Circulating protein biomarkers predict incident hypertensive heart failure independently of N-terminal pro-B-type natriuretic peptide levels
| Autor: | Jan Nilsson, Gunnar Engström, Marju Orho-Melander, Jaana Rysä, Kristoffer Ström, Céline Fernandez, Heikki Ruskoaho, Olle Melander |
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| Přispěvatelé: | Division of Pharmacology and Pharmacotherapy, Drug Research Program, Regenerative pharmacology group |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
lcsh:Diseases of the circulatory (Cardiovascular) system
medicine.medical_specialty hypertension medicine.drug_class prospective cohort heart failure cardiomyocyte 030204 cardiovascular system & hematology 03 medical and health sciences 0302 clinical medicine Diet and cancer Original Research Articles Internal medicine Natriuretic Peptide Brain Gene expression medicine Natriuretic peptide Animals Original Research Article 030212 general & internal medicine Prospective cohort study Urokinase Plasminogen Activator Surface Receptor business.industry Incidence (epidemiology) Hazard ratio protein panel medicine.disease Peptide Fragments Rats 3. Good health Endocrinology lcsh:RC666-701 317 Pharmacy Heart failure Cardiology and Cardiovascular Medicine business Biomarkers |
| Zdroj: | ESC Heart Failure ESC Heart Failure, Vol 7, Iss 4, Pp 1891-1899 (2020) |
| Popis: | Aims: Hypertension is the leading cause for the development of heart failure (HF). Here, we aimed to identify cardiomyocyte stretch-induced circulating biomarkers for predicting hypertension-associated HF. Methods and results: Circulating levels of 149 proteins were measured by proximity extension assay at baseline examination in 4742 individuals from the Malmo Diet and Cancer study. Protein levels were compared with stretch-activated gene expression changes in cultured neonatal rat ventricular myocytes (NRVMs) in response to 1–48 h of mechanical stretch. We also studied the association between protein levels and hypertension and HF incidence using respectively binary logistic and Cox regressions. Levels of 35 proteins were differentially expressed after Bonferroni correction in incident HF vs. control (P < 3.4E−4). Growth differentiation factor-15 (GDF-15), interleukin-6 (IL-6), IL-1 receptor type 1, and urokinase plasminogen activator surface receptor had corresponding mRNA levels up-regulated by stretch in NRVMs at all time points (P < 0.05). These four proteins were individually associated with increased risk of HF after age and sex adjustment [hazard ratio (HR) per standard deviation: 1.19 ≤ HR ≤ 1.49, P ≤ 4.90E−3]. GDF-15 and IL-6 were associated with HF independently of each other (1.22 ≤ HR ≤ 1.33, P ≤ 0.001). In subjects with hypertension, these associations remained significant after further adjustment for N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (1.23 ≤ HR ≤ 1.45, P ≤ 0.001). A higher fasting value of a GDF-15, IL-6 score aggregate was associated with increased risk of hypertensive HF after adjustment for all traditional risk factors for HF and NT-proBNP (HR = 1.31, P = 2.19E−4). Conclusions: Cardiomyocyte mRNA levels of GDF-15 and IL-6 are consistently up-regulated by stretch, and their circulating protein levels predict HF in hypertensive subjects independently of NT-proBNP during long-term follow-up. Our results encourage further studies on lower blood pressure goals in hypertensive subjects with high GDF-15 and IL-6, and interventions targeted at stretch-induced cardiomyocyte expressed biomarkers. (Less) |
| Databáze: | OpenAIRE |
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