Cardiovascular involvement in patients with beta-thalassemia major without cardiac iron overload.

BACKGROUND: Cardiovascular complications are common in beta-thalassemia major (beta-TM), mainly attributed to increased cardiac iron depositions. Early cardiovascular involvement in patients without cardiac symptoms and without cardiac iron overload has not been adequately investigated. METHODS: Twenty six patients (11 males) with beta-TM, on chelation therapy, age 23+/-4 years without cardiac iron overload (measured by magnetic resonance imaging), and 30 age and gender matched healthy controls were included in the study. Carotid-femoral and carotid-radial pulse wave velocity (PWVc-f and PWVc-r) and augmentation index (AI) were measured by SphygmoCor device; carotid intima-media thickness; left ventricular (LV) dimensions and function; left atrial (LA) volume and function were assessed by echocardiography. RESULTS: Patients with beta-TM had higher PWVc-f (8.4+/-1.4 vs 7.2+/-1.1 m/s, p=0.002) and augmentation index (21.7+/-10.9 vs 14.7+/-9.7%, p=0.04) indicating decreased aortic elastic properties; greater LV mass index (72.0+/-13.3 vs 63.8+/-11.5 g/m(2), p=0.04) and greater LA volumes. Multivariate logistic regression analysis revealed that higher PWVc-f was independently associated with higher LV mass [OR 1.74 95%CI (1.09-2.88), p=0.026]; and greater LA dimensions [OR 1.68 95%CI (1.04-2.72), p=0.035]. CONCLUSIONS: In the absence of cardiac iron overload, asymptomatic patients with beta-TM demonstrated aortic stiffening associated with increased LV mass and LA enlargement. These alterations may represent signs of early cardiovascular involvement.

Plasma levels of osteopontin before and 24 h after percutaneous coronary intervention.

OBJECTIVE: Previous studies demonstrated that osteopontin (OPN) was increased after vascular injury, such as atherosclerosis and restenosis following angioplasty. We sought to determine the effects of percutaneous coronary intervention (PCI) on plasma OPN levels compared with coronary arteriography (CA). METHODS: Plasma OPN levels were determined in 103 patients who underwent CA or PCI with stent implantation, at baseline and 24 h after the procedure. Patients were divided into three groups; group I: patients without significant coronary artery stenosis, group II: patients with coronary artery disease in whom only CA was performed, group III: patients with coronary artery disease who had PCI and stent implantation. RESULTS: Plasma OPN levels before the procedure were similar in all three groups. OPN levels 24 h after the procedure were significantly higher only in group III compared with baseline. Among three groups, the OPN levels observed in 24 h were significantly higher in group III compared with group I. Patients in group III had significantly higher OPN values after the procedure, depending on the number of stents implanted (p = 0.03). CONCLUSION: The increase in OPN levels after PCI suggests that vascular injury due to PCI is responsible for this phenomenon.

Relationship between plasma osteopontin and oxidative stress in patients with coronary artery disease.

BACKGROUND: It is known that oxidative stress plays an important role in the pathogenesis of atherosclerosis and that an association exists between osteopontin (OPN) and atherosclerosis. OBJECTIVES: It was proposed that malondialdehyde (MDA), a biomarker of lipid peroxidation and oxidative stress, would be related to plasma OPN levels in patients with coronary artery disease (CAD). METHODS/RESULTS: Plasma OPN and MDA levels were measured in 71 patients (60 males and 11 females; mean age 61.7 +/- 10 years). Fifty-eight patients had significant CAD (group I) and 13 patients were free of CAD as defined angiographically (group II). Plasma OPN was measured by enzyme-linked immunosorbent assay (ELISA), while MDA was determined spectrophotometrically. Multivariate regression analysis revealed that ln-transformed OPN levels were independently associated with MDA after adjustment for age, hypertension and diabetes mellitus (R(2) = 0.278, p = 0.0004 and beta regression coefficient = 0.252 [standard error = 0.0958], p = 0.011). OPN and MDA levels were higher in patients with diabetes (73.6 +/- 36.2 ng/ml versus 56.1 +/- 30.9 ng/ml, p = 0.02 and 2.5 +/- 0.5 microM versus 2.0 +/- 0.5 microM, p = 0.002, respectively). CONCLUSIONS: The association between OPN and MDA levels in patients with CAD suggests an interaction between OPN and oxidative stress. This interaction may play a role in the pathogenesis of atherosclerosis.

Long term cardiovascular effects of oral antidiabetic agents in non-diabetic patients with insulin resistance: double blind, prospective, randomised study.

OBJECTIVE: To study the long term cardiovascular effects of oral antidiabetic agents in non-diabetic patients with insulin resistance. PATIENTS: 181 African American subjects with insulin resistance and normal glucose tolerance test were randomised to receive glipizide 5 mg/day (n = 25), metformin 500 mg/day (n = 59), or placebo (n = 97) for 24 months. Insulin sensitivity, glucose tolerance, lipid profile, left ventricular mass (echocardiography), aortic distensibility (echocardiography, blood pressure), aortic pulse wave velocity (PWV, carotid to femoral artery, Doppler) were measured at baseline and at 12 and 24 months after randomisation. RESULTS: A significant increase in PWV was observed in both glipizide (mean (SEM) change at 24 months 2.8 (2.7) m/s, p = 0.012) and metformin (2.2 (0.7) m/s, p = 0.01) groups during the follow up period. In contrast, PWV remained unchanged in the placebo group. The increase in PWV in the treatment groups was significant compared with placebo (analysis of variance p < 0.05). Other cardiovascular or metabolic variables did not change significantly compared with placebo during follow up. CONCLUSIONS: The observed increase in PWV is consistent with a decrease in the elastic properties of the aorta. The use of oral antidiabetic agents for the prevention of cardiovascular complications in non-diabetic African Americans with insulin resistance needs to be critically evaluated.

Echocardiographic evidence of atrial myopathy in amyloidosis: a case report.

Cardiac involvement occurs in up to 50% of patients with primary amyloidosis. Diffuse amyloid deposits lead to impairment of myocardial systolic and diastolic function. Due to the severe left ventricular diastolic abnormality, left atrial contribution to left ventricular stroke volume remains critical. We report a case of primary amyloidosis where we assessed non-invasively left atrial systolic function.

A morphometric study of the structural characteristics of the aorta in pigs using an image analysis method.

The objective of this study was to evaluate multiple structural characteristics, in addition to vasa vasorum density, in different aortic regions. The aorta of healthy Landrace pigs was divided into four thoracic and three abdominal segments. Transverse sections were reserved for morphometric analysis. Image analysis showed the aortic diameter, the thickness of the media, the number of elastic lamellae and the thickness of elastic membranes being reduced with increased distance from the heart (P < 0.05). The average thickness of lamellar units remained constant in the thoracic, but increased in the abdominal aorta (P < 0.05). The number of lamellar units, contained in the avascular zone of the media, and the density of vasa vasorum decreased peripherally (P < 0.05), still the average thickness of the avascular zone was invariant. In conclusion, the anatomical properties of the vessel wall alter through the aorta, being optimal for the varying stresses to which the aorta is subjected along its length. The distinct aortic parts may exhibit inherent morphological features, responsible for the various pathological processes that affect the aorta.

Expression of PDGF-A, TGFb and VCAM-1 during the developmental stages of experimental atherosclerosis.

PURPOSE: A considerable number of growth factors, cytokines, and adhesion molecules are implicated in the development of atherosclerotic lesions. These molecules interact in a complex network influencing the evolution of several processes, such as lipid metabolism, cellular proliferation and tissue repair. The aim of this study was to evaluate the expression of the growth factors PDGF-A, and TGFb, and the adhesion molecule VCAM-1 in the sequential steps of experimental atherogenesis. METHODS: Forty-two New Zealand white male rabbits were divided into 4 groups. The group A rabbits (n = 8) received normal diet and served as control animals. The remaining groups were fed with a diet enriched with 1% cholesterol and 6% corn oil. The rabbits of group B (n = 9) were sacrificed 1 month after the beginning of the study, of group C (n = 15) after 2 months and of group D (n = 10) after 3 months. In tissue sections of the aortic arch the antibodies of the prementioned factors were detected immunohistochemically. RESULTS: In group A only TGFb and PDGF-A were detectable. In lesions of the first month PDGF-A expression was high but declined towards the third month. VCAM-1 expression was getting more intense up to the second month and subsided thereafter. TGFb expression intensified towards the third month. Changes in the expression of these factors were statistically significant. CONCLUSION: PDGF-A, responsible for the uncontrollable growth of smooth muscle cells, and VCAM-1, regulating monocyte recruitment in the intima, acts mainly during the early stages of atherogenesis. TGFb, one of the main factors controlling the formation of connective tissue matrix, has a gradually increasing expression towards the third month contributing probably to the fibrous plaque formation.

Floppy mitral valve/mitral valve prolapse/mitral valvular regurgitation: effects on the circulation.

The floppy mitral valve prolapses into the left atrium in such a dynamic manner that the prolapsing floppy mitral valve becomes a space-occupying lesion within the left atrium. A significant result of the floppy mitral valve prolapsing into the left atrium during left ventricular systole is the development of a "third chamber" located between the mitral annulus and the prolapsing mitral valve leaflets. Since the blood in the third chamber does not contribute to forward stroke volume, the third chamber may have significant effects on stroke volume and cardiac output. The floppy mitral valve/mitral valve prolapse dynamics also affect left ventricular papillary muscle tension and traction, altering the patterns of left ventricular contraction and relaxation, activating papillary muscle and left ventricular stretch receptors, and contributing to the production of cardiac arrhythmias. Floppy mitral valve innervation patterns with distinct nerve terminals provide a neural basis for brain-heart interactions, augmented by mechanical stimuli from the prolapsing floppy mitral valve. With the onset of mitral valvular regurgitation, and gradual progression of the mitral valve regurgitation from mild, to moderate, to severe, alterations in left atrial and left ventricular chamber size and performance occur, resulting in left atrial and left ventricular myopathy. As a connective tissue disorder, floppy mitral valve/mitral valve prolapse may be associated with abnormal structural and elastic properties of the aorta, with resultant changes in aortic function. Progression of mitral valve regurgitation and the aging process also affect aortic function indices in an adverse manner. The phenomena associated with floppy mitral valve dysfunction, with prolapse of the mitral valve into the left atrium and the unique, resultant forms of mitral valve regurgitation, are dynamic in nature. As the long-term natural history of these interrelated phenomena is being clarified, it is apparent that the floppy mitral valve/mitral valve prolapse/mitral valve regurgitation influences the circulation in a global fashion.

Cardiovascular effects of aging. Interrelationships of aortic, left ventricular, and left atrial function.

BACKGROUND: Previous studies have shown that elastic properties of the aorta decrease, while left atrial dimensions, the contribution of left atrial systole to left ventricular filling, and left ventricular mass increase with age. In most studies, however, aortic function, and ventricular and atrial parameters were performed in different populations, and thus, the earliest manifestation of aging in the cardiovascular system is not known. The present study was undertaken to define the earliest cardiovascular abnormality(ies) occurring in the cardiovascular system with age. PATIENTS AND METHOD: In 181 normotensive subjects (147 females and 34 males) age 22-64 years, left ventricular mass, volumes, function and work (echocardiography and blood pressure), left atrial volumes and stroke volume (biplane area-length method by echo), pulse wave velocity (PWV) (carotid to femoral artery, Doppler), and left atrial kinetic energy were measured simultaneously: left atrial kinetic energy = 1/2 mv2, where m = left atrial stroke volume x 1.06 (blood specific gravity), v = transmitral A wave velocity. Regression analyses were performed to correlate all measured cardiovascular parameters with age. RESULTS: Pulse wave velocity (r = 0.51), left atrial kinetic energy (r = 0.42), and A wave velocity (r = 0.38) were correlated to age, while left ventricular mass, function and work were not. Multiple regression analysis among ten clinical and echocardiographic parameters demonstrated that only age contributed independently to pulse wave velocity; only age and pulse wave velocity were contributed independently to left atrial kinetic energy; and only age contributed independently to A wave velocity. CONCLUSIONS: The data demonstrate that age-related alterations in aortic function and left atrial work (left atrial kinetic energy) can be defined prior to changes in left ventricular structure and systolic function. Simultaneous studies of left atrial, left ventricular, and aortic function are required to better understand the effect of aging on the cardiovascular system.

Spontaneous conversion to sinus rhythm of recent (within 24 hours) atrial fibrillation.

OBJECTIVES: The purpose of the study was to determine the likelihood of spontaneous conversion of recent onset (< 24 hr) paroxysmal atrial fibrillation (Af) to sinus rhythm and to define clinical and echocardiographic characteristics which may predict it. METHODS: One hundred fifty-three consecutive adult patients admitted to the hospital with recent onset Af (< 24 hr) were studied. In each patient history, complete physical examination, 12-lead electrocardiogram, chest X-ray, routine hematological studies, serum electrolytes, troponin, thyroid function studies and a complete echocardiographic evaluation were performed. Patients hemodynamically unstable, with recent myocardial infarction, unstable angina, average ventricular rate > 150 beats/min, hyperthyroidism, congestive heart failure, left ventricular hypertrophy, valvular heart disease, and on antiarrhythmic drugs at the time of admission, were excluded. Patients were monitored without antiarrhythmic therapy for at least 24 hr from the onset of Af. RESULTS: Spontaneous conversion to sinus rhythm occurred in 109 patients (71.2%); among patients with spontaneous conversion 73.4% converted in the first 12 hr. Age, gender, other clinical characteristics, left ventricular dimensions and performance did not separate patients with or without spontaneous conversion. Left atrial size was significantly greater in patients without compared to patients with spontaneous conversion (p < 0.03); likewise increased left atrial size (> 40 mm) was seen more often in patients without compared to patients with spontaneous conversion (45% vs 22%, p < 0.05). CONCLUSIONS: Spontaneous conversion to sinus rhythm occurred in 71% of patients with recent onset (< 24 hr) Af. Left atrial size was the only predictor of spontaneous conversion in this highly selected group of patients.

Floppy Mitral Valve, Mitral Valve Prolapse, and Mitral Valvular Regurgitation.

It is well recognized that the floppy mitral valve (FMV) complex is the central issue in the FMV, mitral valve prolapse (MVP), and mitral valvular regurgitation (MVR) story. MVP associated with the FMV results from the systolic movement of portions or segments of the FMV complex into the left atrium (LA). Prolapse of the FMV results in unique forms of mitral valvular dysfunction and MVR. When the FMV is recognized as the basic point of reference, diagnostic and nosologic characterizations are simplified. Each of the consequences of FMV dysfunction--MVP, MVR, and FMV surface phenomena--are dynamic entities and contribute to the symptoms and clinical course in this patient population. Although MVP may occur in the absence of a FMV in individuals with small left ventricular (LV) volume, hyperdynamic, or hypercontractile LV, we do not consider this phenomenon as part of FMV/MVP/MVR. The natural history of the FMV/MVP/MVR is long, and understanding the life history requires long-term follow-up with serial evaluations. Identification of those individuals with FMV/MVP whose symptoms are related to, or associated with, autonomic nervous system dysfunction (ie, the FMV/MVP syndrome) is important, as this distinction has diagnostic and therapeutic implications. In general, patients with FMV/MVP should receive antibiotic prophylaxis for infective endocarditis. Data suggest that therapy with angiotensin-converting enzyme inhibitors for FMV/MVP and significant MVR may slow the natural regression of the disease. Surgical therapy should be considered in patients with significant MVR and symptoms related to MVR. Explanation for the nature of these symptoms, reassurance, avoidance of volume depletion, catecholamines or other cycle-AMP stimulants and a regular exercise program constitute the basic principles of management for patients with FMV/MVP syndrome.

Safety and effectiveness of oral quinidine in cardioversion of persistent atrial fibrillation.

OBJECTIVES: The effectiveness of oral quinidine for conversion of atrial fibrillation to sinus rhythm was evaluated in 49 patients with persistent atrial fibrillation on anticoagulation therapy. Atrial fibrillation was considered as persistent when the duration was longer than 3 days but less than 6 months. METHODS: Patients received orally one to 7 doses of 150 mg hydroquinidine hydrochloride every one hour until restoration of sinus rhythm, or to a maximum of 7 tablets. Patients who were not converted underwent elective electrical cardioversion. RESULTS: Thirty-nine of 49 patients (79.6%) were converted with quinidine and only one of the remaining 10 was converted with electrical cardioversion. Quinidine had no significant effect on blood pressure or unexpected changes on the QRS duration and the QT interval. Four patients developed gastrointestinal symptoms (8.1%). CONCLUSIONS: Oral quinidine was safe and effective in the conversion of persistent atrial fibrillation to sinus rhythm.

Effect of impaired vasa vasorum flow on the structure and mechanics of the thoracic aorta: implications for the pathogenesis of aortic dissection.

OBJECTIVE: To investigate the alterations of structure and mechanical properties of the aortic wall, resulting from impairment of vasa vasorum flow. METHODS: Eight healthy Landrace pigs were subjected to interruption of vasa vasorum flow to the upper segment of their descending thoracic aorta. Under sterile conditions, the periaortic tissue was excised and the contiguous intercostal arteries were ligated. Ten sham-operated pigs were used as controls. Fifteen days postoperatively, the animals were sacrificed and their upper descending thoracic aortas were removed. Histology, and collagen and elastin content determination by image analysis technique were performed. Mechanical analysis of aortic strips was carried out with a uniaxial tension device and stress-strain curves were obtained. RESULTS: In contrast to normal aortic walls of the control group, histology of the avascular aortas revealed severe ischemic necrosis of the outer media along with abnormal straightening of the elastin and collagen fibers, without significant collagen and elastin content changes. The borderline between the outer ischemic and inner non-ischemic media was sharp, and an outset of dissection was observed at this point. Mechanical analysis showed that at the same level of strain, the ischemic aorta was significantly stiffer at both low (P=0.03) and high strains (P=0. 003). CONCLUSIONS: Impairment of blood supply to the thoracic aorta leads to abnormal morphology of elastin and collagen fibers of the outer media, resulting in increased aortic stiffness under a wide range of stresses. In the clinical setting, decreased vasa vasorum flow, reportedly occurring in arterial hypertension, may increase the stiffness of the outer media of the thoracic aorta and produce interlaminar shear stresses, contributing to the development of aortic dissection.

Effect of quinapril or metoprolol on circadian sympathetic and parasympathetic modulation after acute myocardial infarction.

Abnormal autonomic nervous system impairment in patients with acute myocardial infarction (AMI) has a circadian pattern with the greatest manifestation in the morning hours; it probably plays an important role in the pathogenesis of cardiac arrhythmias and acute ischemic syndromes. Angiotensin-converting enzyme inhibitors improve autonomic function in patients with AMI, but the circadian pattern of this effect has not been studied. Heart rate variability-normalized frequency domain indexes were assessed 5 days (baseline) after the onset of uncomplicated AMI and 30 days after therapy with quinapril (n = 30), metoprolol (n = 30), or placebo (n = 30) with a solid-state digital Holter monitor. Normal subjects (n = 30) were used as controls. Quinapril increased parasympathetic and decreased sympathetic modulation, and improved sympathovagal interactions manifested by an increase in normalized high-frequency power (HFP), and a decrease in normalized low-frequency power (LFP), and their ratio (LFP/HFP) during the entire 24-hour period (p<0.001), with maximal effect on the ratio (p<0.0001) between 02.00 to 04.00 A.M., 08.00 to 11.00 A.M., and 19.00 to 22.00 P.M. (delta% ratio -30%, -32%, and -26%, respectively). Metoprolol increased HFP and decreased LFP and the LFP/HFP ratio mainly between 08.00 A.M. to 12.00 noon, and 19.00 to 22.00 P.M. (delta% ratio -21%, and -12% respectively, p<0.001). Heart rate variability indexes in the placebo group and controls remained unchanged 30 days after the baseline study. In conclusion, quinapril increased parasympathetic, and decreased sympathetic and partially restored sympathovagal interaction in patients with uncomplicated AMI during the entire 24-hour period, with peak effect in the early and late morning and evening hours. Metoprolol had a similar effect during the late morning and evening hours, but at a lower level. These effects may prove beneficial in reducing cardiac arrhythmias and acute ischemic syndromes in past-AMI patients.

Aortic pain: the renaissance of cardiovascular pain and the detection of aortopathy.

Our 19th century predecessors considered the aorta as a source of cardiovascular pain associated with inflammatory aortitis, arterial hypertension, aortic aneurysms, aortic dissection, and aortic valve disease. However, during the 20th century epidemic of coronary artery disease clinicians became concerned with the syndromes associated with myocardial ischemia and infarction, relegating aortic pain syndromes to the role of a differential, "rule out", or diagnosis of exclusion rather than a primary diagnosis. We re-focus attention on a more global approach to cardiovascular pain, approaching thoracic aortic pain syndromes as primary diagnoses, while considering the dynamics and various stages of development of aortic pain syndromes, set within the clinical environment in which these syndromes arise. The central role of aortopathy is our underlying theme since the detection and clinical recognition of aortopathic disorders provide the template for identification of the population at risk for aortic pain syndromes. Clinical history, pedigree development, phenotype recognition, analysis of the elastic properties of the aorta, use of the wide range of sophisticated imaging techniques, and phenotype-genotype correlations provide the bases for the recognition, diagnosis, and management of aortopathy within the clinical setting. A futuristic anticipatory approach towards the diagnosis of aortopathy is outlined with emphasis on earlier recognition and informed clinical management ultimately leading to prevention of the acute and dynamic aortic complications.

Screening of ruptured plaques in patients with coronary artery disease by intravascular ultrasound.

AIM: To visualise the characteristics of ruptured plaques by intravascular ultrasound (IVUS) and to correlate plaque characteristics with clinical symptoms to establish a quantitative index of plaque vulnerability. METHODS: 144 consecutive patients with angina were examined using IVUS. Ruptured plaques, characterised by a plaque cavity and a tear on the thin fibrous cap, were identified in 31 patients (group A), of whom 23 (74%) presented with unstable angina. Plaque rupture was confirmed by injecting contrast medium filling the plaque cavity during IVUS examination. Of the patients without plaque rupture (group B, n = 108), only 19 (18%) had unstable angina. RESULTS: No significant differences were found between groups A and B in relation to plaque and vessel area (p > 0.05). Mean (SD) per cent stenosis in group A was less than in group B, at 56.2 (16.5)% v 67.9 (13.4)%; p < 0.001. Area of the emptied plaque cavity in group A (4.1 (3.2) mm2) was larger than the echolucent zone in group B (1.32 (0.79) mm2) (p < 0.001). The plaque cavity to plaque ratio in group A (38.5 (17.1)%) was larger than the echolucent area to plaque ratio in group B (11.2 (8.9)%) (p < 0.001). The thickness of the fibrous cap in group A was less than in group B, at 0.47 (0.20) mm v 0.96 (0.94) mm; p < 0.001. CONCLUSIONS: Plaques seem to be prone to rupture when the echolucent area is larger than 4.1 (3.2) mm2, when the echolucent area to plaque ratio is greater than 38.5 (17.1)%, and when the fibrous cap is thinner than 0.7 mm. IVUS can identify plaque rupture and vulnerable plaques. This may influence patient management and treatment.

Long-term effect of converting enzyme inhibition on circadian sympathetic and parasympathetic modulation in patients with diabetic autonomic neuropathy.

OBJECTIVE: Autonomic nervous system function in patients with diabetes mellitus (DM), especially those with diabetic autonomic neuropathy (DAN), displays an abnormal circadian pattern compared to normal subjects; this probably plays an important role in the onset of acute cardiovascular syndromes, which display a similar pattern of occurrence with a blunted late morning peak, and an increase of episodes during the night, in comparison to non-diabetic subjects. This study was undertaken to investigate the effect of an angiotensin-converting enzyme inhibitor, quinapril, on the circadian pattern of heart rate variability (HRV), a reliable index of sympathovagal interactions, in patients with definite DAN. METHODS & RESULTS: Normalised HRV frequency domain indices [high frequency power (HFP), reflecting vagal tone, low frequency power (LFP), reflecting both vagal and sympathetic (predominantly) modulation, and their ratio (LFP/HFP), indicative of sympathovagal balance] were assessed in 60 patients with DAN at baseline and one year after therapy with quinapril (n = 30), or placebo (n = 30) on a 24-hour 2-channel electrocardiogram with a solid state Holter monitor. Normal subjects (n = 30) and patients with DM without DAN (n = 30), were used as controls. The baseline circadian variation of fractional normalised power in DAN patients was abolished, with pronounced dominance of LFP over HFP during the whole 24-hour period. After one year of treatment, quinapril increased HFP, decreased LFP and improved their ratio, in the morning (07.00 a.m. to 15.00 p.m.) and night (23.00 p.m. to 07.00 a.m.) time intervals, with maximal effect in the night time interval (HFP = 20%, LFP = -8%, LFP/HFP = -31%; for all comparisons p < 0.05 vs baseline values and p < 0.001 vs one year of placebo). CONCLUSIONS: Quinapril increased HFP and decreased LFP as well as their ratio, all indicative of sympathetic predominance reduction, in patients with DAN at time intervals these indices were most adversely affected (morning and night). Since autonomic function is an important contributor in the pathogenesis of acute coronary events, malignant arrhythmias and sudden cardiac death, improvement of indices related to autonomic function in DAN patients in these time intervals may prove beneficial in clinical practice.