We hypothesized that higher serum levels of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) are associated with lower functional capacity in patients with peripheral arterial disease ([PAD] n = 481, mean age 67, 68% men). Functional capacity was quantified as distance walked on a treadmill for 5 minutes. Patients were divided into 3 groups according to the distance walked: >144 yards (group 1, n = 254); 60 to 144 yards (group 2, n = 80); <60 yards or did not walk (group 3, n = 147). The association between NT-pro-BNP levels and the ordinal 3-level walking distance was assessed using multivariable ordinal logistic regression analyses that adjusted for several possible confounding variables. Higher levels of NT-pro-BNP were associated with a lower ordinal walking category independent of possible confounders (odds ratio [OR] 1.51, 95% confidence interval [CI] 1.28-1.77; P < .001). In conclusion, higher levels of NT-pro-BNP are independently associated with lower functional capacity in patients with PAD and may be a marker of hemodynamic stress in these patients.
BelchJJTopolEJAgnelliG. Critical issues in peripheral arterial disease detection and management: a call to action. Arch Intern Med. 2003;163(8):884–892.
2.
WeitzJIByrneJClagettGP. Diagnosis and treatment of chronic arterial insufficiency of the lower extremities: a critical review. Circulation. 1996;94(11):3026–3049.
3.
CriquiMHDenenbergJOLangerRDFronekA. The epidemiology of peripheral arterial disease: importance of identifying the population at risk. Vasc Med. 1997;2(3):221–226.
4.
MurabitoJMD’AgostinoRBSilbershatzHWilsonWF. Intermittent claudication. A risk profile from the framingham heart study. Circulation. 1997;96(1):44–49.
5.
GornikHLCreagerMA. Contemporary management of peripheral arterial disease: I. cardiovascular risk-factor modification. Cleve Clin J Med. 2006;73(suppl 4):S30–S37.
6.
McDermottMMGreenlandPLiuK. Leg symptoms in peripheral arterial disease: associated clinical characteristics and functional impairment. JAMA. 2001;286(13):1599–1606.
7.
NewmanABNaydeckBLSutton-TyrrellKPolakJFKullerLH. The role of comorbidity in the assessment of intermittent claudication in older adults. J Clin Epidemiol. 2001;54(3):294–300.
8.
Amoh-TontoCAMalikARKondraguntaVAliZKulloIJ. Brachial-ankle pulse wave velocity is associated with walking distance in patients referred for peripheral arterial disease evaluation. Atherosclerosis. 2009;206(1):173–178.
9.
BrewerLCChaiHSBaileyKRKulloIJ. Measures of arterial stiffness and wave reflection are associated with walking distance in patients with peripheral arterial disease. Atherosclerosis. 2007;191(2):384–390.
10.
TokudomeTKishimotoIYamaharaK. Impaired recovery of blood flow after hind-limb ischemia in mice lacking guanylyl cyclase-a, a receptor for atrial and brain natriuretic peptides. Arterioscler Thromb Vasc Biol. 2009;29(10):1516–1521.
11.
JouniHRodehefferRJKulloIJ. Increased serum N-terminal pro-B-type natriuretic peptide levels in patients with medial arterial calcification and poorly compressible leg arteries. Arterioscler Thromb Vasc Biol. 2011;31(1):197–202.
12.
MontagnanaMLippiGFavaC. Ischemia-modified albumin and NT-prohormone-brain natriuretic peptide in peripheral arterial disease. Clin Chem Lab Med. 2006;44(2):207–212.
13.
SvenssonPde FaireUNiklassonUHanssonLOOstergrenJ. Plasma NT-pro-BNP concentration is related to ambulatory pulse pressure in peripheral arterial disease. Blood Press. 2005;14(2):99–106.
14.
DieplingerBPoelzWHaltmayerMMuellerT. Association of adiponectin and amino terminal proBNP in peripheral arterial disease. Clin Chim Acta. 2007;377(1-2):192–197.
15.
MuellerTDieplingerBPoelzWEndlerGWagnerOFHaltmayerM. Amino-terminal pro-B-type natriuretic peptide as predictor of mortality in patients with symptomatic peripheral arterial disease: 5-year follow-up data from the linz peripheral arterial disease study. Clin Chem. 2009;55(1):68–77.
16.
SantosSRookeTWBaileyKRMcConnellJPKulloIJ. Relation of markers of inflammation (C-reactive protein, white blood cell count, and lipoprotein-associated phospholipase a2) to the ankle-brachial index. Vasc Med. 2004;9(3):171–176.
17.
GardnerAWSkinnerJSCantwellBWSmithLK. Progressive vs single-stage treadmill tests for evaluation of claudication. Med Sci Sports Exerc. 1991;23(4):402–408.
18.
HirschATHaskalZJHertzerNR. ACC/AHA 2005 guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): executive summary a collaborative report from the american association for vascular surgery/society for vascular surgery, society for cardiovascular angiography and interventions, society for vascular medicine and biology, society of interventional radiology, and the ACC/AHA task force on practice guidelines (writing committee to develop guidelines for the management of patients with peripheral arterial disease) endorsed by the american association of cardiovascular and pulmonary rehabilitation; national heart, lung, and blood institute; society for vascular nursing; transatlantic inter-society consensus; and vascular disease foundation. J Am Coll Cardiol. 2006;47(6):1239–1312.
19.
LeveyASCoreshJGreeneT. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006;145(4):247–254.
20.
McDermottMMGreenlandPLiuK. The ankle brachial index is associated with leg function and physical activity: the walking and leg circulation study. Ann Intern Med. 2002;136(12):873–883.
21.
LuchnerABurnettJCJrJougasakiMHenseHWRieggerGASchunkertH. Augmentation of the cardiac natriuretic peptides by beta-receptor antagonism: evidence from a population-based study. J Am Coll Cardiol. 1998;32(7):1839–1844.
22.
MaiselASKrishnaswamyPNowakRM. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med. 2002;347(3):161–167.
23.
ChengEMAschSMBrookRH. Suboptimal control of atherosclerotic disease risk factors after cardiac and cerebrovascular procedures. Stroke. 2007;38(3):929–934.
24.
DaoHHEssalihiRBouvetCMoreauP. Evolution and modulation of age-related medial elastocalcinosis: impact on large artery stiffness and isolated systolic hypertension. Cardiovasc Res. 2005;66(2):307–317.
25.
FerreiraITwiskJWVan MechelenWKemperHCStehouwerCD. Current and adolescent levels of cardiopulmonary fitness are related to large artery properties at age 36: the amsterdam growth and health longitudinal study. Eur J Clin Invest. 2002;32(10):723–731.
HerKChoiCParkYShinHWonY. Concomitant peripheral artery disease and asymptomatic coronary artery disease: a management strategy. Ann Vasc Surg. 2008;22(5):649–656.
28.
McDermottMMLiuKCriquiMH. Ankle-brachial index and subclinical cardiac and carotid disease: the multi-ethnic study of atherosclerosis. Am J Epidemiol. 2005;162(1):33–41.
29.
LesterSJTajikAJNishimuraRAOhJKKhandheriaBKSewardJB. Unlocking the mysteries of diastolic function: deciphering the rosetta stone 10 years later. J Am Coll Cardiol. 2008;51(7):679–689.
30.
RubattuSSciarrettaSValentiVStanzioneRVolpeM. Natriuretic peptides: an update on bioactivity, potential therapeutic use, and implication in cardiovascular diseases. Am J Hypertens. 2008;21(7):733–741.
31.
KuhnMVolkerKSchwarzK. The natriuretic peptide/guanylyl cyclase--a system functions as a stress-responsive regulator of angiogenesis in mice. J Clin Invest. 2009;119(7):2019–2030.
32.
ChenHLevineYCGolanDEMichelTLinAJ. Atrial natriuretic peptide-initiated cGMP pathways regulate vasodilator-stimulated phosphoprotein phosphorylation and angiogenesis in vascular endothelium. J Biol Chem. 2008;283(7):4439–4447.
33.
ParkKItohHYamaharaK. Therapeutic potential of atrial natriuretic peptide administration on peripheral arterial diseases. Endocrinology. 2008;149(2):483–491.
34.
ShmilovichHBen-ShoshanJTalR. B-type natriuretic peptide enhances vasculogenesis by promoting number and functional properties of early endothelial progenitor cells. Tissue Eng Part A. 2009;15(9):2741–2749.
35.
CharlesCJEspinerEARichardsAM. Cardiovascular actions of ANF: contributions of renal, neurohumoral, and hemodynamic factors in sheep. Am J Physiol. 1993;264(3 pt 2):R533–R538.
36.
YamaharaKItohHChunTH. Significance and therapeutic potential of the natriuretic peptides/cGMP/cGMP-dependent protein kinase pathway in vascular regeneration. Proc Natl Acad Sci U S A. 2003;100(6):3404–3409.
37.
MukherjeeSMukhopadhyayPPanditKChowdhuryS. Atorvastatin improves arterial stiffness in normotensive normolipidaemic persons with type 2 diabetes. J Indian Med Assoc. 2008;106(11):716–719.
38.
LaufsULa FataVPlutzkyJLiaoJK. Upregulation of endothelial nitric oxide synthase by HMG coA reductase inhibitors. Circulation. 1998;97(12):1129–1135.
39.
AronowWSNayakDWoodworthSAhnC. Effect of simvastatin versus placebo on treadmill exercise time until the onset of intermittent claudication in older patients with peripheral arterial disease at six months and at one year after treatment. Am J Cardiol. 2003;92(6):711–712.
40.
MomsenAHJensenMBNoragerCBMadsenMRVestersgaard-AndersenTLindholtJS. Drug therapy for improving walking distance in intermittent claudication: a systematic review and meta-analysis of robust randomised controlled studies. Eur J Vasc Endovasc Surg. 2009;38(4):463–474.
41.
AhimastosAANatoliAKLawlerABlomberyPAKingwellBA. Ramipril reduces large-artery stiffness in peripheral arterial disease and promotes elastogenic remodeling in cell culture. Hypertension. 2005;45(6):1194–1199.
42.
AhimastosAADartAMLawlerABlomberyPAKingwellBA. Reduced arterial stiffness may contribute to angiotensin-converting enzyme inhibitor induced improvements in walking time in peripheral arterial disease patients. J Hypertens. 2008;26(5):1037–1042.
43.
AnandRGVenturaHOMehraMR. Is heart failure more prevalent in patients with peripheral arterial disease? A meta-analysis. Congest Heart Fail. 2007;13(6):319–322.
