Biomarkers of Myocardial Fibrosis are Associated with Diabetes but not with Coronary Microvascular Dysfunction in Women with Angina and No Obstructive Coronary Artery Disease

2020 ◽  
Author(s):  
Kira Bang Bove ◽  
Naja Dam Mygind ◽  
Signe Holm Nielsen ◽  
Marie Mide Michelsen ◽  
Daria Frestad Bechsgaard ◽  
...  

Abstract Background Coronary microvascular dysfunction (CMD) is highly prevalent in women with no obstructive coronary artery disease and possibly related to myocardial fibrosis caused by excessive extracellular matrix (ECM) remodeling. ECM turnover can be measured in blood indicating fibrotic activity. We hypothesized that women with DM, angina and no obstructive coronary artery disease have increased ECM turnover and that this is associated with CMD.Methods We included 344 women with angina pectoris and no obstructive coronary artery disease (187 with DM, predominantly type II) and 76 asymptomatic women without DM as controls. Biomarkers reflecting formation of type IV and VI collagen (PRO-C4 and PRO-C6) and degradation of type IV, V and VI collagen (C4M, C5M, C6M), mimecan (MIM) and titin (TIM) were measured in all participants. CMD was defined as coronary flow velocity reserve (CFVR) <2.0 assessed by transthoracic Doppler echocardiography.Results Median age was 64.2 (IQR 57.0-70.0), slightly higher in symptomatic women with DM. Median CFVR was 2.21 (1.89-2.55) in symptomatic women with DM, 2.35 (1.96-2.77) in symptomatic women without DM and 2.63 (2.19-2.95) in controls (age-adjusted p for trend<0.001). With exception of CM5, women with DM had significantly higher levels of all ECM biomarkers than women without DM (age-adjusted p<0.01), whereas biomarkers did not differ between symptomatic women without DM and controls. High ECM biomarker levels were associated with HbA1c, high BMI, low HDL and high triglycerides (p=0.003-0.0001). There was no correlation between ECM biomarkers and CFVR.Conclusion Women with angina pectoris and DM had increased levels of myocardial fibrosis biomarkers compared with women without DM. There was no association between CMD and biomarkers of myocardial fibrosis.

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Naja D Mygind ◽  
Marie M Michelsen ◽  
Adam A Pena ◽  
Rebekka Faber ◽  
Jens Kastrup ◽  
...  

Background: Women are more often than men found to have no obstructive coronary artery disease (CAD) when evaluated with a coronary angiogram (CAG) due to angina pectoris and suspected ischemic heart disease. Coronary microvessel dysfunction (CMD) is a possible explanation, and can be assessed by transthoracic Doppler echocardiography (TTDE) with measurement of coronary flow reserve (CFR). Reduced CFR carries an adverse prognosis despite absence of obstructive CAD. The aim of the ongoing iPower study is to evaluate CFR in women with angina pectoris and no obstructive CAD. Methods: Women with angina pectoris and a CAG without obstructive coronary artery disease (>50%) are systematically invited to participate. Assessment includes demographic and clinical data, blood samples and TTE during rest and high-dose dipyridamole stress (0.84mg/kg) with measurement of CFR by Doppler of the left anterior descending artery. Results: To date (May 21st 2014) 3500 women have been screened (flowchart), 793 women have been included (response rate 23%). Mean age was 62.4 (+/-9.6) and the burden of risk factors was relatively high (Table 1). CFR was successfully measured in 763 patients (96%). Median (IQR) CFR was 2.4 (2.0-2.8). Cut-off point for CMD of both 2 and 2.5 has been used previously. In this population, 214 (28%) had a CFR≤2 and 468 (61%) a CFR≤2.5. Conclusions: To our knowledge, iPower is the largest and most comprehensive study systematically assessing CMD in women with angina pectoris and no obstructive CAD. Non-invasive CFR assessment is feasible, and microvascular function impaired in a large proportion. Future follow-up will determine the prognostic value of CFR as a measure of CMD.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ali Ahmad ◽  
Jaskanwal D Sara ◽  
Michel T Corban ◽  
Takumi Toya ◽  
Ilke Ozcan ◽  
...  

Title: Serum NT-proB-type Natriuretic Peptide is associated with Coronary Microvascular Dysfunction in Patients with Angina and Non-obstructive Coronary Artery Disease Authors: Ali Ahmad, MD, Jaskanwal D. Sara, MBChB, Michel T. Corban, MD, Takumi Toya, MD, Ilke Özcan, MD, Lilach O. Lerman, MD PhD, Amir Lerman, MD Introduction: Coronary microvascular dysfunction (CMD) is prevalent in patients with heart failure with preserved ejection fraction. Subclinical ischemia and myocardial fibrosis in CMD might raise filling pressure, a hallmark of HFpEF, which induces secretion of NT-proB-type natriuretic peptide (NTpro-BNP). We sought to explore the relationship between CMD and NT-proBNP. Methods: We studied 698 patients with signs and/or symptoms of ischemia and with non-obstructive CAD (<40% angiographic stenosis) who underwent invasive CMD evaluation and had NT-proBNP checked within 6 weeks. CMD was defined as coronary flow reserve (CFR) (hyperemic flow/baseline flow as measured by the doppler wire) of ≤2.5 in response to intracoronary adenosine injection. Results: Overall mean age was 52.8±12.2 years, and women represented 69% of the patients. Log NT-proBNP showed a modest inverse correlation with CFR (Pearson’s R = -0.22, P<0.0001; Figure 1 ), which remained significant after adjusting for age and gender (Standardized ß coefficient = -0.14; P = 0.001). Patients with CMD had higher levels of NT-proBNP than those without (82 [44-190] vs. 62 (33-130], P <0.0001; Figure 2) . Conclusion: Declining coronary microvascular function is correlated with higher NT-proBNP levels. Patients with CMD had higher levels of NT-proBNP, a marker of elevated LV pressure, contributing to the possible role of CMD in early HFpEF pathophysiology. Keywords: Coronary microvascular dysfunction, NT-proBNP


Author(s):  
Romana Herscovici ◽  
C. Noel Bairey Merz

The role of revascularization in the treatment of obstructive coronary artery disease is well established, and its impact on improving survival has been proven. Nevertheless, patients with signs and symptoms considered of cardiac origin but with no obstructive coronary artery disease on coronary angiography are increasingly seen. Initially described as a ‘paradox’ or cardiac syndrome X and subsequently defined as microvascular angina, angina-like chest pain and evidence of ischaemia with non-obstructive coronary artery disease, is the consequence of altered coronary microvascular response to various stimuli despite non-obstructed epicardial vessels.


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