Letter by Protogerou et al Regarding Article, “Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic Peripheral Artery Disease”
To the Editor:
In the study of Diehm et al,1 the prognostic value of the ankle-brachial index (ABI) as a biomarker of cardiovascular disease in symptomatic patients with peripheral arterial disease and asymptomatic subjects with probable peripheral arterial disease (ABI <0.9) was highlighted. There is another important issue to be discussed relative to the physiology of ABI and its prognostic significance.
From the point of view of cardiovascular physiology, the difference in systolic blood pressure between 2 arteries (eg, the brachial artery and dorsalis pedis artery) originates from the fact that the blood pressure wave is gradually amplified as it travels distally. This is a result, at least in part, of the existence of pressure-wave reflections and arterial stiffness gradient within the arterial tree.2
The spatial amplification of the blood pressure wave is currently being studied intensively in the upper limb.2 It is defined as brachial pulse pressure divided by central (aortic or carotid artery) pulse pressure; it is attenuated by aging resulting from arteriosclerosis,2 not atheromatosis. Moreover, upper-limb pulse pressure amplification is suggested to be a new biomarker of cardiovascular disease3; cardiovascular risk increases as pulse pressure amplification decreases.
Twenty years ago, it was proposed4 and is now accepted5 that wave reflections play a role in the physiology of ABI, at least within the normal range (ABI >1.0). In cross-sectional data, ABI is inversely correlated with age; this observation is expected to be valid even within the normal range of ABI values (>1.0, ie, in subjects without peripheral arterial disease or flow-limiting atheromatosis) and might be verified by the data of Diehm et al. Moreover, in the Diehm et al study, event-free survival seems to decrease even within the normal range of ABI (from 1.5 to 1.0). In such patients, flow-limiting atheromatosis is not expected to be the main modulator of ABI. On the contrary, arterial stiffening and impaired wave reflections are expected to play the “leading role.”
Atheromatosis and arteriosclerosis share common cardiovascular risk factors but are different in nature, representing the 2 sides of atherosclerotic disease. As correctly stated by Perlstein and Creager6 in the editorial accompanying the Diehm et al article, “It’s [ABI] not just about the legs.” We might add that ABI is not just about atheromatosis. Within the normal range, it might serve as a biomarker of arteriosclerosis and pulse pressure amplification. This theory has to be proven by further prospective studies or a subanalysis of the data of Diehm et al.
Diehm C, Allenberg JR, Pittrow D, Mahn M, Tepohl G, Haberl RL, Darius H, Burghaus I, Trampisch HJ, for the German Epidemiological Trial on Ankle Brachial Index Study Group. Mortality and vascular morbidity in older adults with asymptomatic versus symptomatic peripheral artery disease. Circulation. 2009; 120: 2053–2061.
Avolio AP, Van Bortel LM, Boutouyrie P, Cockcroft JR, McEniery CM, Protogerou AD, Roman MJ, Safar ME, Segers P, Smulyan H. Role of pulse pressure amplification in arterial hypertension: experts’ opinion and review of the data. Hypertension. 2009; 54: 375–383.
Hirsch, AT, Haskal, ZJ, Hertzer NR, Bakal, CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM, White CJ, White J, White RA, Antman EM, Smith SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riege B. ACC/AHA 2005 practice guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): 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. Circulation. 2006; 113: 463–654.
Perlstein TS, Creager MA. The ankle-brachial index as a biomarker of cardiovascular risk: it’s not just about the legs. Circulation. 2009; 120: 2033–2035.