Insulin resistance, endothelial function, angiogenic factors and clinical outcome in non-diabetic patients with chest pain without myocardial perfusion defects
| Autor: | Jan Oscarsson, Remi A. Momo, Li-Ming Gan, Peter J. Greasley, Erika Rehnström, Regina Fritsche-Danielson, Sara Svedlund, Helena U. Westergren, Juuso I. Blomster, Karin Wåhlander |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Time Factors Endocrinology Diabetes and Metabolism Coronary Artery Disease 030204 cardiovascular system & hematology Coronary artery disease 0302 clinical medicine Risk Factors Medicine Glucose homeostasis Angiogenic Proteins Endothelial dysfunction Original Investigation Outcome education.field_of_study Middle Aged Vasodilation Cardiology Female Inflammation Mediators Growth factors Cardiology and Cardiovascular Medicine medicine.medical_specialty Population Hyperemia Disease-Free Survival Angina Pectoris Prediabetic State 03 medical and health sciences Insulin resistance Diabetes mellitus Internal medicine Humans education Aged Proportional Hazards Models Angiology Chi-Square Distribution business.industry Vascular Endothelial Growth Factor D Endothelial function medicine.disease 030104 developmental biology Gene Expression Regulation Multivariate Analysis Linear Models Endothelium Vascular Non-obstructive coronary artery disease business Biomarkers |
| Zdroj: | Cardiovascular Diabetology |
| ISSN: | 1475-2840 |
| DOI: | 10.1186/s12933-016-0353-1 |
| Popis: | Background Patients with angina-like symptoms without myocardial perfusion scintigram (MPS)-verified abnormality may still be at risk for cardiovascular events. We hypothesized that insulin resistance could play a role in this population even without diagnosed diabetes. We further explored physiological and blood biomarkers, as well as global gene expression patterns that could be closely related to impaired glucose homeostasis to deepen our mechanistic understanding. Methods A total of 365 non-diabetic patients with suspected myocardial ischemia referred to MPS were enrolled and followed up regarding event-free survival with a median time of 5.1 years. All patients underwent endothelial function assessment by reactive hyperemic index (RHI) using EndoPAT and extensive biomarker analysis. Whole blood global gene expression pathway analysis was performed in a subset of patients. Results Homeostasis model assessment of insulin resistance (HOMA-IR) added independent prognostic value in patients without myocardial perfusion defects. In a multivariable analysis, HOMA-IR was inversely associated with low RHI. Furthermore, elevated HOMA-IR was associated with decreased levels of vascular endothelial growth factor D, stem cell factor and endocan as well as to increased level of interleukin-6. Global gene expression pathway analysis of whole blood cells showed that high HOMA-IR and impaired endothelial function were associated with upregulated pro-inflammatory pathways and down-regulated eukaryotic initiation factor-2 pathway. Conclusions Insulin resistance measured by HOMA-IR is associated with endothelial dysfunction and confers independent prognostic information in non-diabetic patients with chest pain without myocardial perfusion defects. Increased systemic pro-inflammatory state and decreased levels of pro-angiogenic vascular growth factors may be important underlying molecular mechanisms. |
| Databáze: | OpenAIRE |
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