Increased Elastin Degradation in Pseudoxanthoma Elasticum Is Associated with Peripheral Arterial Disease Independent of Calcification

Pseudoxanthoma elasticum (PXE) results in extensive fragmentation and calcification of elastin fibers in the peripheral arteries, which results in peripheral arterial disease (PAD). Current research focuses on the role of calcifications in the pathogenesis of PXE. Elastin degradation and calcification are shown to interact and may amplify each other. This study aims to compare plasma desmosines, a measure of elastin degradation, between PXE patients and controls and to investigate the association between desmosines and (1) arterial calcification, (2) PAD, and (3) PAD independent of arterial calcification in PXE. Plasma desmosines were quantified with liquid chromatography-tandem mass spectrometry in 93 PXE patients and 72 controls. In PXE patients, arterial calcification mass was quantified on CT scans. The ankle brachial index (ABI) after treadmill test was used to analyze PAD, defined as ABI < 0.9, and the Fontaine classification was used to distinguish symptomatic and asymptomatic PAD. Regression models were built to test the association between desmosines and arterial calcification and arterial functioning in PXE. PXE patients had higher desmosines than controls (350 (290–410) ng/L vs. 320 (280–360) ng/L, p = 0.02). After adjustment for age, sex, body mass index, smoking, type 2 diabetes mellitus, and pulmonary abnormalities, desmosines were associated with worse ABI (β (95%CI): −68 (−132; −3) ng/L), more PAD (β (95%CI): 40 (7; 73) ng/L), and higher Fontaine classification (β (95%CI): 30 (6; 53) ng/L), but not with arterial calcification mass. Lower ABI was associated with higher desmosines, independent from arterial calcification mass (β (95%CI): −0.71(−1.39; −0.01)). Elastin degradation is accelerated in PXE patients compared to controls. The association between desmosines and ABI emphasizes the role of elastin degradation in PAD in PXE. Our results suggest that both elastin degradation and arterial calcification independently contribute to PAD in PXE.

Download Full-text

The Limitations of Ankle Brachial Index when used Alone for the Detection/Screening of Peripheral Arterial Disease in a Population with an Increased Prevalence of Diabetes

Journal for Vascular Ultrasound ◽

10.1177/154431670703100304 ◽

2007 ◽

Vol 31 (3) ◽

pp. 149-151 ◽

Cited By ~ 1

Author(s):

Brian P. Hembling ◽

Kelley C. Hubler ◽

Peter M. Richard ◽

William A. O'Keefe ◽

Chelsey Husfloen ◽

...

Keyword(s):

Peripheral Arterial Disease ◽

Ankle Brachial Index ◽

Arterial Disease ◽

Waveform Analysis ◽

Arterial Calcification ◽

Normal Limits ◽

High Prevalence ◽

High Incidence ◽

Doppler Waveform ◽

Peripheral Arterial

A retrospective analysis was performed comparing the effectiveness of ankle brachial index (ABI) to Doppler waveform analysis for the detection of peripheral arterial disease (PAD) in a group of patients with an estimated 31% prevalence of diabetes. A total of 21,199 ankle pressures and corresponding Doppler waveforms were correlated; 8,628, or 41%, of the ankle pressures were within normal limits; 8,335, or 40%, of the ankle pressures were below normal limits; and 4,042, or 19%, of the ankle pressures were noncompressible. Using ABI alone for screening in a population with a high incidence of diabetes is significantly limited because of noncompressible ankle pressures caused by arterial calcification. A total of 19% of the segments evaluated in this population yielded noncompressible vessels. The prevalence of PAD, detected by Doppler waveform analysis in the segments with non-compressible ankle pressures, was 69%. Additional modalities such as Doppler waveform analysis would further increase the accuracy of screening for PAD in this population. Alternately, using the ABI alone for the detection of PAD can be improved by interpreting ABIs greater than 1.2 as positive results because of the high prevalence of PAD in this group.

Download Full-text

Mo-P4:Potential role of a digital palpation method for the measurement of ankle/brachial index in peripheral arterial disease screening

Atherosclerosis Supplements ◽

10.1016/s1567-5688(06)80403-4 ◽

2006 ◽

Vol 7 (3) ◽

pp. 105

Author(s):

A. Clara ◽

J. Merino ◽

A. Planas ◽

A. Braojos ◽

L. Roig ◽

...

Keyword(s):

Peripheral Arterial Disease ◽

Potential Role ◽

Ankle Brachial Index ◽

Arterial Disease ◽

Disease Screening ◽

Digital Palpation ◽

Peripheral Arterial

Download Full-text

Critical analysis and limitations of resting ankle-brachial index in the diagnosis of symptomatic peripheral arterial disease patients and the role of diabetes mellitus and chronic kidney disease

Journal of Vascular Surgery ◽

10.1016/j.jvs.2019.05.050 ◽

2020 ◽

Vol 71 (3) ◽

pp. 937-945 ◽

Cited By ~ 5

Author(s):

Ali F. AbuRahma ◽

Elliot Adams ◽

Joseph AbuRahma ◽

Luis A. Mata ◽

L. Scott Dean ◽

...

Keyword(s):

Diabetes Mellitus ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Peripheral Arterial Disease ◽

Critical Analysis ◽

Ankle Brachial Index ◽

Arterial Disease ◽

Peripheral Arterial

Download Full-text

Correlation between ankle-brachial index and thermography measurements in patients with peripheral arterial disease

Vascular ◽

10.1177/1708538121996573 ◽

2021 ◽

pp. 170853812199657

Author(s):

Jesus Antônio de Carvalho Abreu ◽

Rauirys Alencar de Oliveira ◽

Airton Abrahão Martin

Keyword(s):

Peripheral Arterial Disease ◽

Strong Correlation ◽

Ankle Brachial Index ◽

Arterial Disease ◽

Lower Limbs ◽

Wilcoxon Test ◽

Arterial Calcification ◽

The Mean ◽

Peripheral Arterial ◽

Spearman’S Correlation

Objectives To correlate the ankle-brachial index and photographic thermography findings in patients with peripheral arterial disease. Methods Photographic thermography was performed at the foot level, and ankle-brachial index was measured in 72 lower limbs of 53 patients with peripheral arterial disease who were divided into calcified artery, patients with an ankle-brachial index greater than 1.4; and non-calcified artery classified as asymptomatic, mild, moderate, and severe on the basis of peripheral arterial disease severity. Fisher’s exact test was used for categorical data, and Wilcoxon test was used for numerical data. Results Spearman’s correlation analysis showed a strong correlation (R = 0.7) between the ankle-brachial index and the mean plantar temperature in patients without lower limb artery calcification. Linear regression yielded the predictor equation Y = 3.296 × X + 29.75, wherein ankle-brachial index (X) can be predicted on the basis of temperature values. Spearman’s correlation test showed no significance ( p = 0.2174) in patients with arterial calcification. Kruskal–Wallis test with post hoc analysis using Dunn’s test for multiple comparisons showed that the mean plantar temperature was lower in patients with arterial calcification. Conclusion Photographic thermography findings show a strong correlation with ankle-brachial index in patients with non-calcified arteries.

Download Full-text

The Contribution of Arterial Calcification to Peripheral Arterial Disease in Pseudoxanthoma Elasticum

PLoS ONE ◽

10.1371/journal.pone.0096003 ◽

2014 ◽

Vol 9 (5) ◽

pp. e96003 ◽

Cited By ~ 12

Author(s):

Georges Leftheriotis ◽

Gilles Kauffenstein ◽

Jean François Hamel ◽

Pierre Abraham ◽

Olivier Le Saux ◽

...

Keyword(s):

Peripheral Arterial Disease ◽

Pseudoxanthoma Elasticum ◽

Arterial Disease ◽

Arterial Calcification ◽

Peripheral Arterial

Download Full-text

Aortoiliac and femoropopliteal lesions in patients with concomitant peripheral arterial disease and medial arterial calcification

Ultraschall in der Medizin - European Journal of Ultrasound ◽

10.1055/s-2007-988963 ◽

2007 ◽

Vol 28 (S 1) ◽

Author(s):

S Crisan ◽

D Crisan ◽

S Vesa ◽

M Chirila ◽

C Pestrea ◽

...

Keyword(s):

Peripheral Arterial Disease ◽

Arterial Disease ◽

Arterial Calcification ◽

Peripheral Arterial ◽

Medial Arterial Calcification

Download Full-text

Hallucal thenar index: A new index to detect peripheral arterial disease using laser speckle flowgraphy

Vascular ◽

10.1177/1708538120938935 ◽

2020 ◽

pp. 170853812093893

Author(s):

Kazuhiro Tsunekawa ◽

Fumio Nagai ◽

Tamon Kato ◽

Ikkei Takashimizu ◽

Daisuke Yanagisawa ◽

...

Keyword(s):

Blood Flow ◽

Peripheral Arterial Disease ◽

Operating Characteristic ◽

Ankle Brachial Index ◽

Arterial Disease ◽

Laser Speckle ◽

Laser Speckle Flowgraphy ◽

Skin Perfusion ◽

Peripheral Arterial ◽

Cutaneous Blood

Objectives Laser speckle flowgraphy is a technology using reflected scattered light for visualization of blood distribution, which can be used to measure relative velocity of blood flow easily without contact with the skin within a short time. It was hypothesized that laser speckle flowgraphy may be able to identify foot ischemia. This study was performed to determine whether laser speckle flowgraphy could distinguish between subjects with and without peripheral arterial disease. Materials and methods All subjects were classified based on clinical observations using the Rutherford classification: non-peripheral arterial disease, class 0; peripheral arterial disease group, class 2–5. Rutherford class 6 was one of the exclusion criteria. Laser speckle flowgraphy measured the beat strength of skin perfusion as an indicator of average dynamic cutaneous blood flow change synchronized with the heartbeat. The beat strength of skin perfusion indicates the strength of the heartbeat on the skin, and the heartbeat strength calculator in laser speckle flowgraphy uses the blood flow data to perform a Fourier transform to convert the temporal changes in blood flow to a power spectrum. A total of 33 subjects with peripheral arterial disease and 40 subjects without peripheral arterial disease at a single center were prospectively examined. Laser speckle flowgraphy was used to measure hallucal and thenar cutaneous blood flow, and the measurements were repeated three times. The hallucal and thenar index was defined as the ratio of beat strength of skin perfusion value on hallux/beat strength of skin perfusion value on ipsilateral thenar eminence. The Mann–Whitney U-test was used to compare the median values of hallucal and thenar index and ankle brachial index between the two groups. A receiver operating characteristic curve for hallucal and thenar index of beat strength of skin perfusion was plotted, and a cutoff point was set. The correlation between hallucal and thenar index of beat strength of skin perfusion and ankle brachial index was explored in all subjects, the hemodialysis group, and the non-hemodialysis (non-hemodialysis) group. Results The median value of the hallucal and thenar index of beat strength of skin perfusion was significantly different between subjects with and without peripheral arterial disease (0.27 vs. 0.87, respectively; P < 0.001). The median value of ankle brachial index was significantly different between subjects with and without peripheral arterial disease (0.8 vs. 1.1, respectively; P < 0.001). Based on the receiver operating characteristic of hallucal and thenar index, the cutoff was 0.4416 and the sensitivity, specificity, positive predictive value, and negative predictive value were 68.7%, 95%, 91.7%, and 77.6%, respectively. The correlation coefficients of all subjects, the hemodialysis group, and the non-hemodialysis group were 0.486, 0.102, and 0.743, respectively. Conclusions Laser speckle flowgraphy is a noninvasive, rapid, and widely applicable method. Laser speckle flowgraphy using hallucal and thenar index would be helpful to determine the differences between subjects with and without peripheral arterial disease. The correlation between hallucal and thenar index of beat strength of skin perfusion and ankle brachial index indicated that this index was especially useful in the non-hemodialysis group.

Download Full-text

The Role of Circulating Biomarkers in Peripheral Arterial Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22073601 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3601

Author(s):

Goren Saenz-Pipaon ◽

Esther Martinez-Aguilar ◽

Josune Orbe ◽

Arantxa González Miqueo ◽

Leopoldo Fernandez-Alonso ◽

...

Keyword(s):

Peripheral Arterial Disease ◽

Lower Limb ◽

Prediction Models ◽

Arterial Disease ◽

Cardiac Damage ◽

Thrombotic Occlusion ◽

Medical Treatments ◽

Peripheral Arterial ◽

Inflammatory Molecules

Peripheral arterial disease (PAD) of the lower extremities is a chronic illness predominantly of atherosclerotic aetiology, associated to traditional cardiovascular (CV) risk factors. It is one of the most prevalent CV conditions worldwide in subjects >65 years, estimated to increase greatly with the aging of the population, becoming a severe socioeconomic problem in the future. The narrowing and thrombotic occlusion of the lower limb arteries impairs the walking function as the disease progresses, increasing the risk of CV events (myocardial infarction and stroke), amputation and death. Despite its poor prognosis, PAD patients are scarcely identified until the disease is advanced, highlighting the need for reliable biomarkers for PAD patient stratification, that might also contribute to define more personalized medical treatments. In this review, we will discuss the usefulness of inflammatory molecules, matrix metalloproteinases (MMPs), and cardiac damage markers, as well as novel components of the liquid biopsy, extracellular vesicles (EVs), and non-coding RNAs for lower limb PAD identification, stratification, and outcome assessment. We will also explore the potential of machine learning methods to build prediction models to refine PAD assessment. In this line, the usefulness of multimarker approaches to evaluate this complex multifactorial disease will be also discussed.

Download Full-text