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A Methodological Approach to Non-invasive Assessments of Vascular Function and Morphology
Published on: February 7, 2015
Endothelial dysfunction and brachial intima-media thickness: long term cardiovascular risk with claudication related
Franz Hafner1, Andrea Kieninger1, Andreas Meinitzer2
1Department of Internal Medicine, Division of Angiology, Medical University of Graz, Graz, Austria.
Insights
In peripheral arterial disease, poor flow-mediated dilation, increased intima-media thickness, and elevated asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) levels predict higher cardiovascular mortality risk.
Area of Science:
- Cardiovascular Medicine
- Vascular Biology
- Diagnostic Imaging
Background:
- Endothelial dysfunction is central to atherosclerosis and symptomatic peripheral arterial disease (PAD).
- Intima-media thickness (IMT) is a recognized cardiovascular risk marker, while flow-mediated dilation (FMD) and specific serologic markers assess endothelial function.
- PAD patients with endothelial dysfunction and increased IMT face heightened cardiovascular risk.
Purpose of the Study:
- To investigate the prognostic significance of ultrasound-assessed endothelial function (FMD, IMT) and serologic markers (ADMA, SDMA, L-homoarginine) for cardiovascular mortality in PAD.
- To determine if these parameters can predict long-term cardiovascular outcomes in patients with symptomatic PAD.
Main Methods:
- A prospective cohort study involving 184 patients with symptomatic PAD (Rutherford stages 2-3).
- Measurements included flow-mediated dilation (FMD), brachial intima-media thickness (IMT), and serum levels of asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and L-homoarginine.
- Cardiovascular events were tracked over a mean follow-up of 49.7 months, excluding non-cardiovascular deaths.
Main Results:
- A significant association was found between reduced FMD and increased cardiovascular death (p<0.001).
- Higher brachial IMT (above 0.345 mm) was strongly predictive of cardiovascular mortality (sensitivity 0.714, specificity 0.657, p<0.001).
- Elevated ADMA (above 0.745 µmol/l) and SDMA (above 0.825 µmol/l) levels were significantly linked to increased cardiovascular death (p<0.001 and p=0.030, respectively).
Conclusions:
- In patients with symptomatic PAD, diminished FMD, increased IMT, and elevated ADMA and SDMA are significant indicators of heightened cardiovascular risk.
- These parameters offer valuable prognostic information for cardiovascular mortality in PAD patients.
- Ultrasound and serologic markers of endothelial function can aid in risk stratification for PAD.
Objective:
Endothelial 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.
Design:
monocentric, prospective cohort study.
Methods:
Flow 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.
Results:
Eighty-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).
Conclusion:
In 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.
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