Paola Molino

Plasma Endothelin in NIDDM Patients With and Without Complications

OBJECTIVE To measure plasma endothelin 1 (ET-1) levels in uncomplicated non-insulin-dependent diabetes mellitus (NIDDM) and investigate whether ET levels may be related to angiopathy, blood pressure, metabolic control, or duration of illness. RESEARCH DESIGN AND METHODS Plasma levels of ET-1 were measured in 44 NIDDM patients, of whom 24 had uncomplicated diabetes, 20 had angiopathy, and 10 had hypertension. In 21 patients, the duration of illness was > 10 years, and in 23 the duration of illness was <10 years. Serum creatinine levels, microalbuminuria, and HbA1c were determined simultaneously. Thirty normotensive healthy (nondiabetic) individuals (20 men and 10 women) served as control subjects. RESULTS No significant statistical differences in plasma ET-1 levels were found among all diabetic patients, diabetic patients with and without angiopathy, diabetic patients with different durations of diabetes, and normal subjects. No significant correlation of plasma ET-1 with blood pressure, age, serum creatinine level, duration of diabetes, HbA1c, or diabetic complications was found. CONCLUSIONS Plasma ET-1 levels are similar in patients with NIDDM and healthy subjects and do not seem to act as a marker of diabetic complications.

Blood pressure and heart rate in young thalassemia major patients

The analysis of blood pressure (BP) and heart rate (HR) variability is currently used to investigate the mechanisms responsible for cardiovascular control; therefore, we assessed whether an impairment of 24-h BP and HR profiles and sympathovagal interaction modulating cardiovascular function was present in patients with thalassemia major (TM) in preclinical phase of heart disease. Nine beta-thalassemic patients 18 years old without clinical signs of cardiac failure and 9 age- and sex-matched controls were studied. Twenty-four-hour-ambulatory BP and HR were measured using the SpaceLabs 90207 device. A truncated Fourier series with four harmonics was used to describe the diurnal blood pressure profile. Mean 24-h ambulatory systolic BP, diastolic BP, and mean arterial pressure were significantly lower in TM patients than in normal subjects (P < .05). A significantly higher nighttime HR value was found in TM patients (P < .05). More than 40% of the TM patients did not show a significant diurnal BP and HR rhythm. In TM patients, the overall amplitude of systolic BP, diastolic BP, and HR was significantly lower than in controls (P < .01). The night/day differences of systolic BP, diastolic BP, and HR were significantly lower in TM patients than in normals (P < .01). Furthermore, we performed power spectral analysis on short-term continuous finger BP and HR data in supine position and during passive head-up tilt. Total spectral power of systolic BP was significantly lower in patients than controls (P < .05). Low-frequency (LF) power of systolic BP and diastolic BP and LF/high-frequency (HF) ratio of HR were significantly lower during tilt in TM patients compared to controls (P < .05). High-frequency power of HR was significantly higher in patients than controls (P < .05). The baroreflex gain assessed by alpha-index was the same in supine position but was higher in TM patients during passive tilt (P < .05). An inverse relationship between LF/HF ratio of HR and hemoglobin levels in TM patients was found. Finally, plasma norepinephrine levels were significantly lower in thalassemics (P < .005). In young TM patients in a preclinical stage of heart disease, these findings demonstrated abnormal 24-h BP and HR rhythms and a decreased short-term variability of BP and HR, in particular in the LF range, showing a diminished sympathetic activity.

Baroreflex control of heart rate is impaired in pre-eclampsia.

Autonomic nervous dysfunction, such as parasympathetic and sympathetic impairment, has been suggested as possible cause of pre-eclampsia, but the studies are not conclusive. Our purpose was to assess non-invasively if pre-eclampsia is associated with a decreased baroreflex function. Nine women with pre-eclampsia (PE), eight normotensive pregnant women, and seven healthy normotensive non-pregnant women were studied. Continuous finger blood pressure was recorded by a Portapres device in the left lateral recumbent position and active standing. Baroreflex gain was evaluated by cross-spectral analysis of systolic blood pressure and pulse interval. The result was that baroreflex gain at rest was lower in pre-eclamptic women both compared to non-pregnant and healthy pregnant subjects (P < 0.05). moreover, a decrease of the baroreflex sensitivity was present in all pregnant women in the orthostatic position (P < 0.05). in conclusion pregnancy per se is associated with a decrease in the baroreflex control of the heart, whereas in pre-eclampsia, the baroreflex sensitivity is impaired further.

Twenty-Four-Hour Power Spectral Analysis by Maximum Entropy Method of Blood Pressure in Primary Hyperaldosteronism

In the present study we estimated the periodic profiles and variance structure of systolic blood pressure, diastolic blood pressure, heart rate and mean arterial pressure by using an autoregressive model of power spectrum, Maximum Entropy Method (MEM) in 8 patients with primary aldosteronism, during long-term therapy with nicardipine slow release. The four blood pressure variables were measured at 30-min intervals, using a noninvasive device (Spacelabs 90202) in 8 hypertensive patients of whom 6 with idiopathic aldosteronism (IHA) and 2 with dexamethasone-suppressible aldosteronism (DSH), before and after 24 weeks of 80 mg nicardipine daily. Blood pressure data were processed by MEM and spectral profiles were obtained. During nicardipine therapy all patients showed a significant decrease of 24-h ambulatory blood pressure values (p < 0.01). Before therapy, spectrum analysis by MEM indicated the presence of high frequency distribution of peaks for SBP, DBP, MAP and HR. The MEM power spectrum showed an increase in amplitude of sharp peaks of systolic, diastolic, MAP and heart rate in all patients after therapy at 24 h corresponding to the circadian rhythm blood pressure. Furthermore, the trend of these variables synchronized themselves in the same period after 24 weeks of nicardipine therapy, with spectral patterns of blood pressure similar to those of normotensive subjects. This chronobiologic approach, by Maximum Entropy Method, may be used as an alternative statistical analysis to search for possible rhythmic behavior of ambulatory blood pressure data before and after pharmacological treatment in secondary hypertensive patients.

Fourier analysis of circadian blood pressure profile in secondary hypertension

Different types of statistical methods have been used for circadian blood pressure (BP) rhythm analysis in secondary forms of hypertension. In the present study, we used the two-step statistical approach by Fourier analysis with four harmonics for the parametrization of the diurnal BP pattern in secondary hypertension. In 43 essential hypertensives (EH), eight patients with aldosterone producing adenoma (APA), 25 with idiopathic hyperaldosteronism (IHA), four with glucocorticoid remediable hyperaldosteronism (GRH) and seven with renovascular hypertension (RVH), 24-h ambulatory BP was measured. The diurnal BP and heart rate (HR) rhythm was present in more than 70% of patients with secondary hypertension, without significant differences with EH and despite the attenuation in the degree of the nocturnal BP fall. In conclusion, the statement that secondary hypertension is characterized by an abnormal diurnal rhythm of BP is a gross over-simplification. Our findings suggest that the two-step method with four harmonics Fourier analysis may represent a useful method and a more complete statistical approach to providing circadian parametrization of the 24-h profile in secondary hypertension.

Spectral characteristics of heart rate and blood pressure variability in primary aldosteronism

A disturbance of the autonomic cardiovascular function has been postulated in primary aldosteronism as a possible mechanism for hypertension. Using the method of spectral analysis of heart rate and blood pressure variability, the aim of this study was to assess sympathovagal interactions modulating cardiovascular function and baroreflex control in patients with primary aldosteronism. Seventeen patients (7 with adenomas and 10 with idiopathic hyperaldosteronism) and a control group of 11 essential hypertensives (EH) and 10 normotensive subjects were studied. Continuous finger blood pressure was measured using a Finapres device and heart rate was measured using an electrocardiographic monitor. The studies were conducted in each patient for 20 min in the supine position and 10 min during a passive head-up tilt to 60 degrees. The low frequency and the low frequency-to-high frequency ratio of systolic and diastolic blood pressures were significantly higher both in primary aldosteronism and in EH patients compared with normotensives (P < .01). Impaired response to tilt was found in the heart rate and blood pressure variability in primary aldosteronism and EH patients; the increase in low frequency was smaller than in normotensives. Baroreflex gain (assessed by alpha index) was less in primary aldosteronism and EH patients as compared with normotensives. These findings may suggest that volume expansion or sympathetically mediated central translocation of the blood volume, or both, could stimulate the cardiopulmonary receptors and impair the baroreflex gain. Our findings suggest that an enhanced peripheral vascular responsiveness to a normal sympathetic outflow may be involved in the pathogenesis of hypertension in primary aldosteronism.

Levels of plasma neuropeptide Y and other vasoactive substances during head-up tilt in normal and essential hypertensive subjects

Neuropeptide Y, a potent vasoconstrictor peptide with 36 amino acid residues, is co-stored and released with catecholamines in sympathetic nerve endings. In this study responses in circulating neuropeptide Y induced by baroreceptor activation during change from the supine to the head-up position was measured in normal subjects and untreated essential hypertensives. Furthermore, the relationships with plasma catecholamines, endothelin-1, renin and serotonin were studied. No significant differences of plasma neuropeptide Y were found between normotensive and hypertensive subjects, before or after postural changes, and there was no correlation with a range of the vasoactive substances studied. Our results suggest that plasma neuropeptide Y does not increase with noradrenaline on sympathetic activation during postural stress both in normals and in hypertensive subjects. In man, measurement of plasma neuropeptide Y during head-up tilt does not provide a useful estimation of sympathetic nervous activity.