Pro-inflammatory biomarkers in women with non-obstructive angina pectoris and coronary microvascular dysfunction

Abstract

Background Studies that evaluate larger numbers of protein biomarkers in patients with coronary microvascular dysfunction (CMD) have not previously been performed, and very little is known concerning the pathogenetic mechanisms leading to CMD. Our objective was to analyze associations between a broad cardiovascular disease (CVD) protein biomarker assay and CMD, and further explore internal biomarker relations in order to identify possible targets for future treatment interventions. Methods In 174 women with angina pectoris and no significant obstructive coronary artery disease (<50% stenosis on invasive coronary angiography), CMD was assessed by transthoracic Doppler echocardiography measuring coronary flow velocity reserve (CFVR). Blood samples were analyzed with a CVD proteomic panel encompassing 92 biomarkers. The relation between biomarkers and CFVR was evaluated by regression analysis, and possible interrelations between significant biomarkers were investigated by principal component analysis (PCA). Results Median age (SD) was 64 years (9.8), median CFVR (IQR) was 2.3 (1.9–2.7), and 28% of patients had CFVR < 2.0. Eighteen biomarkers were significantly correlated with CFVR. In PCA, 8 of the biomarkers significantly related to CFVR showed high loadings on principal component 1 (PC1). The component scores of PC1 were significantly related to CFVR ( p = 0.002). The majority of the 8 interrelated PC1 biomarkers were related to the pro-inflammatory TNF-α – IL-6 – CRP pathway. Conclusion Eighteen protein biomarkers were significantly associated with CMD. Eight biomarkers were interrelated in PCA, and share connection with pro-inflammatory pathways, highlighting a possible important role of inflammation in CMD.

Smoking, alcohol and opioids effect on coronary microcirculation: an update overview

“…Multiple studies have linked chronic inflammatory disorders such as lupus, rheumatoid arthritis, and inflammatory bowel disease with higher risk of developing CMD [ 61 – 63 ]. Others confirmed this result finding a significant correlation between systemic inflammatory markers (mostly plasma CRP) and risk of CMD [ 64 – 66 ]. Recently, Schroder et al assessed the differential blood protein profile of CMD patients and healthy volunteers.…”

“…Recently, Schroder et al assessed the differential blood protein profile of CMD patients and healthy volunteers. Interestingly, the main differentially expressed protein biomarkers they found to be associated with CMD were several pro-inflammatory factors, related to the TNF-α-IL-6-CRP pathway [ 66 ]. Smoking is conventionally considered to induce inflammation based on studies who rely on self-reports on smoking status [ 67 – 70 ].…”

Inflammation, non-endothelial dependent coronary microvascular function and diastolic function—Are they linked?

“…In smaller studies we have previously found several biomarkers of inflammation and vascular dysfunction to be associated with non-endothelial dependent CMD in women with angina symptoms but no flow limiting CAD [15,16]. Here we explore the hypothesis that subclinical inflammation is linked to coronary microvascular function and cardiac diastolic function, and that the effect of inflammation on diastolic function is partly mediated by non-endothelial dependent CMD (Fig 1).…”

Berries and Their Polyphenols as a Potential Therapy for Coronary Microvascular Dysfunction: A Mini-Review

“…Further, increased ROS can contribute to activation of redox-dependent inflammatory mediators exacerbating inflammation. Patients with CMD express higher systemic concentrations of tumor necrosis factor (TNF)-α [ 36 , 37 ]. In fact, TNF-α inhibition in patients with CMD significantly improves CFR [ 38 ].…”