TY  - JOUR
AB  - AIMS: Recent evidence points towards a distinct obese phenotype among patients with heart failure with preserved ejection fraction (HFpEF). We aimed to identify differentially expressed circulating biomarkers in obese HFpEF patients and link them to disease severity and outcomes. METHODS AND RESULTS: From the LIFE-Heart study, 999 patients with HFpEF and 999 patients without heart failure (no-HF) were selected and 92 circulating serum biomarkers were measured using a proximity extension assay. Elevation of identified biomarkers was validated in 220 patients from the Aldo-DHF trial with diagnosed HFpEF. HFpEF patients were older and had more comorbidities including coronary artery disease and type 2 diabetes as compared to no-HF patients (p<0.05 for all). After adjusting for covariates, Adrenomedullin (ADM), Galectin-9 (Gal-9), Thrombospondin-2 (THBS-2), CD4, and TNF-related apoptosis-inducing ligand receptor 2 (TRAIL-R2) were significantly higher in obese HFpEF (BMI≥30 kg/m2 , n=464) patients as compared to lean HFpEF (BMI<30 kg/m2 , n=535) and obese no-HF patients (BMI≥30 kg/m2 , n=387) (p<0.001 for both), those findings were verified in the Aldo-DHF validation cohort (p<0.001). Except for CD4 these proteins were associated with increased estimates of left atrial pressure in a linear fashion. Importantly, ADM, TRAIL-R2 and CD4 were associated with increased mortality in obese HFpEF patients after adjusting for covariates. CONCLUSION: Obese HFpEF patients exhibit higher circulating biomarkers of volume expansion (ADM), myocardial fibrosis (THBS-2) and systemic inflammation (Gal-9, CD4) compared to obese non-HFpEF or lean HFpEF. These findings support the clinical definition of a distinct obese HFpEF phenotype and might merit further investigation. This article is protected by copyright. All rights reserved.
AU  - Kresoja, K.P.*
AU  - Rommel, K.P.*
AU  - Wachter, R.*
AU  - Henger, S.*
AU  - Besler, C.*
AU  - Klöting, N.
AU  - Schnelle, M.*
AU  - Hoffmann, A.
AU  - Büttner, P.*
AU  - Ceglarek, U.*
AU  - Thiele, H.*
AU  - Scholz, M.*
AU  - Edelmann, F.*
AU  - Blüher, M.
AU  - Lurz, P.*
C1  - 62529
C2  - 50933
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
SP  - 1633-1644
TI  - Proteomics to improve phenotyping in obese patients with heart failure with preserved ejection fraction.
JO  - Eur. J. Heart Fail.
VL  - 23
IS  - 10
PB  - Wiley
PY  - 2021
SN  - 1388-9842
ER  - 

TY  - JOUR
AB  - AIMS: The natriuretic peptides BNP and NT-proBNP are potent cardiac markers, but knowledge of long-term changes is sparse. We thus quantified determinants of change in BNP and NT-proBNP in a study of south German residents (KORA). METHODS AND RESULTS: A total of 1005 men and women (age 25-74 years, mean 48 years) underwent physical examination and echocardiography at baseline and at follow-up after 10 years. The current analysis comprised 877 subjects with dual measurements of BNP and NT-proBNP. Both markers increased in both sexes (P < 0.001) during the 10-year follow-up, and higher levels in women persisted across time (P for sex difference <0.001). Among baseline covariates, predictors for 10-year change of NT-proBNP, BNP, or both were age, sex, diabetes status, and heart rate (multivariable regression analysis, each P < 0.05). However, changes of covariates over the 10-year follow-up were much stronger determinants. Specifically, incident myocardial infarction, new beta-blocker medication, and increased cardiac parameters (left atrial diameter, LV end-diastolic diameter, and LV mass index) were associated with increasing BNP, NT-proBNP, or both, whereas increased heart rate, haematocrit, and body mass index (BMI) were associated with decreasing BNP and NT-proBNP (all P < 0.05). CONCLUSION: Next to ageing and sex, a variety of changes in covariates reflecting the sequelae of cardiac remodelling as well as myocardial infarction and diabetes influence long-term changes of BNP and NT-proBNP. Of note, diabetes and increased BMI exert opposite effects. For interpretation of individual marker concentrations, a host of covariates needs to be considered, especially in subjects without prevalent or incident cardiac disease.
AU  - Luchner, A.*
AU  - Behrens, G.*
AU  - Stritzke, J.*
AU  - Markus, M.*
AU  - Stark, K.*
AU  - Peters, A.
AU  - Meisinger, C.
AU  - Leitzmann, M.*
AU  - Hense, H.-W.*
AU  - Schunkert, H.*
AU  - Heid, I.M.*
C1  - 25228
C2  - 31850
SP  - 859-867
TI  - Long-term pattern of brain natriuretic peptide and N-terminal pro brain natriuretic peptide and its determinants in the general population: Contribution of age, gender, and cardiac and extra-cardiac factors.
JO  - Eur. J. Heart Fail.
VL  - 15
IS  - 8
PB  - Oxford Univ. Press
PY  - 2013
SN  - 1388-9842
ER  - 

TY  - JOUR
AB  - BNP is a marker of systolic left ventricular dysfunction (LVSD) and heart failure. To assess BNP for the detection of diastolic dysfunction in the general population, we examined 1678 subjects within an age- and sex-stratified survey (MONICA Augsburg). BNP was measured using a commercially available RIA (Shionogi).BNP increased in subjects with diastolic dysfunction (mean 20.3±4.7 pg/ml vs. control 9.6±0.5 pg/ml, p<0.001), but to a lesser extent than in subjects with LV hypertrophy (LVH, mean 37.3±49.1 pg/ml, p<0.001 vs. control) or LVSD (mean 76.2±23.2 pg/ml, p<0.001 vs. control). Individuals with sole diastolic abnormality displayed BNP concentrations at the control level (mean 9.7±1.7 pg/ml). In univariate analysis, age, BMI, systolic blood pressure, left atrial size, LV mass index, diastolic dysfunction and EF displayed a significant correlation with BNP (p<0.001). However, LV mass index displaced diastolic dysfunction as a significant predictor of BNP in multivariate analysis. Upon ROC analysis, sensitivity and specificity for the detection of diastolic dysfunction by BNP were only 61% and 55%, respectively. Nevertheless, a normal BNP test virtually excluded the presence of diastolic dysfunction and concomitant LVH (NPV 99.9%).Increased BNP concentrations in subjects with diastolic dysfunction are strongly related to LVH. Population-wide screening for diastolic dysfunction with BNP cannot be recommended although a normal BNP test usually excludes diastolic dysfunction and LV hypertrophy.
      
      
      	 
AU  - von Lukowicz, T.*
AU  - Fischer, M.*
AU  - Hense, H.W.*
AU  - Döring, A.
AU  - Stritzke, J.*
AU  - Riegger, G.*
AU  - Schunkert, H.*
AU  - Luchner, A.*
C1  - 266
C2  - 23101
SP  - 525-531
TI  - BNP as a marker dysfunction in the general population: Importance of left ventricular hypertrophy.
JO  - Eur. J. Heart Fail.
VL  - 7
IS  - 4
PY  - 2005
SN  - 1388-9842
ER  -