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Mogensen, I., Alving, K., Dahlen, S.-E., James, A., Forsberg, B., Ono, J., . . . Malinovschi, A. (2019). Fixed airflow obstruction relates to eosinophil activation in asthmatics. Clinical and Experimental Allergy, 49(2), 155-162
Open this publication in new window or tab >>Fixed airflow obstruction relates to eosinophil activation in asthmatics
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2019 (English)In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 49, no 2, p. 155-162Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Some asthmatics develop irreversible chronic airflow obstruction, for example, fixed airflow obstruction (fixed-AO). This is probably a consequence of airway remodelling, but neither its relation to inflammation nor which asthma biomarkers can be clinically useful are elucidated. We hypothesized that the presence of type 2 inflammation relates to fixed-AO.

OBJECTIVES: To evaluate the presence of four markers for type 2 inflammation in fixed airflow obstruction among asthmatics.

METHODS: This was a cross-sectional study of 403 participants with asthma, aged 17-75 years, from three Swedish centres. Fixed airflow obstruction was defined as forced expiratory volume during the first second (FEV1 ) over forced vital capacity (FVC) being below the lower limit of normal (LLN). The following type 2 inflammation markers were assessed: exhaled nitric oxide (FeNO), serum periostin, serum eosinophil cationic protein (S-ECP), and urinary eosinophil-derived neurotoxin (U-EDN).

RESULTS: Elevated U-EDN (values in the highest tertile, ≥65.95 mg/mol creatinine) was more common in subjects with fixed-AO vs. subjects without fixed-AO: 55% vs. 29%, P < 0.001. Elevated U-EDN related to increased likelihood of having fixed-AO in both all subjects and never-smoking subjects, with adjusted (adjusted for sex, age group, use of inhaled corticosteroids last week, atopy, early-onset asthma, smoking history, and packyears) odds ratios (aOR) of 2.38 (1.28-4.41) and 2.51 (1.04-6.07), respectively. In a separate analysis, having both elevated S-ECP (>20 μg/L) and U-EDN was related to having the highest likelihood of fixed-AO (aOR (95% CI) 6.06 (2.32-15.75)). Elevated serum periostin or FeNO did not relate to fixed-AO.

CONCLUSIONS AND CLINICAL RELEVANCE: These findings support that type 2 inflammation, and in particular eosinophil inflammation, is found in asthma with fixed-AO. This could indicate a benefit from eosinophil-directed therapies. Further longitudinal studies are warranted to investigate causality and relation to lung function decline.

National Category
Medical and Health Sciences Immunology in the medical area
Research subject
Clinical Physiology
Identifiers
urn:nbn:se:uu:diva-372784 (URN)10.1111/cea.13302 (DOI)000457469600003 ()30365193 (PubMedID)
Funder
Swedish Heart Lung FoundationSwedish Research CouncilVårdal FoundationStockholm County CouncilSwedish Asthma and Allergy AssociationSwedish Foundation for Strategic Research
Available from: 2019-01-09 Created: 2019-01-09 Last updated: 2019-03-08Bibliographically approved
Jonsson, N., Gille-Johnson, P., Martling, C.-R., Xu, S., Venge, P. & Mårtensson, J. (2019). Performance of plasma measurement of neutrophil gelatinase-associated lipocalin as a biomarker of bacterial infections in the intensive care unit. Journal of critical care, 53, 264-270
Open this publication in new window or tab >>Performance of plasma measurement of neutrophil gelatinase-associated lipocalin as a biomarker of bacterial infections in the intensive care unit
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2019 (English)In: Journal of critical care, ISSN 0883-9441, E-ISSN 1557-8615, Vol. 53, p. 264-270Article in journal (Refereed) Published
Abstract [en]

Purpose: To assess the value of dimeric neutrophil-gelatinase associated lipocalin (NGAL) as an early marker of bacterial infection and its response to antibiotic therapy in intensive care unit (ICU) patients.

Materials & methods: We measured daily plasma dNGAL in 198 patients admitted to a mixed ICU. Likelihood of infection was determined with International Sepsis Forum criteria. Wemeasured dNGAL in 145 healthy controls to establish normal values.

Results: ICU patients had higher dNGAL than healthy controls. A suspected or confirmed infection was independently associated with 90% (95% CI 15-215%) higher dNGAL than absence of infection. We observed no association between acute kidney injury and dNGAL. Diagnostic accuracy at antibiotic treatment initiation, assessed with area under the receiver-operating characteristics curve (AUC-ROC), for dNGAL was 0.70 (95% CI 0.60-0.79). AUC-ROC for dNGAL 24 h before antibiotic treatment initiation was 0.54 (95% CI 0.41-0.66). The mean (95% CI) change of dNGAL in the first 2 days after appropriate antibiotic therapy initiation was -31 (-49,-13)%.

Conclusions: In our cohort of ICU patients, plasma dNGAL was associated with presence of bacterial infections independent of AKI but it performed poor as a predictor of infections. Following antibiotic therapy, dNGAL markedly decreased-supporting further exploration of dNGAL-guided antibiotic de-escalation.

Place, publisher, year, edition, pages
W B SAUNDERS CO-ELSEVIER INC, 2019
National Category
Anesthesiology and Intensive Care Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-392117 (URN)10.1016/j.jcrc.2019.07.001 (DOI)000478566600043 ()31301642 (PubMedID)
Funder
Stockholm County Council
Available from: 2019-09-06 Created: 2019-09-06 Last updated: 2019-09-06Bibliographically approved
Venge, P. (2018). Human neutrophil lipocalin (HNL) as a biomarker of acute infections. Upsala Journal of Medical Sciences, 123(1), 1-8
Open this publication in new window or tab >>Human neutrophil lipocalin (HNL) as a biomarker of acute infections
2018 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 1, p. 1-8Article, review/survey (Refereed) Published
Abstract [en]

The early and accurate discrimination between bacterial and viral causes of acute infections is the key to a better use of antibiotics and will help slow down the fast-growing resistance to commonly used antibiotics. This discrimination is in the vast majority of cases possible to achieve by blood assay of the biomarker human neutrophil lipocalin (HNL), which we showed to be uniquely increased in patients suffering from bacterial infections. In serum, sensitivities and specificities of >90% are achieved in both adults and children. In order to eliminate the need to produce serum, a whole-blood assay with an assay time of <10 min was developed in which blood neutrophils are activated to release HNL. The diagnostic accuracy of this assay also showed sensitivities and specificities of >90% in most infectious diseases and was clearly superior to contemporary assays such as blood neutrophil counts, C-reactive protein, procalcitonin, and expression of CD64 on blood neutrophils. This format lends itself to the development of a point-of-care HNL assay and will be a major step forward to accomplish the goal of accurately diagnosing patients with symptoms of acute infections within 10 min at the emergency room or at the doctor's office.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2018
Keywords
Clinical chemistry, immunoassays, infectious diseases
National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-356901 (URN)10.1080/03009734.2017.1420112 (DOI)000428060300001 ()29473432 (PubMedID)
Available from: 2018-08-09 Created: 2018-08-09 Last updated: 2018-08-09Bibliographically approved
Eggers, K. M., Lindahl, B., Venge, P. & Lind, L. (2018). Predictors of 10-year changes in levels of N-terminal pro B-type natriuretic peptide and cardiac troponin I in the elderly. International Journal of Cardiology, 257, 300-305
Open this publication in new window or tab >>Predictors of 10-year changes in levels of N-terminal pro B-type natriuretic peptide and cardiac troponin I in the elderly
2018 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 257, p. 300-305Article in journal (Refereed) Published
Abstract [en]

Background: Measurement of N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) might be useful for monitoring of cardiovascular disease in the elderly. However, it is not clear whether changes in these biomarkers are associated with changes in the cardiovascular risk profile and if this pattern could be modified by changes in lifestyle habits or medications.

Methods: We measured levels of NT-proBNP and cTnI in community-dwelling subjects (PIVUS study) upon visits scheduled at age 70 (n = 1007), 75 (n = 825) and 80 (n = 602). The associations of these biomarkers with repeated measurements of clinical variables (risk factors, lifestyle habits, echocardiographic data and medications) were investigated using sex-adjusted linear mixed random effect models.

Results: NT-proBNP and cTnI were positively associated with increasing age. NT-proBNP, but not cTnI, was affected by changes of renal function and the degree of obesity. NT-proBNP was more closely related than cTnI to changes in echocardiographic estimates of cardiac geometry and function. Biomarker levels and/or their changes were inversely associated with a physically more active lifestyle (both NT-proBNP and cTnI) and statin treatment at age 70 (only cTnI). Changes in smoking status or antihypertensive treatment had no effect on biomarker levels.

Conclusions: Changes in NT-proBNP and cTnI levels are associated with different patterns of cardiovascular disease burden when using a longitudinal approach. However, levels of both biomarkers and their changes also reflect changes in the cardiovascular risk profile that might be modifiable. This is an important aspect for the use of any cardiovascular biomarker in an elderly population.

Place, publisher, year, edition, pages
ELSEVIER IRELAND LTD, 2018
Keywords
Biomarkers, Cardiovascular risk, Cardiac troponin, NT-pro B-type natriuretic peptide, Longitudinal changes
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-351561 (URN)10.1016/j.ijcard.2017.10.095 (DOI)000427530200074 ()29506712 (PubMedID)
Funder
Swedish Heart Lung Foundation, 20100947Swedish Society of Medicine, SLS-248691
Available from: 2018-05-30 Created: 2018-05-30 Last updated: 2019-01-24Bibliographically approved
Kehoe, K., Noels, H., Theelen, W., De Hert, E., Xu, S., Verrijken, A., . . . De Meester, I. (2018). Prolyl carboxypeptidase activity in the circulation and its correlation with body weight and adipose tissue in lean and obese subjects. PLoS ONE, 13(5), Article ID e0197603.
Open this publication in new window or tab >>Prolyl carboxypeptidase activity in the circulation and its correlation with body weight and adipose tissue in lean and obese subjects
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2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 5, article id e0197603Article in journal (Refereed) Published
Abstract [en]

Background Prolyl carboxypeptidase (PRCP) is involved in the regulation of body weight, likely by hydrolysing alpha-melanocyte-stimulating hormone and apelin in the hypothalamus and in the periphery. A link between PRCP protein concentrations in plasma and metabolic disorders has been reported. In this study, we investigated the distribution of circulating PRCP activity and assessed its relation with body weight and adipose tissue in obese patients and patients who significantly lost weight. Methods PRCP activity was measured using reversed-phase high-performance liquid chromatography in different isolated blood fractions and primary human cells to investigate the distribution of circulating PRCP. PRCP activity was measured in serum of individuals (n = 75) categorized based on their body mass index (BMI < 25.0; 25.0-29.9; 30.0-39.9; >= 40.0 kg/m(2)) and the diagnosis of metabolic syndrome. Differences in serum PRCP activity were determined before and six months after weight loss, either by diet (n = 45) or by bariatric surgery (n = 24). Potential correlations between serum PRCP activity and several metabolic and biochemical parameters were assessed. Additionally, plasma PRCP concentrations were quantified using a sensitive ELISA in the bariatric surgery group. Results White blood cells and plasma contributed the most to circulating PRCP activity. Serum PRCP activity in lean subjects was 0.83 +/- 0.04 U/L and increased significantly with a rising BMI (p<0.001) and decreased upon weight loss (diet, p<0.05; bariatric surgery, p<0.001). The serum PRCP activity alteration reflected body weight changes and was found to be positively correlated with several metabolic parameters, including: total, abdominal and visceral adipose tissue. Plasma PRCP concentration was found to be significantly correlated to serum PRCP activity (0.865; p<0.001). Additionally, a significant decrease (p<0.001) in plasma PRCP protein concentration (mean +/- SD) before (18.2 +/- 3.7 ng/mL) and 6 months after bariatric surgery (15.7 +/- 2.7 ng/mL) was found. Conclusion Our novel findings demonstrate that white blood cells and plasma contributed the most to circulating PRCP activity. Additionally, we have shown that there were significant correlations between serum PRCP activity and various metabolic parameters, and that plasma PRCP concentration was significantly correlated to serum PRCP activity. These novel findings on PRCP activity in serum support further investigation of its in vivo role and involvement in several metabolic diseases.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE, 2018
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-357006 (URN)10.1371/journal.pone.0197603 (DOI)000432348900077 ()29772029 (PubMedID)
Available from: 2018-08-13 Created: 2018-08-13 Last updated: 2018-08-13Bibliographically approved
Blom, K., ElShafie, A. I., Jönsson, U.-B., Rönnelid, J., Håkansson, L. & Venge, P. (2018). The genetically determined production of the alarmin eosinophil-derived neurotoxin is reduced in visceral leishmaniasis. Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), 126(1), 85-91
Open this publication in new window or tab >>The genetically determined production of the alarmin eosinophil-derived neurotoxin is reduced in visceral leishmaniasis
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2018 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 126, no 1, p. 85-91Article in journal (Refereed) Published
Abstract [en]

Visceral leishmaniasis (VL) is the most severe form of leishmaniasis. Recent findings indicate that dendritic cells have a key role in the defense against the Leishmania parasite and that the activity of this cell may be modified by the eosinophil secretory protein eosinophil-derived neurotoxin (EDN). We hypothesized that the interactions between dendritic cells and EDN might be of importance in the disease development. Cellular content of EDN was analyzed by ELISA. The single-nucleotide polymorphisms at positions 405, 416, and 1122 in the EDN gene were analyzed by real-time PCR with TaqMan((R)) reagents. The study cohorts comprised 239 Sudanese subjects (65 healthy controls and 174 with VL) and 300 healthy Swedish controls. The eosinophil content of EDN was lower in VL as compared with controls (p < 0.0001). The EDN405 (G>C) genotype distribution was similar among Swedish and Sudanese controls, whereas VL subjects had a higher prevalence of the EDN405-GG genotype (p < 0.0001). The content of EDN in the eosinophils was closely linked to the EDN405 polymorphism (p = 0.0002). Our findings suggest that the predisposition to acquire VL is related to the genetic polymorphism of the EDN gene and the reduced production by the eosinophil of this gene product.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
Visceral leishmaniasis, kala-azar, eosinophil granulocyte, polymorphism, RNASE2
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-338960 (URN)10.1111/apm.12780 (DOI)000418846700011 ()29193305 (PubMedID)
Available from: 2018-01-18 Created: 2018-01-18 Last updated: 2018-02-27Bibliographically approved
Venge, P., van Lippen, L., Blaschke, S., Christ, M., Geier, F., Giannitsis, E., . . . Semjonow, V. (2017). Equal clinical performance of a novel point-of-care cardiac troponin I (cTnI) assay with a commonly used high-sensitivity cTnI assay. Clinica Chimica Acta, 469, 119-125
Open this publication in new window or tab >>Equal clinical performance of a novel point-of-care cardiac troponin I (cTnI) assay with a commonly used high-sensitivity cTnI assay
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2017 (English)In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 469, p. 119-125Article in journal (Refereed) Published
Abstract [en]

Background: Efficient rule-out of acute myocardial infarction (MI) facilitates early disposition of chest pain patients in emergency departments (ED). Point-of-care (POC) cardiac troponin (cTn) may improve patient throughput. We compared the diagnostic accuracy of a novel cTnI test (Minicare cTnI, Philips), with current POC cTnI (I-Stat, Abbott) and high-sensitivity central laboratory cTnI (hs-cTnI; Architect, Abbott) assays.

Methods: The clinical performance of the assays were compared in samples from 450 patients from a previous clinical evaluation of Minicare cTnI.

Results: Minicare cTnI correlated with Architect hs-cTnI (r(2) = 0.85, p < 0.0001) and I-Stat cTnI (r(2) = 0.93, p < 0.0001). Areas under the receiver operating characteristics curves were 0.87-0.91 at admission (p = ns) and 0.96-0.97 3 h after admission (p = ns). The negative predictive values (NPV) at admission were 95% ((92-97%, 95% CI) for Minicare cTnI and increased to 99% (97-100%) at 2-4 h, and similar to Architect hs-cTnI (98%, 96-100%), but higher than I-Stat cTnI (95%, 92-97%; p < 0.01). Negative likelihood ratios (LR) after 2-4 h were 0.06 (0.02-0.17, 95% CI) for Minicare cTnI, 0.11 (0.05-0.24) for Architect hs-cTnI (p = 0.02) and 0.28 (0.18-0.43) for I-Stat cTnI (p < 0.0001). The clinical concordances between Minicare cTnI and Architect hs-cTnI were 92% (admission) and 95% (2-4 h), with lower concordances between Minicare cTnI and I-Stat cTnI (83% and 78%, respectively; p = 0.007).

Conclusions: The Minicare cTnI POC assay may become useful for prompt and safe ruling-out of AMI in ED patients with suspected AMI using a guideline supported 0/3 h sampling protocol.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2017
Keywords
Cardiac troponin I, Acute myocardial infarction, Point-of-care, Emergency medicine
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-326220 (URN)10.1016/j.cca.2017.03.023 (DOI)000401879100019 ()28347675 (PubMedID)
Available from: 2017-07-06 Created: 2017-07-06 Last updated: 2017-07-06Bibliographically approved
Venge, P., Eriksson, A.-K., Douhan Håkansson, L. & Pauksen, K. (2017). Human Neutrophil Lipocalin in Activated Whole Blood Is a Specific and Rapid Diagnostic Biomarker of Bacterial Infections in the Respiratory Tract. Clinical and Vaccine Immunology, 24(7), Article ID UNSP e00064.
Open this publication in new window or tab >>Human Neutrophil Lipocalin in Activated Whole Blood Is a Specific and Rapid Diagnostic Biomarker of Bacterial Infections in the Respiratory Tract
2017 (English)In: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 24, no 7, article id UNSP e00064Article in journal (Refereed) Published
Abstract [en]

The distinction between bacterial and viral causes of infections of the respiratory tract is a major but important clinical challenge. We investigated the diagnostic performance of human neutrophil lipocalin (HNL) in respiratory tract infections compared to those of C-reactive protein (CRP) and procalcitonin (PCT). Patients were recruited from the emergency department and from a primary care unit (n = 162). The clinical diagnosis with regard to bacterial or viral cause of infection was complemented with objective microbiological/serological testing. HNL was measured in whole blood after preactivation with the neutrophil activator formyl-methionine-leucine-phenylalanine (fMLP) (B-HNL), and CRP and PCT were measured in plasma. Head-to-head comparisons of the three biomarkers showed that B-HNL was a superior diagnostic means to distinguish between causes of infections, with areas under the concentration-time curve (AUCs) of receiver operating characteristic (ROC) analysis for HNL of 0.91 (95% confidence interval [CI], 0.83 to 0.96) and 0.92 (95% CI, 0.82 to 0.97) for all respiratory infections and for upper respiratory infections, respectively, compared to 0.72 (95% CI, 0.63 to 0.80) and 0.68 (95% CI, 0.56 to 0.79) for CRP, respectively (P = 0.001). In relation to major clinical symptoms of respiratory tract infections (cough, sore throat, stuffy nose, and signs of sinusitis), AUCs varied between 0.88 and 0.93 in those patients with likely etiology (i.e., etiology is likely determined) of infection, compared to 0.63 and 0.71 for CRP, respectively, and nonsignificant AUCs for PCT. The diagnostic performance of B-HNL is superior to that of plasma CRP (P-CRP) and plasma PCT (P-PCT) in respiratory tract infections, and the activity specifically reflects bacterial challenge in the body. The rapid and accurate analysis of HNL by point-of-care technologies should be a major advancement in the diagnosis and management of respiratory infections with respect to antibiotic treatment.

Keywords
antibiotic resistance, biomarker, lipocalin, point of care, respiratory infection
National Category
Immunology
Identifiers
urn:nbn:se:uu:diva-330026 (URN)10.1128/CVI.00064-17 (DOI)000404927700006 ()
Available from: 2017-10-13 Created: 2017-10-13 Last updated: 2017-10-31Bibliographically approved
Yu, Z., Jing, H., Hongtao, P., Furong, J., Yuting, J., Xu, S. & Venge, P. (2016). Distinction between bacterial and viral infections by serum measurement of human neutrophil lipocalin (HNL) and the impact of antibody selection. JIM - Journal of Immunological Methods, 432, 82-86
Open this publication in new window or tab >>Distinction between bacterial and viral infections by serum measurement of human neutrophil lipocalin (HNL) and the impact of antibody selection
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2016 (English)In: JIM - Journal of Immunological Methods, ISSN 0022-1759, E-ISSN 1872-7905, Vol. 432, p. 82-86Article in journal (Refereed) Published
Abstract [en]

The distinction between acute infections of bacterial or viral causes is clinically important, but often very difficult even for experienced doctors. Previous studies indicated that serum measurements of HNL (Human Neutrophil Lipocalin) might be a superior diagnostic means in this regard, but also indicated that the antibody conformation of the HNL assay might have an impact on the diagnostic performance. The aim of the present report was to examine this further. Methods: Several different (n = 24) HNL ELISA assays were developed using different combinations of monoclonal and polyclonal HNL antibodies. Sera were collected from healthy persons (n = 188) and from 155 patients with acute infections.before any antibiotics treatment. The patients were diagnosed as having bacterial (n = 69) or viral causes (n = 86) of their infections. Plasma and serum were also examined by Western blotting using HNL-specific polyclonal antibodies. Results: The optimal assay format for the distinction between bacterial and viral infection resulted in an area under the receiver operating characteristics curve (AuROC) for S-HNL of 0.98. (95% CI 0.94-1.00) as compared to 0.83 (0.76-0.88) for blood neutrophil counts and 0.69 (0.61-0.76) for S-CRP. Results also showed that different assay formats of HNL identified monomeric and dimeric HNL differently, the monomeric HNL being elevated in viral infections and the dimeric HNL being elevated in bacterial infections. Conclusion: We conclude that serum theasurement of HNL is a superior diagnostic means to distinguish between acute infections caused by bacteria or virus. For optimal clinical performance the immunoassay should address conformational epitopes in the dimeric HNL.

Keywords
Lipocalin, Acute Infection, Diagnosis, CRP, Neutrophil
National Category
Biochemistry and Molecular Biology Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-297883 (URN)10.1016/j.jim.2016.02.014 (DOI)000375886900011 ()26899825 (PubMedID)
Available from: 2016-06-29 Created: 2016-06-28 Last updated: 2018-01-10Bibliographically approved
Eggers, K. M., Kempf, T., Larsson, A., Lindahl, B., Venge, P., Wallentin, L., . . . Lind, L. (2016). Evaluation of Temporal Changes in Cardiovascular Biomarker Concentrations Improves Risk Prediction in an Elderly Population from the Community. Clinical Chemistry, 62(3), 485-493
Open this publication in new window or tab >>Evaluation of Temporal Changes in Cardiovascular Biomarker Concentrations Improves Risk Prediction in an Elderly Population from the Community
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2016 (English)In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 62, no 3, p. 485-493Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: There is increasing interest in measurements of cardiovascular (CV) biomarker concentrations for risk prediction in the general population. We investigated the prognostic utility of a panel of novel CV biomarkers and their changes over time.

METHODS: We measured concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), midregional proadrenomedullin, high-sensitivity cardiac troponin I, growth-differentiation factor-15 (GDF-15), soluble ST2 (sST2), and galectin-3 at baseline and 5 years later in 1016 elderly individuals participating in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Assessed outcomes included all-cause mortality and fatal and nonfatal CV events (in participants without CV disease at baseline) during 10 years of follow-up.

RESULTS: GDF-15 exhibited the strongest association with all-cause mortality (n = 158) with a hazard ratio (HR) per 1-SD increase in standardized ln GDF-15 of 1.68 (95% CI, 1.44-1.96). NT-proBNP was the only biomarker to predict CV events (n = 163; HR 1.54 [95% CI, 1.30-1.84]). GDF-15 and NT-proBNP also improved metrics of discrimination and reclassification of the respective outcomes. Changes in GDF-15 concentrations between 70 and 75 years predicted all-cause mortality whereas changes in NT-proBNP predicted both outcomes. The other biomarkers and their temporal changes provided only moderate prognostic value apart from sST2 which had a neutral relationship with adverse events.

CONCLUSIONS: Evaluation of temporal changes in GDF-15 and NT-proBNP concentrations improves risk prediction in an elderly population. These findings are of considerable interest given the emphasis on biomarkers as tools to identify and monitor at-risk individuals with preclinical and potentially modifiable stages of CV disease.

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-274582 (URN)10.1373/clinchem.2015.246876 (DOI)000371225200013 ()26769752 (PubMedID)
Funder
Swedish Heart Lung Foundation, 20100947
Available from: 2016-01-23 Created: 2016-01-23 Last updated: 2017-11-30Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-5863-790x

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