Sex Differences in 1-Year Outcomes After Percutaneous Coronary Intervention in the Veterans Health Administration

Introduction

Cardiovascular disease is the leading cause of death in the United States accounting for over 610,000 deaths each year. ¹ Despite the belief that heart disease is a “man's disease,” a similar number of women and men die annually from heart disease in the United States. ¹ However, women and men experience cardiovascular disease very differently, with sex differences in certain risk factors, clinical symptoms, presentation for evaluation, and referral for appropriate cardiovascular treatment. ^{2 –6} Moreover, compared to men, women have lower utilization of evidence-based treatments for cardiovascular disease and lower quality of care, especially younger women. ^{7 –11}

Percutaneous coronary intervention (PCI), or coronary angioplasty, is a nonsurgical procedure for treating obstructive coronary artery disease (CAD, including unstable angina, acute MI, and multivessel CAD). Over the last few decades, advancements in PCI have reduced inhospital and long-term major adverse cardiovascular events (MACE) and mortality in patients undergoing coronary interventions. ^12,13 However, evidence on sex differences in outcomes after PCI has been mixed ^{14 –19} and chiefly relies on studies based on local or regional samples or multisite registries rather than national samples or population-based data.

The Veterans Health Administration (VA) healthcare system is the largest national healthcare delivery system in the United States, with electronic medical record data and a cardiac catheterization laboratory clinical quality program called the VA Clinical Assessment Reporting and Tracking (CART) Program, ²⁰ which is capable of elucidating sex differences in PCI outcomes on a national scale. As the leading cause of hospitalization for Veterans, ²¹ cardiovascular disease is a serious issue for the VA. Veterans are at higher risk of heart disease than the general population with their risk compounded by their increased prevalence of comorbidities linked with cardiovascular disease, including diabetes, spinal cord injury, and posttraumatic stress disorder (PTSD). ^21,22

With the twofold increase in the population of women Veterans utilizing VA services in the last decade alone, ²³ the VA has made a concentrated effort to identify gender disparities in quality of care. In the VA, both women and men patients use any outpatient VA and primary care services comparably, but women Veterans tend to use more services than men: in FY12, women Veterans were more likely to be frequent users (six of more) and heavy users (12 or more) of outpatient VA care across all age groups, were more likely to be heavy users of primary care (six or more primary care visits), were more likely to use mental health or substance use disorder services, and were twice as likely to have utilized at least one day of non-VA (fee) medical care than men Veterans. ^23,24 Prior research has shown that women Veterans have more risk factors for cardiovascular disease, including higher low-density lipoprotein (LDL) cholesterol levels than Veteran men after adjustments for age. ²⁵ They also have higher rates for military sexual trauma, which is associated with a higher risk for PTSD, depression, and anxiety. ²⁶ In terms of treatment, a prior study demonstrated that women Veterans undergoing diagnostic cardiac catheterization at the VA had lower rates of obstructive CAD than men Veterans and had lower 1-year mortality and all-cause rehospitalization rates. ²⁷ However, whether women with obstructive CAD after PCI have similar outcomes to men with obstructive CAD is unknown.

The aim of this study was to examine sex differences in 1-year major adverse cardiac outcomes in a national population of patients undergoing PCI at VA facilities by assessing sex differences in 1-year postprocedural outcomes, including rehospitalization for myocardial infarction (MI), all-cause mortality, and MACE. This research advances the current literature by (1) capturing a population of all PCI patients in a national medical care system; (2) including patients with significant comorbidities; and (3) including a younger female population presenting with cardiovascular risks, a population that has been historically understudied due to limited inclusion in research. ³ Because women Veterans are at increased risk and utilize VA services differently than their male counterparts, ^23,24 we hypothesized that men and women Veterans had different outcomes after PCI.

Materials and Methods

Results

The study population consisted of 64,757 Veterans who underwent PCI during the study period, including 1,040 women (1.6%). Patient characteristics at time of procedure are shown in Table 1 by sex. Female Veterans were younger than male Veterans (median age 60 vs. 64 years, respectively; p < 0.0001), more likely to be black (23% vs. 12%; p < 0.0001), obese (52% vs. 48%; p < 0.007), and have chronic depression (53% vs. 36%; p < 0.0001). Female Veterans were less likely to have common cardiovascular risk factors such as hypertension (88% vs. 91%; p = 0.0012) and hyperlipidemia (86% vs. 91%; p < 0.0001). For cholesterol, females had higher median overall cholesterol (186.0 vs. 162.3; p < 0.0001) and higher median LDL (105.5 vs. 90.6; p < 0.0001), but they also had higher median high-density lipoprotein (HDL 43.3 vs. 37.0; p < 0.0001) than the males. They also had significantly lower Framingham risk scores: only 8% were high risk compared to 29% of men (p < 0.0001). Furthermore, female Veterans were less likely to have cardiovascular disease such as CHF (21% vs. 25%; p = 0.0041), PAD (20% vs. 24%; p = 0.0011), prior MI (33% vs. 38%; p = 0.0009), and prior coronary artery bypass grafting (CABG; 18% vs. 29%; p < 0.0001) compared to male Veterans. For PCI indication, female Veterans were more likely to present with ACS, whereas male Veterans were more likely to present with stable angina and unknown/other reasons. There were no significant sex differences in tobacco use and diabetes.

One-year post-PCI outcomes in the overall population are shown in Table 2. Rates for rehospitalization for MI were 2.1% for females and 2.5% for males (p-value = 0.57). Mortality was 3.5% for females and 4.9% for males (p-value = 0.14), and MACE was 5.4% for females and 6.9% for males (p-value = 0.18). There were no significant sex differences in the base Cox proportional hazards models (model 1, sex and age only; results not shown) for any of the outcomes, and sex remained nonsignificant in all adjusted Cox proportional hazards models (model 4 shown on Table 3).

Discussion

The objective of this study was to examine sex differences in 1-year major adverse cardiovascular outcomes, including mortality for the national population of patients undergoing PCI at VA cardiac catheterization laboratories. We found no significant sex differences in 1-year post-PCI outcomes for this national population: women and men treated at VA cardiac catheterization laboratories experienced comparable rates of rehospitalization for MI, mortality, and MACE one year post-PCI. There were no sex differences even before adjusting for Framingham risk, race, obesity, other cardiovascular diagnoses (CHF, CAD, PAD, and COPD), and indication for PCI indicating that although the men tended to be sicker and at higher risk on most cardiovascular indicators at presentation for PCI than women, both groups still experienced similar outcomes. Our results are consistent with the prior studies showing that men and women experience similar 1-year post-PCI mortality, ^{16,37 –39} MI, ³⁷ and MACE; ³⁷ however, unlike the prior literature, we found no significant differences in outcomes by sex even before adjusting for sex differences in risk.

This research is one of the first studies of sex differences and PCI on a national population of patients in a healthcare system, including 1-year mortality, MI, and MACE. Unlike prior studies, where women were older and estrogen protection over the years may have been a factor in delaying the onset of cardiovascular disease, ^{16,37 –42} the women in our study were younger on average than the men. Yet, we still found no significant sex differences. Consistent with prior research, ^{16,37 –40,42} women were more likely to have some comorbidities (i.e., depression and obesity) than the men, yet lower rates of prior cardiac events or traditional cardiac risk factors. Veterans have on average two more comorbidities than the general population ^43,44 and have higher rates of depression and other mental health conditions. ⁴⁵ Therefore, the Veteran population undergoing PCI was considerably sicker than cohorts in prior studies, yet comparable outcomes by sex remained.

Much of the inconsistency in the literature on sex differences in outcomes after PCI has focused on short-term outcomes showing women at increased risk for some complications ^{14 –19,37,46} and similar outcomes for others. ^{14,16,38,40,47} Perhaps contemporary improvements in PCI ^12,13 have alleviated previously seen gender differences in short-term MACE and mortality outcomes post-PCI. At the VA specifically, there may be more equitable use of bleeding avoidance strategies and other therapies, which were previously shown to be used less often with female patients in other cohorts, ¹⁵ thus leading to more equitable outcomes. Another possibility is that women who survive the early complications of PCI have a survival advantage in the long term. Given that two studies with even longer term outcomes (30–36 months) found similar risk for MI ⁴⁸ and actual lower risk of mortality for women, ^40,48 future research should focus on the full spectrum of the cardiovascular healing process post-PCI that spans from inhospital complications through multiyear follow-up.

Our findings support comparable treatment outcomes for women and men Veterans post-PCI; however, our data were limited to those patients seen in the cardiac laboratory for PCI and cannot address any sex/gender-related referral bias. Because past research has demonstrated sex differences in diagnosis and referral for noninvasive testing in the general population, ³ additional research is needed to evaluate referral patterns and timing to the cardiac procedures. Examinations of these patterns over time can also examine whether delays in presentation to emergency departments have changed for women and men with increased public education and awareness campaigns such as the American Heart Association's Go Red for Women. ⁴⁹ As many cardiac emergencies are treated at the closest emergency room, which may or may not be VA, the focus on VA cardiac catheterization laboratories could have led to underreporting of events that were treated outside the VA and not recorded in the VA electronic medical record. Even though the CART data capture all procedures done outside of the VA that are paid for by the VA (fee basis files), future work should focus on understanding dual treatment both inside and outside the VA healthcare system. Finally, even though our analyses combined multiple years of national VA data and included over 1,000 women Veterans, the number of women Veterans undergoing PCI and experiencing postprocedural outcomes compared to men was small. This sample size restricted the number of covariates and interaction terms we could include in the final multivariable risk models, and we may have been underpowered to detect differences in the outcomes examined, particularly rehospitalization for MI. However, our estimates suggest that there are no clinically meaningful differences in these outcomes by sex. As the population of women Veterans continues to increase, there is an opportunity to continue to monitor sex differences in PCI outcomes.

Conclusions

The results are consistent with work from United States and international registries while expanding the broader literature to demonstrate similar 1-year post-PCI mortality, MI, and MACE rates for men and women in a national population of patients who are sicker and have more mental health issues than the general population. Despite the presence of these factors that usually reduce access to definitive care, we found no sex differences in outcomes: women and men Veterans experience similar post-PCI 1-year major adverse cardiac outcomes. Although the number of women Veterans at the VA has more than doubled in the last decade, ²³ women are still a numerical minority at the VA. Given that the populations of men and women Veteran are different, especially in terms of age, race, cardiovascular risk factors, and indication for PCI, future research should examine interactive effects on sex and these factors in this growing population.