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Luigina Guasti

Publications and source records attributed to Luigina Guasti.

16 recordsLinked to original sources

Mixed cranial nerve neuroma revealing itself as baroreflex failure.

We report here the first case of baroreflex failure due to a mixed cranial nerve neuroma in which the clinical manifestations (recurrent severe hypertensive crisis, hypotension) due to baroreflex arc impairment preceded the clinical diagnosis of brain tumour and neurosurgery by a few months. Given the clinical suspicion of baroreflex failure, even in the absence of iatrogenic clues, we propose that the patient's study should include neuroradiologic evaluation of the ponto-cerebellar angulus.

Acute Disease↗

Angiotensin II type 1 receptor expression on human leukocyte subsets: a flow cytometric and RT-PCR study.

The renin-angiotensin system plays a key role in the regulation of cardiovascular functions and in particular angiotensin II type 1 receptor (AT1R)-operated pathways are involved in the modulation of inflammation in the vascular wall. In the present study we assessed the pattern of expression of AT1Rs on different human circulating leukocyte subsets. Venous blood was obtained from healthy male subjects. Leukocyte subsets were purified by immunomagnetic cell sorting or identified in whole blood using multiparametric cytometric analysis. RT-PCR analysis showed that AT1R mRNA was expressed in polymorphonuclear leukocytes (PMNs), monocytes, B-lymphocytes, and, to a lesser extent, T-lymphocytes. Flow cytometric analysis revealed that the frequency of expression of AT1Rs was: PMNs>monocytes>or=B-lymphocytes>>T-lymphocytes, while receptor density per positive cells was: PMNs>or=B-lymphocytes>T-lymphocytes>or=monocytes. AT1Rs are expressed on PMNs, monocytes, T- and B-lymphocytes, however the expression pattern is peculiar to each subset, possibly suggesting distinct roles in the various cell types. Investigating the expression and the functional role of AT1Rs on circulating leukocyte subsets, as well as their possible modifications in disease conditions before and after pharmacological treatments, is likely to provide novel clues to the comprehension of the mechanisms involved in the therapeutic efficacy of currently available agents.

Adult↗

Metabolic syndrome and morphofunctional characteristics of the left ventricle in clinically hypertensive nondiabetic subjects.

BACKGROUND: The study was aimed to evaluate the impact of the metabolic syndrome on left ventricular (LV) structure and function in nondiabetic patients, never treated with antihypertensive or lipid-lowering drugs. METHODS: Eighty-eight patients, with recent finding of clinic BP >140 or 90 mm Hg, underwent 24-h blood pressure (BP) monitoring, echocardiogram, evaluation for metabolic syndrome (Adult Treatment Panel III criteria). RESULTS: Metabolic syndrome was diagnosed in 38 subjects (43.2%) (metabolic syndrome+). Age, gender, 24-h systolic and diastolic BP were similar between metabolic syndrome+ and metabolic syndrome- groups, whereas body mass index, clinic and 24-h heart rate, fasting glycemia, and triglycerides were significantly higher and HDL-cholesterol lower in metabolic syndrome + subjects. The prevalence of sustained hypertension (24-h BP >125 or 80 mm Hg) was similar between the two groups. Relative wall thickness and LV mass were significantly greater in the metabolic syndrome+ group, also after correction for body mass index. The LV systolic function was similar between the two groups, whereas all the parameters of diastolic function, but the mitral E/A ratio, were significantly lower in the metabolic syndrome+ group. From multiple regression analysis the main independent determinant of LV mass index was the presence of metabolic syndrome, followed by the 24-h systolic BP. CONCLUSIONS: Nondiabetic patients with metabolic syndrome showed more pronounced alterations of LV geometry and function compared with subjects without metabolic syndrome. These greater preclinical myocardial abnormalities were not accounted for by difference in age, gender, or 24-h BP and can be reasonably ascribed to the interplay of the metabolic syndrome components, making the metabolic syndrome in itself a relevant clinical problem, possibly a cardiovascular disease equivalent, that deserves aggressive treatment.

Blood Pressure↗

Angiotensin-converting enzyme inhibitors influence left ventricular mass and function independently of the antihypertensive effect.

In our retrospective study, we evaluated whether ACE inhibitors can influence left ventricular (LV) morphofunctional characteristics in essential hypertension independently of the antihypertensive effect. We studied 21 hypertensive patients (group 1) before and after at least 18 months of treatment with ACE inhibitors that did not induce any blood pressure (BP) reduction; as a control group, we evaluated 19 hypertensive patients (group 2) not treated with antihypertensive drugs during the same period. At baseline, the 2 groups, neither one previously treated with antihypertensive drugs, were not significantly different with regard to sex, age, body mass index, 24-hour BP, and heart rate; LV mass index was similar between the groups, whereas LV diastolic indices were significantly lower in group 1. At the second evaluation, body mass index, 24-hour BP, and heart rate were unchanged in both groups; LV mass index was significantly decreased in group 1 and increased in group 2. LV diastolic parameters were significantly improved in group 1, whereas in group 2, diastolic function was significantly deteriorated. In conclusion, our clinical study shows that ACE inhibitors can induce LV hypertrophy regression and improvement of diastolic function also in the absence of any antihypertensive effect.

Angiotensin-Converting Enzyme Inhibitors↗

Simvastatin treatment modifies polymorphonuclear leukocyte function in high-risk individuals: a longitudinal study.

BACKGROUND: Although extensive experimental evidence supports a primary role of polymorphonuclear leukocytes (PMNs) in atherosclerosis, few data exist concerning the functional properties of these cells and their pharmacological modulation in high-risk individuals. OBJECTIVE: The production of the proinflammatory chemokine interleukin-8 (IL-8), migration and chemotaxis, and reactive oxygen species (ROS) generation were investigated in a longitudinal study in PMNs obtained from high-risk individuals during statin treatment. As a secondary endpoint we compared PMN function of high-risk patients with that of controls. METHODS AND RESULTS: PMNs were isolated from 21 high-risk individuals before treatment and 3 and 30 days after the beginning of simvastatin treatment, and from healthy controls. During treatment a significant reduction was observed both in resting (P = 0.009) and N-formyl-Met-Leu-Phe (fMLP)-stimulated (P = 0.008) IL-8 production, and in the chemotactic index (P = 0.038), whereas ROS generation did not significantly change. In comparison with cells from controls, PMNs obtained from patients before starting simvastatin treatment showed higher resting and fMLP-stimulated IL-8 release (P = 0.007 and P = 0.002, respectively) and ROS generation (resting, P = 0.009; and fMLP-stimulated, P = 0.046), whereas migration and the chemotactic index did not significantly differ. CONCLUSIONS: An activation of neutrophils is present in high-risk individuals, shown by the enhanced production of IL-8, and increased ROS generation. The 4-week statin treatment is able to reduce the cell capability to produce IL-8, and to decrease chemotaxis, thus affecting the proinflammatory properties of PMNs.

Female↗

Effect of glycemic control on left ventricular diastolic function in type 1 diabetes mellitus.

Left ventricular (LV) diastolic dysfunction is a main feature of diabetic heart disease. The aim of this prospective study was to evaluate the influence of glycemic control on diastolic function in type 1 diabetes mellitus. Thirty-six normotensive (24-hour blood pressure <130/80 mm Hg) subjects with inadequately controlled (glycated hemoglobin >7%) type 1 diabetes, without clinically detectable heart disease, were enrolled. After the basal evaluation, insulin therapy was modified to improve glycemic control. Glycated hemoglobin, LV echocardiography, 24-hour blood pressure monitoring, and laboratory tests were repeated after 6 months in all patients and after 12 months in 27 patients. At the basal evaluation, LV anatomy and systolic function were normal in all, and diastolic function was impaired in 14 patients. After 6 months, the mean values of body mass index, 24-hour blood pressure, and LV anatomy and systolic function were unchanged; mean glycated hemoglobin was decreased (p < 0.001), and mean values of diastolic parameters were significantly improved. After 12 months, the mean values of all blood pressure, metabolic, and LV parameters were unchanged. Percent changes of diastolic parameters were inversely correlated with percent changes of glycated hemoglobin, considering changes from the basal to the 6-month evaluation, as well as changes from the 6- to the 12-month evaluation. In conclusion, in normotensive patients with type 1 diabetes, a close relation was found between glycemic control and LV diastolic function, which improves when glycemic control improves. Therefore, diastolic dysfunction can be prevented or reversed, at least partly, by tight glycemic control.

Adult↗

Thyroid hormone regulation of cell migration and oxidative metabolism in polymorphonuclear leukocytes: clinical evidence in thyroidectomized subjects on thyroxine replacement therapy.

Migration and superoxide anion (O2-) generation were studied in polymorphonuclear leukocytes (PMNs) from 14 athyreotic patients, previously treated by total thyroidectomy and radioiodine therapy for differentiated thyroid carcinoma, and from age- and sex-matched euthyroid healthy controls. Patients were studied twice: in hypothyroidism (visit 1) and after TSH-suppressive L-T4 replacement therapy (visit 2). Random migration and N-formyl-Met-Leu-Phe (fMLP) 0.1-microM induced chemotaxis were similar in cells from patients at both visit 1 and visit 2 and from healthy controls. On the contrary, resting O2- generation in cells from patients was significantly lower than control values, both at visit 1 and 2. At visit 1, fMLP 0.1 muM-induced O2- generation was significantly lower than control values, while phorbol-myristate acetate (PMA) 100-ng/ml induced O2- generation was similar in cells from patients and from controls. At visit 2 both responses increased, resulting in fMLP-induced O2- generation superimposable to control values and PMA-induced O2- generation significantly higher with respect to both visit 1 and cells from controls. In vitro exposure of PMNs from healthy subjects to L-T4 did not affect O2- generation in resting cells, and significantly increased that induced by fMLP or PMA only at high, supra-physiological concentrations. Neither TSH nor T3 had significant effects at any of the concentrations tested. The present results document the existence of a correlation between thyroid status and oxidative metabolism of human PMNs, which is however unlikely to depend upon a direct action of thyroid hormones on these cells.

Adult↗

Global link between heart rate and blood pressure oscillations at rest and during mental arousal in normotensive and hypertensive subjects.

UNLABELLED: Complex phenomena modulate the interplay between heart rate and blood pressure variability, in particular after adjustments induced by stimuli or in pathophysiological conditions. This study sought to investigate in 25 hypertensive and 16 normotensive male subjects whether relationships operating at rest may be preserved after a central nervous system arousal induced by a mental stress test. As a secondary endpoint, we evaluated the potential changes of the components of heart rate and blood pressure variability during stress. RESULTS: A significant correlation was observed between components of RR and systolic blood pressure (SBP) variability (p<0.0001), after controlling for the subject's status (normotensive vs. hypertensive) and for stress-steps (baseline condition, during stress test and recovery). Moreover, the multiple regression model accounted for the potential effects of the baseline alpha(LF) value and for the baseline heart rate and systolic blood pressure. The relationship operating between the LF/HF(RR) ratio and LF/HF(SBP) ratio was not different either at the different steps of stress test (interaction: p=0.87) or in the two groups of normotensive and hypertensive subjects (interaction: p=0.76). The variables of RR and SBP variabilities were modified during stress and recovery. In particular, the LF/HF(RR) ratio and LF/HF(SBP) ratio increased during stress and decreased during recovery. CONCLUSIONS: The association between heart rate and blood pressure oscillations was preserved during central nervous system arousal by mental stress both in normotensives and hypertensives. A central integration may account for this constant relationship, the correlation being independent from baseline heart rate, blood pressure and baroreflex sensitivity.

Adult↗

Isolated office hypertension: a 3-year follow-up study.

The study aimed to evaluate, over a 3-year period, the progression towards sustained hypertension and left ventricular (LV) changes in patients with isolated office (IO) hypertension (office BP>140 and/or 90 mmHg, daytime BP<130/80 mmHg). After 3 years from the basal evaluation, 38 subjects with basal normal BP and 42 subjects with basal IO hypertension underwent a second 24-h BP monitoring and echocardiography; 19 patients of the basal IO hypertension group were not revaluated because they had already developed ambulatory hypertension and were on antihypertensive treatment. At the second evaluation, the 38 normotensive subjects had unchanged BP and LV parameters; 25 IO hypertensives have developed sustained hypertension. Considering them together with the 19 patients already treated, 72% of 61 IO hypertensives developed ambulatory hypertension over a 3-year period. The patients who subsequently developed hypertension differed from the group who did not only for lower basal values of LV diastolic parameters; all the patients with basal LV hypertrophy and/or preclinical diastolic impairment subsequently developed sustained hypertension. In conclusion, IO hypertensive patients show a high rate of progression towards sustained hypertension. Basal LV hypertrophy and/or preclinical diastolic dysfunction were the only markers of a greater risk of becoming hypertensives.

Adult↗

Changes in plasma lipids during renin-angiotensin system blockade by combination therapy (enalapril plus valsartan) in patients with diabetes and hypertension.

There is experimental evidence of an interaction between the angiotensin system and lipid metabolism. The aim of this study was to evaluate whether a block of the angiotensin system achieved both by ACE inhibition and angiotensin II-AT1 receptor blockade could affect the plasma lipid profile and, if so, what relationship exists between these possible changes and glucose metabolism and blood pressure. In 50 patients with type 2 diabetes and hypertension, treated with diabetes drugs and enalapril, we evaluated the glycemic and lipid profile together with the HOMA insulin-resistance index, blood pressure and microalbuminuria at baseline and 3 months after the addition of valsartan. At the second evaluation, blood pressure was reduced as expected, whereas the glycemic profile, the HOMA index, and the body mass index were unchanged. Total cholesterol, LDL-c, and apoprotein B were reduced during combination therapy (P = 0.003, P = 0.001, and P = 0.004, respectively), plasma HDL-c was slightly though significantly increased (P = 0.024), whereas apoprotein A and triglyceride levels did not change. After adjustment for the insulin resistance index and for blood pressure, the reduction of LDL-c and apoprotein B and the increase in HDL-c remained significant. The variation in lipid profile was not related to the changes in blood pressure. Moreover, the addition of valsartan to enalapril was associated with a reduction in microalbuminuria, which remained significant after adjustment for LDL-c or blood pressure changes. Thus, the greater degree of renin-angiotensin system blockade or specific pharmacodynamic effects of valsartan could account for the changes in plasma lipid profile observed in this study.

Diabetes Mellitus, Type 2↗

Circadian blood pressure variability is associated with autonomic and baroreflex-mediated modulation of the sinoatrial node.

OBJECTIVE: The day-night variability of blood pressure (BP) is of interest in the analysis of ambulatory blood pressure monitoring (ABPM). The aim of this study was to investigate whether the nocturnal BP reduction was associated with the autonomic and baroreflex-mediated modulation of the sinoatrial node in normotensive and hypertensive subjects. METHODS AND RESULTS: 63 consecutive untreated male subjects (40 hypertensive and 23 normotensive) were studied. Spectral parameters of RR interval variability and the alphaLF index (a measure of baroreflex gain) were calculated at rest. Then all the subjects performed a 24-h ABPM. RESULTS: As regards the relationships involving 24-h BP and resting heart rate (HR) and HR variability parameters, a significant correlation was found between mean RR and both systolic and diastolic nocturnal BP falls (r = 0.40, p < 0.001, r = 0.32, p < 0.01, respectively); moreover, a significant correlation was found between the nocturnal fall of systolic BP and both the LF/HF ratio and absolute power of HF (r = -0.25, p < 0.05 and r = 0.29, p < 0.05, respectively). The alphaLF index was significantly associated with the nocturnal diastolic BP fall (r = 0.26, p < 0.05) whereas the association with the systolic fall did not reach statistical significance (r = 0.23, p = 0.07). CONCLUSIONS: The relationship found between the nocturnal reduction of BP and both the LF/HF ratio and HF power of RR variability suggests that factors influencing the sympatho-vagal modulation to the heart are associated with the day-night variability of blood pressure. Moreover, the relationship between BP fall and the spontaneous baroreflex sensitivity index alphaLF, may indicate a role of the baroreflex-mediated arc function in the BP adjustments occurring during the night.

Adult↗

Hypertension-related hypoalgesia, autonomic function and spontaneous baroreflex sensitivity.

OBJECTIVE: The mechanisms involved in the relationship between pain perception and hypertension are poorly understood. This study has sought to investigate whether the spontaneous baroreflex sensitivity and the autonomic nervous system balance are related to hypertension-associated hypoalgesia. METHODS: In the morning, 73 untreated male subjects (45 hypertensives, 28 normotensives) were submitted to a simultaneous recording of electrocardiographic and blood pressure signals in resting condition. The tracings were analysed off-line to evaluate the spectral components of the low frequency (LF) and high frequency (HF) powers (autoregressive algorithm; LF/HF ratio used in subsequent analysis as an index of sympathovagal balance), and the alphaLF (alphaLF), an index of baroreflex sensitivity. After the rest period, the subjects underwent dental pain perception evaluation (pulpar tester: test current increasing from 0 to 0.03 mA, expressed in relative Units) to determine the dental pain threshold and tolerance. Afterwards, a 24-h ambulatory blood pressure monitoring was performed. RESULTS: A significant relationship was observed between alphaLF and pain threshold (r = -0.34; p = 0.003). When a multivariate analysis was computed to control for age, 24-h systolic pressure and LF/HF ratio, alphaLF was a predictive independent factor associated with pain threshold (model p = 0.019; r = -0.31; p = 0.025). Moreover, the 24-h systolic pressure was independently associated with pain threshold (model p = 0.019; r = 0.30, p = 0.031). The relationship between alphaLF and relative tolerance was not statistically significant. When the association between the LF/HF ratio and pain sensitivity was assessed as a secondary endpoint, no significant relationship was observed. Since no significant interaction was found, the effect of alphaLF and LF/HF ratio on pain perception was assumed to be similar in normotensive and hypertensive subjects. CONCLUSIONS: The relationship found between unstimulated baroreflex sensitivity and pain threshold suggests a modulation of pain perception by baroreflex pathways in hypertension-associated hypoalgesia. In a baseline condition, the autonomic nervous system balance does not seem to influence pain sensitivity.

Adult↗

Relation of extent of nocturnal blood pressure decrease to cardiovascular remodeling in never-treated patients with essential hypertension.

The clinical significance of the extent of a decrease in nocturnal blood pressure (BP) and the resulting classification of hypertensives as "dipper" (decrease in BP >10% day BP) or "nondipper" (decrease in BP <10% day BP) has been questioned recently. The aim of our study was to evaluate if the extent of a nocturnal BP decrease, established on the basis of a single 24-hour BP monitoring, is related to cardiovascular remodeling in essential hypertension. We enrolled 253 never-treated essential hypertensives (24-hour BP > or = 140 and/or 90 mm Hg); for each patient we recorded 24-hour BP, left ventricular (LV) echocardiogram, Doppler transmitral flow velocities, and carotid-femoral pulse-wave velocities. A dipper BP profile was found in 161 patients, whereas 92 patients were nondippers. The 2 groups did not differ with regard to age, gender, body mass index, 24-hour and daytime BP, and 24-hour, daytime, and nighttime heart rate. All LV morphologic characteristics LV systolic and diastolic functional parameters, mitral Doppler-derived diastolic indexes, as well as carotid-femoral pulse-wave velocity, and aortic index distensibility were not significantly different between dippers and nondippers. The prevalence of LV hypertrophy and diastolic dysfunction was also similar between the 2 groups. The extent of a decrease in nocturnal BP did not correlate with any cardiovascular parameter. In conclusion, in never-treated hypertensives, the extent of a nocturnal BP decrease is not related to LV morpho-functional characteristics and aortic distensibility; therefore, the nondipping status established on the basis of a single 24-hour BP monitoring does not identify hypertensive patients with greater cardiovascular damage.

Adult↗

Changes in pain perception during treatment with angiotensin converting enzyme-inhibitors and angiotensin II type 1 receptor blockade.

OBJECTIVES: Besides the well-known role of the angiotensin system in blood pressure control, an interaction of angiotensin and pain perception has been suggested. This study sought to investigate whether an angiotensin converting enzyme inhibitor, which facilitates bradykinins, algesic peptides, and/or an AT1 receptor antagonist may modify hypertension-related hypoalgesia in humans. The study was approved by the ethical committee of our Department. METHODS: A total of 22 hypertensive patients were submitted to dental pulp stimulation to obtain the dental pain threshold and tolerance, and to 24 h blood pressure monitoring together with a control group of 55 normotensives. Then the hypertensives were randomized to enalapril or losartan treatment and were re-evaluated (dental pain perception and ambulatory monitoring) after 8 weeks of the first treatment and after an additional 8 weeks of the second treatment. RESULTS: Untreated hypertensives showed a reduced perception to painful stimuli when compared with normotensives. A significant reduction of both pain threshold and tolerance was observed during the anti-hypertensive treatments (Friedman test: P = 0.007 and P = 0.006, respectively). Pain sensitivity was similar during the two treatments and it did not differ from pain sensitivity values of normotensive controls. ANCOVAs were computed to evaluate the relationship between anti-hypertensive agents and pain sensitivity, after controlling for blood pressure. A 24 h mean pressure served as covariate, removing any effect of blood pressure; a significant difference was observed entering both pain threshold and tolerance as dependent variables (F = 5.28, P = 0.0076; F = 8.16, P = 0.0007, respectively). CONCLUSIONS: Both the angiotensin converting enzyme inhibitor enalapril and the AT1 receptor blocking agent losartan acted similarly on pain threshold and tolerance, pain sensitivity being increased during the two anti-hypertensive treatments. The blood pressure reduction during drug assumption could not account for the pain sensitivity changes observed. The latter may be due to a specific pharmacodynamic mechanism mediated through angiotensin II AT1 receptors.

Adult↗

Aldosterone antagonist improves diastolic function in essential hypertension.

Experimental studies demonstrated that mineralocorticoid antagonists prevent or reverse myocardial fibrosis. Therefore, we tested the hypothesis that the aldosterone antagonist canrenone can improve left ventricular diastolic function in essential hypertension. Using digitized M-mode echocardiography and 24-hour blood pressure monitoring (ABPM), we realized a prospective, randomized, controlled study on 34 never-treated essential hypertensives with left ventricular diastolic dysfunction. Echocardiogram and ABPM were repeated after 6 months of effective antihypertensive treatment with ACE inhibitors and calcium antagonists (second evaluation) and then after a 6-month period with 17 patients randomly assigned to add canrenone 50 mg/d to the previous treatment (third evaluation). At the basal evaluation 32 patients had left ventricular concentric hypertrophy, and 2 patients had left ventricular concentric remodeling. All the patients had normal left ventricular systolic function. At the second evaluation blood pressure was reduced (P<0.0001), left ventricular mass index decreased (P<0.0001), and diastolic function improved (P<0.0001). After randomization, the canrenone and control groups had similar 24-hour blood pressure and left ventricular morpho-functional characteristics. At the third evaluation, despite unchanged blood pressure and similar decrease of left ventricular mass index, the canrenone group, compared with control group, showed a significantly greater increase in left ventricular diastolic indices. In essential hypertension, a low dose of aldosterone antagonist added to antihypertensive treatment significantly improved left ventricular diastolic function. This improvement, not accounted for by changes in blood pressure and left ventricular mass, can be therefore ascribed to a direct action of the drug on the myocardium.

Antihypertensive Agents↗

Relationship between a genetic predisposition to hypertension, blood pressure levels and pain sensitivity.

INTRODUCTION: The aim of this study was to determine whether the degree of blood pressure elevation and/or a genetic predisposition to hypertension have a major role in determining a reduced pain perception in hypertensives. The reasons underlying the relationship between blood pressure elevation and pain perception mechanisms are not completely understood. METHODS: One hundred and four untreated hypertensive patients (65 subjects with and 39 without a positive parental history of hypertension) together with a control group of 42 subjects (20 normotensive offspring of normotensive parents, and 22 normotensive offspring of hypertensive parents) were submitted to standard blood pressure evaluation, 24-h blood pressure monitoring and dental pain perception evaluation. RESULTS: Both pain threshold and tolerance were found to be higher in hypertensive than normotensive subjects (P < 0.0001 and P < 0.015, respectively). Positive significant correlations were found between both 24-h systolic and diastolic pressure and the pain perception variables. When a 2 x 2 ANOVA test was performed, factoring for the effects of both blood pressure status and family history of hypertension on pain sensitivity, a significant effect was revealed only for blood pressure status. Moreover, after controlling for blood pressure by a covariate analysis, no significant difference was found between the subjects with or without hypertensive parents as regards pain perception variables. CONCLUSIONS: Pain sensitivity is correlated to blood pressure levels whereas the parental history of hypertension per se does not affect the pain perception pattern. Thus, the degree of blood pressure elevation, more than a genetic predisposition to hypertension may influence the mechanisms leading to hypalgesia in hypertension.

Adult↗