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

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.