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

被引:25
作者
Westergren, Helena U. [1 ]
Svedlund, Sara [1 ,2 ]
Momo, Remi A.
Blomster, Juuso I. [1 ]
Wahlander, Karin
Rehnstrom, Erika
Greasley, Peter J.
Fritsche-Danielson, Regina
Oscarsson, Jan
Gan, Li-Ming [1 ,2 ,3 ]
机构
[1] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden
[2] Sahlgrens Univ Hosp, Dept Clin Physiol, Gothenburg, Sweden
[3] AstraZeneca R&D, Gothenburg, Sweden
来源
CARDIOVASCULAR DIABETOLOGY | 2016年 / 15卷
关键词
Non-obstructive coronary artery disease; Insulin resistance; Outcome; Endothelial function; Growth factors; CORONARY-ARTERY-DISEASE; INCREMENTAL PROGNOSTIC VALUE; TYPE-2; DIABETES-MELLITUS; STABLE ANGINA-PECTORIS; COMPUTED-TOMOGRAPHY; SKELETAL-MUSCLE; FLOW RESERVE; FATTY-ACIDS; DYSFUNCTION; INFLAMMATION;
D O I
10.1186/s12933-016-0353-1
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
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页数:12
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