Abstract
ObjectiveEndothelial dysfunction plays a key role in the development, progression, and clinical manifestation of atherosclerosis, and in symptomatic peripheral arterial disease, endothelial dysfunction and enlarged intima-media thickness might be associated with increased cardiovascular risk. Flow-mediated dilatation and serologic parameters are used to evaluate individual endothelial function. Brachial intima-media thickness, a less recognized parameter of cardiovascular risk, is independently associated with coronary artery disease. The aim of this study was to evaluate the prognostic value of ultrasound and serologic parameters of endothelial function in relation to cardiovascular mortality in peripheral arterial disease.Designmonocentric, prospective cohort study.MethodsFlow mediated dilatation and brachial intima-media thickness were assessed in 184 (124 male) patients with peripheral arterial disease (Rutherford stages 2–3). Serologic parameters of endothelial function included asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and L-homoarginine. Cardiovascular events were recorded during a follow-up of 99.1±11.1 months. Subjects who died of noncardiovascular causes were excluded from further analysis.ResultsEighty-two patients (44.6%) died during follow-up after a mean duration of 49.7±28.3 months. There were 49 cardiovascular deaths (59.8%) and 33 other deaths (40.2%). Flow mediated dilatation was associated with cardiovascular death [1.17% (0.0, 4.3) vs. 4.1% (1.2, 6.4), p<0.001]. Intima-media thickness was greater in patients who succumbed to cardiovascular disease [0.37 mm (0.30, 0.41)] than in survivors [0.21 mm (0.15, 0.38), p<0.001]. Brachial intima-media thickness above 0.345 mm was most predictive of cardiovascular death, with sensitivity and specificity values of 0.714 and 0.657, respectively (p<0.001). Furthermore, ADMA levels above 0.745 µmol/l and SDMA levels above 0.825 µmol/l were significantly associated with cardiovascular death (p<0.001 and 0.030).ConclusionIn symptomatic peripheral arterial disease, decreased flow mediated dilatation, enlarged intima-media thickness, and elevated levels of ADMA and SDMA were associated with increased cardiovascular risk.
Highlights
Peripheral arterial disease (PAD) is a major health care burden [1]
Intima-media thickness was greater in patients who succumbed to cardiovascular disease [0.37 mm (0.30, 0.41)] than in survivors [0.21 mm (0.15, 0.38), p,0.001]
In symptomatic peripheral arterial disease, decreased flow mediated dilatation, enlarged intima-media thickness, and elevated levels of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) were associated with increased cardiovascular risk
Summary
Peripheral arterial disease (PAD) is a major health care burden [1]. PAD, as the manifestation of atherosclerosis in peripheral arteries, generally occurs in elderly patients and is commonly related to a variety of cardiovascular risk factors. Patients with symptomatic and asymptomatic PAD are at heightened risk for myocardial infarction, stroke, and cardiovascular and all-cause mortality [2,3]. Brachial flow-mediated dilatation (FMD) is a validated, non-invasive ultrasound technique that measures endothelial dysfunction to predict cardiovascular risk [4,5,6,7]. NO drives the primary mechanism for FMD in healthy individuals, but the importance of other vasodilating agents like prostacyclin and endothelial hyperpolarizing factor may vary substantially in disease
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