Increased Collagen Turnover Is a Feature of Fibromuscular Dysplasia and Associated With Hypertrophic Radial Remodeling: A Pilot, Urine Proteomic Study

Author(s):  
Agnieszka Latosinska ◽  
Rosa Maria Bruno ◽  
Marco Pappaccogli ◽  
Alessandra Bacca ◽  
Christophe Beauloye ◽  
...  

Fibromuscular dysplasia (FMD), a nonatherosclerotic, noninflammatory disease of medium-sized arteries, is an underdiagnosed disease. We investigated the urinary proteome and developed a classifier for discrimination of FMD from healthy controls and other diseases. We further hypothesized that urinary proteomics biomarkers may be associated with alterations in medium-sized, but not large artery geometry and mechanics. The study included 33 patients with mostly multifocal, renal FMD who underwent in depth arterial exploration using ultra-high frequency ultrasound. The cohort was separated in a training set of 23 patients with FMD from Belgium and an independent test set of 10 patients with FMD from Italy. For each set, controls matched 2:1 were selected from the Human Urinary Proteome Database. The specificity of the classifier was tested in 700 additional controls from general population studies, patients with chronic kidney disease (n=66) and coronary artery disease (n=31). Three hundred thirty-five urinary peptides, mostly related to collagen turnover, were identified in the training cohort and combined into a classifier. When applying in the test cohort, the area under the receiver operating characteristic curve was 1.00, 100% specificity at 100% sensitivity. The classifier maintained a high specificity in additional controls (98.3%), patients with chronic kidney (90.9%) and coronary artery (96.8%) diseases. Furthermore, in patients with FMD, the proteomic score was positively associated with radial wall thickness and wall cross-sectional area. In conclusion, a proteomic score has the potential to discriminate between patients with FMD and controls. If confirmed in a wider and more diverse cohort, these findings may pave the way for a noninvasive diagnostic test of FMD.

2020 ◽  
Vol 35 (6) ◽  
pp. 1022-1022
Author(s):  
Abramson D ◽  
White D ◽  
Resch Z ◽  
Ovsiew G ◽  
Soble J

Abstract Objective The Boston Naming Test (BNT) has recently been proposed as an embedded performance validity test (PVT) with high specificity/low sensitivity; however, this has not been replicated. This study therefore aimed to cross-validate findings in a mixed clinical neuropsychiatric sample. Method This cross-sectional study of 136 primary monolingual English-speaking patients who completed the BNT during outpatient evaluation was 57% female/43% male, 38% Caucasian, 39% African American, 16% Hispanic, and 6% Asian with mean age of 47.7 years (SD = 16.6) and mean education of 14.0 years (SD = 2.7). In total, 109/136 (80%) were classified as valid and 27/136 (20%) as invalid based on 4 independent criterion PVTs. Results Respective mean BNT raw/T-scores were 49.5 (SD = 9.2)/45.3 (SD = 10.9) for the valid group and 45.8 (SD = 8.2)/41.1 (SD = 7.8) for the invalid group. Analyses of variance fell just above significance for both BNT raw F(1, 134) = 3.75, p = .05 and T-scores F(1, 134) = 3.55, p = .06. Receiver operator characteristic curve analysis for the raw score was significant, with an area under the curve (AUC) of .67 (p < .01) and an optimal cutoff of ≤ 35 (4% specificity/90% sensitivity). BNT raw scores remained significant after removing bilingual participants, (AUC = .68; p < .01), with identical psychometric properties. In contrast, analysis of BNT T-scores (AUC = .61; p = .08) were nonsignificant. Conclusions Overall, results showed that the BNT cannot psychometrically distinguish valid versus invalid performance and therefore has questionable utility as a PVT in a mixed clinical setting. Findings contribute to a growing literature base cautioning against the indiscriminate use of measures of actual cognitive ability as validity indicators, particularly in populations with cognitive impairment.


Author(s):  
Stéphane Jaisson ◽  
Mohsen Kerkeni ◽  
Izabella C.R. Santos-Weiss ◽  
Faouzi Addad ◽  
Mohammed Hammami ◽  
...  

AbstractCarbamylation is a non-enzymatic post-translational modification of proteins that has been recently identified as a non-traditional risk factor for atherosclerosis. The aim of this study was to determine whether serum homocitrulline (HCit), a characteristic carbamylation-derived product, was related to the presence and the severity of coronary artery disease (CAD).Forty-five control subjects and 109 patients were included in this cross-sectional study. After coronary angiography, the patients were classified as non-CAD patients (patients with normal arteries, n=33) and CAD patients (n=76). The severity of CAD was then evaluated using the Gensini scoring system. Serum total HCit concentrations were determined by LC-MS/MS.Serum HCit concentrations were significantly (p<0.001) higher in CAD patients than in control or non-CAD subjects. The receiver operating characteristic curve analysis showed an area under the curve equal to 0.908 (95% confidence interval, 0.853–0.964, p<0.001) and a threshold HCit concentration of 0.16 mmol/mol Lys for predicting the presence of CAD (78.9% sensitivity and 78.8% specificity). HCit concentrations significantly (p<0.001) increased concomitantly with the severity of CAD and were positively correlated with Gensini scores (r=0.725, p<0.001) as well as with the number of stenotic coronary arteries (p<0.001). Furthermore, in a multiple stepwise regression analysis, HCit was significantly (p<0.001) and independently associated with the presence of CAD, the Gensini score, and the number of stenotic arteries (standardized β values of 0.525, 0.722, and 0.642, respectively).Our results demonstrate that serum HCit concentrations are increased during CAD and are positively associated with the severity of the disease.


Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Rosa Maria Bruno ◽  
Nicole Di Lascio ◽  
Daniela Guarino ◽  
Saverio Vitali ◽  
Piercarlo Rossi ◽  
...  

Aim: This case-control study is aimed at identifying radial vascular wall abnormalities in patients with fibromuscular dysplasia (FMD). Methods: High-frequency ultrasound scans of the radial arteries and of FMD patients and healthy controls were obtained by Vevo MD (70 MHz probe, FUJIFILM, VisualSonics, Toronto, Canada). Radial wall showed in all individuals two echogenic interfaces: the 1 st ( lumen-media) and the 2 nd (media-adventitia). Intima-media (IMT), adventitia (AT), and global thickness (IMAT) were measured and wall cross-sectional area (WCSA) calculated. The disarray level of the two echogenic interfaces was assessed calculating the root mean square error (RMSE) between 20 gray-level profiles crossing the two interfaces and the profile obtained averaging them. For each echogenic interface, the RMSE was normalized for the maximum value of the corresponding mean profile (RMSE/mean). Results: 11 treated hypertensive female FMD patients and 8 healthy control women (C) were enrolled (age 52±5 vs 45±13 years, p=0.51; BMI 26±3 vs 23±3, p=0.12; mean BP 97±7 vs 85±10, p=0.01). Radial internal diameter was similar (1.938±0.432 vs 1.701±0.532 mm, p=0.21). IMT (0.166±0.037 vs 0.128±0.022 mm, p=0.03), AT (0.114±0.029 vs 0.083±0.019 mm, p=0.008) and IMAT (0.281±0.042 vs 0.211±0.027 mm, p=0.003) were higher in FMD. Wall/lumen ratio was similar and WCSA increased in FMD, calculated with either IMT or IMAT. The maximum values of 1 st (121±43 vs 157±22, p=0.09) and 2 nd interface 109 ±44 vs133±18, p=0.09) tended to be lower, whereas RMSE/mean was higher in FMD (1 st 1.31±0.24 vs 0.83±0.32, p=0.006; 2 nd 1.37±0.38 vs 0.94±0.32, p=0.03). The difference was attenuated for the 1 st but not for the 2 nd interface when considering age and mean BP as covariates (p=0.054 and p=0.016 respectively). Conclusions: Wall ultrastructure of radial arteries of hypertensive FMD patients showed eutrophic remodeling. Furthermore, a peculiar “blurred” pattern occurred, characterized of loss of echogenicity and inhomogeneity of the two echogenic layers, independent of age and mean BP.


Cardiology ◽  
2017 ◽  
Vol 139 (1) ◽  
pp. 25-32 ◽  
Author(s):  
Cai De Jin ◽  
Moo Hyun Kim ◽  
Eun Ju Kang ◽  
Young Rak Cho ◽  
Tae Ho Park ◽  
...  

Background: Diminished vascular tone is an established biomarker of heart damage. Little is known about the extent of coronary vessel tone (CVT) with spasm as assessed by dual-acquisition multidetector computed tomography angiography (MCTA) in patients with vasospastic angina (VSA). Objective: We evaluated the CVT modulated by intravenous nitrate injection (INI) using MCTA imaging in VSA patients. Methods: Twenty-one VSA patients (60 ± 9 years; 76% males) who underwent initial MCTA (without morning vasodilation), followed by an intracoronary ergonovine provocation test were included. Within 3 days after the initial MCTA patients received INI followed by 28-vessel segment spasm analyzed by MCTA 3D software, applying the following formula as the definition of CVT index (CVTI): (CSAIV nitrate - CSAinitial/CSAIV nitrate) ×100 %, where CSA is the cross-sectional area. Results: Compared to the initial MCTA measures, the INI provocation resulted in the significant increase of average diameter and CSA at the spasm site (2.60 mm [2.11-3.16] vs. 1.42 mm [1.13-2.13]; 5.37 mm2 [3.67-7.54] vs. 1.62 mm2 [1.02-3.02]; p < 0.001). The CVTI at the spastic segments was higher than at the proximal reference segments (41.0% [21.8-52.3] vs. 18.8% [5.9-26.6] for CVTI diameter; 65.1% [38.6-77.0] vs. 33.9% [5.2-48.1] for CVTI CSA, respectively). To predict VSA, the cut-off value for CVTI diameter was 38.6% (AUC 0.777; 95% CI 0.653-0.901) and 62.5% (AUC 0.779; 95% CI 0.657-0.902) for CVTI CSA in a receiver-operating characteristic curve analysis, with 57.1% sensitivity and 92.9% specificity. Conclusions: This novel imaging technique for assessing CVT by dual-acquisition MCTA after applying INI provocation is suitable for the detection of coronary artery spasm in patients with VSA.


2020 ◽  
Vol 41 (46) ◽  
pp. 4400-4411 ◽  
Author(s):  
Shen Lin ◽  
Zhigang Li ◽  
Bowen Fu ◽  
Sipeng Chen ◽  
Xi Li ◽  
...  

Abstract Aims Facial features were associated with increased risk of coronary artery disease (CAD). We developed and validated a deep learning algorithm for detecting CAD based on facial photos. Methods and results We conducted a multicentre cross-sectional study of patients undergoing coronary angiography or computed tomography angiography at nine Chinese sites to train and validate a deep convolutional neural network for the detection of CAD (at least one ≥50% stenosis) from patient facial photos. Between July 2017 and March 2019, 5796 patients from eight sites were consecutively enrolled and randomly divided into training (90%, n = 5216) and validation (10%, n = 580) groups for algorithm development. Between April 2019 and July 2019, 1013 patients from nine sites were enrolled in test group for algorithm test. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated using radiologist diagnosis as the reference standard. Using an operating cut point with high sensitivity, the CAD detection algorithm had sensitivity of 0.80 and specificity of 0.54 in the test group; the AUC was 0.730 (95% confidence interval, 0.699–0.761). The AUC for the algorithm was higher than that for the Diamond–Forrester model (0.730 vs. 0.623, P &lt; 0.001) and the CAD consortium clinical score (0.730 vs. 0.652, P &lt; 0.001). Conclusion Our results suggested that a deep learning algorithm based on facial photos can assist in CAD detection in this Chinese cohort. This technique may hold promise for pre-test CAD probability assessment in outpatient clinics or CAD screening in community. Further studies to develop a clinical available tool are warranted.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Paul Nderitu ◽  
◽  
Joan M. Nunez do Rio ◽  
Rajna Rasheed ◽  
Rajiv Raman ◽  
...  

AbstractScreening effectively identifies patients at risk of sight-threatening diabetic retinopathy (STDR) when retinal images are captured through dilated pupils. Pharmacological mydriasis is not logistically feasible in non-clinical, community DR screening, where acquiring gradable retinal images using handheld devices exhibits high technical failure rates, reducing STDR detection. Deep learning (DL) based gradability predictions at acquisition could prompt device operators to recapture insufficient quality images, increasing gradable image proportions and consequently STDR detection. Non-mydriatic retinal images were captured as part of SMART India, a cross-sectional, multi-site, community-based, house-to-house DR screening study between August 2018 and December 2019 using the Zeiss Visuscout 100 handheld camera. From 18,277 patient eyes (40,126 images), 16,170 patient eyes (35,319 images) were eligible and 3261 retinal images (1490 patient eyes) were sampled then labelled by two ophthalmologists. Compact DL model area under the receiver operator characteristic curve was 0.93 (0.01) following five-fold cross-validation. Compact DL model agreement (Kappa) were 0.58, 0.69 and 0.69 for high specificity, balanced sensitivity/specificity and high sensitivity operating points compared to an inter-grader agreement of 0.59. Compact DL gradability model performance was favourable compared to ophthalmologists. Compact DL models can effectively classify non-mydriatic, handheld retinal image gradability with potential applications within community-based DR screening.


2021 ◽  
Vol 27 ◽  
pp. 107602962199972
Author(s):  
Ming Yu ◽  
Hanyun Zhou ◽  
Qingan Li ◽  
Juan Ding ◽  
Hongxia Shuai ◽  
...  

We investigated the association between serum adenosine deaminase and coronary artery calcification (CAC) in type 2 diabetes mellitus (T2DM) patients. The cross-sectional study included 459 patients with T2DM, the clinical and laboratory tests were performed, and all T2DM patients were separated into the 3 groups based on the tertile of serum adenosine deaminase levels. In the baseline data, the CAC score had statistically significant differences between the 3 groups (p < 0.001). Serum adenosine deaminase levels were positively correlated with CAC score in T2DM patients (r = 0.355, p < 0.001). The results of multiple linear regression analysis showed that serum adenosine deaminase was independent positively correlated with CAC score in T2DM patients (r = 0.255, p < 0.001). Receiver-operating characteristic curve analysis showed that area under curve was 0.750 to identify T2DM patients with CAC. Serum adenosine deaminase levels are correlated with CAC scores in T2DM patients, clinically, serum adenosine deaminase should be considered as an underlying marker to determine the severity of atherosclerosis in T2DM patients.


2014 ◽  
pp. 48-56
Author(s):  
Van Thi Tran ◽  
Van Bang Le ◽  
Thị Thu Huong Hoang

Aim: Some studies have linked the present of chronic obstructive oulmonary disease (COPD) to coronary artery disease (CAD). Low grade systemic inflammation occurs in patients with COPD as well as patients with CAD. This study was designed to find out the concentration differences of hs-CRP and TNF-a in patients having both chronic obstructive pulmonary and coronary artery diseases with those having either. Methods: A cross - sectional descriptive study was conducted in 200 patients undergoing a coronary artery angiography in the Heart Institute, Thong Nhat Hospital and 115 People Hospital. COPD was diagnosed using GOLD classification. Result: Our study had shown that the levels of hs-CRP and TNF-a were statistically increased in patients with COPD, CAD as well as in patients who had COPD with CAD (p<0,05). The levels of hs-CRP were higher in CAD than in COPD nad the levels of TNF-a were higher in COPD than in CAD. In patients with COPD and CAD, there were increased the levels of both hs-CRP and TNF-a in serum. Conclusion: Systemic inflammation presents in both COPD and CAD. Key words: hs-CRP, TNF-a, coronary artery disease (CAD).


Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 949
Author(s):  
Cecil J. Weale ◽  
Don M. Matshazi ◽  
Saarah F. G. Davids ◽  
Shanel Raghubeer ◽  
Rajiv T. Erasmus ◽  
...  

This cross-sectional study investigated the association of miR-1299, -126-3p and -30e-3p with and their diagnostic capability for dysglycaemia in 1273 (men, n = 345) South Africans, aged >20 years. Glycaemic status was assessed by oral glucose tolerance test (OGTT). Whole blood microRNA (miRNA) expressions were assessed using TaqMan-based reverse transcription quantitative-PCR (RT-qPCR). Receiver operating characteristic (ROC) curves assessed the ability of each miRNA to discriminate dysglycaemia, while multivariable logistic regression analyses linked expression with dysglycaemia. In all, 207 (16.2%) and 94 (7.4%) participants had prediabetes and type 2 diabetes mellitus (T2DM), respectively. All three miRNAs were significantly highly expressed in individuals with prediabetes compared to normotolerant patients, p < 0.001. miR-30e-3p and miR-126-3p were also significantly more expressed in T2DM versus normotolerant patients, p < 0.001. In multivariable logistic regressions, the three miRNAs were consistently and continuously associated with prediabetes, while only miR-126-3p was associated with T2DM. The ROC analysis indicated all three miRNAs had a significant overall predictive ability to diagnose prediabetes, diabetes and the combination of both (dysglycaemia), with the area under the receiver operating characteristic curve (AUC) being significantly higher for miR-126-3p in prediabetes. For prediabetes diagnosis, miR-126-3p (AUC = 0.760) outperformed HbA1c (AUC = 0.695), p = 0.042. These results suggest that miR-1299, -126-3p and -30e-3p are associated with prediabetes, and measuring miR-126-3p could potentially contribute to diabetes risk screening strategies.


Angiology ◽  
2021 ◽  
pp. 000331972098459
Author(s):  
Yao-dong Ding ◽  
Yu-qiang Pei ◽  
Rui-Wang ◽  
Jia-xin Yang ◽  
Ying-xin Zhao ◽  
...  

We investigated the association between plasma microRNA (miR)-204 and coronary artery calcification (CAC) in patients with type 2 diabetes mellitus (T2DM). We consecutively enrolled 179 individuals with T2DM who underwent coronary computed tomography at Anzhen Hospital from January 2015 to September 2016. The CAC score (CACS) was expressed in Agatston units and >10 Hounsfield units were defined as CAC-positive status. Significant CAC was observed in 98 (54.7%) patients. Plasma miR-204 levels (relative expression) were significantly lower in patients with significant CAC than controls (1.001 ± 0.100 vs 0.634 ± 0.211, P < .001). Plasma miR-204 levels were also negatively correlated with the glycosylated hemoglobin A1c (HbA1c) level (r = −0.702, P < .001), CACS (r = −0.710, P < .001), and the United Kingdom Prospective Diabetes Study (UKPDS) score (r = −0.355, P < .001). After multivariate logistic analyses, plasma miR-204 levels were still significantly and independently associated with the presence of CAC (odds ratio = 0.103, CI = 0.018-0.583, P < .001) after adjustment for conventional risk factors. Receiver operating characteristic curve analysis showed that plasma miR-204 levels can predict the severity and extent of CAC, and the specificity was higher than that of the traditional risk factors UKPDS score and HbA1c. In conclusion, the downregulation of miR-204 was independently associated with CAC in patients with T2DM.


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