Peripheral Arterial Disease in Women

The past decade has led to significant and exciting advances in the evaluation and treatment of cardiovascular disease. Peripheral arterial disease (PAD), in particular, has received increased attention due to national awareness programs such as PARTNERS (PAD Awareness Risk and Treatment: New Resources for Survival) and to advances in minimally invasive techniques to treat symptomatic patients. Still, sex-based differences have a significant impact on access to care, diagnosis, and treatment.

A clinical vignette illustrates the case in point. A 50-year-old woman with a history of tobacco use presented with progressive exertional right-lower-extremity pain. She was diagnosed and treated initially for a presumed radiculopathy, by her primary care physician. After 3 years, her symptoms progressed to pain at rest and a computed tomographic angiogram revealed severe aortoiliac disease (Fig. 1). This was treated successfully via an endovascular approach (Fig. 2). She was also found to have coronary artery disease with severe stenosis of her left circumflex and right coronary arteries, which was also treated percutaneously. Gender bias likely led to a misdiagnosis due to the expectation that a relatively young woman was more likely to have a radicular process than PAD.

Fig. 1 Computed tomographic angiography shows occlusion of the right common iliac artery. The left common iliac artery was also found to have severe disease. A Lap-Band® esophageal device (Allergan, Inc.; Irvine, Calif) is seen incidentally in the image.

Fig. 2 A) Digital subtraction angiography of the abdominal aorta and iliac arteries shows occlusion of the right common iliac artery and severe stenosis of the proximal left common iliac artery. B) Angiography after aortoiliac reconstruction with “kissing” stents shows resolution of the stenosis.

Data from 6,880 patients in 344 primary care clinics suggest that the prevalence of peripheral vascular disease in women is lower than in men before the age of 70, approaches that of men after the age of 80, and becomes higher than in men after the age of 85.¹ In the PARTNERS program, the prevalence of PAD in at-risk individuals (both men and women) seen in primary care practices was 29% of those aged 70 or older and of those aged 50 to 69 who had a history of tobacco use or diabetes mellitus. The risk factors for PAD in men and women are similar: smoking and diabetes mellitus, in particular, are powerful predictors of disease progression and outcome.² In addition, an evaluation of biomarkers in women found that the risk of incident symptomatic peripheral vascular disease could be predicted from baseline levels of soluble intercellular adhesion molecule-1 (sICAM-1), high-sensitivity C-reactive protein, high-density-lipoprotein cholesterol (HDL-C), and total cholesterol–HDL-C ratio.³

As illustrated by the clinical vignette, a high degree of clinical suspicion is important in the evaluation of women with lower-extremity PAD, because over 80% of such patients are asymptomatic or have atypical leg pain.² In a population of older, disabled women, as many as two thirds of individuals with PAD had no exertional leg symptoms.⁴ Of interest is the finding that women have a lower calf-muscle hemoglobin oxygen saturation in response to exercise, which contributes to lower absolute claudication distance. This finding correlates with the ankle–brachial index (ABI).⁵ The ABI—a simple, bedside, office-based test—has a high sensitivity and specificity for the diagnosis of lower-extremity arterial disease and provides important prognostic information. Patients who have ABIs of less than 0.9 or higher than 1.3 have a higher cardiovascular-event rate and all-cause death rate.⁶ Symptomatic status is also an important predictor of outcomes in patients who present with critical limb ischemia, for they have a 6-month mortality rate of 20%.⁷

Aggressive risk-factor modification is essential to reduce the risk of such cardiovascular events as myocardial infarction and stroke. Antiplatelet therapy with clopidogrel has been shown to reduce the incidence of ischemic events. The HMG-CoA reductase inhibitors carry a Class I indication, and angiotensin-converting enzyme (ACE) inhibitors carry a Class II indication in the American College of Cardiology/American Heart Association peripheral vascular disease guidelines. Despite this, aspirin, statins, and ACE inhibitors are infrequently prescribed upon discharge of patients hospitalized for peripheral vascular surgery, in comparison with those hospitalized for cardiovascular surgery.⁸ This is particularly true in women, who are less likely to receive antiplatelet, lipid-lowering, and β-blocker therapy in the presence of either peripheral or cardiovascular disease.^9,10

The treatment options for vascular disease are similar for both sexes; however, women are less often offered surgical revascularization. The reasons for this are incompletely understood. Later age at disease onset, smaller vessel size, worse surgical outcomes with both surgical and endovascular therapy, and psychosocial factors have been proposed to contribute to these differences. Despite similar surgical outcomes with carotid endarterectomy, women have been offered surgery less often in every age group studied, which indicates that reasons beyond age and surgical risk are in play.¹¹

A large retrospective review from 3 state databases—involving 372,692 inpatient discharges after lower-extremity revascularization—revealed that women were more likely to present with advanced peripheral vascular disease. Women also had higher mortality rates with open surgical procedures. This trend was accentuated in women who had preexisting cerebrovascular disease. In addition, the complication rates from open surgical procedures—in particular, the rates of perioperative in-fection and perioperative bleeding—were higher in women.¹²

Further research is needed to explain disparities in care, such as the causes behind delay in treatment. Which clinical variables are associated with poor outcomes in women? Which social barriers affect access? Then too, advances in technology may help decrease procedural morbidity rates in women.