Peripheral arterial disease (PAD) in women is an under-recognized, understudied, and undertreated disorder. The magnitude of this problem can be realized from the fact that 21% to 67% of documented symptoms or diagnoses upon admission in nursing home residents are consistent with PAD.¹ Nearly 75% to 90% of nursing home residents are women, aged 65 years or older. PAD may therefore be a large contributor to disability in this population. Adding to the problem is the fact that 48% of women aged 65 to 75 years live alone, without readily available, adequate support at home, potentially resulting in the need for an extended care facility. Therefore, it seems it would be in society’s best interest, in terms of costs and disability, to prevent, identify, treat, and better study PAD in women.

Women are obviously different from men in terms of anatomy and physiology, but may also differ in terms of clinical presentation of disease states and response to treatment. In general, women tend to have smaller, less-compliant arteries, which may translate into the need for different devices and techniques to treat PAD. Even though less is known about the natural history of PAD in women, none can argue about the disability that it can cause across the genders. Cardiovascular disease is the number 1 cause of death in women and a recent survey showed only 50% of respondents understood this to be true.²

Women tend to be underrepresented in clinical studies, but it is unclear if lower prevalence of some subtypes of PAD contributes to this or if there is a true bias against including women. There are few studies aimed at PAD in women alone and fewer that perform significant subgroup analyses of PAD in women. We have yet to elicit whether there is a difference in vascular biology between the genders and whether women react differently to various treatments for vascular disease than men. There may be questions raised if physicians treat women with vascular disease differently than men. Herein, we will review the 3 major subtypes of PAD: carotid atherosclerotic disease (Figure 11-1), lower extremity arterial disease, and aneurysmal disease, specifically in women, with respect to biology, treatment, and outcome.

It may prove important to determine the difference between the genders in regards to carotid artery anatomy and physiology. In general, there are differences in carotid artery diameter between women and men from the age 25 years and onward.³ Both genders, however, experience an increase in diameter as well as a decrease in compliance with age, which most likely contributes to the increased formation of atherosclerotic lesions later in life. In fact, a reduced compliance in women aged 45 to 60 years has been found when compared with men aged 60 to 70 years. Likewise, enlargement of carotid artery diameter with advancing age is less marked in women than in men. These underlying anatomic differences may make women more vulnerable to increased arterial injury and hence, they may respond differently to traditional treatment therapies. It is unclear if there also exists a hemodynamic difference in women’s arterial flow, which may also contribute to gender differences.

Different plaque composition may contribute to the tendency of a lesion to become symptomatic. Histological examinations of surgical specimen of women have suggested that women may possess more fibrous plaque, making it more stable than the more lipid-laden plaque of men⁴ (Figure 11-2). MRI examination of plaque also demonstrated that men may possess a thinner or ruptured fibrous cap, have a higher degree of lipid in the core, and experience more subplaque hemorrhage than women⁵ (Figure 11-3). In addition to these findings, women may have a lower concentration of inflammatory cells.⁶ This may help explain the higher incidence of stroke in men <75 years, as these characteristics may be associated with symptomatic lesions.

In addition to vascular biology, differences may exist between the genders in terms of treatment outcome of carotid artery disease. Several large randomized, controlled trials have suggested this to be the case for both symptomatic and asymptomatic patients.^7,8,9,10 Women, in general, were found to have a higher operative risk for carotid endarterectomy (CEA) (Figure 11-4), but a lower risk from medical treatment, making some question the benefit of CEA in women. However, women tended to be underrepresented in these studies.

Data is conflicting as to whether women actually undergo CEA at a lower rate than men with similar degree of stenosis and symptomotology.^11,12,13,14 Since the randomized controlled studies cited previously in which women were not specifically studied, several large population studies, retrospective reviews, and database analyses have examined the role of gender in the outcomes after CEA in women versus men. These have shown that CEA can be safely performed in women without significant differences in perioperative stroke and mortality rates.^15,16,17,18 Long-term outcomes, including recurrence rates, were also found to be similar; therefore, the net benefit after CEA in women was found to be equivalent to men, whether symptomatic or asymptomatic. In fact, the typical longer life expectancy of women was maintained after CEA, supporting surgical management of carotid artery disease as an established treatment modality for women.¹⁹ Truly, it is difficult to say if women are actually treated differently than men in clinical practice.

With the advent of carotid artery stenting (CAS) (Figure 11-5), there may be questions raised regarding the utility of this procedure in women who naturally have smaller, less-compliant arteries. In general, women as a subgroup were underrepresented in most of the large CAS trials.^20,21,22 In general, similar perioperative stroke rates after CAS were found in women and men, suggesting stenting to be a viable alternative to CEA in women. Other single-center series suggest the short-term complication rate, as well as long-term outcome after CAS, including restenosis, to be similar between men and women.^23,24 One might question whether stenting might turn out to be better suited for women, in order to avoid manipulating a small vessel and suturing it directly, with the concomitant trauma. Certainly, appropriately sized and designed stents for women may eventually yield better outcomes as well.

In 2005, the US Preventative Task Force recommended that men aged 65 to 75, who have ever smoked, undergo a screening aortic duplex for abdominal aortic aneurysm (AAA) (Figure 11-6) upon entry into the Medicare program.²⁵ The Task Force recommended against primary aortic aneurysm screening for women. This recommendation was based on the decreased prevalence of AAA in women versus men and the theoretical increased risk to women undergoing such screening, who might sustain psychological injury or undergo increased number of surgeries with concomitant risks. These recommendations were based on only 4 studies outside of the United States and women were underrepresented in all of them. Any psychological side effects were found to be short lived.²⁶ Certainly, the prevalence of AAA in women is less than men, but the associations with smoking, age, and family history are similar.²⁷ Women also tended to have higher associated cerebrovascular disease prevalence. When screening women with multiple other atherosclerotic risk factors, the prevalence of AAA increased significantly, implying that routine AAA screening in women at risk seems justifiable, based on prevalence in this group.²⁸

A higher percentage of women compared to men present with ruptured AAA,²⁹ and these aneurysms tend to rupture aortas in these women tend to rupture at a smaller size than men. In many studies, the 30-day and in-hospital mortality for women is significantly higher than men.^30,31 This may also be related to women being older at the time of presentation than men, with the concomitant increased comorbidities that often come with age.³² These differences would also support the routine screening for AAA in women at risk; despite the lower prevalence, the increased morbidity and mortality for women specifically justifies identifying the problem in order to decrease the complications and other implications for society.

Modern AAA management involves offering patients open and/or endovascular repair (EVAR) (Figures 11-7 and 11-8). It has been found that endovascular AAA (Figure 11-9) repair lowers the complication rate and 30-day mortality for all-comers over open AAA repair. It is typically preferred by the patients because it results in a shortened hospital stay and recuperation period. Unfortunately, a lower proportion of women than men undergo endovascular repair.^33,34 Many factors may contribute to this discrepancy, including shorter, more angled aneurysm necks just below the renal arteries, where proximal fixation of an endograft is based (Figure 11-10). Women also tend to have smaller diameter iliac arteries with more calcification (Figure 11-11), which may prevent the introduction of a large bore endograft through a smaller access site and into the aorta without trauma to the vessels traversed (Figure 11-12). More EVARs are aborted in women than in men³⁵ and there is a higher intraoperative complication rate, often related to the need for iliac reconstruction after injury.³⁶ Despite potential intraoperative challenges, women and men have been found to have similar perioperative morbidity and mortality rates, supporting EVAR as a viable therapy for AAA in women.