- Email: [email protected]
The Exercise Ankle-Brachial Index
JACC: CARDIOVASCULAR INTERVENTIONS
VOL. 8, NO. 9, 2015
ª 2015 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER INC.
ISSN 1936-8798/$36.00 http://dx.doi.org/10.1016/j.jcin.2015.06.006
EDITORIAL COMMENT
The Exercise Ankle-Brachial Index A Leap Forward in Noninvasive Diagnosis and Prognosis* Douglas E. Drachman, MD,y Joshua A. Beckman, MDz
A
therosclerosis is a systemic process with clin-
usually covered by Medicare, whereas those with
ical manifestations primarily determined by
indeterminate or lower ratings are not covered, as
the vascular territory involved. The 3 most
a result of the Affordable Care Act. PAD remains
common territories include coronary heart disease,
underdiagnosed, represents a large segment of pa-
cerebrovascular disease, and peripheral artery dis-
tients who do not receive adequate risk-lowering
ease (PAD), with less common clinical sequelae due
treatment (2), and has an accurate diagnostic test
to involvement of the renal arteries, mesenteric ves-
(ABI) (3) that adds as much information to the 5 Fra-
sels, and aorta. It is estimated that 8 to 10 million
mingham risk factors in risk prediction as adding high-
Americans have PAD. The prevalence of PAD is
density lipoprotein to the other 4 risk factors (4,5).
approximately 5% in persons age 40 to 50 years and
Despite the fact there is now a medication approved
18% in those above 80 years (1). Despite the epidemic
for PAD (vorapaxar) that will not be prescribed in the
levels of PAD, the disease remains largely underdiag-
absence of diagnosis, the determination of the United
nosed and undertreated.
States Preventive Services Task Force not to reim-
Currently, there are 2 major obstacles that impede
burse the use of ABI represents an enormous obstacle
the diagnosis of PAD. First, the most straightforward,
to the identification, treatment, and reduction of
reliable, and inexpensive study for the identification
death and disability of patients with PAD.
of PAD—the ankle-brachial index (ABI)—is not a
A second significant obstacle to the diagnosis of
covered service for patients who are asymptomatic.
PAD is the fact that most patients do not present with
Compounding this issue is the fact that the majority of
“typical” claudication symptoms readily recognized
patients with PAD do not manifest leg pain, which
by health care professionals. PAD is commonly cate-
would be more readily identified by clinicians and
gorized by symptom status. Although nearly one-half
would meet criteria for reimbursement for ABI-based
of those with PAD are asymptomatic, the remaining
evaluation. The fact that the ABI is not covered for
one-half have symptoms ranging from intermittent
the assessment of asymptomatic patients largely re-
claudication, where muscular ischemic pain develops
flects the recommendations developed by the United
following a predictable amount of exertion, to critical
States Preventive Services Task Force. Screening ser-
limb ischemia, where risk of amputation may be sig-
vices given an “A” or “B” rating by the task force are
nificant 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
*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. From the yCardiology Division, Massachusetts General Hospital, Boston, Massachusetts; and the zCardiovascular Division, Brigham and Women’s
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
Hospital, Boston, Massachusetts. Dr. Drachman serves on the advisory
that develops with exercise but does not force them
board of Abbott Vascular, Inc.; and has received research grant support
to stop walking; pain that does not have the typical
from Atrium Medical Corporation and Lutonix/Bard. Dr. Beckman has
quality of muscular ischemia but does stop them
served as a consultant for Bristol-Myers Squibb, Merck, Novartis, and AstraZeneca; has received an investigation grant from BMS; and is on the
from walking; leg pain that occurs both with exertion
board of VIVA physicians.
and at rest; or, no leg pain, but a very low functional
1246
Drachman and Beckman
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 8, NO. 9, 2015 AUGUST 17, 2015:1245–7
ABI and Revascularization
status (i.e., walking fewer than 6 blocks/week).
does not permit evaluation of whether asymptomatic
Additional studies by McDermott (7) have demon-
patients were treated with revascularization, and—if
strated that patients with PAD have a lower level of
so—at what ABI or post-exercise ABI threshold.
physical activity, are functionally impaired, and
Because symptom, limb-specific, and physiological
decline at a faster rate than those without PAD. Even
outcomes were not available, conclusions regarding
patients with “asymptomatic” PAD have diminished
the best practice for revascularization versus exercise
functional capacity, as measured by the inability to
therapy are not feasible.
walk a quarter mile or climb stairs without assistance
The examination of the effect of post-exercise ABI
(7). Similarly, even in the setting of leg pain associ-
on prognosis in this study reinforces findings from
ated with activity, the symptoms do not commonly
prior evaluations in this field. Sheikh et al. (9) identi-
match those classically described in textbooks. Inad-
fied that an abnormal post-exercise ABI was a robust,
equate recognition of the true manifestations of PAD
independent predictor of all-cause mortality in the
may, therefore, consign patients with undiagnosed
context of normal resting ABI. Diehm et al. (10)
disease to worsened cardiovascular and limb out-
examined the getABI study database of 6,468 pa-
comes. One difficult question, once the diagnosis of
tients and concluded that the finding of an abnormal
PAD is made, is which patient would be likely to need
post-exercise ABI did not provide additional prog-
revascularization? It is in this space that Hammad
nostic information to that derived from an abnormal
et al. (8) have added to our understanding.
resting ABI.
SEE PAGE 1238
In addition to the data concerning revascularization, it is interesting to note that patients with a
In this issue of JACC: Cardiovascular Interventions,
normal resting ABI did not have an increased risk of
Hammad et al. (8) report a single-center retrospective
cardiovascular events, independent of the effects of
database analysis of 2,791 consecutive patients who
exercise on ankle pressure. This provides confirma-
underwent exercise ABI. Patients were divided into
tory data concerning the risk of cardiovascular events
4 groups: normal resting ankle-brachial index (NR)
in patients with PAD; the current definition is a
and normal post-exercise ankle-brachial index (NE),
reasonable place to increase risk factor modification to
NR and abnormal post-exercise ankle-brachial index
reduce cardiovascular morbidity and mortality. Clin-
(AE), abnormal resting (AR) and NE, and AR/AE.
ical trials that have permitted looser entry criteria
The incidence of lower extremity revascularization,
have found no benefit with the addition of antiplatelet
major adverse cardiovascular events (MACE), and
therapy (11). Yet, it also reconfirms the value of the
all-cause mortality were compared between each of
resting ABI as a screening tool and the imperative to
the 4 groups.
provide it as a 1-time screening opportunity to pa-
The authors identified that, compared with in-
tients in the Medicare cohort. We know that the cur-
dividuals with NR/NE ABI, those with NR/AE had a
rent system leaves many patients undiagnosed and
higher incidence of revascularization but no differ-
undertreated. Using the National Health and Nutrition
ence in MACE or all-cause mortality. Among patients
Survey, Pande et al. (2) studied patients with PAD but
with abnormal resting ABI, those with abnormal post-
not established cardiac disease and showed that 81%
exercise ABI (AR/AE) were also more likely to undergo
did not take statins, 73% did not take antiplatelet
revascularization than were those with normal post-
agents, and 79% took neither an angiotensin receptor
exercise ABI (AR/NE), but they also had no statisti-
blocker or angiotensin-converting enzyme inhibitor.
cal difference in MACE or all-cause mortality. Of note,
In fact, more than one-half of the subjects were taking
AR/AE did confer a significantly higher risk of MACE
no preventive therapies at all! In comparison, those
than NR/NE (hazard ratio: 1.44, 95% confidence in-
subjects taking 2 or more preventive therapies had a
terval: 1.09 to 1.90, p ¼ 0.009) and a trend toward
65% reduction in mortality.
increased all-cause mortality.
The findings presented by Hammad et al. (8) reflect
The findings of this study demonstrate that
the outcome of a single-center retrospective study,
revascularization strategies were used significantly
and are therefore subject to the expected design
more often in patients with abnormal post-exercise
related limitations: patient selection bias, patient
ABI, and therefore with more severe, flow-limiting
follow-up out of network, and the fundamental
PAD. The retrospective nature of the study, however,
question of whether the test of interest (exercise ABI)
does not permit the comparison of patient symptom-
supports the use of revascularization, the primary
atic status to the physiological severity of disease
endpoint of the study. Despite these limitations,
(measured ABI) or to the operator’s propensity to
Hammad et al. (8) have provided us with important
pursue revascularization. Moreover, the study design
insight regarding patient prognosis and selection
Drachman and Beckman
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 8, NO. 9, 2015 AUGUST 17, 2015:1245–7
ABI and Revascularization
for revascularization. More data, however, would
even greater leap forward for clinician insight and
help develop an algorithm for a broader array of
patient-centered care.
therapies. If the study had examined the effect of exercise therapy, alone or in conjunction with
REPRINT REQUESTS AND CORRESPONDENCE: Dr.
revascularization, so that the benefits of the each
Joshua A. Beckman, Cardiovascular Division, Brigham
therapy could be evaluated on the basis of patient
& Women’s Hospital, 75 Francis Street, Boston, Mas-
clinical presentation, the findings would represent an
sachusetts 02115. E-mail: [email protected].
REFERENCES 1. Fowkes FG, Rudan D, Rudan I, et al. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet 2013;382: 1329–40. 2. Pande RL, Perlstein TS, Beckman JA, Creager MA. Secondary prevention and mortality in peripheral artery disease: National Health and Nutrition Examination Study, 1999 to 2004. Circulation 2011;124:17–23. 3. Aboyans V, Criqui MH, Abraham P, et al. Measurement and interpretation of the anklebrachial index: a scientific statement from the American Heart Association. Circulation 2012;
calculations to measure usefulness of new biomarkers. Stat Med 2011;30:11–21.
on lower extremity revascularization. J Am Coll Cardiol Intv 2015;8:1238–44.
5. Lin JS, Olson CM, Johnson ES, Whitlock EP. The
9. Sheikh MA, Bhatt DL, Li J, Lin S, Bartholomew JR. Usefulness of postexercise ankle-brachial index to predict all-cause mortality. Am J Cardiol 2011;107:
ankle-brachial index for peripheral artery disease screening and cardiovascular disease prediction among asymptomatic adults: a systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med 2013;159:333–41. 6. McDermott MM, Greenland P, Liu K, et al. Leg symptoms in peripheral arterial disease: associated clinical characteristics and functional impairment. JAMA 2001;286:1599–606. 7. McDermott MM. Functional impairment in peripheral artery disease and how to improve it in
126:2890–909.
2013. Curr Cardiol Rep 2013;15:347.
4. Pencina MJ, D’Agostino RB Sr., Steyerberg EW. Extensions of net reclassification improvement
8. Hammad TA, Strefling JA, Zellers PR, et al. The effect of post-exercise ankle-brachial index
778–82. 10. Diehm C, Darius H, Pittrow D, et al. Prognostic value of a low post-exercise ankle brachial index as assessed by primary care physicians. Atherosclerosis 2011;214:364–72. 11. Fowkes FG, Price JF, Stewart MC, et al. Aspirin for prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial. JAMA 2010;303:841–8.
KEY WORDS ankle brachial index, exercise, peripheral artery disease
1247
VOL. 8, NO. 9, 2015
ª 2015 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER INC.
ISSN 1936-8798/$36.00 http://dx.doi.org/10.1016/j.jcin.2015.06.006
EDITORIAL COMMENT
The Exercise Ankle-Brachial Index A Leap Forward in Noninvasive Diagnosis and Prognosis* Douglas E. Drachman, MD,y Joshua A. Beckman, MDz
A
therosclerosis is a systemic process with clin-
usually covered by Medicare, whereas those with
ical manifestations primarily determined by
indeterminate or lower ratings are not covered, as
the vascular territory involved. The 3 most
a result of the Affordable Care Act. PAD remains
common territories include coronary heart disease,
underdiagnosed, represents a large segment of pa-
cerebrovascular disease, and peripheral artery dis-
tients who do not receive adequate risk-lowering
ease (PAD), with less common clinical sequelae due
treatment (2), and has an accurate diagnostic test
to involvement of the renal arteries, mesenteric ves-
(ABI) (3) that adds as much information to the 5 Fra-
sels, and aorta. It is estimated that 8 to 10 million
mingham risk factors in risk prediction as adding high-
Americans have PAD. The prevalence of PAD is
density lipoprotein to the other 4 risk factors (4,5).
approximately 5% in persons age 40 to 50 years and
Despite the fact there is now a medication approved
18% in those above 80 years (1). Despite the epidemic
for PAD (vorapaxar) that will not be prescribed in the
levels of PAD, the disease remains largely underdiag-
absence of diagnosis, the determination of the United
nosed and undertreated.
States Preventive Services Task Force not to reim-
Currently, there are 2 major obstacles that impede
burse the use of ABI represents an enormous obstacle
the diagnosis of PAD. First, the most straightforward,
to the identification, treatment, and reduction of
reliable, and inexpensive study for the identification
death and disability of patients with PAD.
of PAD—the ankle-brachial index (ABI)—is not a
A second significant obstacle to the diagnosis of
covered service for patients who are asymptomatic.
PAD is the fact that most patients do not present with
Compounding this issue is the fact that the majority of
“typical” claudication symptoms readily recognized
patients with PAD do not manifest leg pain, which
by health care professionals. PAD is commonly cate-
would be more readily identified by clinicians and
gorized by symptom status. Although nearly one-half
would meet criteria for reimbursement for ABI-based
of those with PAD are asymptomatic, the remaining
evaluation. The fact that the ABI is not covered for
one-half have symptoms ranging from intermittent
the assessment of asymptomatic patients largely re-
claudication, where muscular ischemic pain develops
flects the recommendations developed by the United
following a predictable amount of exertion, to critical
States Preventive Services Task Force. Screening ser-
limb ischemia, where risk of amputation may be sig-
vices given an “A” or “B” rating by the task force are
nificant 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
*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. From the yCardiology Division, Massachusetts General Hospital, Boston, Massachusetts; and the zCardiovascular Division, Brigham and Women’s
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
Hospital, Boston, Massachusetts. Dr. Drachman serves on the advisory
that develops with exercise but does not force them
board of Abbott Vascular, Inc.; and has received research grant support
to stop walking; pain that does not have the typical
from Atrium Medical Corporation and Lutonix/Bard. Dr. Beckman has
quality of muscular ischemia but does stop them
served as a consultant for Bristol-Myers Squibb, Merck, Novartis, and AstraZeneca; has received an investigation grant from BMS; and is on the
from walking; leg pain that occurs both with exertion
board of VIVA physicians.
and at rest; or, no leg pain, but a very low functional
1246
Drachman and Beckman
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 8, NO. 9, 2015 AUGUST 17, 2015:1245–7
ABI and Revascularization
status (i.e., walking fewer than 6 blocks/week).
does not permit evaluation of whether asymptomatic
Additional studies by McDermott (7) have demon-
patients were treated with revascularization, and—if
strated that patients with PAD have a lower level of
so—at what ABI or post-exercise ABI threshold.
physical activity, are functionally impaired, and
Because symptom, limb-specific, and physiological
decline at a faster rate than those without PAD. Even
outcomes were not available, conclusions regarding
patients with “asymptomatic” PAD have diminished
the best practice for revascularization versus exercise
functional capacity, as measured by the inability to
therapy are not feasible.
walk a quarter mile or climb stairs without assistance
The examination of the effect of post-exercise ABI
(7). Similarly, even in the setting of leg pain associ-
on prognosis in this study reinforces findings from
ated with activity, the symptoms do not commonly
prior evaluations in this field. Sheikh et al. (9) identi-
match those classically described in textbooks. Inad-
fied that an abnormal post-exercise ABI was a robust,
equate recognition of the true manifestations of PAD
independent predictor of all-cause mortality in the
may, therefore, consign patients with undiagnosed
context of normal resting ABI. Diehm et al. (10)
disease to worsened cardiovascular and limb out-
examined the getABI study database of 6,468 pa-
comes. One difficult question, once the diagnosis of
tients and concluded that the finding of an abnormal
PAD is made, is which patient would be likely to need
post-exercise ABI did not provide additional prog-
revascularization? It is in this space that Hammad
nostic information to that derived from an abnormal
et al. (8) have added to our understanding.
resting ABI.
SEE PAGE 1238
In addition to the data concerning revascularization, it is interesting to note that patients with a
In this issue of JACC: Cardiovascular Interventions,
normal resting ABI did not have an increased risk of
Hammad et al. (8) report a single-center retrospective
cardiovascular events, independent of the effects of
database analysis of 2,791 consecutive patients who
exercise on ankle pressure. This provides confirma-
underwent exercise ABI. Patients were divided into
tory data concerning the risk of cardiovascular events
4 groups: normal resting ankle-brachial index (NR)
in patients with PAD; the current definition is a
and normal post-exercise ankle-brachial index (NE),
reasonable place to increase risk factor modification to
NR and abnormal post-exercise ankle-brachial index
reduce cardiovascular morbidity and mortality. Clin-
(AE), abnormal resting (AR) and NE, and AR/AE.
ical trials that have permitted looser entry criteria
The incidence of lower extremity revascularization,
have found no benefit with the addition of antiplatelet
major adverse cardiovascular events (MACE), and
therapy (11). Yet, it also reconfirms the value of the
all-cause mortality were compared between each of
resting ABI as a screening tool and the imperative to
the 4 groups.
provide it as a 1-time screening opportunity to pa-
The authors identified that, compared with in-
tients in the Medicare cohort. We know that the cur-
dividuals with NR/NE ABI, those with NR/AE had a
rent system leaves many patients undiagnosed and
higher incidence of revascularization but no differ-
undertreated. Using the National Health and Nutrition
ence in MACE or all-cause mortality. Among patients
Survey, Pande et al. (2) studied patients with PAD but
with abnormal resting ABI, those with abnormal post-
not established cardiac disease and showed that 81%
exercise ABI (AR/AE) were also more likely to undergo
did not take statins, 73% did not take antiplatelet
revascularization than were those with normal post-
agents, and 79% took neither an angiotensin receptor
exercise ABI (AR/NE), but they also had no statisti-
blocker or angiotensin-converting enzyme inhibitor.
cal difference in MACE or all-cause mortality. Of note,
In fact, more than one-half of the subjects were taking
AR/AE did confer a significantly higher risk of MACE
no preventive therapies at all! In comparison, those
than NR/NE (hazard ratio: 1.44, 95% confidence in-
subjects taking 2 or more preventive therapies had a
terval: 1.09 to 1.90, p ¼ 0.009) and a trend toward
65% reduction in mortality.
increased all-cause mortality.
The findings presented by Hammad et al. (8) reflect
The findings of this study demonstrate that
the outcome of a single-center retrospective study,
revascularization strategies were used significantly
and are therefore subject to the expected design
more often in patients with abnormal post-exercise
related limitations: patient selection bias, patient
ABI, and therefore with more severe, flow-limiting
follow-up out of network, and the fundamental
PAD. The retrospective nature of the study, however,
question of whether the test of interest (exercise ABI)
does not permit the comparison of patient symptom-
supports the use of revascularization, the primary
atic status to the physiological severity of disease
endpoint of the study. Despite these limitations,
(measured ABI) or to the operator’s propensity to
Hammad et al. (8) have provided us with important
pursue revascularization. Moreover, the study design
insight regarding patient prognosis and selection
Drachman and Beckman
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 8, NO. 9, 2015 AUGUST 17, 2015:1245–7
ABI and Revascularization
for revascularization. More data, however, would
even greater leap forward for clinician insight and
help develop an algorithm for a broader array of
patient-centered care.
therapies. If the study had examined the effect of exercise therapy, alone or in conjunction with
REPRINT REQUESTS AND CORRESPONDENCE: Dr.
revascularization, so that the benefits of the each
Joshua A. Beckman, Cardiovascular Division, Brigham
therapy could be evaluated on the basis of patient
& Women’s Hospital, 75 Francis Street, Boston, Mas-
clinical presentation, the findings would represent an
sachusetts 02115. E-mail: [email protected].
REFERENCES 1. Fowkes FG, Rudan D, Rudan I, et al. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet 2013;382: 1329–40. 2. Pande RL, Perlstein TS, Beckman JA, Creager MA. Secondary prevention and mortality in peripheral artery disease: National Health and Nutrition Examination Study, 1999 to 2004. Circulation 2011;124:17–23. 3. Aboyans V, Criqui MH, Abraham P, et al. Measurement and interpretation of the anklebrachial index: a scientific statement from the American Heart Association. Circulation 2012;
calculations to measure usefulness of new biomarkers. Stat Med 2011;30:11–21.
on lower extremity revascularization. J Am Coll Cardiol Intv 2015;8:1238–44.
5. Lin JS, Olson CM, Johnson ES, Whitlock EP. The
9. Sheikh MA, Bhatt DL, Li J, Lin S, Bartholomew JR. Usefulness of postexercise ankle-brachial index to predict all-cause mortality. Am J Cardiol 2011;107:
ankle-brachial index for peripheral artery disease screening and cardiovascular disease prediction among asymptomatic adults: a systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med 2013;159:333–41. 6. McDermott MM, Greenland P, Liu K, et al. Leg symptoms in peripheral arterial disease: associated clinical characteristics and functional impairment. JAMA 2001;286:1599–606. 7. McDermott MM. Functional impairment in peripheral artery disease and how to improve it in
126:2890–909.
2013. Curr Cardiol Rep 2013;15:347.
4. Pencina MJ, D’Agostino RB Sr., Steyerberg EW. Extensions of net reclassification improvement
8. Hammad TA, Strefling JA, Zellers PR, et al. The effect of post-exercise ankle-brachial index
778–82. 10. Diehm C, Darius H, Pittrow D, et al. Prognostic value of a low post-exercise ankle brachial index as assessed by primary care physicians. Atherosclerosis 2011;214:364–72. 11. Fowkes FG, Price JF, Stewart MC, et al. Aspirin for prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial. JAMA 2010;303:841–8.
KEY WORDS ankle brachial index, exercise, peripheral artery disease
1247