Effect of chronic quinapril administration on heart rate variability in patients with diabetic autonomic neuropathy.
OBJECTIVE
Heart rate variability (HRV) time and frequency domain indexes are strong predictors of malignant arrhythmias and sudden cardiac death. Patients with diabetic autonomic neuropathy (DAN) have an increased cardiovascular mortality rate compared with diabetic patients without DAN.


METHODS
The present double-blind, randomized, and placebo-controlled study analyzed the effect of quinapril, an ACE inhibitor, on HRV time and frequency domain variables in patients with DAN. Forty patients (17 men and 23 women) of a mean age of 51 (range 19-68) years, free of coronary artery disease and arterial hypertension, were randomized into a quinapril or placebo group. HRV was recorded at months 0, 3, and 6. The parameters measured were 1) time domain indexes: SD of all 24-h R-R intervals (intervals between consecutive electrocardiogram R waves), or SDNN/24-h; mean of SD of R-R intervals of all 5-min segements (SDNN/5-min); root-mean-square of the differences 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 analogous 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 parasympathetic activity: pNN50 (P < 0.01). RMSSD (P < 0.05), and HFP in absolute 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 without DAN and healthy control subjects.


CONCLUSIONS
Our findings suggest 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 reduction of the risk for malignant ventricular arrhythmias in these patients.
Kontopoulos
A G
AG
Division of Cardiology, Aristotelian University, Hippocration Hospital, Thessaloniki, Greece.
Athyros
V G
VG
Didangelos
T P
TP
Papageorgiou
A A
AA
Avramidis
M J
MJ
Mayroudi
M C
MC
Karamitsos
D T
DT
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D001342:Autonomic Nervous System Diseases / Q000188:drug therapy* / Q000503:physiopathology; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000077583:Quinapril; D012016:Reference Values; D044005:Tetrahydroisoquinolines; D013997:Time Factors; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D000077583:Quinapril