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

Westergren HU, Svedlund S, Momo RA, Blomster JI, Wåhlander K, Rehnström E, Greasley PJ, Fritsche-Danielson R, Oscarsson J, Gan LM - Cardiovasc Diabetol (2016)

Bottom Line: 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.Increased systemic pro-inflammatory state and decreased levels of pro-angiogenic vascular growth factors may be important underlying molecular mechanisms.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. helena.westergren@gu.se.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

A flow-scheme illustrating the patient recruitment process
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Fig1: A flow-scheme illustrating the patient recruitment process

Mentions: A total of 365 consecutive non-diabetic patients with chest pain referred to Sahlgrenska University Hospital in Gothenburg, Sweden due to suspected myocardial ischemia, were recruited to the study between 2006 and 2008 (Fig. 1). At a separate occasion within 2 weeks following clinical MPS examination, all patients underwent examinations of peripheral endothelial function. Overnight fasting blood samples were taken post examination of endothelial function. All patients underwent a standardized interview of medical history including history of diabetes, known CAD, smoking status and current cardiovascular medication. Patients with previous diabetes diagnosis, fasting plasma glucose ≥7.0 mmol/L or glycated haemoglobin A1c (HbA1c) level >48 mmol/mol were excluded from the study. Known CAD was defined as previous coronary artery bypass grafting, percutaneous coronary intervention or myocardial infarction (MI) and was collected from patients’ medical records. All participants provided written informed consent. The study complies with the declaration of Helsinki and was approved by the Local Ethics Committee at the University of Gothenburg.Fig. 1


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

Westergren HU, Svedlund S, Momo RA, Blomster JI, Wåhlander K, Rehnström E, Greasley PJ, Fritsche-Danielson R, Oscarsson J, Gan LM - Cardiovasc Diabetol (2016)

A flow-scheme illustrating the patient recruitment process
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4759743&req=5

Fig1: A flow-scheme illustrating the patient recruitment process
Mentions: A total of 365 consecutive non-diabetic patients with chest pain referred to Sahlgrenska University Hospital in Gothenburg, Sweden due to suspected myocardial ischemia, were recruited to the study between 2006 and 2008 (Fig. 1). At a separate occasion within 2 weeks following clinical MPS examination, all patients underwent examinations of peripheral endothelial function. Overnight fasting blood samples were taken post examination of endothelial function. All patients underwent a standardized interview of medical history including history of diabetes, known CAD, smoking status and current cardiovascular medication. Patients with previous diabetes diagnosis, fasting plasma glucose ≥7.0 mmol/L or glycated haemoglobin A1c (HbA1c) level >48 mmol/mol were excluded from the study. Known CAD was defined as previous coronary artery bypass grafting, percutaneous coronary intervention or myocardial infarction (MI) and was collected from patients’ medical records. All participants provided written informed consent. The study complies with the declaration of Helsinki and was approved by the Local Ethics Committee at the University of Gothenburg.Fig. 1

Bottom Line: 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.Increased systemic pro-inflammatory state and decreased levels of pro-angiogenic vascular growth factors may be important underlying molecular mechanisms.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. helena.westergren@gu.se.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus