Insulin resistance, endothelial function, angiogenic factors and clinical outcome in non-diabetic patients with chest pain without myocardial perfusion defects

Cardiovascular Diabetology

Original Investigation

Karin Wåhlander¹  Regina Fritsche-Danielson¹  Remi A. Momo¹  Jan Oscarsson¹  Erika Rehnström¹  Peter J. Greasley¹  Helena U. Westergren²  Juuso I. Blomster³  Sara Svedlund⁴  Li-Ming Gan⁵ 

[1] AstraZeneca R&D, Gothenburg, Sweden;Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden;Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden;AstraZeneca R&D, Gothenburg, Sweden;Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden;Department of Clinical Physiology, Sahlgrenska University Hospital, Gothenburg, Sweden;Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden;Department of Clinical Physiology, Sahlgrenska University Hospital, Gothenburg, Sweden;AstraZeneca R&D, Gothenburg, Sweden;

关键词: Non-obstructive coronary artery disease;    Insulin resistance;    Outcome;    Endothelial function;    Growth factors;   

DOI  :  10.1186/s12933-016-0353-1

 received in 2016-01-05, accepted in 2016-02-09,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundPatients 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.MethodsA 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.ResultsHomeostasis 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.ConclusionsInsulin 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.

【 授权许可】

CC BY   
© Westergren et al. 2016