Author + information
- †Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts
- ‡Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts
- ↵∗Reprint requests and correspondence:
Dr. Joshua A. Beckman, Cardiovascular Division, Brigham & Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115.
Atherosclerosis is a systemic process with clinical manifestations primarily determined by the vascular territory involved. The 3 most common territories include coronary heart disease, cerebrovascular disease, and peripheral artery disease (PAD), with less common clinical sequelae due to involvement of the renal arteries, mesenteric vessels, and aorta. It is estimated that 8 to 10 million Americans have PAD. The prevalence of PAD is approximately 5% in persons age 40 to 50 years and 18% in those above 80 years (1). Despite the epidemic levels of PAD, the disease remains largely underdiagnosed and undertreated.
Currently, there are 2 major obstacles that impede the diagnosis of PAD. First, the most straightforward, reliable, and inexpensive study for the identification of PAD—the ankle-brachial index (ABI)—is not a covered service for patients who are asymptomatic. Compounding this issue is the fact that the majority of patients with PAD do not manifest leg pain, which would be more readily identified by clinicians and would meet criteria for reimbursement for ABI-based evaluation. The fact that the ABI is not covered for the assessment of asymptomatic patients largely reflects the recommendations developed by the United States Preventive Services Task Force. Screening services given an “A” or “B” rating by the task force are usually covered by Medicare, whereas those with indeterminate or lower ratings are not covered, as a result of the Affordable Care Act. PAD remains underdiagnosed, represents a large segment of patients who do not receive adequate risk-lowering treatment (2), and has an accurate diagnostic test (ABI) (3) that adds as much information to the 5 Framingham risk factors in risk prediction as adding high-density lipoprotein to the other 4 risk factors (4,5). Despite the fact there is now a medication approved for PAD (vorapaxar) that will not be prescribed in the absence of diagnosis, the determination of the United States Preventive Services Task Force not to reimburse the use of ABI represents an enormous obstacle to the identification, treatment, and reduction of death and disability of patients with PAD.
A second significant obstacle to the diagnosis of PAD is the fact that most patients do not present with “typical” claudication symptoms readily recognized by health care professionals. PAD is commonly categorized by symptom status. Although nearly one-half of those with PAD are asymptomatic, the remaining one-half have symptoms ranging from intermittent claudication, where muscular ischemic pain develops following a predictable amount of exertion, to critical limb ischemia, where risk of amputation may be significant unless revascularization is pursued. Most patients with symptomatic PAD, however, have symptoms that defy the classic description of claudication. McDermott et al. (6) have reported that atypical symptoms are far more prevalent than classic, predictable ischemic muscular burning or aching on exertion that dissipates with a predictable amount of rest. Instead, patients may experience pain that develops with exercise but does not force them to stop walking; pain that does not have the typical quality of muscular ischemia but does stop them from walking; leg pain that occurs both with exertion and at rest; or, no leg pain, but a very low functional status (i.e., walking fewer than 6 blocks/week). Additional studies by McDermott (7) have demonstrated that patients with PAD have a lower level of physical activity, are functionally impaired, and decline at a faster rate than those without PAD. Even patients with “asymptomatic” PAD have diminished functional capacity, as measured by the inability to walk a quarter mile or climb stairs without assistance (7). Similarly, even in the setting of leg pain associated with activity, the symptoms do not commonly match those classically described in textbooks. Inadequate recognition of the true manifestations of PAD may, therefore, consign patients with undiagnosed disease to worsened cardiovascular and limb outcomes. One difficult question, once the diagnosis of PAD is made, is which patient would be likely to need revascularization? It is in this space that Hammad et al. (8) have added to our understanding.
In this issue of JACC: Cardiovascular Interventions, Hammad et al. (8) report a single-center retrospective database analysis of 2,791 consecutive patients who underwent exercise ABI. Patients were divided into 4 groups: normal resting ankle-brachial index (NR) and normal post-exercise ankle-brachial index (NE), NR and abnormal post-exercise ankle-brachial index (AE), abnormal resting (AR) and NE, and AR/AE. The incidence of lower extremity revascularization, major adverse cardiovascular events (MACE), and all-cause mortality were compared between each of the 4 groups.
The authors identified that, compared with individuals with NR/NE ABI, those with NR/AE had a higher incidence of revascularization but no difference in MACE or all-cause mortality. Among patients with abnormal resting ABI, those with abnormal post-exercise ABI (AR/AE) were also more likely to undergo revascularization than were those with normal post-exercise ABI (AR/NE), but they also had no statistical difference in MACE or all-cause mortality. Of note, AR/AE did confer a significantly higher risk of MACE than NR/NE (hazard ratio: 1.44, 95% confidence interval: 1.09 to 1.90, p = 0.009) and a trend toward increased all-cause mortality.
The findings of this study demonstrate that revascularization strategies were used significantly more often in patients with abnormal post-exercise ABI, and therefore with more severe, flow-limiting PAD. The retrospective nature of the study, however, does not permit the comparison of patient symptomatic status to the physiological severity of disease (measured ABI) or to the operator’s propensity to pursue revascularization. Moreover, the study design does not permit evaluation of whether asymptomatic patients were treated with revascularization, and—if so—at what ABI or post-exercise ABI threshold. Because symptom, limb-specific, and physiological outcomes were not available, conclusions regarding the best practice for revascularization versus exercise therapy are not feasible.
The examination of the effect of post-exercise ABI on prognosis in this study reinforces findings from prior evaluations in this field. Sheikh et al. (9) identified that an abnormal post-exercise ABI was a robust, independent predictor of all-cause mortality in the context of normal resting ABI. Diehm et al. (10) examined the getABI study database of 6,468 patients and concluded that the finding of an abnormal post-exercise ABI did not provide additional prognostic information to that derived from an abnormal resting ABI.
In addition to the data concerning revascularization, it is interesting to note that patients with a normal resting ABI did not have an increased risk of cardiovascular events, independent of the effects of exercise on ankle pressure. This provides confirmatory data concerning the risk of cardiovascular events in patients with PAD; the current definition is a reasonable place to increase risk factor modification to reduce cardiovascular morbidity and mortality. Clinical trials that have permitted looser entry criteria have found no benefit with the addition of antiplatelet therapy (11). Yet, it also reconfirms the value of the resting ABI as a screening tool and the imperative to provide it as a 1-time screening opportunity to patients in the Medicare cohort. We know that the current system leaves many patients undiagnosed and undertreated. Using the National Health and Nutrition Survey, Pande et al. (2) studied patients with PAD but not established cardiac disease and showed that 81% did not take statins, 73% did not take antiplatelet agents, and 79% took neither an angiotensin receptor blocker or angiotensin-converting enzyme inhibitor. In fact, more than one-half of the subjects were taking no preventive therapies at all! In comparison, those subjects taking 2 or more preventive therapies had a 65% reduction in mortality.
The findings presented by Hammad et al. (8) reflect the outcome of a single-center retrospective study, and are therefore subject to the expected design related limitations: patient selection bias, patient follow-up out of network, and the fundamental question of whether the test of interest (exercise ABI) supports the use of revascularization, the primary endpoint of the study. Despite these limitations, Hammad et al. (8) have provided us with important insight regarding patient prognosis and selection for revascularization. More data, however, would help develop an algorithm for a broader array of therapies. If the study had examined the effect of exercise therapy, alone or in conjunction with revascularization, so that the benefits of the each therapy could be evaluated on the basis of patient clinical presentation, the findings would represent an even greater leap forward for clinician insight and patient-centered care.
↵∗ Editorials published in JACC: Cardiovascular Interventions reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Interventions or the American College of Cardiology.
Dr. Drachman serves on the advisory board of Abbott Vascular, Inc.; and has received research grant support from Atrium Medical Corporation and Lutonix/Bard. Dr. Beckman has served as a consultant for Bristol-Myers Squibb, Merck, Novartis, and AstraZeneca; has received an investigation grant from BMS; and is on the board of VIVA physicians.
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