FABP4 and Cardiovascular Events in Peripheral Arterial Disease

Höbaus, Clemens; Herz, Carsten Thilo; Pesau, Gerfried; Wrba, Thomas; Koppensteiner, Renate; Schernthaner, Gerit‐Holger

doi:10.1177/0003319717728226

Cited by 23 publications

(21 citation statements)

References 34 publications

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“…The 18 articles that were not selected studied α-defensin, 21 matrix metalloproteinase 10, 59 galectin-3, 60 soluble tumor necrosis–like weak inducer of apoptosis, 61 ferritin, 62 activated protein C–protein C inhibitor complex, 63 angiopoietin-related growth factor, 64 fatty acid–binding protein 4, 65 alkyl-phosphatidylcholine and alkenylphosphatidylcholine lipids, 66 high-density lipoprotein cholesterol, 66 malondialdehyde-modified low-density lipoprotein, 67 lipoprotein-associated phospholipase A2, 68 cardiac troponin I, 69 phosphate, 70 carboxy-terminal telopeptide of type I collagen, 15 cholinesterase, 71 eicosapentaenoic acid/arachidonic acid ratio, 72 or endothelin-1. 73 …”

Section: Resultsmentioning

confidence: 99%

Plasma Biomarkers to Predict Cardiovascular Outcome in Patients With Peripheral Artery Disease

Kremers

Wübbeke

Mees

et al. 2020

ATVB

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Objective: Patients with lower extremity peripheral artery disease (PAD) are at increased risk of major adverse cardiovascular events. Numerous plasma biomarkers have been investigated in lower extremity PAD, but none are used for clinical risk assessments. We aimed to provide a comprehensive overview of biomarker testing in PAD as a first step to improve risk stratification. Approach and Results: A systematic literature review in MEDLINE/PubMed, Cochrane, and Embase was performed, identifying all studies investigating plasma biomarkers in association with cardiovascular events and mortality in lower extremity PAD. Forty-seven studies comprising 21 473 PAD patients met our criteria and were included. Effect estimates were provided by the studies based on a minimum follow-up of 1 year. Meta-analyses were performed by pooling studies per biomarker for each end point. Patients with increased high-sensitivity CRP (C-reactive protein) levels had a relative risk of 1.86 (1.48–2.33) for major adverse cardiovascular events and a relative risk of 3.49 (2.35–5.19) for mortality. Increased fibrinogen and d -dimer levels were associated with an increased relative risk of mortality of 2.08 (1.46–2.97) and 2.22 (1.24–3.98), respectively. Additionally, patients with increased NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity cTnT (cardiac troponin T) levels were at an even higher risk of mortality with relative risks of 4.50 (2.98–6.81) and 3.33 (2.70–4.10), respectively. Conclusions: This systematic review identifies promising biomarkers representing different pathophysiological processes implicated in lower extremity PAD, including high-sensitivity CRP, neutrophil-lymphocyte ratio, fibrinogen, d -dimer, NT-proBNP, and high-sensitivity cTnT. Clinical implementation should be preceded by a management study to test the utility of a combination of these markers for individual risk stratification. Ultimately, this may contribute to tailored treatment and increased effectiveness of current treatment strategies in PAD.

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Section: Resultsmentioning

confidence: 99%

Plasma Biomarkers to Predict Cardiovascular Outcome in Patients With Peripheral Artery Disease

Kremers

Wübbeke

Mees

et al. 2020

ATVB

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“…Tuncman et al provided genetic support for the involvement of A-FABP in atherosclerosis in humans, where a reduction in A-FABP activity generated a metabolically favorable phenotype 29 while Furuhashi et al showed that inhibiting A-FABP is effective against severe atherosclerosis and type 2 diabetes in mice 30 . Human studies showed an association between A-FABP and coronary heart disease 31 and has also been shown to be associated with peripheral arterial disease 32 . According to one study, A-FABP reduces the expression of leptin in mice adipocytes 33 , while another study in leptin deficient mice showed an impaired gene expression for lipid utilization for, amongst other proteins, A-FABP 34 .…”

Section: Discussionmentioning

confidence: 99%

Using proximity extension proteomics assay to discover novel biomarkers associated with circulating leptin levels in patients with type 2 diabetes

Vavruch

Nowak

Feldreich

et al. 2020

Sci Rep

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We aimed to discover novel associations between leptin and circulating proteins which could link leptin to the development of cardiovascular disease in patients with type 2 diabetes (T2DM). In a discovery phase, we investigated associations between 88 plasma proteins, assessed with a proximity extension assay, and plasma leptin in a cohort of middle-aged patients with T2DM. Associations passing the significance threshold of a False discovery rate of 5% (corresponding to p < 0.0017) were replicated in patients with T2DM in an independent cohort. We also investigated if proteins mediated the longitudinal association between plasma leptin and the incidence of major cardiovascular events (MACE). One protein, adipocyte fatty acid binding protein (A-FABP), was significantly associated with leptin in both the discovery phase [95% CI (0.06, 0.17) p = 0.00002] and the replication cohort [95% CI (0.12, 0.39) p = 0.0003]. Multiplicative interaction analyses in the two cohorts suggest a stronger association between A-FABP and leptin in men than in women. In longitudinal analyses, the association between leptin and MACE was slightly attenuated after adding A-FABP to the multivariate model. Our analysis identified a consistent association between leptin and A-FABP in two independent cohorts of patients with T2DM, particularly in men. Trial registration: ClinicalTrials.gov identifier NCT 01049737. Abbreviations ADM Adrenomedullin A-FABP Adipocyte fatty acid binding protein BMI Body mass index CARDIPP Cardiovascular risk factors in patients with diabetes-a prospective study in primary care CHD Coronary heart disease CRP C-reactive protein CVD Cardiovascular disease HDL High density lipoprotein HR Hazard ratio LDL Low density lipoprotein LOD Limit of detection MACE Major adverse cardiac events PCR Polymerase chain reaction

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“…In line with TWEAK, preclinical evidence supports a cardioprotective role for PON3 (which was also independently associated with incident HF in the multivariable model). FABP4 is predominantly expressed in macrophages and adipose tissue where it regulates fatty acids storage and lipolysis; FABP4 is also an important mediator of inflammation that has been associated with higher risk of cardiovascular events 60,61 . RARRES2 (or chemerin) is an adipose-derived signalling molecule that regulates adipogenesis and adipocyte metabolism, and it has also been associated with higher risk of cardiovascular events 62,63 .…”

Section: Metabolism Clustermentioning

confidence: 99%

Proteomic Bioprofiles and Mechanistic Pathways of Progression to Heart Failure

Ferreira

Verdonschot

Collier

et al. 2019

Circ: Heart Failure

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Background: Identifying the mechanistic pathways potentially associated with incident HF may provide a basis for novel preventive strategies. Methods and Results:To identify proteomic biomarkers and the potential underlying mechanistic pathways that may be associated with incident HF defined as first hospitalization for HF, a nestedmatched case-control design was used with cases (incident HF) and controls (without HF) selected from 3 cohorts (>20,000 individuals). Controls were matched on cohort, follow-up time, age, and sex.Two independent sample sets (a "discovery" set, with 286 cases and 591 controls and a "replication" set with 276 cases and 280 controls) were used to discover and replicate the findings. 252 circulating proteins in the plasma were studied. Adjusting for the matching variables age, sex, and follow-up time (and correcting for multiplicity of tests), 89 proteins were found to be associated with incident HF in the discovery phase, of which 38 were also associated with incident HF in the replication phase.These 38 proteins pointed to 4 main network clusters underlying incident HF: 1) inflammation and apoptosis, indicated by the expression of the TNF-family members; 2) extracellular matrix remodelling, angiogenesis and growth, indicated by the expression of proteins associated with collagen metabolism, endothelial function and vascular homeostasis; 3) blood pressure regulation, indicated by the expression of natriuretic peptides and proteins related to the renin angiotensin aldosterone system; and 4) metabolism, associated with cholesterol and atherosclerosis.Conclusion: Clusters of biomarkers associated with mechanistic pathways leading to HF were identified linking inflammation, apoptosis, vascular function, matrix remodelling, blood pressure control and metabolism. These findings provide important insight on the pathophysiological mechanisms leading to HF.

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FABP4 and Cardiovascular Events in Peripheral Arterial Disease

Cited by 23 publications

References 34 publications

Plasma Biomarkers to Predict Cardiovascular Outcome in Patients With Peripheral Artery Disease

Plasma Biomarkers to Predict Cardiovascular Outcome in Patients With Peripheral Artery Disease

Using proximity extension proteomics assay to discover novel biomarkers associated with circulating leptin levels in patients with type 2 diabetes

Proteomic Bioprofiles and Mechanistic Pathways of Progression to Heart Failure

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