Angiology
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Vascular Reactivity Is Impaired and Associated With Walking Ability in Patients With Intermittent Claudication Rita de Cassia Gengo e Silva, Nelson Wolosker, Juan Carlos Yugar-Toledo and Fernanda Marciano Consolim-Colombo ANGIOLOGY published online 5 August 2014 DOI: 10.1177/0003319714545486 The online version of this article can be found at: http://ang.sagepub.com/content/early/2014/08/05/0003319714545486
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Original Article
Vascular Reactivity Is Impaired and Associated With Walking Ability in Patients With Intermittent Claudication
Angiology 1-7 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003319714545486 ang.sagepub.com
Rita de Cassia Gengo e Silva, RN, PhD1, Nelson Wolosker, MD, PhD2, Juan Carlos Yugar-Toledo, MD, PhD3, and Fernanda Marciano Consolim-Colombo, MD, PhD4
Abstract We verified whether vascular reactivity is impaired and whether there is any association between vascular reactivity, walking ability, and peripheral artery disease (PAD) severity in patients with intermittent claudication (IC). We studied 63 patients and 17 age- and sex-matched volunteers without PAD. Vascular reactivity was evaluated in the brachial artery during reactive hyperemia (flow-mediated dilation [FMD]) and after a sublingual single dose of nitroglycerin (nitroglycerin-induced vasodilation [NID]). Walking ability was verified by a 6-minute walk test. Vascular reactivity and walking ability were significantly worse in patients with IC compared with control participants. The ankle–brachial index correlated with FMD, NID, as well as total and pain-free distances. The NID and walking ability progressively decreased as PAD severity increased. Walking ability correlated with NID but not with FMD. In patients with IC, vascular reactivity is impaired and is related to the severity of PAD and to walking ability. Keywords peripheral arterial disease, intermittent claudication, vasodilation, muscle, smooth, vascular, endothelium, vascular, walking
Introduction Intermittent claudication (IC) is the major symptom of peripheral arterial disease (PAD). Peripheral artery disease is described as pain in the lower limbs during ambulation that frequently includes 1 or both calves and recovery after stopping the activity.1,2 It is an atherosclerotic disease associated1-2 with high increased risk of lower limb dysfunction.3-5 There is considerable evidence that both IC and low ankle–brachial index (ABI) are related to the severity of PAD and lower limb functional decline.5-8 The onset and progression of atherosclerosis is a complex phenomenon that involves endothelial dysfunction. The endothelium is able to modulate vascular tone, caliber, and blood flow response to various stimuli.9-12 Its dysfunction may be manifested by abnormal vasoreactivity, which expresses the imbalance between vasodilators and vasoconstrictors. Vascular reactivity is assessed by methods that evaluate flow-mediated dilation (FMD) and nitroglycerin-induced vasodilation (NID). Impaired FMD has been reported in patients with PAD and IC.13-16 However, whether vascular reactivity is related to the severity of the disease in patients with IC remains unclear. Moreover, there is scarce information regarding the relationship between functional decline and vascular reactivity. We
aimed to verify whether vascular reactivity is impaired and whether there is any association between vascular reactivity, walking ability, and the severity of PAD in patients with IC.
Methods Design and Patients This was a cross-sectional study in which 63 patients diagnosed with IC by clinical symptoms and an ABI 0.90, and 17 ageand sex-matched volunteers with no arterial disease or known atherosclerotic risk factors were enrolled. The patients were 1
Medical Surgical Department, School of Nursing, University of Sao Paulo, Sao Paulo, Brazil 2 Vascular and Endovascular Surgery Department, Claudication Unit, Medical School, University of Sao Paulo, Sao Paulo, Brazil 3 Medical School, Sao Jose do Rio Preto, Sao Paulo, Brazil 4 Laboratory of Human Clinical Investigation of Hypertension Unit, Heart Institute (InCor), Medical School, University of Sao Paulo, Sao Paulo, Brazil Corresponding Author: Rita de Cassia Gengo e Silva, Medical Surgical Department, School of Nursing, University of Sao Paulo, 419 Eneas de Carvalho Aguiar, Av 3rd floor Sao Paulo, CEP 05403, Brazil. Email: [email protected]
Downloaded from ang.sagepub.com at UCSF LIBRARY & CKM on September 12, 2014
2
Angiology
under clinical treatment at the Claudication Department (Clinical Hospital, Medical School, University of Sao Paulo) and consisted of 35 (55.6%) men, with a mean age of 62.2 + 8.1 years. The mean ABI was 0.59 + 0.14 (ABI range 0.260.87). All participants were classified as Fontaine II. We excluded patients with a body mass index >40 kg/m2, an ABI 1.30, renal insufficiency, and amputation of the lower limbs at any level. All participants were instructed to abstain from alcohol, tobacco, and caffeine 48 hours prior to the study, to abstain from food for 5 hours prior to the study, and not to use any medication on the day of data collection. This study was approved by the ethics committee of the Clinical Hospital, Medical School, University of Sao Paulo. All participants completed a consent form.
Nitroglycerin. Baseline diameter was recorded for 1 minute, and the blood flow velocity was recorded for 15 seconds prior to nitroglycerin administration. A sublingual single dose (0.45 mg) was administered. After 5 minutes, the brachial diameter was recorded for 1 minute, and the blood flow velocity was recorded for 15 seconds.
Ankle–Brachial Index Measurements
Walking Ability
Participants rested in the supine position for 5 minutes before ABI measurement. An appropriately sized blood pressure (BP) cuff was placed over both left and right brachial arteries and above each malleolus. The cuff was inflated to 20 mm Hg above the audible systolic BP (SBP). Using a hand-held Doppler probe (Medmega, Sao Paulo, Brazil), we measured the SBP in each artery following a standardized sequence: the left arteries (brachial, dorsalis pedis, and posterior tibial) and the right arteries (dorsalis pedis, posterior tibial, and brachial). The ABI was calculated for each leg by the ratio between the highest SBP in the leg and the highest SBP in the arms.
Walking ability was verified with a 6-minute walk test.17 Participants were instructed to walk up and down a 20-m corridor for 6 minutes after being instructed to cover as much distance as possible, according to their tolerance, and to describe all symptoms during the walk.
Blood flow velocity and shear rate. The blood flow velocity was calculated automatically by the ultrasonography computer device. The shear rate was calculated as an estimation of shear stress, which was considered as the ratio between simultaneously quantified mean blood flow velocity (5-second periods) and basal vessel diameter. It was used to estimate the stimulus during reactive hyperemia.
Data Analysis Determination of ABI. The lower ABI was used. Patients were classified according to disease severity based on the ABI: normal (0.90-1.29), mild (0.70-0.89), moderate (0.50-0.69), and severe (
http://ang.sagepub.com/
Vascular Reactivity Is Impaired and Associated With Walking Ability in Patients With Intermittent Claudication Rita de Cassia Gengo e Silva, Nelson Wolosker, Juan Carlos Yugar-Toledo and Fernanda Marciano Consolim-Colombo ANGIOLOGY published online 5 August 2014 DOI: 10.1177/0003319714545486 The online version of this article can be found at: http://ang.sagepub.com/content/early/2014/08/05/0003319714545486
Published by: http://www.sagepublications.com
Additional services and information for Angiology can be found at: Email Alerts: http://ang.sagepub.com/cgi/alerts Subscriptions: http://ang.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav
>> OnlineFirst Version of Record - Aug 5, 2014 What is This?
Downloaded from ang.sagepub.com at UCSF LIBRARY & CKM on September 12, 2014
Original Article
Vascular Reactivity Is Impaired and Associated With Walking Ability in Patients With Intermittent Claudication
Angiology 1-7 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003319714545486 ang.sagepub.com
Rita de Cassia Gengo e Silva, RN, PhD1, Nelson Wolosker, MD, PhD2, Juan Carlos Yugar-Toledo, MD, PhD3, and Fernanda Marciano Consolim-Colombo, MD, PhD4
Abstract We verified whether vascular reactivity is impaired and whether there is any association between vascular reactivity, walking ability, and peripheral artery disease (PAD) severity in patients with intermittent claudication (IC). We studied 63 patients and 17 age- and sex-matched volunteers without PAD. Vascular reactivity was evaluated in the brachial artery during reactive hyperemia (flow-mediated dilation [FMD]) and after a sublingual single dose of nitroglycerin (nitroglycerin-induced vasodilation [NID]). Walking ability was verified by a 6-minute walk test. Vascular reactivity and walking ability were significantly worse in patients with IC compared with control participants. The ankle–brachial index correlated with FMD, NID, as well as total and pain-free distances. The NID and walking ability progressively decreased as PAD severity increased. Walking ability correlated with NID but not with FMD. In patients with IC, vascular reactivity is impaired and is related to the severity of PAD and to walking ability. Keywords peripheral arterial disease, intermittent claudication, vasodilation, muscle, smooth, vascular, endothelium, vascular, walking
Introduction Intermittent claudication (IC) is the major symptom of peripheral arterial disease (PAD). Peripheral artery disease is described as pain in the lower limbs during ambulation that frequently includes 1 or both calves and recovery after stopping the activity.1,2 It is an atherosclerotic disease associated1-2 with high increased risk of lower limb dysfunction.3-5 There is considerable evidence that both IC and low ankle–brachial index (ABI) are related to the severity of PAD and lower limb functional decline.5-8 The onset and progression of atherosclerosis is a complex phenomenon that involves endothelial dysfunction. The endothelium is able to modulate vascular tone, caliber, and blood flow response to various stimuli.9-12 Its dysfunction may be manifested by abnormal vasoreactivity, which expresses the imbalance between vasodilators and vasoconstrictors. Vascular reactivity is assessed by methods that evaluate flow-mediated dilation (FMD) and nitroglycerin-induced vasodilation (NID). Impaired FMD has been reported in patients with PAD and IC.13-16 However, whether vascular reactivity is related to the severity of the disease in patients with IC remains unclear. Moreover, there is scarce information regarding the relationship between functional decline and vascular reactivity. We
aimed to verify whether vascular reactivity is impaired and whether there is any association between vascular reactivity, walking ability, and the severity of PAD in patients with IC.
Methods Design and Patients This was a cross-sectional study in which 63 patients diagnosed with IC by clinical symptoms and an ABI 0.90, and 17 ageand sex-matched volunteers with no arterial disease or known atherosclerotic risk factors were enrolled. The patients were 1
Medical Surgical Department, School of Nursing, University of Sao Paulo, Sao Paulo, Brazil 2 Vascular and Endovascular Surgery Department, Claudication Unit, Medical School, University of Sao Paulo, Sao Paulo, Brazil 3 Medical School, Sao Jose do Rio Preto, Sao Paulo, Brazil 4 Laboratory of Human Clinical Investigation of Hypertension Unit, Heart Institute (InCor), Medical School, University of Sao Paulo, Sao Paulo, Brazil Corresponding Author: Rita de Cassia Gengo e Silva, Medical Surgical Department, School of Nursing, University of Sao Paulo, 419 Eneas de Carvalho Aguiar, Av 3rd floor Sao Paulo, CEP 05403, Brazil. Email: [email protected]
Downloaded from ang.sagepub.com at UCSF LIBRARY & CKM on September 12, 2014
2
Angiology
under clinical treatment at the Claudication Department (Clinical Hospital, Medical School, University of Sao Paulo) and consisted of 35 (55.6%) men, with a mean age of 62.2 + 8.1 years. The mean ABI was 0.59 + 0.14 (ABI range 0.260.87). All participants were classified as Fontaine II. We excluded patients with a body mass index >40 kg/m2, an ABI 1.30, renal insufficiency, and amputation of the lower limbs at any level. All participants were instructed to abstain from alcohol, tobacco, and caffeine 48 hours prior to the study, to abstain from food for 5 hours prior to the study, and not to use any medication on the day of data collection. This study was approved by the ethics committee of the Clinical Hospital, Medical School, University of Sao Paulo. All participants completed a consent form.
Nitroglycerin. Baseline diameter was recorded for 1 minute, and the blood flow velocity was recorded for 15 seconds prior to nitroglycerin administration. A sublingual single dose (0.45 mg) was administered. After 5 minutes, the brachial diameter was recorded for 1 minute, and the blood flow velocity was recorded for 15 seconds.
Ankle–Brachial Index Measurements
Walking Ability
Participants rested in the supine position for 5 minutes before ABI measurement. An appropriately sized blood pressure (BP) cuff was placed over both left and right brachial arteries and above each malleolus. The cuff was inflated to 20 mm Hg above the audible systolic BP (SBP). Using a hand-held Doppler probe (Medmega, Sao Paulo, Brazil), we measured the SBP in each artery following a standardized sequence: the left arteries (brachial, dorsalis pedis, and posterior tibial) and the right arteries (dorsalis pedis, posterior tibial, and brachial). The ABI was calculated for each leg by the ratio between the highest SBP in the leg and the highest SBP in the arms.
Walking ability was verified with a 6-minute walk test.17 Participants were instructed to walk up and down a 20-m corridor for 6 minutes after being instructed to cover as much distance as possible, according to their tolerance, and to describe all symptoms during the walk.
Blood flow velocity and shear rate. The blood flow velocity was calculated automatically by the ultrasonography computer device. The shear rate was calculated as an estimation of shear stress, which was considered as the ratio between simultaneously quantified mean blood flow velocity (5-second periods) and basal vessel diameter. It was used to estimate the stimulus during reactive hyperemia.
Data Analysis Determination of ABI. The lower ABI was used. Patients were classified according to disease severity based on the ABI: normal (0.90-1.29), mild (0.70-0.89), moderate (0.50-0.69), and severe (
