Coronary microvascular dysfunction: the importance of markers of sympathetic activity and autonomic imbalance

Aim . To study the relationship between adrenomedullin, catestatin, norepinephrine and heart rate variability (HRV) parameters with coronary microvascular dysfunction (CMD) in patients with non-obstructive coronary artery disease (CAD). Material and methods . The study included 29 patients (55 (51; 63) years) with preserved left ventricular ejection fraction (63 (61; 66)%) and non-obstructive CAD. Serum biomarker levels were assessed at baseline and after 12-month follow-up using enzyme immunoassay. Standard semiquantitative scores of myocardial perfusion impairment and myocardial flow parameters were assessed using dynamic single-photon emission computed tomography. In the absence of obstructive CAD, a decrease in myocardial flow reserve (MFR) ≤2 was regarded as CMD. HRV indices were determined using 24-hour ECG monitoring. Results . Depending on CMD, patients were divided into 2 following groups: CMD+ (n=14) and CMD- (n=15). According to 24-hour ECG monitoring, patients with CMD showed a decrease in HRV and sympathetic activity. Cathestatin levels significantly correlated with myocardial flow at rest (r=0,329; p=0,019) and HRV parameters as follows: mean duration of all R-R (N-N) intervals of sinus rhythm (mean NN) (r=-0,410; p=0,001), SDANN (r=-0,276; p=0,036) and SDNNidx (r=0,287; p=0,029). Norepinephrine concentrations were interrelated only with CFR (r=-0,295; p=0,037), and adrenomedullin — with mean NN (r=0,272; p=0,038). Biomarker levels did not differ significantly between the groups at baseline and after 12 months. At the same time, norepinephrine levels remained virtually unchanged during prospective follow-up, while catestatin levels in CMD+ patients tended to increase by 11,7% (p=0,632), and in the CMD- group — by 16,1% (p=0,632), and adrenomedullin — by 19,4% (p=0,325) and 23,7% (p=0,527), respectively. Independent factors associated with CMD were sympathetic suppression, expressed as a decrease in square root of the mean squared differences of successive NN intervals (rMSSD) ≤60 ms (odds ratio 1,065; 95% confidence interval 1,005-1,675; p=0,001) and body mass index ≥27,8 kg/m 2 (odds ratio 1,061; 95% confidence interval 0,998-1,668; p=0,001). Conclusion . Norepinephrine, adrenomedullin, and catestatin levels did not differ significantly between patients with and without CMD. However, catestatin concentrations were associated with resting myocardial flow and HRV parameters, while norepinephrine values — with CFR, and adrenomedullin — with mean NN.