Soluble urokinase plasminogen activator receptor is in contrast to high-sensitive C-reactive-protein associated with coronary artery calcifications in healthy middle-aged subjects

Sørensen, Mette Hjortdal; Gerke, Oke; Eugen‐Olsen, Jesper; Munkholm, Henrik; Lambrechtsen, Jess; Sand, Niels Peter Rønnow; Mickley, Hans; Rasmussen, Lars Melholt; Olsen, Michael Hecht; Diederichsen, Axel Cosmus Pyndt

doi:10.1016/j.atherosclerosis.2014.08.035

Cited by 42 publications

(26 citation statements)

References 31 publications

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“…Although the biomarkers that were significantly associated with incident cancer trended toward abnormal values in patients with cancer, the median levels were virtually within the normal reference ranges, complicating clinical decision making. However, patients with no abnormalities detected had low CRP and suPAR levels-which were comparable to that of healthy people in the general population, including blood donors [38][39][40] -while patients receiving a diagnosis had increased CRP and suPAR levels, especially patients with incident cancer. Both CRP and suPAR contributed to an improved negative predictive value.…”

Section: Discussionmentioning

confidence: 86%

Inflammatory biomarkers and cancer: CRP and suPAR as markers of incident cancer in patients with serious nonspecific symptoms and signs of cancer

Rasmussen

Schultz

Gaardsting

et al. 2017

Intl Journal of Cancer

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In Denmark, patients with serious nonspecific symptoms and signs of cancer (NSSC) are referred to the diagnostic outpatient clinics (DOCs) where an accelerated cancer diagnostic program is initiated. Various immunological and inflammatory biomarkers have been associated with cancer, including soluble urokinase plasminogen activator receptor (suPAR) and the pattern recognition receptors (PRRs) pentraxin‐3, mannose‐binding lectin, ficolin‐1, ficolin‐2 and ficolin‐3. We aimed to evaluate these biomarkers and compare their diagnostic ability to classical biomarkers for diagnosing cancer in patients with NSSC. Patients were included from the DOC, Department of Infectious Diseases, Copenhagen University Hospital Hvidovre. Patients were given a final diagnosis based on the combined results from scans, blood work and physical examination. Weight loss, Charlson score and previous cancer were registered on admission, and plasma concentrations of biomarkers were measured. The primary outcome was incident cancer within 1 year. Out of 197 patients included, 39 patients (19.8%) were diagnosed with cancer. Patients with cancer were significantly older and had a higher burden of comorbidities and previous cancer diagnoses compared to patients who were not diagnosed with cancer. Previous cancer, C‐reactive protein (CRP) and suPAR were significantly associated with newly diagnosed cancer during follow‐up in multiple logistic regression analyses adjusted for age, sex and CRP. Neither any of the PRRs investigated nor self‐reported weight loss was associated with cancer. In this study, previous cancer, CRP and suPAR were significantly associated with cancer diagnosis in patients with NSSC. Ficolin‐1‐3, MBL and pentraxin‐3 were not associated with cancer.

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Section: Discussionmentioning

confidence: 86%

Inflammatory biomarkers and cancer: CRP and suPAR as markers of incident cancer in patients with serious nonspecific symptoms and signs of cancer

Rasmussen

Schultz

Gaardsting

et al. 2017

Intl Journal of Cancer

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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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“…Soluble urokinase plasminogen activator receptor (suPAR) is a marker of immune activation thought to be involved in the pathogenesis of kidney disease; suPAR concentrations have also been associated with mortality and cardiovascular disease in the general population (without comorbidities), in critically ill patients, patients with cerebrovascular disease, HIV infection, and kidney disease . In contrast to hs‐CRP, elevated suPAR is reportedly associated with the presence of CAC as well as peripheral arterial disease . Whether suPAR levels provide further benefit in risk stratification in African Americans (AA) with T2D has not been studied.…”

Section: Introductionmentioning

confidence: 99%

“…[9][10][11][12][13][14][15][16][17][18][19][20][21] In contrast to hs-CRP, elevated suPAR is reportedly associated with the presence of CAC as well as peripheral arterial disease. 22,23 Whether suPAR levels provide further benefit in risk stratification in African Americans (AA) with T2D has not been studied. We sought to characterize determinants of suPAR levels in patients with T2D and to ascertain whether suPAR is a predictor of CAC and whether its levels are useful for predicting mortality beyond conventional clinical characteristics, CAC, and hs-CRP.…”

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confidence: 99%

Predicting Mortality in African Americans With Type 2 Diabetes Mellitus: Soluble Urokinase Plasminogen Activator Receptor, Coronary Artery Calcium, and High‐Sensitivity C‐Reactive Protein

Hayek

Divers

Raad

et al. 2018

JAHA

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BackgroundType 2 diabetes mellitus is a major risk factor for cardiovascular disease; however, outcomes in individual patients vary. Soluble urokinase plasminogen activator receptor (suPAR) is a bone marrow–derived signaling molecule associated with adverse cardiovascular and renal outcomes in many populations. We characterized the determinants of suPAR in African Americans with type 2 diabetes mellitus and assessed whether levels were useful for predicting mortality beyond clinical characteristics, coronary artery calcium (CAC), and high‐sensitivity C‐reactive protein (hs‐CRP).Methods and ResultsWe measured plasma suPAR levels in 500 African Americans with type 2 diabetes mellitus enrolled in the African American‐Diabetes Heart Study. We used Kaplan‐Meier curves and Cox proportional hazards models adjusting for clinical characteristics, CAC, and hs‐CRP to examine the association between suPAR and all‐cause mortality. Last, we report the change in C‐statistics comparing the additive values of suPAR, hs‐CRP, and CAC to clinical models for prediction of mortality. The suPAR levels were independently associated with female sex, smoking, insulin use, decreased kidney function, albuminuria, and CAC. After a median 6.8‐year follow‐up, a total of 68 deaths (13.6%) were recorded. In a model incorporating suPAR, CAC, and hs‐CRP, only suPAR was significantly associated with mortality (hazard ratio 2.66, 95% confidence interval 1.63‐4.34). Addition of suPAR to a baseline clinical model significantly improved the C‐statistic for all‐cause death (Δ0.05, 95% confidence interval 0.01‐0.10), whereas addition of CAC or hs‐CRP did not.ConclusionsIn African Americans with type 2 diabetes mellitus, suPAR was strongly associated with mortality and improved risk discrimination metrics beyond traditional risk factors, CAC and hs‐CRP. Studies addressing the clinical usefulness of measuring suPAR concentrations are warranted.

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Soluble urokinase plasminogen activator receptor is in contrast to high-sensitive C-reactive-protein associated with coronary artery calcifications in healthy middle-aged subjects

Cited by 42 publications

References 31 publications

Inflammatory biomarkers and cancer: CRP and suPAR as markers of incident cancer in patients with serious nonspecific symptoms and signs of cancer

Inflammatory biomarkers and cancer: CRP and suPAR as markers of incident cancer in patients with serious nonspecific symptoms and signs of cancer

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

Predicting Mortality in African Americans With Type 2 Diabetes Mellitus: Soluble Urokinase Plasminogen Activator Receptor, Coronary Artery Calcium, and High‐Sensitivity C‐Reactive Protein

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