Increased plasma level of soluble urokinase plasminogen activator receptor is associated with incidence of heart failure but not atrial fibrillation

Borné, Yan; Persson, Margaretha; Melander, Olle; Smith, J Gustav; Engström, Gunnar

doi:10.1002/ejhf.49

Cited by 52 publications

(44 citation statements)

References 48 publications

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“…In the last decade, circulating biomarkers, such as N-terminal pro brain natriuretic peptide (NT-proBNP), have been studied for prediction of incident HF [7][8][9][10] . A recently published study 10 , also investigated the association of multiple proteins with incident HF for "prediction" purposes; these proteins (n=80) added little gain to the prognostic model including natriuretic peptides.…”

Section: Introductionmentioning

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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Section: Introductionmentioning

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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“…Elevated plasma levels of suPAR have been associated with coronary calcification,2 systemic inflammation3 and heart failure 4…”

Section: Introductionmentioning

confidence: 99%

Serum heart-type fatty acid-binding protein decreases and soluble isoform of suppression of tumorigenicity 2 increases significantly by long-term physical activity

Sponder

Lichtenauer

Wernly

et al. 2019

Journal of Investigative Medicine

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The aim of this prospective study was to investigate the influence of long-term physical activity on biomarkers for myocyte ischemia (heart-type fatty acid-binding protein, H-FABP), matrix remodelling/vascular stress (soluble isoform of suppression of tumorigenicity 2, sST2) and inflammation (soluble urokinase-type plasminogen activator receptor, suPAR). In this prospective observational study 109 subjects were recruited, 98 completed the study. Subjects were asked to perform exercise within the calculated training pulse for 8 months. The performance gain was measured/quantified by bicycle stress tests at the beginning and end of the observation period. Twenty-seven subjects with a performance gain <2.9% were excluded. suPAR, H-FABP and sST2 were measured in serum at baseline and after 2, 4 and 8 months by ELISA. We found a significant decrease in H-FABP (1.86 (0.86) to 1.29 (0.98) ng/mL; p<0.01) and a significant increase in sST2 levels (6126 (2759) to 6919 (3720) pg/mL; p=0.045) during the observation period of 8 months while there was no remarkable change in suPAR levels. We interpret the activity-induced decrease in H-FABP as sign of lower subclinical myocardial ischemia and better perfusion, probably due to a more economic metabolization and electrolyte balance. The increase in sST2 might reflect physiological sports-induced vascular stress. As H-FABP and sST2 play an important role in the pathomechanism of ischemic cardiomyopathy (iCMP) further studies should investigate the influence of regular physical activity on these biomarkers in a population of patients with iCMP.Trial registration number NCT02097199.

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“…The discovery of new biomarkers for heart failure could not only improve the assessment of heart failure risk, but also provide insights into the underlying pathophysiology. In the last decade, a few circulating biomarkers, such as growth differentiation factor 15 (GDF‐15), and urokinase‐type plasminogen activator surface receptor (U‐PAR) have been suggested as predictors of incident heart failure, but have generally only provided a modest improvement in risk prediction beyond established cardiovascular risk factors and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) …”

Section: Introductionmentioning

confidence: 99%

Circulating proteins as predictors of incident heart failure in the elderly

Stenemo

Nowak

Byberg

et al. 2017

European J of Heart Fail

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Aims To identify novel risk markers for incident heart failure using proteomic profiling of 80 proteins previously associated with cardiovascular pathology. Methods and results Proteomic profiling (proximity extension assay) was performed in two community‐based prospective cohorts of elderly individuals without heart failure at baseline: the Prospective Investigation of the Vasculature in Uppsala Seniors [PIVUS, n = 901, median age 70.2 (interquartile range 70.0–70.3) years, 80 events]; and the Uppsala Longitudinal Study of Adult Men [ULSAM, n = 685, median age 77.8 (interquartile range 76.9–78.1) years, 90 events]. Twenty‐nine proteins were associated with incident heart failure in the discovery cohort PIVUS after adjustment for age and sex, and correction for multiple testing. Eighteen associations replicated in ULSAM. In pooled analysis of both cohorts, higher levels of nine proteins were associated with incident heart failure after adjustment for established risk factors: growth differentiation factor 15 (GDF‐15), T‐cell immunoglobulin and mucin domain 1 (TIM‐1), tumour necrosis factor‐related apoptosis‐inducing ligand receptor 2 (TRAIL‐R2), spondin‐1 (SPON1), matrix metalloproteinase‐12 (MMP‐12), follistatin (FS), urokinase‐type plasminogen activator surface receptor (U‐PAR), osteoprotegerin (OPG), and suppression of tumorigenicity 2 (ST2). Of these, GDF‐15, U‐PAR, MMP‐12, TRAIL‐R2, SPON1 and FS were associated with worsened echocardiographic left ventricular systolic function at baseline, while only TIM‐1 was positively associated with worsened diastolic function (P < 0.02 for all). Conclusion Proteomic profiling identified several novel associations between proteins involved in apoptosis, inflammation, matrix remodelling, and fibrinolysis with incident heart failure in elderly individuals. Our results encourage additional studies investigating the underlying mechanisms and the clinical utility of our findings.

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Increased plasma level of soluble urokinase plasminogen activator receptor is associated with incidence of heart failure but not atrial fibrillation

Cited by 52 publications

References 48 publications

Proteomic Bioprofiles and Mechanistic Pathways of Progression to Heart Failure

Proteomic Bioprofiles and Mechanistic Pathways of Progression to Heart Failure

Serum heart-type fatty acid-binding protein decreases and soluble isoform of suppression of tumorigenicity 2 increases significantly by long-term physical activity

Circulating proteins as predictors of incident heart failure in the elderly

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