EFFECT OF CHRONIC QUINAPRIL ADMINISTRATION ON HEART-RATE-VARIABILITY IN PATIENTS WITH DIABETIC AUTONOMIC NEUROPATHY

OBJECTIVE - Heart rate variability (HRV) time and frequency domain ind exes are strong predictors of malignant arrhythmias and sudden cardiac death. Patients with diabetic autonomic neuropathy (DAN) have an incr eased cardiovascular mortality rate compared with diabetic patients wi thout DAN. RESEARCH DESIGN AND METHODS - The present double-blind, ran domized, and placebo-controlled study analyzed the effect of quinapril , an ACE inhibitor, on HRV time and frequency domain variables in pati ents with DAN. Forty patients (17 men and 23 women) of a mean age of 5 1 (range 19-68) years, free of coronary artery disease and arterial hy pertension, were randomized into a quinapril or placebo group. HRV was recorded at months 0, 3, and 6. The parameters measured were I) time domain indexes: SD of all 24-h R-R intervals (intervals between consec utive electrocardiogram R waves), or SDNN/24-h; mean of SD of R-R inte rvals of all 5-min segements (SDNN/5-min); root-mean-square of the dif ferences of successive R-R intervals (RMSSD); and percentage of the R- R intervals differing more than 50 ms (pNN50); and 2) frequency domain indexes: total power (TP), high-frequency power (HFP), low-frequency power (LFP), and very-low-frequency power (VLFP). HRV level of the 40 patients were compared with one of 20 matched diabetic patients, of an alogous glycemic control without DAN, and 20 healthy control subjects. RESULTS - Quinapril, compared with placebo, increased total HRV: SDNN /24-h (P < 0.05), TP (P < 0.05), and HRV parameters related to parasym pathetic activity: pNN50 (P < 0.01), RMSSD (P < 0.05), and HFP in abso lute and normalized units (P < 0.01). LFP/HFP ratio was decreased (P < 0.01). Despite the beneficial effect of quinapril on parasympathetic variables of HRV these remained less than those of diabetic patients w ithout DAN and healthy control subjects. CONCLUSIONS - Our findings su ggest that quinapril significantly increases parasympathetic activity in patients with DAN 3 months after treatment initiation and sustains this effect until the 6th month. This might contribute to the reductio n of the risk for malignant ventricular arrhythmias in these patients.