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/m² (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.

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