Prognostic implications of autonomic function assessed by analyses of catecholamines and heart rate variability in stable angina pectoris

Abstract

Objective: To assess the prognostic impact of autonomic activity, as reflected by catecholamines and heart rate variability (HRV), in patients with stable angina pectoris.

Design: Double blind, randomised treatment with metoprolol or verapamil. 24 hour ambulatory ECG, used for frequency domain analyses of HRV, and symptom limited exercise tests at baseline and after one month of treatment. Catecholamine concentrations were measured in plasma (rest and exercise) and urine.

Setting: Single centre at a university hospital.

Patients: 641 patients (449 men) with stable angina pectoris.

Main outcome measures: Cardiovascular (CV) death, non-fatal myocardial infarction (MI).

Results: During follow up (median 40 months) there were 27 CV deaths and 26 MIs. Patients who died of CV causes had lower total power and high (HF), low (LF), and very low (VLF) frequency components of HRV. HRV was not altered in patients who suffered non-fatal MI. Catecholamines did not differ between patients with and those without events. Metoprolol increased HRV. Verapamil decreased noradrenaline (norepinephrine) excretion. Multivariate Cox analyses showed that total power, HF, LF, and VLF independently predicted CV death (also non-sudden death) but not MI. LF:HF ratios and catecholamines were not related to prognosis. Treatment effects on HRV did not influence prognosis.

Conclusions: Low HRV predicted CV death but not non-fatal MI. Neither the LF:HF ratio nor catecholamines carried any prognostic information. Metoprolol and verapamil influenced LF, HF, and catecholamines differently but treatment effects were not related to prognosis.

Figures

Figure 1

Treatment effects on venous plasma catecholamine concentrations at rest and after exercise for patients who performed an exercise test and had plasma catecholamines measured at baseline and after one month on study drugs. All patients are shown in panel A, and patients without run-in treatment are shown in panel B. Values are mean and 95% confidence interval of the mean. Plasma catecholamines at rest (circles) and after exercise (squares). Open symbols indicate verapamil treated patients and closed symbols metoprolol treated. *p

Figure 2

Treatment effects on urinary catecholamine excretion during the day and at night for patients with a minimum of 17 hours of ambulatory ECG registration and urinary catecholamine measurements at baseline and after one month on study drugs. All patients are shown in panel A, and patients without run-in treatment in panel B. Values are mean and 95% confidence interval of the mean. Urine catecholamine excretion during the day (squares) and at night (circles). Open symbols indicate verapamil treated patients and closed symbols metoprolol treated. *p

Figure 3

Treatment effects on heart rate variability in the frequency domain for patients with adequate ambulatory ECG registrations both at baseline and after one month on study drugs. All patients are shown in panel A, and patients without run-in treatment are shown in panel B. Values are mean and 95% confidence interval of the mean. Total power (squares); very low frequency (VLF) (diamonds); low frequency (LF) (circles); high frequency (HF), (triangles). Open symbols indicate verapamil treated patients and closed symbols metoprolol treated. *p

Figure 4

Kaplan-Meier plots illustrating the risk for cardiovascular death in patients above or below the median for the different frequency domains of heart rate variability measured at baseline. Panel A shows the result for total power, panel B for low frequency (LF), panel C for high frequency (HF), and panel D for the LF:HF ratio. Please note the scale break on the y axis. Solid line = above the median; dotted line = below the median.