| 1. |
- Albert, Christian, et al.
(författare)
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Neutrophil Gelatinase-Associated Lipocalin Measured on Clinical Laboratory Platforms for the Prediction of Acute Kidney Injury and the Associated Need for Dialysis Therapy : A Systematic Review and Meta-analysis
- 2020
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Ingår i: American Journal of Kidney Diseases. - : Elsevier BV. - 0272-6386 .- 1523-6838. ; 76:6, s. 826-
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Forskningsöversikt (refereegranskat)abstract
- Rationale & Objective: The usefulness of measures of neutrophil gelatinase-associated lipocalin (NGAL) in urine or plasma obtained on clinical laboratory platforms for predicting acute kidney injury (AKI) and AKI requiring dialysis (AKI-D) has not been fully evaluated. We sought to quantitatively summarize published data to evaluate the value of urinary and plasma NGAL for kidney risk prediction.Study Design: Literature-based meta-analysis and individual-study-data meta-analysis of diagnostic studies following PRISMA-IPD guidelines.Setting & Study Populations: Studies of adults investigating AKI, severe AKI, and AKI-D in the setting of cardiac surgery, intensive care, or emergency department care using either urinary or plasma NGAL measured on clinical laboratory platforms.Selection Criteria for Studies: PubMed, Web of Science, Cochrane Library, Scopus, and congress abstracts ever published through February 2020 reporting diagnostic test studies of NGAL measured on clinical laboratory platforms to predict AKI.Data Extraction: Individual-study-data meta analysis was accomplished by giving authors data specifications tailored to their studies and requesting standardized patient-level data analysis.Analytical Approach: Individual-study-data meta analysis used a bivariate time-to-event model for interval-censored data from which discriminative ability (AUC) was characterized. NGAL cutoff concentrations at 95% sensitivity, 95% specificity, and optimal sensitivity and specificity were also estimated. Models incorporated as confounders the clinical setting and use versus nonuse of urine output as a criterion for AKI. A literature-based meta-analysis was also performed for all published studies including those for which the authors were unable to provide individual-study data analyses.Results: We included 52 observational studies involving 13,040 patients. We analyzed 30 data sets for the individual-study-data meta-analysis. For AKI, severe AKI, and AKI-D, numbers of events were 837, 304, and 103 for analyses of urinary NGAL, respectively; these values were 705, 271, and 178 for analyses of plasma NGAL. Discriminative performance was similar in both meta-analyses. Individual-study-data meta-analysis AUCs for urinary NGAL were 0.75 (95% CI, 0.73-0.76) and 0.80 (95% CI, 0.79-0.81) for severe AKI and AKI-D, respectively; for plasma NGAL, the corresponding AUCs were 0.80 (95% CI, 0.790.81) and 0.86 (95% CI, 0.84-0.8 6). Cutoff concentrations at 95% specificity for urinary NGAL were >580 ng/mL with 27% sensitivity for severe AKI and >589 ng/mL with 24% sensitivity for AKI-D. Corresponding cutoffs for plasma NGAL were >364 ng/mL with 44% sensitivity and >546 ng/mL with 26% sensitivity, respectively.Limitations: Practice variability in initiation of dialysis. Imperfect harmonization of data across studies. Conclusions: Urinary and plasma NGAL concentrations may identify patients at high risk for AKI in clinical research and practice. The cutoff concentrations reported in this study require prospective evaluation.
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| 2. |
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| 3. |
- Kubica, Jacek, et al.
(författare)
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Prolonged antithrombotic therapy in patients after acute coronary syndrome : A critical appraisal of current European Society of Cardiology guidelines
- 2020
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Ingår i: CARDIOLOGY JOURNAL. - : VM Media SP. zo.o VM Group SK. - 1897-5593 .- 1898-018X. ; 27:6, s. 661-676
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Tidskriftsartikel (refereegranskat)abstract
- The increased risk of non-cardiovascular death in patients receiving clopidogrel or prasugrel in comparison with the placebo group in the Dual Antiplatelet Therapy (DAPT) trial in contrast to the decreased risk of cardiovascular death and all-cause death seen in patients treated with low-dose ticagrelor in the EU label population of the PEGASUS-TIMI 54 trial, resulted in inclusion in the 2020 ESC NSTE-ACS guidelines the recommendation for use of clopidogrel or prasugrel only if the patient is not eligible for treatment with ticagrelor. The prevalence of the primary outcome composed of cardiovascular death, stroke, or myocardial infarction was lower in the low-dose rivaroxaban and acetylsalicylic acid (ASA) group than in the ASA-alone group in the COMPASS trial. Moreover, all-cause mortality and cardiovascular mortality rates were lower in the rivaroxaban-plus-ASA group. Comparison of the PEGASUS-TIMI 54 and COMPASS trial patient characteristics clearly shows that each of these treatment strategies should be addressed at different groups of patients. A greater benefit in post-acute coronary syndrome (ACS) patients with a high risk of ischemic events and without high bleeding risk may be expected with ASA and ticagrelor 60 mg b.i.d. when the therapy is continued without interruption or with short interruption only after ACS. On the other hand, ASA and rivaroxaban 2.5 mg b.i.d. seems to be a better option when indications for dual antithrombotic therapy (DATT) appear after a longer time from ACS (more than 2 years) and/or from cessation of DAPT (more than 1 year) and in patients with multiple vascular bed atherosclerosis. Thus, both options of DATTs complement each other rather than compete, as can be presumed from the recommendations. However, a direct comparison between these strategies should be tested in future clinical trials.
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| 4. |
- Maisel, Alan, et al.
(författare)
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State of the art : Using natriuretic peptide levels in clinical practice
- 2008
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 10:9, s. 824-839
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Tidskriftsartikel (refereegranskat)abstract
- Natriuretic peptide (NP) levels (B-type natriuretic peptide (BNP) and N-terminal proBNP) are now widely used in clinical practice and cardiovascular research throughout the world and have been incorporated into most national and international cardiovascular guidelines for heart failure. The role of NP levels in state-of-the-art clinical practice is evolving rapidly. This paper reviews and highlights ten key messages to clinicians:•NP levels are quantitative plasma biomarkers of heart failure (HF).•NP levels are accurate in the diagnosis of HF.•NP levels may help risk stratify emergency department (ED) patients with regard to the need for hospital admission or direct ED discharge.•NP levels help improve patient management and reduce total treatment costs in patients with acute dyspnoea.•NP levels at the time of admission are powerful predictors of outcome in predicting death and re-hospitalisation in HF patients.•NP levels at discharge aid in risk stratification of the HF patient.•NP-guided therapy may improve morbidity and/or mortality in chronic HF.•The combination of NP levels together with symptoms, signs and weight gain assists in the assessment of clinical decompensation in HF.•NP levels can accelerate accurate diagnosis of heart failure presenting in primary care.•NP levels may be helpful to screen for asymptomatic left ventricular dysfunction in high-risk patients.
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| 5. |
- Marino, Rossella, et al.
(författare)
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Diagnostic and short-term prognostic utility of plasma pro-enkephalin (pro-ENK) for acute kidney injury in patients admitted with sepsis in the emergency department
- 2015
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Ingår i: Journal of Nephrology. - : Springer Science and Business Media LLC. - 1724-6059 .- 1121-8428. ; 28:6, s. 717-724
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Tidskriftsartikel (refereegranskat)abstract
- Background Acute kidney injury (AKI) aggravates the prognosis of patients with sepsis. Reliable biomarkers for early detection of AKI in this setting are lacking. Enkephalins influence kidney function, and may have a role in AKI from sepsis. We utilized a novel immunoassay for plasma proenkephalin (pro-ENK), a stable surrogate marker for endogenous enkephalins, in patients hospitalized with sepsis, in order to assess its clinical utility. Methods In an observational retrospective study we enrolled 101 consecutive patients admitted to the emergency department (ED) with suspected sepsis. Plasma levels of pro-ENK and neutrophil gelatinase-associated lipocalin (NGAL) were evaluated at ED arrival for their association with presence and severity of AKI and 7-day mortality. Results pro-ENK was inversely correlated to creatinine clearance (r = -0.72) and increased with severity of AKI as determined by RIFLE (risk, injury, failure, loss of function, end-stage renal disease) stages (p < 0.0001; pro-ENK median [interquartile range, IQR]) pmol/l: no AKI: 71 [41-97]; risk: 72 [51-120]; injury: 200 [104-259]; failure: 230 [104-670]; loss of function: 947 [273-811]. The majority of septic patients without AKI or at risk had pro-ENK concentrations within the normal range. While NGAL was similarly associated with AKI severity, it was strongly elevated already in septic patients without AKI. pro-ENK added predictive information to NGAL for detecting kidney dysfunction (added chi(2) 10.0, p = 0.0016). Admission pro-ENK outperformed creatinine clearance in predicting 7-day mortality (pro-ENK: chi(2) 13.4, p < 0.001, area under curve, AUC 0.69; creatinine clearance: chi(2) 4, p = 0.045, AUC: 0.61), and serial measurement improved prediction. Conclusions Use of pro-ENK in septic patients can detect the presence and severity of AKI. Moreover, pro-ENK is highly predictive of short-term mortality and could enable early identification of patients at risk of death.
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| 6. |
- Meijers, Wouter C., et al.
(författare)
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Biomarkers and low risk in heart failure. Data from COACH and TRIUMPH
- 2015
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Ingår i: European Journal of Heart Failure. - : WILEY-BLACKWELL. - 1388-9842 .- 1879-0844. ; 17:12, s. 1271-1282
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Tidskriftsartikel (refereegranskat)abstract
- AimTraditionally, risk stratification in heart failure (HF) emphasizes assessment of high risk. We aimed to determine if biomarkers could identify patients with HF at low risk for death or HF rehospitalization. Methods and resultsThis analysis was a substudy of The Coordinating Study Evaluating Outcomes of Advising and Counselling in Heart Failure (COACH) trial. Enrolment of HF patients occurred before discharge. We defined low risk as the absence of death and/or HF rehospitalizations at 180days. We tested a diverse group of 29 biomarkers on top of a clinical risk model, with and without N-terminal pro-B-type natriuretic peptide (NT-proBNP), and defined the low risk biomarker cut-off at the 10th percentile associated with high positive predictive value. The best performing biomarkers together with NT-proBNP and cardiac troponin I (cTnI) were re-evaluated in a validation cohort of 285 HF patients. Of 592 eligible COACH patients, the mean (SD) age was 71 (+/- 11) years and median (IQR) NT-proBNP was 2521 (1301-5634) pg/mL. Logistic regression analysis showed that only galectin-3, fully adjusted, was significantly associated with the absence of events at 180days (OR 8.1, 95% confidence interval 1.06-50.0, P=0.039). Galectin-3, showed incremental value when added to the clinical risk model without NT-proBNP (increase in area under the curve from 0.712 to 0.745, P=0.04). However, no biomarker showed significant improvement by net reclassification improvement on top of the clinical risk model, with or without NT-proBNP. We confirmed our results regarding galectin-3, NT-proBNP, and cTnI in the independent validation cohort. Conclusion We describe the value of various biomarkers to define low risk, and demonstrate that galectin-3 identifies HF patients at (very) low risk for 30-day and 180-day mortality and HF rehospitalizations after an episode of acute HF. Such patients might be safely discharged.
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| 7. |
- Melander, Olle, et al.
(författare)
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Comparison of cardiovascular disease and cancer prevalence between Mediterranean and north European middle-aged populations (The Cilento on Ageing Outcomes Study and The Malmö Offspring Study)
- 2021
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Ingår i: Internal and Emergency Medicine. - : Springer Science and Business Media LLC. - 1828-0447 .- 1970-9366. ; 16:6, s. 1567-1572
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Tidskriftsartikel (refereegranskat)abstract
- Mediterranean diet protects from both cardiovascular disease (CVD) and cancer. In the 1960s, Ancel Keys defined the concept of Mediterranean diet in the South Italian region of Cilento and proposed it as a key factor for healthy ageing in the region. The aim of the current study was to compare the prevalence of CVD and cancer between a middle-aged population from Cilento and those of a Northern European population from Malmö, Sweden. We clinically characterized two middle-aged (50–67 years of age) population-based samples from Cilento (n = 809) and Malmö (n = 1025), Sweden, respectively. Logistic regression was used to calculate odds ratios (95% confidence interval) for disease prevalence in Malmö versus Cilento inhabitants adjusted for age and sex (model 1) and adjusted for all cardiometabolic risk factors (model 2). The prevalence of hypertension, current smoking, diabetes mellitus and levels of body mass index and triglycerides were lower, whereas HDL-cholesterol was higher in Malmö than in Cilento. LDL-cholesterol was higher and estimated glomerular filtration rate was lower in Malmö than in Cilento. The odds ratio for cardiovascular disease in Malmö versus Cilento inhabitants was 1.13 (0.69–1.87) (P = 0.62) in model 1, whereas it was significantly elevated in model 2 [2.03 (1.14–3.60) (P = 0.016)]. Moreover, the odds ratio for cancer in Malmö versus Cilento was 2.78 (1.81–4.27) (P < 0.001) in model 1 and 3.11 (1.97–4.92) (P < 0.001) in model 2. The higher odds of CVD and cancer in Malmö versus Cilento, when risk factors were accounted for, suggests the existence of unknown protective factors in Cilento.
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| 8. |
- Molvin, John, et al.
(författare)
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Bioactive adrenomedullin, proenkephalin A and clinical outcomes in an acute heart failure setting
- 2019
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Ingår i: Open Heart. - : BMJ. - 2053-3624. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- Objectives In an acute heart failure (AHF) setting, proenkephalin A 119-159 (penKid) has emerged as a promising prognostic marker for predicting worsening renal function (WRF), while bioactive adrenomedullin (bio-ADM) has been proposed as a potential marker for congestion. We examined the diagnostic value of bio-ADM in congestion and penKid in WRF and investigated the prognostic value of bio-ADM and penKid regarding mortality, rehospitalisation and length of hospital stay in two separate European AHF cohorts. Methods Bio-ADM and penKid were measured in 530 subjects hospitalised for AHF in two cohorts: Swedish HeArt and bRain failure inVESTigation trial (HARVEST-Malmö) (n=322, 30.1% female; mean age 75.1+11.1 years; 12 months follow-up) and Italian GREAT Network Rome study (n=208, 54.8% female; mean age 78.5+9.9 years; no follow-up available). Results PenKid was associated with WRF (area under the curve (AUC) 0.65, p<0.001). In multivariable logistic regression analysis of the pooled cohort, penKid showed an independent association with WRF (adjusted OR (aOR) 1.74, p=0.004). Bio-ADM was associated with peripheral oedema (AUC 0.71, p<0.001), which proved to be independent after adjustment (aOR 2.30, p<0.001). PenKid was predictive of in-hospital mortality (OR 2.24, p<0.001). In HARVEST-Malmö, both penKid and bio-ADM were predictive of 1-year mortality (aOR 1.34, p=0.038 and aOR 1.39, p=0.030). Furthermore, bio-ADM was associated with rehospitalisation (aOR 1.25, p=0.007) and length of hospital stay (β=0.702, p=0.005). Conclusion In two different European AHF cohorts, bio-ADM and penKid perform as suitable biomarkers for early detection of congestion severity and WRF occurrence, respectively, and are associated with pertinent clinical outcomes.
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| 9. |
- Ottosson, Filip, et al.
(författare)
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Metabolome-Defined Obesity and the Risk of Future Type 2 Diabetes and Mortality
- 2022
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 45:5, s. 1260-1267
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Obesity is a key risk factor for type 2 diabetes; however, up to 20% of patients are normal weight. Our aim was to identify metabolite patterns reproducibly predictive of BMI and subsequently to test whether lean individuals who carry an obese metabolome are at hidden high risk of obesity-related diseases, such as type 2 diabetes.RESEARCH DESIGN AND METHODS: Levels of 108 metabolites were measured in plasma samples of 7,663 individuals from two Swedish and one Italian population-based cohort. Ridge regression was used to predict BMI using the metabolites. Individuals with a predicted BMI either >5 kg/m2 higher (overestimated) or lower (underestimated) than their actual BMI were characterized as outliers and further investigated for obesity-related risk factors and future risk of type 2 diabetes and mortality.RESULTS: The metabolome could predict BMI in all cohorts (r2 = 0.48, 0.26, and 0.19). The overestimated group had a BMI similar to individuals correctly predicted as normal weight, had a similar waist circumference, were not more likely to change weight over time, but had a two times higher risk of future type 2 diabetes and an 80% increased risk of all-cause mortality. These associations remained after adjustments for obesity-related risk factors and lifestyle parameters.CONCLUSIONS: We found that lean individuals with an obesity-related metabolome have an increased risk for type 2 diabetes and all-cause mortality compared with lean individuals with a healthy metabolome. Metabolomics may be used to identify hidden high-risk individuals to initiate lifestyle and pharmacological interventions.
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