Biomedical subjects

G Parrinello

Publications and source records attributed to G Parrinello.

At least 19 recordsLinked to original sources

PubMed2006

Common polymorphisms of the growth hormone (GH) receptor do not correlate with the growth response to exogenous recombinant human GH in GH-deficient children.

CONTEXT: GH acts through the GH receptor (GHR), whose polymorphisms might affect the growth response to recombinant human GH (rhGH). OBJECTIVE: The objective of this study was to investigate possible influences of GHR polymorphisms on the growth response to rhGH in GH-deficient (GHD) children. DESIGN: This was a 2-yr study (first year, spontaneous growth; second year, growth during rhGH treatment). SETTING: This study was performed at a referral center. PATIENTS: Fifty-four prepubertal GHD children (11 females; mean age, 7.8 yr; sd, 3.96) were studied. INTERVENTION: Patients were treated with rhGH (0.2 mg/kg.wk) for at least 1 yr after diagnosis. Growth velocity (GV) was measured 1 yr before treatment and during the first treatment year. GHR exons were amplified by PCR using pairs of intronic primers. The presence of single or multiple mismatches in the PCR products was revealed by denaturing high-pressure liquid chromatography. For exons in which mismatches were found by denaturing high-pressure liquid chromatography, direct sequencing was performed by automatic sequencer. MAIN OUTCOME MEASURES: Before the start of treatment, the mean height (Ht) sd score was -1.93 (sd, 0.70), and the mean GV sd score was -1.49 (sd, 1.26). RESULTS: The posttreatment (first 12 months) mean GV sd score was 3.55 (sd, 3.27). Molecular analysis revealed a high frequency of GHR polymorphisms; in particular: exon 3 deletion (Del 3) in 26 subjects (48%), polymorphism 504 A>G at codon 168 of exon 6 in 44 (82%), and polymorphism 1576 A>C at codon 526 of exon 10 in 35 (65%). In most patients, these different polymorphisms recurred in association. We found no significant differences in GV between the groups of subjects defined by the polymorphic genotypes. CONCLUSION: The most common GHR polymorphisms, alone or in association, do not appear to affect the growth response to rhGH in GHD children.

Child↗

PubMed2006

Obesity: a main factor of metabolic syndrome?

The metabolic syndrome (MS) is a common metabolic disorder that has been recently related to the increasing prevalence of obesity. The disorder is defined in various ways, but in the near future a new definition(s) will be applicable worldwide. The pathophysiology has been largely attributed, in the past years, to insulin-resistance, even if several epidemiological and pathophysiological data are attractive to indicate visceral obesity as a main factor in the occurrence of the MS, promoting new definitions and re-evaluation of the pathogenesis of this syndrome. In this review, we have analyzed the role of visceral obesity in the new definition of the MS such as the pathophysiological role of the abnormal fat distribution in the occurrence of this syndrome. In view of this, relationships between visceral obesity, free fatty acids, dyslipidaemia and insulin-resistance have been reported. In addition, the effects of some adipocytokines and other proinflammatory factors produced by fat accumulation on the appearance of the MS have been also emphasized. Finally, according to recommendations of several international societies, the role of the life-style change and of the weight loss in the prevention and treatment both of obesity and of other associated risk factors has been analyzed.

Adipose Tissue↗

PubMed2005

Left ventricular filling abnormalities and obesity-associated hypertension: relationship with overproduction of circulating transforming growth factor beta1.

This study has been designed to evaluate the relationship among transforming growth factor beta1 (TGFbeta1) and some measurements of diastolic function in a population of hypertensive subjects with normal left ventricular ejection fraction. We studied 67 hypertensive outpatients who according to their BMI levels were subdivided into three groups: lean (L), overweight (OW) and obese (OB) hypertensives (HT). Circulating TGFbeta1 and M- and B-mode echocardiography was determined. All hypertensives were further subgrouped, according to European Society of Cardiology Guidelines, into two subsets of patients with normal diastolic function or with diastolic dysfunction. Prevalence of left ventricular hypertrophy (LVH) was determined in all the groups. TGFbeta1, left ventricular mass (LVM), LVM/h(2.7), E-wave deceleration time and isovolumic relaxation time (IVRT) were significantly (P < 0.005) higher and E/A velocity ratio was significantly (P < 0.05) lower in OW-HT and OB-HT than in L-HT. Prevalence of LVH was significantly higher (P < 0.03) in group OB-HT than in L-HT. TGFbeta1 (P < 0.004), LVM/h(2.7) (P < 0.001) and prevalence of LVH were (P < 0.01) significantly higher in hypertensives with diastolic dysfunction than hypertensives with normal diastolic function. TGFbeta1 levels were positively correlated with BMI (r = 0.60; P < 0.0001), LVM/h(2.7) (r = 0.28; P < 0.03), IVRT (r = 0.30; P < 0.02) and negatively with E/A ratio (r = -0.38; P < 0.002) in all HT. Multiple regression analysis indicated that TGFbeta1, BMI and IVRT were independently related to E/A ratio explaining 71% of its variability (r = 0.84; P < 0.0001). This relationship was independent of LVH, age and HR suggesting that TGFbeta1 overproduction may be considered a pathophysiological mechanism in the development of left ventricular filling abnormalities in obesity-associated hypertension.

Adult↗

PubMed2004

Early carotid atherosclerosis and cardiac diastolic abnormalities in hypertensive subjects.

Despite the fact that it is known that hypertension may be associated to early atherosclerosis manifestations, few data are to date available on the relationship between early carotid abnormalities and left ventricular diastolic dysfunction. To address this issue, 142 hypertensive patients (64 females and 78 males) younger than 55 years, at the first diagnosis of mild-to-moderate essential hypertension (WHO/ISH criteria), were selected from a database consisting of 3541 subjects referred to ultrasound cardiovascular laboratory in the last 5 years. Carotid intima-media thickness (IMT) was detected by high-resolution vascular ultrasound and left ventricular structure and function by the use of Doppler echocardiography. According to carotid IMT values, all patients were subgrouped into two groups consisting of 89 (62.6%) pts with IMT > or = 1 mm (A) and 53 (37.4%) pts with IMT < 1 mm (B). Our results show that isovolumic relaxation time (IVRT), deceleration time of E velocity (EDT) and left ventricular relative wall thickness (LV-RWT) were significantly (P < 0.05) higher in group A (IVRT 112 +/- 8.9 ms; EDT 288 +/- 21.8 ms; LV-RWT 0.40 +/- 0.08) than in group B (IVRT 92.3 +/- 4.6 ms; EDT 203.3 +/- 27.01 ms; LV- RWT 0.37 +/- 0.06). Moreover, the prevalence of left ventricular hypertrophy (LVH) was significantly (P < 0.01) higher in group A (30/89; 33.7%) than in group B (8/53; 15%). A positive correlation (P < 0.001) between IMT, EDT and IVRT was found only in hypertensives without LVH. These results are consistent with the indication that IMT evaluation has to be recommended both in hypertensive patients with LVH and in those without LVH, but with left ventricular diastolic dysfunction. This approach might improve the prognostic stratification of hypertensive subjects and it might be suitable to recognize the subset of patients at a higher risk of cardiovascular disease or events early.

Adult↗

PubMed2003

Transcranial Doppler and risk of recurrence in patients with stroke and patent foramen ovale.

The importance of patent foramen ovale (PFO) in stroke of unknown cause remains disputed, as PFO may be present in up to 20% of normal people and in a high proportion of patients with non-vascular disorders. Recent evidence suggests that the amount of right-to-left shunt (RLS) may be the crucial factor for stroke occurrence and relapse. The aim of the study was to assess predictors of recurrence in PFO-related stroke patients with particular emphasis on amount of shunting. Patients less than 61 years old who had been admitted for a PFO-related stroke within the previous 5 years, were re-evaluated on a follow-up visit. The clinical syndrome, residual disability, vascular risk factors and number of relapses as the index event were assessed. RLS sizing was semi-quantitatively performed with saline-enhanced transcranial Doppler (TCD), by assuming a cut-off of more or less 10 bubbles recorded in the cerebral vessels as a criterion to discriminate large versus small shunt, respectively. Thereafter patients were prospectively followed-up for a median time of 23 months. Total follow-up was 61 months. Fifty-nine patients (M/F = 23/36, mean age 43 +/- 13) were studied. Overall there were 23 relapses in 13 patients. The amount of shunting was the only significant independent variable associated with relapse: at the end of the follow-up period the recurrence rate was 0.66 and 8.2% per patient per year in patients with small and large shunt, respectively. This difference was statistically significant (chi2 = 10.39, P = 0.0012; OR 17.05, 95% CI 2.10-755.22). In patients with PFO-related stroke, the amount of RLS as assessed with TCD is the only independent predictor of relapse. PFO sizing is mandatory in patients with PFO.

Female↗

PubMed2002

Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women.

The authors investigated the dose-effect relation between alcohol drinking and hepatocellular carcinoma (HCC) in men and women separately, also considering hepatitis B and hepatitis C virus infections. They enrolled 464 subjects (380 men) with a first diagnosis of HCC as cases and 824 subjects (686 men) unaffected by hepatic diseases as controls; all were hospitalized in Brescia, northern Italy, in 1995-2000. Spline regression models showed a steady linear increase in the odds ratio of HCC for increasing alcohol intake, for values of >60 g of ethanol per day, with no substantial differences between men and women. Duration of drinking and age at start had no effect on the odds ratio when alcohol intake was considered. Former drinkers who had stopped 1-10 years previously had a higher risk of HCC than current drinkers did. The effect of alcohol drinking was evident even in the absence of hepatitis B or hepatitis C virus infection. In addition, a synergism between alcohol drinking and either infection was found, with approximately a twofold increase in the odds ratio for each hepatitis virus infection for drinkers of >60 g per day.

Adult↗

PubMed2002

Relationship between transforming growth factor beta1 and progression of hypertensive renal disease.

In this study the role of circulating transforming growth factor beta1 (TGFbeta1) on progression of renal hypertensive disease has been investigated. Fifty consecutive outpatients with essential hypertension were enrolled and divided into three groups, according to their urinary albumin excretion (UAE). Group A comprised 10 hypertensives with UAE 20 < 300 mg/24 h (microalbuminuric group); Group C encompassed 19 hypertensives with UAE >or= 300 mg/24 h (proteinuric group). In all patients UAE by immunonephelometric assay, circulating TGFbeta1 by a solid phase specific sandwich ELISA technique, BUN and creatinine by routine laboratory methods were determined. In addition, left ventricular telediastolic internal diameter, interventricular septum diastolic (IVSTd), posterior wall thickness, total and normalised to height(2.7) left ventricular mass, relative wall thickness and left ventricular ejection fraction by M-B Mode echocardiography were calculated. Our results indicated that TGFbeta1 levels were significantly (P < 0.05) higher in Group B and C than Group A and in Group C than Group B. In addition IVSTd values were significantly (P < 0.05) higher in both Group B and C than Group A. An evident, but not significant, higher prevalence of subjects with left ventricular hypertrophy were observed in Group C as compared with other groups. In all hypertensive subjects TGFbeta1 correlated directly with UAE (P < 0.0001) but not with BMI, LVM/h(2.7) and mean blood pressure. Our data indicated that TGFbeta1 might be considered a useful marker to evaluate the severity and progression of hypertensive renal disease. Additional long-term clinical data are needed to evaluate whether inhibition of TGFbeta1 system may prolong the time to the ESRD in hypertensive patients.

Albuminuria↗

PubMed2002

Chromogranin A in heart failure; a novel neurohumoral factor and a predictor for mortality.

BACKGROUND: In chronic heart failure, several hormonal systems are activated with diagnostic and prognostic implications. We tested the hypotheses that serum Chromogranin-A (CgA) -- a 49 kDa acid protein present in the secretor granules of neuroendocrine cells -- is increased in chronic heart failure and that CgA levels are a predictive factor for mortality. METHOD AND RESULTS: In 160 patients with chronic heart failure, we measured serum CgA and other neuroendocrine hormones. The results showed that CgA is increased in chronic heart failure and the increase is related to the clinical severity of the syndrome: CgA levels in New York Heart Failure (NYHA) class II (median 146.9 ng x ml(-1), inter-quartiles 108.3-265.5) were significantly higher (P<0.05) than in class I (median 109.7 ng x ml(-1), inter-quartiles 96.7-137.6), and significantly lower (P<0.05) than in class III (median 279.0 ng x ml(-1), inter-quartiles 203.6-516.1). Class IV patients showed the highest serum levels of CgA (median 545.0 ng. ml(-1), inter-quartiles 231.8-1068.3), being statistically significantly different from class III patients (P<0.001). The association between survival and some recognized variables of prognostic significance, including CgA was also studied. The results showed that ejection fraction, noradrenaline, atrial natriuretic peptide, NYHA class and CgA were significant univariate prognosticators; however, in the multivariate analysis by the Cox proportional-hazard model, CgA and NYHA class were the only independent predictive factors for mortality (P<0.005, RR=1.22, 95% CI=1.06-1.41 and P=0.04, RR=1.58, 95% CI=1.02-2.46, respectively). CONCLUSIONS: CgA is a pro-hormone, precursor of several active fragments likely to exert biological effects in chronic heart failure. CgA serum levels are increased in patients with chronic heart failure and are a predictive factor for mortality.

Adult↗

PubMed2002

Revascularization of hibernating myocardium: rate of metabolic and functional recovery and occurrence of oxidative stress.

BACKGROUND: Left ventricular (LV) dysfunction due to coronary artery disease (CAD) may improve after revascularization in patients with hibernating myocardium (HM). METHODS AND RESULTS: We compared the rate of metabolic (arterial-great cardiac vein differences of lactate, glucose and pyruvate) and functional (intra-operative transesophageal and epicardial echocardiography) recovery and occurrence of oxidative stress (myocardial release of oxidized glutathione (GSSG)) early after surgical revascularization, in patients with CAD, LV dysfunction and HM (n=16) vs those with preserved LV function (n=15). By comparing the two groups, we observed that, after de-clamping, in patients with HM (a) the kinetic of lactate production was converted to extraction (P<0.01 at 1, 5, 10 and 20 min after revascularization), (b) myocardial extraction of pyruvate increased (P<0.01 during the first 5 min after revascularization), (c) GSSG release was less and of shorter duration (P<0.01 at all times), (d) segmental wall motion score improved from 2.4+/-0.3 to 1.7+/-0.5 (P<0.01) as did the thickening of the akinetic territories corresponding to the antero-distal septum and to the distal anterior wall regions (to 36+/-23%, and to 36+/-13%, respectively). There was a correlation between the rate of recovery of metabolic and functional indices. CONCLUSIONS: The contractile and metabolic recovery of HM is more rapid than that of non-HM, and it is not accompanied by oxidative stress.

Blood Glucose↗

PubMed2002

Can losartan improve cardiac performance during the treadmill exercise test in hypertensive subjects?

Systolic blood pressure (SBP) normally increases during exercise. This increase is frequently exaggerated in hypertensive individuals. The aim of our study was to evaluate the antihypertensive effects of losartan at peak exercise and on cardiac performance during the treadmill test in individuals with essential hypertension. Forty subjects with a mean age of 44.2 +/- 12.4 years and with mild-to-moderate essential hypertension were enrolled. After a 14-day washout period, all selected subjects were given a treadmill exercise test using the modified Bruce protocol for exercise. The test was performed at the end of the washout period (step 0), again after 1 month (step 1), after 3 months (step 2) and after 6 months (step 3) of losartan administration (50 mg/daily per oral). Heart rate, SBP and diastolic blood pressure (DBP) were measured at rest and at maximal exercise. Exercise duration and double product were also recorded. In all patients who completed the study, a significant reduction from baseline in SBP at rest was found at 3 and 6 months (p < 0.05). No significant reduction from baseline in SBP at peak exercise was observed. No significant changes from baseline were found in double product, DBP, heart rate or exercise time. The results of our study suggest that losartan is effective in reducing blood pressure only at rest but is unable to improve exercise BP response or cardiac performance in subjects with mild-to-moderate essential hypertension.

Adult↗

PubMed2001

Amyloid precursor protein in platelets: a peripheral marker for the diagnosis of sporadic AD.

BACKGROUND: An altered pattern of amyloid precursor protein (APP) forms consisting in a reduced ratio between the upper (130 kDa) and the lower (106 to 110 kDa) immunoreactivity bands has been described in platelets of patients with AD. OBJECTIVE: To evaluate the sensitivity and the specificity of platelet APP forms' ratio (APPr) as a marker for AD. METHODS: Eighty-five patients with probable AD and 95 control subjects (CON), including healthy individuals and neurologic patients, entered the study. Platelet APPr was evaluated by means of Western Blot analysis and immunostaining in the whole platelet homogenate, and calculated by the ratio between the optical density (OD) of the upper (130 kDa) and the lower (106 to 110 kDa) APP immunoreactive bands. RESULTS: Mean APPr levels were decreased in AD patients (mean OD +/- SD = 0.35 +/- 0.18) compared with the CON group (mean OD +/- SD = 0.92 +/- 0.38) (DF 1, 178, p < 0.0001). Accuracy levels measured by Receiver Operating Curve analysis showed that a cut-off level of 0.57 resulted in a sensitivity of 88.2% and a specificity of 89.4%, with an area under the curve of 0.945. APPr levels were significantly associated with disease severity (mild AD versus moderate AD: p < 0.0001; moderate AD versus severe AD: p < 0.05). CONCLUSION: Platelet APPr allowed to differentiate AD from normal aging and other dementing disorders with high sensitivity and specificity. These findings suggest that platelet APPr may be of help as an adjunctive diagnostic tool in clinical practice.

Aged↗

PubMed2001

Preliminary observations on haemodynamics during physiological stress conditions following 'double-orifice' mitral valve repair.

OBJECTIVE: The 'double-orifice' (DO) technique has been proposed to simplify mitral valve repair (MVRep) in particular settings of mitral insufficiency. However, the haemodynamic effects of such a redesigned valve are poorly documented, particularly during stress conditions. Thus, we sought to evaluate the haemodynamic changes during exercise conditions after the DO procedure. METHODS: Twenty-seven selected patients were enrolled for this study. Mean age was 60 +/- 14 years (range 31--80 years). All patients had had severe mitral regurgitation and normal LV function preoperatively, and had undergone DO as isolated procedure for MVRep. Annular remodelling was associated in 24 cases (Carpentier classic ring in 13 patients and autologous pericardium in 11 patients, respectively). Postoperatively, haemodynamic data were recorded at baseline and during supine exercise test at submaximal workloads by means of transthoracic echocardiography. A logistic regression analysis was applied to evaluate the association between the observed haemodynamic changes and surgical technique. RESULTS: Mean follow-up was 47 +/- 20 months. Significant residual mitral insufficiency (grade three over four) was found in five patients at baseline assessment, and in six patients at peak exercise. Transmitral pressure gradient showed a significant (P < 0.001) increase in both peak and mean values at peak exercise (from 7 +/- 4 to 17 +/- 10 and from 3 +/- 2 to 8 +/- 6 mmHg, respectively). Pulmonary hypertension was observed in six patients (moderate in all cases) at rest and in 13 patients (moderate in seven cases and severe in five cases) at peak exercise. We did not find any correlation between the haemodynamic data and surgical factors. CONCLUSIONS: This study indicates that though effective mitral valve competence is achieved in the majority of operated patients, DO repair may induce impaired diastolic mitral dynamism in some cases, particularly during exercise conditions. Further investigations are required to thoroughly elucidate the overall mechanics of a DO valve, especially at strenuous cardiocirculatory states.

Adult↗

PubMed2001

The double-orifice technique for mitral valve reconstruction: predictors of postoperative outcome.

OBJECTIVE: The 'double-orifice' (DO) technique has been recently proposed as an additional option in mitral valve repair (MVR). However, little is known regarding the long-term postoperative outcome and the predictors of DO results. Therefore, the aim of this study was to evaluate our clinical series and to identify prognostic factors of DO repair. METHODS: From 1992, 75 patients underwent DO procedure because of severe mitral regurgitation. The study population consisted of 48 male and 27 female patients with a mean age of 58+/-13 years (range 16-80 years). The aetiology of mitral incompetence was Barlow disease in 30 cases, rheumatic disease in 18 cases, acute or healed endocarditis in 16 cases and other causes in 11 cases. Carpentier rigid ring was used in 38 patients, whereas autologous pericardium was used in 24 patients. Thirteen patients had no annuloplasty procedure. Statistical analysis included univariate and multivariate Cox proportional models to evaluate the predictors of the DO failure. RESULTS: There were four hospital and three late deaths with a survival rate of 92% at 8 years. Mean follow-up was 42+/-24 months (range 1-93 months). Twelve patients underwent reoperation (five cases of early failure) and had valve replacement, leading to 80% freedom from reoperation at 8 years. At follow-up, 13 patients had no mitral regurgitation, 36 patients had trivial or mild mitral incompetence, whereas eight patients had moderate or severe mitral insufficiency at transthoracic echocardiography. Preoperative low left ventricular ejection faction, pulmonary arterial hypertension and marked left atrial enlargement were predictors (P<0.05) of DO failure at univariate analysis. Pericardial annuloplasty was also a risk factor (P<0.05) for unsuccessful DO repair at long term. Cox proportional multivariate analysis confirmed left atrial dilatation, pulmonary hypertension and pericardial annuloplasty as independent predictors of unfavourable postoperative results. CONCLUSIONS: This study suggests that preoperative factors, like pulmonary hypertension and severe left atrial dilatation, may predict late DO failure. Our findings also indicate that pericardial annuloplasty may negatively influence mitral valve reconstruction at long term when DO is employed in MVR.

Adolescent↗

PubMed2001

Long-term results of coronary artery bypass grafting procedure in the presence of left ventricular dysfunction and hibernating myocardium.

OBJECTIVE: Long-term left ventricular (LV) performance and patient outcome after coronary artery bypass grafting (CABG) procedure in the presence of depressed LV function and hibernating myocardium (HM) have been poorly determined. Therefore, we prospectively evaluated patients undergoing CABG with severe LV dysfunction and HM to elucidate postoperative prognosis. METHODS: We enrolled 120 consecutive patients undergoing CABG with severe LV dysfunction and HM as assessed by dobutamine echocardiography and by rest-redistribution radionuclide (Thallium-201) study. Mean patient age was 60+/-9 years (range 31-77 years). Mean preoperative LVEF was 28%+/-9 (range 10-40%). All patients underwent echocardiographic study to assess LV recovery of function intraoperatively, prior to hospital discharge, at 3 months, at 1 year, and yearly during the follow-up. Univariate and multivariate analysis were performed to to evaluate predictors of postoperative survival. RESULTS: There were 2 hospital (1.6%) and 15 late (12.5%) deaths, mainly for heart failure, leading to an actuarial survival of 80+/-6% and 60+/-9% at 5 and 8 years, respectively. LVEF significantly improved perioperatively (from 28+/-9% to 40+/-2%, P<0.01). Increase in LVEF, however, was gradually offset over the time (EF of 33+/-9%, 32+/-8%, and 30+/-9% at 3 months, and 12 months, and 8 years after surgery, respectively). Furthermore, patients who experienced limited LV functional recovery perioperatively had a more remarkable decline of LVEF thereafter, and suffered from recurrence of heart failure symptoms (freedom from heart failure 82+/-5% and 60+/-8% at 4 and 8 years respectively). Advanced preoperative NYHA Class, and age were independent risks factors for reduced postoperative survival. Preoperative angina and use of arterial conduits apparently did not influence patient morbidity and mortality at long term. CONCLUSION: CABG procedure in the presence of HM enhances LV recovery of function and has a favourable prognosis. Functional benefit of the left ventricle, however, appears to be time-limited, despite remarkable improvement in patient functional capacity. Advanced preoperative heart failure, minimal perioperative improvement of LVEF, and age account for a poor long-term prognosis.

Adult↗

PubMed2001

Carotid atherosclerosis in hypercholesterolemic patients: relationship with cardiovascular events.

BACKGROUND AND AIM: Extracranial cerebrovascular atherosclerosis is a common feature of hypercholesterolemia and carotid lesions are good predictors of cardiovascular events in the general population. Factors associated with the carotid damage of hypercholesterolemic patients and their relationships with the occurrence of clinical events are investigated in this study. METHODS AND RESULTS: One hundred and seventeen cardiovascular event-free hypercholesterolemic subjects underwent a complete clinical examination to look for additional risk factors. A blood sample was collected for lipoprotein determination and an ultrasound high resolution B-mode imaging examination of the common carotid arteries was performed. Patients were treated according to the current guidelines during a 4-yr follow-up and all major cardiovascular events were recorded. The prevalence of subjects with increased intima-media thickness and plaque was 21.4% and 29.9% respectively, higher than in normolipidemic controls. Carotid lesions were significantly related to age, hypertension and LDL-cholesterol and HDL-cholesterol levels. The relative risk of developing a major clinical event was 3.92 (95% CI 1.54-9.95, p < 0.004) among categories of carotid status. At multivariate analysis, cardiovascular events were independently related to the diagnosis of familial hypercolesterolemia (FH), baseline carotid score and mean levels of LDL-cholesterol and HDL-cholesterol during the follow-up. CONCLUSIONS: Common risk factors cooperate with plasma lipoprotein levels in increasing the frequency of carotid lesions of hypercholesterolemic patients. Since such lesions are useful predictors of clinical events, B-mode ultrasound evaluation of the carotids should be routinely included in the management of these patients.

Age Factors↗

PubMed2000

Reduction of oxidative stress by carvedilol: role in maintenance of ischaemic myocardium viability.

OBJECTIVES: To differentiate the impact of the beta-blocking and the anti-oxidant activity of carvedilol in maintaining myocardium viability. METHODS: Isolated rabbit hearts, subjected to aerobic perfusion, or low-flow ischaemia followed by reperfusion, were treated with two doses of carvedilol, one dose (2.0 microM) with marked negative inotropic effect due to beta-blockage and the other (0.1 microM) with no beta-blockage nor negative inotropism. Carvedilol was compared with two doses of propranolol, 1.0 - without - and 5.0 microM - with negative inotropic effect. Anti-oxidant activity was measured as the capacity to counteract the occurrence of oxidative stress and myocardium viability as recovery of left ventricular function on reperfusion, membrane damage and energetic status. RESULTS: Carvedilol counteracted the ischemia and reperfusion induced oxidative stress: myocardial content of reduced glutathione, protein and non-protein sulfhydryl groups after ischaemia and particularly after reperfusion, was higher in hearts treated with carvedilol, while the myocardial content of oxidised glutathione was significantly reduced (0.30+/-0.03 and 0.21+/-0.02 vs. 0.39+/-0.03 nmol/mg prot, both P<0.01, in 0.1 and 2.0 microM). At the same time, carvedilol improved myocardium viability independently from its beta-blocking effect. On the contrary, propranolol maintained viability only at the higher dose, although to a lesser extent than carvedilol. This suggests that the effects of propranolol are dependent on energy saving due to negative inotropism. The extra-protection observed with carvedilol at both doses is likely due to its anti-oxidant effect. CONCLUSIONS: Our data show that the anti-oxidant activity of carvedilol is relevant for the maintenance of myocardium viability.

Adenosine Diphosphate↗

PubMed2000

Effects of high-dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as a bolus, in refractory congestive heart failure.

BACKGROUND: Diuretics, have been accepted as first-line treatment in refractory heart failure, but a lack of response is a frequent event. A randomised single blind study was performed to evaluate the effects of the combination of high-dose furosemide and small-volume hypertonic saline solution (HSS) infusion in the treatment of refractory NYHA class IV congestive heart failure (CHF). MATERIALS AND METHODS: Sixty patients (21 F/39 M) with refractory CHF (NYHA class IV) of different etiologies, unresponsive to high oral doses of furosemide, ACE-inhibitors, digitalis, and nitrates, aged 65-90 years, were enrolled. They had to have an ejection fraction (EF) <35%, serum creatinine <2 mg/dl, BUN </=60 mg/dl, a reduced urinary volume and a low natriuresis. The patients were randomised in two groups (single blind): group 1 (11 F/19 M) received an i.v. infusion of furosemide (500-1000 mg) plus HSS (150 ml of 1.4-4.6% NaCl) b.i.d. in 30 min. Group 2 (10 F/20 M) received an i.v. bolus of furosemide (500-1000 mg) b.i.d., without HSS, during a period lasting 6-12 days. Both groups received KCl (20-40 mEq.) i.v. to prevent hypokalemia. All patients underwent at entry a physical examination, measurement of body weight (BW), blood pressure (BP), heart rate (HR), evaluation of signs of CHF, and controls of serum Na, K, Cl, bicarbonate, albumin, uric acid, creatinine, urea and glycemia and daily during hospitalization, as well as the daily output of urine for, Na, K and Cl measurements. Chest X-ray, ECG and echocardiogram were obtained at entry during and at the discharge. During the treatment and after discharge the daily dietary Na intake was 120 mmol with a drink fluid intake of 1000 ml daily. An assessment of BW and 24-h urinary volume, serum and urinary laboratory parameters, until reaching a compensated state, were performed daily, when i.v. furosemide was replaced with oral administration (250-500 mg/day). After discharge, patients were followed as outpatients weekly for the first 3 months and subsequently once per month. RESULTS: The groups were similar for age, sex, EF, risk factors, treatment and etiology of CHF. All patients showed a clinical improvement. Six patients in both groups had hyponatremia (from 120 to 128 mEq./l) at entry. A significant increase in daily diuresis in both groups was observed (from 390+/-155 to 2100+/-626, and from 433+/-141 to 1650+/-537 ml/24 h, P<0.05). Natriuresis (from 49+/-15 to 198+/-28 mEq./24 h) was higher in group 1 vs. group 2 (from 53.83+/-12 to 129+/-39 mEq./24 h, P<0.05). Serum Na (from 135.9+/-6.8 to 142.2+/-3. 8 mEq./l, P<0.05) increased in the group 1 and decreased in the group 2 (from 134.7+/-7.9 to 130.1+/-4.3 mEq./l). Serum K was decreased (from 4.4+/-0.6 to 3.9+/-0.6, and 4.6+/-9 to 3.6+/-0.5 mEq. /l, P<0. 05) in both groups. BW was reduced (from 73.8+/-9.1 to 63. 8+/-8.8, and from 72.9+/-10.2 to 64.5+/-7.5 kg, P<0. 05) in both groups. Group 2 showed more patients in NYHA class III than group 1 (18 vs. 2 patients, P<0.05). Group 2 showed an increase of serum creatinine. Serum uric acid increased in both groups. BP values decreased, and HR was corrected to normal values in both groups. Group 2 showed a longer hospitalization time than group receiving HHS infusion (11.67+/-1.8 vs. 8.57+/-2.3 days, P<0.001). In the follow-up (6-12 months), none of the patients from group 1 were readmitted to the hospital and they maintained the NYHA class achieved at the discharge. Group 2 showed 12 patients readmitted to hospital and a higher class than at discharge. CONCLUSION: Our data suggest that the combination of furosemide with HSS is feasible and it appears that this combination produces an improvement of hemodynamic and clinical parameters, reduces the hospitalization time and maintains the obtained results over time in comparison with those receiving high-dose furosemide as bolus.

Aged↗

PubMed2000

Effect of long-term losartan administration on renal haemodynamics and function in hypertensive patients.

In this study the efficacy and safety of long-term losartan administration on renal haemodynamics were evaluated in mild to moderate hypertension. After a run-in period with placebo, 18 hypertensives without renal or cardiovascular disease were allocated to losartan (50 mg/die for one year) treatment. Renal haemodynamic measurements included renal plasma flow (ERPF) and glomerular filtration rate (GFR) by standardized radioisotope study. Effective renal blood flow (ERBF), filtration fraction (FF), and renal vascular resistance (RVR) were also calculated. Blood pressure was evaluated monthly, whereas renal haemodynamics and function were detected at baseline and after 6 and 12 months of losartan administration. Losartan induced a significant (p < 0.001) decrease in SBP, DBP, and MBP versus baseline values both at 6 months and at 12 months. In addition a significant decrease in RVR (p < 0.001) and in FF (p < 0.05) was also seen. In addition RVR values at 1 year of treatment were higher than their values at 6 months, but this difference was not significant. Our data indicated that long-term control in blood pressure induced by losartan administration was associated with a maintained renal function after 6 months of treatment, but these favourable effects were attenuated after 1 year of treatment.

Antihypertensive Agents↗