Meta-analysis and meta-regression analysis of biomarkers for abdominal aortic aneurysm

Stather, P.W.; Sidloff, David; Dattani, Nikesh; Gokani, V.J.; Choke, Edward; Sayers, Robert D.; Bown, Matthew J.

doi:10.1002/bjs.9593

Cited by 79 publications

(61 citation statements)

References 127 publications

(525 reference statements)

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“…These include markers related to thrombus remodeling (eg, D-dimer), the extracellular matrix (eg, aminoterminal propeptide of type III procollagen), proteolytic enzymes (eg, matrix metalloproteinase-9), lipids (eg, high-density lipoprotein), and inflammation (eg, interleukin-6). 53,54 In contrast, there have been fewer studies investigating circulating markers associated with AAA progression. Studies of this type are difficult to design and carry out for many reasons.…”

Section: Current Research To Identify Circulating Markers Of Aaa Progmentioning

confidence: 99%

Surrogate Markers of Abdominal Aortic Aneurysm Progression

Wanhainen

Mani

Golledge

2016

ATVB

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Abstract-The natural course of many abdominal aortic aneurysms (AAA) is to gradually expand and eventually rupture and monitoring the disease progression is essential to their management. In this publication, we review surrogate markers of AAA progression. AAA diameter remains the most widely used and important marker of AAA growth. Wanhainen et al Surrogate Markers of Aneurysm Progression 237in all studies when a standardized protocol is used. 7,8 One of the challenging aspects to assessing maximum AAA diameter is the variety of methods that can potentially be used and the lack of reporting of the exact techniques used in individual studies. Variations may occur in the plane of acquisition (eg, coronal or sagittal), the axis of measurement (eg, axial or orthogonal), the position of the measuring calipers (eg, inner to inner or outer to outer), the relationship with the cardiac cycle (systole versus diastole), and the selected region of the AAA. 9 It has been suggested that diameters measured perpendicular to the aorta centerline (orthogonal), rather than within the axial plane, are more representative of the true AAA diameter. 4,6 With ultrasound, measurements within the anteroposterior, rather than the transverse plane, have been reported to be more reproducible. 4 There is no current consensus on how to place the calipers when measuring the diameter with ultrasound. Methods used include the outer-to-outer method, where calipers are placed on the outer layer of the aortic wall; the inner-to-inner method, where calipers are placed on the inner layer of the aortic wall; and the leading edge-to-leading edge method, where calipers are placed on the outer layer of the anterior wall and the inner layer of the posterior wall ( Figure 1). Much of the reported variation in ultrasound measured AAA diameter is likely because of the variation in caliper placement. 5,10 The UK Small Aneurysm Trial 11 is based on the measurement of AAA diameter on the outer-to-outer method, and this method has been adopted into the current UK intervention criteria. 12 The inner-to-inner method was used in the Multicentre Aneurysm Screening Study, 13 and consequently it is used in the current UK National Health Service AAA screening programme.14 The leading edgeto-leading edge method is used in the current Swedish AAA screening programme.15 Studies comparing these methods show there is a significant difference in diameters measured with the different methods, which has an impact on the reported prevalence rates of AAA. 5,10 In a Swedish AAA screening study, the difference in mean diameter was 4 mm between inner-toinner and outer-to-outer, which resulted in an astonishing 77% difference in AAA prevalence (ie, 1.3% compared with 2.3%). 5A systematic review of 15 studies reported considerable variation in small AAA growth rates (mean, −0.3 to +4.0 mm/y). 15 The variation could not be explained by differences in initial AAA diameter alone. 16 The authors suggested that methodological issues, such as differences in imaging modalities, variation ...

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Section: Current Research To Identify Circulating Markers Of Aaa Progmentioning

confidence: 99%

Surrogate Markers of Abdominal Aortic Aneurysm Progression

Wanhainen

Mani

Golledge

2016

ATVB

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“…Most commonly, investigators have measured blood concentrations of analytes to assess its possible role in the pathogenesis or progression of AAA, 8,18,19 and recently Folsom et al. 16 found that multiple positive biomarkers of inflammation identify a subgroup of patients at high risk of AAA.…”

Section: Discussionmentioning

confidence: 99%

Prediction of abdominal aortic aneurysm calcification by means of variation of high-sensitivity C-reactive protein

Garrafa

Giacomelli

Ravanelli

et al. 2016

JRSM Cardiovascular Disease

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ObjectiveAbdominal aortic aneurysms are a major cause of death in developed countries, and thrombus and calcification of the aneurysm have been linked to increased complications. This study was conducted in order to identify the biochemical marker associated to the presence of intraluminal thrombus or calcification progression of the aneurysm.DesignSeveral clinical laboratory parameters were measured in patients with abdominal aortic aneurysms, in particular those already demonstrated to be related to the pathology, such as lipoprotein (a), white blood cell count, fibrinogen and high-sensitivity C-reactive protein. Most of the patients were analysed for the presence of thrombus or aorta calcification using CT angiography.ResultsUnlike previous findings, we found no association between intraluminal thrombus formation and lipoprotein (a), but we evidenced that patients with lower grade of calcification tend to have higher plasma high-sensitivity C-reactive protein values compared with patients with a higher degree of calcification. Instead, no association was found with either white blood cell count or fibrinogen level.ConclusionsThis study suggests that high-sensitivity C-reactive protein is a useful biomarker to assess the evolution of calcification and could be used in triaging patients to identify those who should undergo a rapid imaging, thus allowing prompt initiation of treatment or rule-out suspicious patients from non-essential imaging repetition.

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“…Clinical and epidemiological studies consistently link low HDL cholesterol levels to an elevated risk of cardiovascular disease. A recent meta-analysis also revealed a negative association of HDL cholesterol levels with AAA in most studies10. HDLs are additionally a transport platform for constitutive and non-permanently associated plasma proteins.…”

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confidence: 91%

Quantitative HDL Proteomics Identifies Peroxiredoxin-6 as a Biomarker of Human Abdominal Aortic Aneurysm

Burillo

Jorge

Martínez-López

et al. 2016

Sci Rep

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High-density lipoproteins (HDLs) are complex protein and lipid assemblies whose composition is known to change in diverse pathological situations. Analysis of the HDL proteome can thus provide insight into the main mechanisms underlying abdominal aortic aneurysm (AAA) and potentially detect novel systemic biomarkers. We performed a multiplexed quantitative proteomics analysis of HDLs isolated from plasma of AAA patients (N = 14) and control study participants (N = 7). Validation was performed by western-blot (HDL), immunohistochemistry (tissue), and ELISA (plasma). HDL from AAA patients showed elevated expression of peroxiredoxin-6 (PRDX6), HLA class I histocompatibility antigen (HLA-I), retinol-binding protein 4, and paraoxonase/arylesterase 1 (PON1), whereas α-2 macroglobulin and C4b-binding protein were decreased. The main pathways associated with HDL alterations in AAA were oxidative stress and immune-inflammatory responses. In AAA tissue, PRDX6 colocalized with neutrophils, vascular smooth muscle cells, and lipid oxidation. Moreover, plasma PRDX6 was higher in AAA (N = 47) than in controls (N = 27), reflecting increased systemic oxidative stress. Finally, a positive correlation was recorded between PRDX6 and AAA diameter. The analysis of the HDL proteome demonstrates that redox imbalance is a major mechanism in AAA, identifying the antioxidant PRDX6 as a novel systemic biomarker of AAA.

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Meta-analysis and meta-regression analysis of biomarkers for abdominal aortic aneurysm

Abstract: A wide variety of biomarkers are dysregulated in patients with AAA, but their clinical value is yet to be established. Future research should focus on the most relevant biomarkers of AAA, and how they could be used clinically.

Cited by 79 publications

References 127 publications

Surrogate Markers of Abdominal Aortic Aneurysm Progression

Surrogate Markers of Abdominal Aortic Aneurysm Progression

Prediction of abdominal aortic aneurysm calcification by means of variation of high-sensitivity C-reactive protein

Quantitative HDL Proteomics Identifies Peroxiredoxin-6 as a Biomarker of Human Abdominal Aortic Aneurysm

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