| 1. |
- Barchetta, Ilaria, et al.
(författare)
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Circulating pro-neurotensin levels predict bodyweight gain and metabolic alterations in children
- 2021
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Ingår i: Nutrition, Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753. ; 31:3, s. 902-910
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Neurotensin (NT) is an intestinal peptide released after fat ingestion, which regulates appetite and facilitates lipid absorption. Elevated plasma levels of its stable precursor pro-neurotensin (pro-NT) are associated with type 2 diabetes, obesity and cardiovascular mortality in adult populations; no data on pro-NT and metabolic disease are available in children. Aim of the study was to evaluate plasma pro-NT in relation to the presence of obesity in children, and to test if high pro-NT associates with the development of metabolic impairment later in life. Methods and results: For this longitudinal retrospective study, we studied 151 overweight/obese children undergoing metabolic evaluations at University of Cagliari, Italy. Pro-NT was also assessed in 46 normal-weight, age-, sex-comparable normal-weight children, selected as a reference group. At the baseline, pro-NT was comparable between overweight/obese and normal-weight children and correlated positively with age (p < 0.001), triglycerides (p < 0.001) and inversely with HDL levels (p = 0.008). Plasma pro-NT associated with high triglycerides with OR = 5.9 (95%CI: 1.24–28.1; p = 0.026) after adjustment for multiple confounders. At the 6.5-year follow-up, high basal pro-NT associated with impaired β-cell function to compensate for insulin-resistance (disposition index: r = −0.19, p = 0.035) and predicted bodyweight increase, as indicated by percentage change of standard deviation score BMI (median(95%CI) = +20.8(+4.9-+27.5)% in the highest tertile), independently from age, sex, triglycerides and insulin-resistance (standardized β = 0.24; p = 0.036). Conclusions: Elevated pro-NT levels in children are significantly associated with weight gain later in life and may represent a marker of susceptibility to metabolic impairment in presence of obesity.
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| 2. |
- Bronton, Kevin, et al.
(författare)
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Bioactive adrenomedullin a prognostic biomarker in patients with mild to moderate dyspnea at the emergency department : an observational study
- 2022
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Ingår i: Internal and Emergency Medicine. - : Springer Science and Business Media LLC. - 1828-0447 .- 1970-9366. ; 17:2, s. 541-550
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Tidskriftsartikel (refereegranskat)abstract
- Acute dyspnea with underlying congestion is a leading cause of emergency department (ED) visits with high rates of hospitalization. Adrenomedullin is a vasoactive neuropeptide hormone secreted by the endothelium that mediates vasodilation and maintains vascular integrity. Plasma levels of biologically active adrenomedullin (bio-ADM) predict septic shock and vasopressor need in critically ill patients and are associated with congestion in patients with acute heart failure (HF) but the prognostic value in unselected dyspneic patients at the ED is unknown. The purpose of this study is to test if bio-ADM predicts adverse outcomes when sampled in patients with acute dyspnea at presentation to the ED. In this single-center prospective observational study, we included 1402 patients from the ADYS (Acute DYSpnea at the Emergency Department) cohort in Malmö, Sweden. We fitted logistic regression models adjusted for sex, age, N-terminal pro-B-type natriuretic peptide (NT-proBNP), creatinine, and C-reactive protein (CRP) to associate bio-ADM plasma levels to mortality, hospitalization, intravenous (IV) diuretic treatment and HF diagnosis. Using receiver operating characteristic (ROC) curve analysis we evaluated bio-ADM discrimination for these outcomes compared to a reference model (sex, age, NT-proBNP, creatinine, and CRP). Model performance was compared by performing a likelihood ratio test on the deviances of the models. Bio-ADM (per interquartile range from median) predicts both 90-day mortality [odds ratio (OR): 1.5, 95% confidence interval (CI) 1.2–2.0, p < 0.002] and hospitalization (OR: 1.5, 95% CI 1.2–1.8, p < 0.001) independently of sex, age, NT-proBNP, creatinine, and CRP. Bio-ADM statistically significantly improves the reference model in predicting mortality (added χ2 9.8, p = 0.002) and hospitalization (added χ2 14.1, p = 0.0002), and is associated with IV diuretic treatment and HF diagnosis at discharge. Plasma levels of bio-ADM sampled at ED presentation in acutely dyspneic patients are independently associated with 90-day mortality, hospitalization and indicate the need for decongestive therapy.
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| 3. |
- Egerstedt, Anna, et al.
(författare)
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Bioactive adrenomedullin for assessment of venous congestion in heart failure
- 2022
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Ingår i: ESC Heart Failure. - : Wiley. - 2055-5822. ; 9:5, s. 3543-3555
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Bioactive adrenomedullin (bio-ADM) is a vascular-derived peptide hormone that has emerged as a promising biomarker for assessment of congestion in decompensated heart failure (HF). We aimed to evaluate diagnostic and prognostic performance of bio-ADM for HF in comparison to amino-terminal pro-B-type natriuretic peptide (NT-proBNP), with decision thresholds derived from invasive haemodynamic and population-based studies. Methods and results: Normal reference ranges for bio-ADM were derived from a community-based cohort (n = 5060). Correlations with haemodynamic data were explored in a cohort of HF patients undergoing right heart catheterization (n = 346). Mortality and decision cutoffs for bio-ADM was explored in a cohort of patients presenting in the ER with acute dyspnoea (n = 1534), including patients with decompensated HF (n = 570). The normal reference range was 8–39 pg/mL. The area under the receiver operating characteristic curve (AUROC) for discrimination of elevated mean right atrial pressure (mRAP) and pulmonary arterial wedge pressure (PAWP) was 0.74 (95% CI = 0.67–0.79) and 0.70 (95% CI = 0.64–0.75), respectively, with optimal bio-ADM decision cutoff of 39 pg/mL, concordant with cubic spline analyses. NT-proBNP discriminated PAWP slightly better than mRAP (AUROC 0.73 [95% CI = 0.68–0.79] and 0.68 [95% CI = 0.61–0.75]). Bio-ADM correlated with (mRAP, r = 0.55) while NT-proBNP correlated with PAWP. Finally, a bio-ADM decision cutoff of 39 pg/mL associated with 30 and 90 day mortality and conferred a two-fold increased odds of HF diagnosis, independently from NT-proBNP. Conclusions: Bio-ADM tracks with mRAP and associates with measures of systemic congestion and with mortality in decompensated HF independently from NT-proBNP. Our findings support utility of bio-ADM as a biomarker of systemic venous congestion in HF and nominate a decision threshold.
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| 4. |
- Fawad, Ayesha, et al.
(författare)
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Plasma Proneurotensin and Prediction of Cause-Specific Mortality in a Middle-aged Cohort During Long-term Follow-up
- 2022
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 107:3, s. 1204-1211
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Neurotensin is associated with cardiometabolic diseases but its role with mortality risk in humans is unknown.OBJECTIVE: This work aims to examine the prediction of proneurotensin (Pro-NT) with respect to total and cause-specific mortality in a middle-aged cohort.METHODS: In the population-based middle-aged cohort (n = 4632; mean age, 57 years) of the Malmö Diet and Cancer Study, Pro-NT was assessed and total as well as cause-specific mortality was studied. Main cause of death was based on the International Classification of Diseases.RESULTS: During a mean follow-up of 20 ± 3 years, 950 men and 956 women died. There was significantly increased mortality risk in individuals belonging to the highest quartile (Q) of Pro-NT (Q4, Pro-NT ≥ 149 pmol/L) compared with Qs 1 to 3 (Pro-NT < 149 pmol/L), hazard ratio (HR), 95% CI of 1.29 (1.17-1.42; P < .001). Data were adjusted for sex and age. No significant interaction was observed between Pro-NT and sex on mortality risk. Individuals within Q4 vs Qs 1 to 3 had an HR of 1.41 (95% CI, 1.18-1.68; P < .001) for death due to cardiovascular disease (n = 595/4632); 2.53 (95% CI, 1.37-4.67; P = .003), due to digestive tract disease (n = 42/4632), 1.62 (95% CI, 1.04-2.52; P = .032) due to mental and behavioral disease (n = 90/4632); and 1.91 (95% CI, 1.15-3.19; P = .013) due to unspecific causes (n = 64/4632). There was no significant relationship between Pro-NT and deaths due to cancer, infections, neurological, or other causes. Adjustment for cardiovascular risk factors only marginally changed these results.CONCLUSION: The relationship between Pro-NT and total mortality risk was mainly driven by cardiovascular mortality, but high Pro-NT also predicts death from digestive, mental, and behavioral disease and deaths attributed to unspecific causes.
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| 5. |
- Johansson, Madeleine, et al.
(författare)
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Circulating levels of growth hormone in postural orthostatic tachycardia syndrome
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Postural orthostatic tachycardia syndrome (POTS) is a cardiovascular autonomic disorder with poorly understood etiology and underlying pathophysiology. Since cardiovascular morbidity has been linked to growth hormone (GH), we studied GH levels in patients with POTS. We conducted an age-sex-matched case-control study in patients with POTS (age 31 ± 9 years; n = 42) and healthy controls (32 ± 9 years; n = 46). Plasma GH levels were measured using high-sensitivity chemiluminescence sandwich immunoassay. The burden of orthostatic intolerance symptoms was assessed by the Orthostatic Hypotension Questionnaire (OHQ), consisting of a symptom assessment scale (OHSA) and a daily activity scale (OHDAS). POTS patients had significantly higher composite OHQ score than controls, more symptoms and less activity. Supine heart rate and diastolic blood pressure (BP), but not systolic BP, were significantly higher in POTS. Median plasma GH levels were significantly lower in POTS (0.53 ng/mL) than controls (2.33 ng/mL, p = 0.04). GH levels were inversely related to OHDAS in POTS and supine systolic BP in POTS and controls, but not heart rate neither group. POTS is associated with lower GH levels. Impairment of daily life activities is inversely related with GH in POTS. A higher supine diastolic BP is inversely associated with GH levels in POTS and healthy individuals.
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| 6. |
- Johansson, Madeleine, et al.
(författare)
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Downregulation of growth hormone in postural orthostatic tachycardia syndrome: insights from the SYSTEMA cohort
- 2020
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Ingår i: European Heart Journal, Supplement. - : Oxford University Press (OUP). - 1520-765X .- 0195-668X .- 1522-9645. ; 41:Issue Supplement_2
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Konferensbidrag (refereegranskat)abstract
- Background Postural orthostatic tachycardia syndrome (POTS) is a variant of cardiovascular autonomic disorder occurring predominantly in young women. POTS is characterized by an excessive heart rate increase when assuming upright posture accompanied by symptoms of orthostatic intolerance. The pathophysiology of POTS has not been fully established and is believed to be multifactorial. Purpose We aimed to investigate the alterations in circulating growth hormone level in POTS. Methods We conducted an age-matched case-control study enrolling 42 patients with POTS (age 31±9 years; 36 women) verified by positive head-up tilt testing and cardiovascular autonomic tests, and 46 controls (32±9 years; 35 women) with negative active standing test and no history of syncope, orthostatic intolerance and endocrine disease. We measured plasma levels of growth hormone using a high-sensitivity chemiluminescence immunoassay in relation to presence of POTS diagnosis. All study participants completed the validated Orthostatic Hypotension Questionnaire (OHQ), consisting of two components: the symptoms assessment scale (OHSA) and daily activity scale (OHDAS) to evaluate the burden of symptoms. We applied standard statistical tests for group differences. Growth hormone values were log-transformed and standardized before the group comparison. Results POTS patients had significantly lower plasma levels of growth hormone (ng/mL) (median=0.53, IQR, 0.10–2.83 vs. median=2.33, IQR, 0.26–7.2, p=0.04) than controls. Levels of growth hormone were reversely related to OHDAS (p=0.049) among POTS patients. Supine heart rate was significantly higher in POTS patients (69.0±11.1 beats/min vs. 63.3±10.8 beats/min, p=0.02), as well as diastolic blood pressure (72.9±9.1 mmHg vs. 69.0±8.5 mmHg, p=0.04). We observed no significant difference in supine systolic blood pressure (116.6±13.3 mmHg vs. 115.2±10.0 mmHg, p=0.60). POTS patients had a significantly higher composite OHQ score than controls (60.0±18.6 vs. 4.2±7.5, p<0.001), as well as OHSA (36.2±10.0 vs. 3.6±6.4, p<0.001) and OHDAS (23.8±9.7 vs. 0.6±1.3, p<0.001). Conclusion(s) Our study shows that patients with POTS have significantly reduced plasma levels of circulating growth hormone. Lower growth hormone levels among POTS patients are associated with increased impairment of daily life activities. Further studies are necessary to confirm our findings in the independent populations and explain the mechanisms behind this alteration.
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| 7. |
- Lundberg, Oscar, et al.
(författare)
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Bioactive adrenomedullin in sepsis patients in the emergency department is associated with mortality, organ failure and admission to intensive care
- 2022
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:4, s. 1-16
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAdrenomedullin is a vasoactive hormone with potentially prognostic and therapeutic value, which mainly has been investigated in intensive care unit (ICU) settings. The triaging in the emergency department (ED) of patients to the right level of care is crucial for patient outcome.ObjectivesThe primary aim of this study was to investigate the association of bioactive adrenomedullin (bio-ADM) with mortality among sepsis patients in the ED. Secondary aims were to investigate the association of bio-ADM with multiple organ failure (MOF), ICU admission and ED discharge.MethodsIn this prospective observational cohort study, adult sepsis patients in the ED (2013–2015) had blood samples collected for later batch analysis of bio-ADM. Odds ratios (OR) with 95% confidence interval (CI) for bio-ADM were calculated.ResultsBio-ADM in 594 sepsis patients was analyzed of whom 51 died within 28 days (8.6%), 34 developed severe MOF, 27 were ICU admitted and 67 were discharged from the ED. The median (interquartile range) bio-ADM was 36 (26–56) and 63 (42–132) pg/mL among survivors and non-survivors, respectively, 81 (56–156) pg/mL for patients with severe MOF and 77 (42–133) pg/mL for ICU admitted patients. Each log-2 increment of bio-ADM conferred an OR of 2.30 (95% CI 1.74–3.04) for mortality, the adjusted OR was 2.39 (95% CI 1.69–3.39). The area under the receiver operating characteristic curve of a prognostic mortality model based on demographics and biomarkers increased from 0.80 to 0.86 (p = 0.02) when bio-ADM was added. Increasing bio-ADM was associated with severe MOF, ICU admission and ED discharge with adjusted ORs of 3.30 (95% CI 2.13–5.11), 1.75 (95% CI 1.11–2.77) and 0.46 (95% CI 0.32–0.68), respectively.ConclusionBio-ADM in sepsis patients in the ED is associated with mortality, severe MOF, ICU admission and ED discharge, and may be of clinical importance for triage of sepsis patients in the ED.
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| 8. |
- Lundberg, Oscar H.M., et al.
(författare)
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Circulating bioactive adrenomedullin as a marker of sepsis, septic shock and critical illness
- 2020
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Biomarkers can be of help to understand critical illness and to identify and stratify sepsis. Adrenomedullin is a vasoactive hormone, with reported prognostic and potentially therapeutic value in sepsis. The primary aim of this study was to investigate the association of circulating bioactive adrenomedullin (bio-ADM) levels at intensive care unit (ICU) admission with mortality in sepsis patients and in a general ICU population. Secondary aims included the association of bio-ADM with organ failure and the ability of bio-ADM to identify sepsis. Methods: In this retrospective observational study, adult patients admitted to one of four ICUs during 2016 had admission bio-ADM levels analysed. Age-adjusted odds ratios (OR) with 95% CI for log-2 transformed bio-ADM, and Youden’s index derived cut-offs were calculated. The primary outcome was 30-day mortality, and secondary outcomes included the need for organ support and the ability to identify sepsis. Results: Bio-ADM in 1867 consecutive patients were analysed; 632 patients fulfilled the sepsis-3 criteria of whom 267 had septic shock. The median bio-ADM in the entire ICU population was 40 pg/mL, 74 pg/mL in sepsis patients, 107 pg/mL in septic shock and 29 pg/mL in non-septic patients. The association of elevated bio-ADM and mortality in sepsis patients and the ICU population resulted in ORs of 1.23 (95% CI 1.07–1.41) and 1.22 (95% CI 1.12–1.32), respectively. The association with mortality remained after additional adjustment for lactate in sepsis patients. Elevated bio-ADM was associated with an increased need for dialysis with ORs of 2.28 (95% CI 2.01–2.59) and 1.97 (95% CI 1.64–2.36) for the ICU population and sepsis patients, respectively, and with increased need of vasopressors, OR 1.33 (95% CI 1.23–1.42) (95% CI 1.17–1.50) for both populations. Sepsis was identified with an OR of 1.78 (95% CI 1.64–1.94) for bio-ADM, after additional adjustment for severity of disease. A bio-ADM cut-off of 70 pg/mL differentiated between survivors and non-survivors in sepsis, but a Youden’s index derived threshold of 108 pg/mL performed better. Conclusions: Admission bio-ADM is associated with 30-day mortality and organ failure in sepsis patients as well as in a general ICU population. Bio-ADM may be a morbidity-independent sepsis biomarker.
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