸ Minor vascular complications were defined as any of the following:hematoma > 10 cm, arteriovenous fistulae or pseudoaneurysm. Major vascular complications were defined as: death due to vascular complications, vascular repair, major vascular bleeding (> 3 gm Hgb drop due to access site bleeding or retroperitoneal bleeding), vessel occlusion or loss of pulse.¹⁸

Statistical methods. Descriptive statistics (means and standard deviation of continuous factors, frequency counts and relative frequencies of categorical factors) were calculated and compared for statistical significance using the Wilcoxon rank sum test for continuous factors and chi-square testing for categorical factors. Annual trends of vascular complications were tested by the Cochran-Armitage trend test. Univariate associations between selected covariates and vascular complications were examined using the Wald chi-square test. Initially, logistic regression modeling was used to assess multivariate predictors of vascular complications using generalized estimating equations to account for repeated measures.¹⁹ All potentially significant (p < 0.10) univariate predictors of vascular complications were considered for selection in the multivariate models. All previously known clinically significant independent predictors of vascular complications (i.e., sheath size) were retained in all models. Other nonsignificant variables (p > 0.05) were removed stepwise until all remaining covariates were either clinically or statistically significant predictors of outcome. SAS, version 9.1 statistical software package (SAS Institute, Cary, North Carolina) was used for all statistical analysis.

Results

A total of 18,467 diagnostic cardiac catheterization procures were performed, including 7,922 in women and 10,545 in men. A total of 12,568 PCIs were performed, including 4,194 in women and 8,374 in men. The baseline clinical and procedural covariates by gender are shown in Table 1. Statistical differences in baseline characteristics included a higher body surface area and incidence of smoking in men and a higher incidence of diabetes and hypertension in women, although only the difference in body surface area may be clinically meaningful. Procedural covariates were in general clinically similar for men and women. Access site management was similar in women and men with vascular closure device use in approximately one-third of both groups.

For the entire study period, any vascular complication, major vascular complications and minor vascular complications were infrequent, but occurred more often in women than men: 2.0% vs. 1.0%, 1.2% vs. 0.4%, and 1.3% vs. 0.8%, respectively, all p < 0.05 (Table 2). Similar trends were observed for both diagnostic cardiac catheterization and for PCI. The unadjusted odds ratio for any vascular complication in women compared to men for all procedures was 2.03 (1.68–2.46), 2.69 (2.04–3.53) for major vascular complica-tions and 1.79 (1.43–2.25) for minor vascular complications.

Predictors of vascular complications. For the entire study population over the entire study period, female gender was one of the strongest independent predictors of an increased risk of vascular complications. Other factors that were independent predictors of increased vascular complications included closure device failure, history of renal failure, peripheral vascular disease, sheath size, age and procedure type (PCI) (Figure 1). Similar results were observed for PCI and CATH procedures. Independent predictors of vascular complications are shown for both men and women in Figure 2. Closure device failure, history of renal failure, peripheral vascular disease, sheath size and age were all associated with an independent increased risk of vascular complication in men. Qualitatively similar results were observed for women.

Temporal trends in the incidence of vascular complications. The incidence of any vascular complications for women and men by year of procedure and procedure type is plotted in Figure 3. The incidence of vascular complications was significantly higher for women than men in all years of the study except for 2002 and 2005. However, the incidence of vascular complications decreased significantly over the course of the study; p < 0.001 for trend, both for men and women. The outcomes for women were qualitatively and quantitatively similar for both CATH and PCI procedures.

To examine potential reasons for the decrease in vascular complications observed during the course of the study, we evaluated the relative frequency of the risk factors shown to affect the risk of vascular complications from the multivariate regression model. In 2005, compared to 1998, closure device failure and sheath size decreased, and BSA increased in women — all of which would be associated with a lower risk of vascular complications in women in 2005 compared to 1998 (Figure 4). We also compared the odds ratio of any vascular complication in women compared to men for each year of the study before and after adjusting for the distributionand effect of confounding variables identified in the multivariate regression analysis. For all procedures in 1998, the unadjusted odds ratio of any vascular complication for women compared to men was 1.84 (1.22–2.77), and the adjusted odds ratio was 1.58 (0.90–2.77). In 2005, the unadjusted odds ratio was 1.65 (0.75–3.62), and the adjusted odds ratio was 0.97 (0.33–2.87).

Discussion

In this large, contemporary, single-center experience spanning 8 years, the incidence of vascular complications including both minor and major types after cardiac catheterization and PCI procedures was higher in women compared to men. This gender difference persisted after adjusting for baseline and procedural confounders, with female gender emerging as one of the strongest independent predictor of any vascular complication in the study. However, we also observed that the incidence of vascular complications in women decreased over the course of the study. This appeared to be the result of the use of smaller sheath sizes and fewer closure device failures over the course of the study period. However, the relative risk of vascular complications in women compared to men remained increased over the time period of the study, except in the last year of the study. These observations provide strong evidence that the risk of vascular complications following CATH and PCI procedures in women has been substantially lowered using current techniques of catheterization, although the increased risk of vascular complications in women compared to men has not been convincingly eliminated.

The increased risk of complications for women undergoing cardiac procedures including PCI compared to men has been extensively studied.^1–4,6,7 Most previous studies observed an increase in complications in women compared to men, although this has not been a universal finding. These studies have also noted that factors which may independently influence the risk of complications are seen more often in women than men. Thus, the increase in the propensity for vascular complications seen in women likely represents both an intrinsic bio-logic risk as well as a relative increase in the distribution of adverse covariates.^8,20,21 Our observations support this concept as adjusting for predictors of vascular complications reduced, but did not entirely eliminate, the risk of vascular complications in women compared to men over the course of the study.

The largest report of vascular complications to date (166,200 patients with 53,655 devices), the ACC-NCDR (registry), reported a higher incidence of vascular complications in women compared to men in the year 2001, with a two-fold increase in the risk of any vascular complication for women compared to men.¹² These findings were extended in a subsequent report of vascular complications in the fourth quarter of 2003, where women were found to have a multivariate adjusted odds ratio of any vascular complication of 1.73 (1.38–2.17) compared to men after cardiac catheterization.^13,14 In their final multivariate model, sheath size and renal failure were also independently predictive of increased vascular complications, whereas age, race and body mass index were not predictive factors.

Several factors impacted the relative risk of vascular complications in women in this study. First, the year in which the procedure was performed had a substantial effect on the incidence of vascular complications. There was a significant decrease in the overall incidence of vascular complications as well as a decrease in the relative risk of vascular complications in women compared to men over the course of the study. This appears to be a particularly strong effect in the subgroup of patients undergoing cardiac catheterization. Second, throughout the duration of the study, sheath sizes used for both CATH and PCI procedures became smaller. This appeared to translate into fewer vascular complications. Other factors not evaluated in the study such as better patient selection and greater operator and institutional experience in vascular access management may have affected the incidence of vascular complications. Successful vascular hemostasis with a vascular closure device did improve over the course of the study, suggesting that greater experience may have translated into better outcomes. However, further studies will need to be evaluated to more precisely define the role of operator and institutional experience in reducing vascular complications following cardiac procedures.

Study Limitations

This study is subject to the limitations of observational studies. Reporting biases because of variations in clinical follow up may have influenced the apparent lower incidence of vascular complications, but are unlikely to have biased the results in favor of one gender over another.

Acknowledgements. We gratefully acknowledge Tammy Davis for manuscript preparation, and Aruna Joel, Sabrina Smith and Robin Taylor for data collection and database entry.

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