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Toe brachial index predicts major acute cardiovascular events in patients with type 2 diabetes independently of arterial stiffness
Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Endocrinology.
Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.ORCID iD: 0000-0002-4757-9051
Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. 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. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.ORCID iD: 0000-0002-7130-9158
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2020 (English)In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 161, article id 108040Article in journal (Refereed) Published
Abstract [en]

Objective: Our aim was to analyze the predictive value of toe brachial index (TBI) as a risk marker for future major adverse cardiovascular events (MACE) and all-cause mortality in patients with type 2 diabetes (T2D). Methods: TBI was measured in 741 patients with T2D in 2005-2008. Conventional risk factors for vascular disease as well as non-invasive measurements such as pulse-wave velocity (PWV) and intima-media thickness (IMT) of the carotid arteries were estimated. MACE was defined as cardiovascular death or hospitalization for non fatal myocardial infarction or non fatal stroke. Patients were followed for incidence of MACE using the national Swedish Cause of Death Registry and the Inpatient Register. Results: During the follow-up for a period of 9 years MACE occurred in 97 patients and 85 patients died. TBI tertile, 1 versus 3, was significantly related to MACE (HR 2.67, 95%CI 1.60-4.50; p < 0.001) and to all-cause mortality (HR 1.98, 95%CI 1.16-3.83; p = 0.01). TBI tertile 1 as compared to TBI tertile 3 predicted MACE, but not all-cause mortality, independently of age, sex, diabetes duration and treatment, antihypertensive treatment, previous cardiovascular diseases, office systolic blood pressure, HbA1c, LDL cholesterol, estimated glomerular filtration rate, body mass index, current smoking PWV, IMT and carotid plaque presence (HR 3.39, 95%CI 1.53-7.51; p = 0.003 and HR 1.81, 95%CI 0.87-3.76; p = 0.1, respectively). Conclusions: Low TBI predicts an increased risk for MACE independently of arterial stiffness in patients with type 2 diabetes. Trial registration: Clinical Trials.gov number NCT 01049737. Registered January 14, 2010. (C) 2020 Elsevier B.V. All rights reserved.

Place, publisher, year, edition, pages
ELSEVIER IRELAND LTD , 2020. Vol. 161, article id 108040
Keywords [en]
Type 2 diabetes; Toe pressure; Toe brachial index; Cardiovascular events
National Category
Cardiology and Cardiovascular Disease
Identifiers
URN: urn:nbn:se:liu:diva-165093DOI: 10.1016/j.diabres.2020.108040ISI: 000520852000033PubMedID: 32006647OAI: oai:DiVA.org:liu-165093DiVA, id: diva2:1423727
Available from: 2020-04-15 Created: 2020-04-15 Last updated: 2025-02-10
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)
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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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Simona Chisalita, IoanaWijkman, Magnus

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Division of Diagnostics and Specialist MedicineFaculty of Medicine and Health SciencesDepartment of EndocrinologyDepartment of Internal Medicine in NorrköpingDepartment of Emergency Medicine in LinköpingDepartment of EndocrinologyPrimary Health Care Center Cityhälsan CentrumDivision of Prevention, Rehabilitation and Community MedicinePrimary Health Care Center Ödeshög
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