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. RESEARCH DESIGN AND 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.

Effect of quinapril or metoprolol on heart rate variability in post-myocardial infarction patients.

The effect of quinapril or metoprolol on heart rate variability (HRV) indexes was studied in patients who had recovered from acute myocardial infarction. Patients with stable coronary artery disease and normal volunteers were used as controls. Sixty patients with uncomplicated myocardial infarction (aged 32 to 74 years [mean 56.7]) were randomized to quinapril (n = 25), metoprolol (n = 25), and placebo (n = 10). HRV was assessed 5 days (baseline) and 35 days after the onset of acute myocardial infarction. After the baseline studies, the post-myocardial infarction patients were treated with metoprolol (50 to 100 mg/day), quinapril (5 to 10 mg/day), or placebo. Twenty patients with stable coronary artery disease and 20 healthy volunteers, age- and sex-matched to myocardial infarction patients, were used as controls. Compared with placebo, quinapril and metoprolol increased HRV indexes significantly 35 days after the onset of myocardial infarction. HRV indexes were not statistically different between the 2 treatment groups. At baseline and after therapy, HRV was similar in patients with anterior or inferior wall myocardial infarction. HRV 35 days after the onset of myocardial infarction was not different from HRV in patients with stable coronary artery disease, but was decreased when compared with that in normal volunteers. Data suggest that quinapril has the same beneficial effect on HRV indexes as metoprolol in patients who have recovered from uncomplicated acute myocardial infarction.

Long-term effect of gemfibrozil on coronary heart disease risk profile of patients with primary combined hyperlipidaemia.

BACKGROUND: The purpose of the present study was to assess the effect of gemfibrozil on 12 independent coronary heart disease risk factors in patients with primary combined hyperlipidaemia. METHODS: One hundred and five patients (62 men and 43 women), aged 53.2 +/- 4.8 years, were studied. The 10-year probability of myocardial infarction for the patients was calculated using the TYPMI (Ten-Year Probability for Myocardial Infarction) computer program, which is constructed to co-evaluate 12 independent coronary artery disease risk factors. All patients followed a lipid-lowering diet and placebo for 3 months. At month 0, the patients received 1200 mg gemfibrozil daily, divided into two equal doses, for a period of 12 months. At months -3, 0, 1, 3, 6, and 12, total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides [only if the low-density lipoprotein (LDL) cholesterol to high-density lipoprotein cholesterol ratio was above 5], systolic blood pressure, plasma glucose, left ventricular mass index, and plasma fibrinogen were measured. Smoking habits, sex, age, physical activity and family history of coronary heart disease were also evaluated. The mean 10-year probability of myocardial infarction of all 105 patients at month 0 was 27.8%. This was significantly higher than the anticipated probability (10.4%, P < 0.001), resulting from an age- and sex-matched group of general population. RESULTS: During the third month of treatment, the following changes were recorded: total cholesterol -17%, LDL cholesterol -18%, very-low-density lipoprotein (VLDL) cholesterol -45%, HDL cholesterol 20%, triglycerides -43%, apoprotein B -12%, apoprotein A-I 9% and plasma fibrinogen -21%. The estimated risk for myocardial infarction was reduced to 13.5% (delta m = -51%). All changes were significant and sustained until the twelfth treatment month. None of the patients were withdrawn from the study because of adverse effects of the treatment. CONCLUSION: Gemfibrozil reduces the estimated risk for myocardial infarction in patients with primary combined hyperlipidaemia at a level no different from the one of the general population. This beneficial effect of gemfibrozil, which was expressed by the third month and was evident for some time afterwards, was attributed to a significant reduction of triglyceride and fibrinogen levels, an increase of HDL cholesterol concentrations and a moderate decrease of total cholesterol and LDL cholesterol levels.