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Plasma copeptin and markers of arterial disorder in patients with type 2 diabetes, a cross-sectional study
Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology.
Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Heart Center, Department of Clinical Physiology in Linköping.ORCID iD: 0000-0002-5716-5098
Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping. Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Region Östergötland, Medicine Center, Department of Endocrinology.ORCID iD: 0000-0002-9982-3554
Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Primary Care Center, Primary Health Care Center Ekholmen.ORCID iD: 0000-0003-1617-3179
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2024 (English)In: Cardiovascular Diabetology, E-ISSN 1475-2840, Vol. 23, no 1, article id 200Article in journal (Refereed) Published
Abstract [en]

Objectives There is currently limited understanding of the relationship between copeptin, the midregional portion of proadrenomedullin (MRproADM) and the midregional fragment of the N-terminal of proatrial natriuretic peptide (MRproANP), and arterial disorders. Toe brachial index (TBI) and aortic pulse wave velocity (aPWV) are established parameters for detecting arterial disorders. This study evaluated whether copeptin, MRproADM, and MRproANP were associated with TBI and aPWV in patients with type 2 diabetes with no history of cardiovascular disease (CVD).

Methods In the CARDIPP study, a cross-sectional analysis of 519 patients with type 2 diabetes aged 55–65 years with no history of CVD at baseline, had complete data on copeptin, MRproADM, MRproANP, TBI, and aPWV was performed. Linear regression analysis was used to investigate the associations between conventional CVD risk factors, copeptin, MRproADM, MRproANP, TBI, and aPWV.

Results Copeptin was associated with TBI (β–0.0020, CI–0.0035– (–0.0005), p = 0.010) and aPWV (β 0.023, CI 0.002–0.044, p = 0.035). These associations were independent of age, sex, diabetes duration, mean 24-hour ambulatory systolic blood pressure, glycated hemoglobin A1c, total cholesterol, estimated glomerular filtration rate, body mass index, and active smoking.

Conclusions Plasma copeptin may be a helpful surrogate for identifying individuals at higher risk for arterial disorders.

Place, publisher, year, edition, pages
Springer, 2024. Vol. 23, no 1, article id 200
Keywords [en]
Type 2 diabetes, Copeptin, MRproADM, MRproANP, Toe brachial index, Pulse wave velocity, Cardiovascular disease
National Category
Endocrinology and Diabetes Cardiology and Cardiovascular Disease
Identifiers
URN: urn:nbn:se:liu:diva-204549DOI: 10.1186/s12933-024-02291-2ISI: 001249211800001PubMedID: 38867292OAI: oai:DiVA.org:liu-204549DiVA, id: diva2:1869509
Funder
Linköpings universitet
Note

Funding Agencies|Region Ostergotland [RO-966396]; King Gustaf V and Queen Victoria Freemason Foundation grants; Medical Research Council of Southeast Sweden supported CARDIPP; Linkoping University

Available from: 2024-06-13 Created: 2024-06-13 Last updated: 2025-02-10Bibliographically approved
In thesis
1. Underneath The Obvious: The markers of disease not yet manifested : Evaluation of cardiovascular risk markers in patients with type 2 diabetes and the role of plasma biomarkers in patients presenting to the emergency department with chest pain and/or shortness of breath
Open this publication in new window or tab >>Underneath The Obvious: The markers of disease not yet manifested : Evaluation of cardiovascular risk markers in patients with type 2 diabetes and the role of plasma biomarkers in patients presenting to the emergency department with chest pain and/or shortness of breath
2024 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cardiovascular disease (CVD) is the leading cause of death globally, and diabetes mellitus (DM) is increasingly prevalent worldwide. People with DM are at a higher risk of developing heart-related complications that can lead to serious health issues and death. Chest pain (CP) and shortness of breath (SOB) are common manifestations of cardiopulmonary disorders. These symptoms often prompt people to seek emergency medical care.

Risk stratification involves assessing a patient's probability of experiencing complications and premature death. Determining the necessary interventions to improve the patients' health outcomes is essential. Healthcare professionals encounter daily challenges in risk stratification. Identifying new and clinically relevant markers for improved risk stratification is crucial.

This thesis aims to assess whether blood biomarkers could predict the risk of adverse events and prognosis in emergency care patients with CP and/or SOB. Additionally, this work evaluates risk markers for identifying patients with higher risk of CVD and premature death in type 2 diabetes (T2DM) patients.

Papers I and II assessed the predictive values of copeptin, mid-regional pro-adrenomedullin (MRproADM), and mid-regional pro-atrial natriuretic peptide (MRproANP) as potential markers for risk stratification in emergency departments (ED). These studies were based on the ABBA population, a single-center observational study conducted at the Linköping Hospital ED.

In Paper I, age, sex, oxygen saturation, heart rate, National Early Warning Score (NEWS) category, and copeptin were found to be associated with admission to a hospital ward from the ED. Copeptin was found to have an added predictive value for admission compared to NEWS alone.

In Paper II, MRproADM levels >0.75 nmol/L and multimorbidity were significantly associated with readmission and/or death within 90 days. MRproADM improved the predictive value of readmission and/or death within 90 days compared to age, sex, and multimorbidity combined. 

Papers III, IV, and V were based on CARDIPP, a research program aimed at identifying markers for CVD in T2DM patients. This population-based study involved primary care patients aged 55−65, with a baseline survey conducted between 2005 and 2008. The cohort was monitored for CVD morbidity and mortality from a national registry.

In Paper III, patients with T2DM and low toe brachial index (TBI) had an increased risk of major adverse cardiovascular events (MACE) independent of arterial stiffness.

In Paper IV, we found that an increasing copeptin level was significantly associated with MACE. Patients with copeptin levels ≥5.6 pmol/L had an unfavorable risk for MACE, independent of traditional CVD risk factors and left ventricular mass index.

Paper V found that copeptin was associated with TBI and aortic pulse wave velocity (aPWV), both markers of arterial disorders, independent of traditional CVD risk factors.

In conclusion, early analysis of copeptin may be helpful for patient risk assessments. MRproADM and multimorbidity may predict the risk of readmission and/or death within 90 days. In patients with T2DM, low TBI, and elevated copeptin levels may serve as important indicators for increased risk of MACE. Copeptin may be a helpful surrogate for identifying individuals at higher risk of arterial disorders.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2024. p. 83
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1926
Keywords
Risk stratification, Biomarker, Emergency, Diabetes, Cardiovascular disease
National Category
Cardiology and Cardiovascular Disease
Identifiers
urn:nbn:se:liu:diva-209952 (URN)10.3384/9789180757171 (DOI)9789180757164 (ISBN)9789180757171 (ISBN)
Public defence
2024-12-19, Granitsalen, Building 440, Campus US, Linköping, 13:00 (Swedish)
Opponent
Supervisors
Note

Funding: Grants from the County Council of Östergötland, King Gustav V and Queen Victoria Freemason Foundation, and the Medical Research Council of Southeast Sweden supported this study.

Available from: 2024-11-19 Created: 2024-11-19 Last updated: 2025-02-10Bibliographically approved

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Davidson, Lee TiEngvall, JanChisalita, Ioana SimonaÖstgren, Carl JohanNyström, Fredrik

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Department of Emergency Medicine in LinköpingFaculty of Medicine and Health SciencesDivision of Clinical Chemistry and PharmacologyDivision of Diagnostics and Specialist MedicineCenter for Medical Image Science and Visualization (CMIV)Department of Clinical Physiology in LinköpingDepartment of EndocrinologyDivision of Prevention, Rehabilitation and Community MedicinePrimary Health Care Center EkholmenPrimary Health Care Center Cityhälsan Centrum
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