Absence of an independent association between serum uric acid and left ventricular mass in Caucasian hypertensive women and men.

BACKGROUND AND AIM: Experimentally uric acid may induce cardiomyocyte growth and interstitial fibrosis of the heart. However, clinical studies exploring the relationship between serum uric acid (SUA) and left ventricular (LV) mass yielded conflicting results. The aim of our study was to evaluate the relationships between SUA and LV mass in a large group of Caucasian essential hypertensive subjects. METHODS AND RESULTS: We enrolled 534 hypertensive patients free of cardiovascular complications and without severe renal insufficiency. In all subjects routine blood chemistry, including SUA determination, echocardiographic examination and 24 h ambulatory blood pressure (BP) monitoring were obtained. In the overall population we observed no significant correlation of SUA with LV mass indexed for height(2.7) (LVMH(2.7)) (r = 0.074). When the same relationship was analysed separately in men and women, we found a statistically significant correlation in female gender (r = 0.27; p < 0.001), but not in males (r = -0.042; p = NS). When we grouped the study population in sex-specific tertiles of SUA, an increase in LVMH(2.7) was observed in the highest tertiles in women (44.5 ± 15.6 vs 47.5 ± 16 vs 55.9 ± 22.2 g/m(2.7); p < 0.001), but not in men. The association between SUA and LVMH(2.7) in women lost statistical significance in multiple regression analyses, after adjustment for age, 24 h systolic BP, body mass index, serum creatinine and other potential confounders. CONCLUSIONS: Our findings do not support an independent association between SUA and LV mass in Caucasian men and women with arterial hypertension.

Favorable clinical heart and bone effects of anti-thyroid drug therapy in endogenous subclinical hyperthyroidism.

Although subclinical hyperthyroidism (SCH) has been associated with increased risk of osteoporosis and cardiac arrhythmias, its treatment is still controversial. This study was designed as a prospective, randomized, intervention, control-study with a 1-year follow-up in order to investigate whether normalization of serum TSH in SCH using methimazole has favorable bone and heart clinical effects. Fourteen patients with endogenous SCH (not Graves' disease) were enrolled, 7 (5 women/2 men; group T) were treated with methimazole (2.5-7.5 mg/day), and 7 (5 women/2 men; group C) were followed without treatment; 10 healthy subjects were also included in the study as controls. Serum free-T3 (FT3), free-T4 (FT4) and TSH, thyroid echography, bone stiffness index (SI), as measured by heel ultrasonometry, and 24-h electrocardiography monitoring were obtained. SCH patients exhibited higher systolic and diastolic blood pressure than control subjects. They also had a significantly higher number of both ventricular premature beats (VPB) (mean+/-SEM: 681+/-238 vs 6+/-2 beats/24 h; p<0.02) and atrial premature beats (APB) (mean+/-SEM: 495+/-331 vs 7+/-2 beats/24 h; p<0.0001), and a lower SI (66+/-5 vs 96+/-3; p<0.001). Twelve months after normalization of TSH with the use of methimazole, the number of VPB decreased significantly (947+/-443 vs 214+/-109 beats/24 h; p<0.05) while it remained unchanged in untreated SCH patients (414+/-163 vs 487+/-152 beats/24 h; p=ns). An insignificant therapy effect was observed as far as APB were concerned (826+/-660 vs 144+/-75 beats/24 h; p=ns), however their number increased significantly in the untreated group (463+/-49 vs 215+/-46 beats/24 h; p<0.05). The SI increased significantly as a result of therapy in group T (64.1+/-4.8 vs 70.0+/-5.3; p<0.02) and was further reduced in group C at the end of the study (69.1+/-7.3 vs 62.9+/-7.1; p<0.001). No adverse effect was observed in group T. In conclusion, anti-thyroid therapy seems to have favor-able bone and heart clinical effects in subjects with endogenous SCH.

Metabolic syndrome in subjects with essential hypertension: relationships with subclinical cardiovascular and renal damage.

It has long been recognized that arterial hypertension is often a part of a larger constellation of anthropometric and metabolic abnormalities that includes abdominal (or visceral) obesity, a characteristic dyslipidemia (low high-density lipoprotein cholesterol and high triglycerides), glucose intolerance, insulin-resistance and hyperuricemia. These traits occur simultaneously to a greater degree than would be expected by chance alone, supporting the existence of a discrete disorder that, over the years, has been defined by a variety of terms, including plurimetabolic syndrome, the deadly quartet, dysmetabolic syndrome, insulin resistance syndrome, cardiometabolic syndrome and more recently metabolic syndrome (MS). In last years some scientific organizations proposed working definitions for MS. Among these definitions, the one suggested by the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP-ATPIII) is the simplest and the most commonly applied. The MS is extremely common worldwide. This high prevalence is of considerable concern because accumulating evidences suggest that the MS, even without type 2 diabetes, carries an increased risk for cardiovascular and renal events. Recently it has been demonstrated that the adverse prognostic impact of MS may also be extended to hypertensive patients. Some recent studies reported an increased prevalence of left ventricular hypertrophy, diastolic dysfunction, early carotid atherosclerosis, impaired aortic distensibility, hypertensive retinopathy and microalbuminuria in hypertensive patients with MS when compared to those without it. The increased occurrence of these early signs of subclinical target organ damage, most of which are recognized as significant independent predictors of adverse cardiovascular and renal outcomes, may partially explain the association of the MS with a higher cardiovascular and renal risk.

The GENIUS web portal--an easy way to access the Grid.

OBJECTIVE: The development of computational Grids is making huge amounts of computing power and data storage available for a lot of scientific applications. At this stage of development, the use of the Grid is mainly based on Command Line Interface (CLI) tools that are not very friendly and can be considered an obstacle to the use of these powerful tools. The objective of this paper is to present a solution to this problem. METHODS: To ease the access of new users to the grid the GENIUS (Grid Enabled web eNvironment for site Independent User job Submission) grid portal has been jointly developed by INFN and NICE within the context of both the Italian INFN Grid and the European DataGrid Projects. Here we devote particular care to the description of job creation and submission and the services for transparent access to user's data and applications. RESULTS: Using GENIUS, the obstacle of complicated CLI can be overtaken and simple web interfaces can be built for specific user communities and applications. Here we show examples in the field of bio-medical applications. CONCLUSIONS: The use of Grid can be made easy with the use of Grid portals such as GENIUS.

Influence of metabolic syndrome on hypertension-related target organ damage.

OBJECTIVES: The aim of our study was to analyse, in a wide group of essential hypertensive patients without diabetes mellitus, the influence of metabolic syndrome (MS) (defined according to the criteria laid down in the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults) on markers of preclinical cardiac, renal and retinal damage. DESIGN: Cross-sectional study. SETTING: Outpatient hypertension clinic. SUBJECTS AND METHODS: A total of 353 young and middle-aged hypertensives, free from cardiovascular and renal diseases (and 37% of whom had MS), underwent echocardiographic examination, microalbuminuria determination and non-mydriatic retinography. RESULTS: When compared with subjects without MS, hypertensive patients with MS exhibited more elevated left ventricular (LV) mass (either normalized by body surface area or by height elevated by a power of 2.7), higher myocardial relative wall thickness, albumin excretion rate (AER) and a greater prevalence of LV hypertrophy (57.7% vs. 25.1%; P < 0.00001), of microalbuminuria (36.2% vs. 19.3%; P = 0.002) and of hypertensive retinopathy (87.7% vs. 48.4%; P < 0.00001). These results held even after correction for age, 24-h blood pressures, duration of hypertension, previous antihypertensive therapy, and gender distribution. The independent relationships between LV mass and MS, and between AER and MS, were confirmed in multivariate regression models including MS together with its individual components. CONCLUSIONS: MS may amplify hypertension-related cardiac and renal changes, over and above the potential contribution of each single component of this syndrome. As these markers of target organ damage are well-known predictors of cardiovascular events, our results may partly explain the enhanced cardiovascular risk associated with MS.

Relationship between albumin excretion rate and aortic stiffness in untreated essential hypertensive patients.

OBJECTIVES: To evaluate, in a group of nondiabetic essential hypertensive patients with normal renal function, the relationship between albumin excretion rate (AER) and carotid-femoral pulse wave velocity (PWV), as an index of aortic stiffness. DESIGN: Cross-sectional study. SETTING: Outpatient hypertension clinic. SUBJECTS: Seventy patients with mild-to-moderate essential hypertension, aged 42 +/- 8 years, never pharmacologically treated. All subjects underwent routine laboratory tests, 24-h ambulatory blood pressure (BP) monitoring, measurement of carotid-femoral PWV, by means of a computerized method, and AER. RESULTS: Microalbuminuric patients (AER > or = 20 microg min(-1); n = 19), when compared with normoalbuminuric subjects, showed more elevated 24-h BP (136/88 +/- 10/10 vs. 128/83 +/- 7/6 mmHg; P < 0.001 and P = 0.013, for systolic and diastolic BP respectively) and higher values of carotid-femoral PWV (10.4 +/- 2 m s(-1) vs. 9.2 +/- 1.3; P = 0.006). This latter difference remained statistically significant, even after correction by ancova for 24-h systolic and diastolic BP, and body mass index (BMI, P = 0.016). Univariate regression analysis disclosed a tight correlation between AER and carotid-femoral PWV (r = 0.42; P = 0.0003). This association was confirmed in a multiple regression model (beta = 0.35; P = 0.009) in which, as independent variables, besides PWV, 24-h BP, age, serum glucose values, smoking status, gender and BMI, were added. CONCLUSIONS: Our results seem to confirm that microalbuminuria may represent the early renal manifestation of a widespread vascular dysfunction, and therefore it is an integrated marker of cardiovascular risk.

Pulsatile and steady 24-h blood pressure components as determinants of left ventricular mass in young and middle-aged essential hypertensives.

In order to explore the relations between left ventricular mass (LVM) and the pulsatile (pulse pressure) and steady (mean pressure) components of the blood pressure (BP) curve, 304 young and middle-aged essential hypertensive patients were studied by means of 24-h ambulatory BP monitoring and echocardiography. In the overall study population, both the BP components showed significant correlations with LVM. These correlations were unevenly distributed in the subgroups of subjects younger and in those older than 50 years. While in this latter subgroup, in multivariate analysis, both 24-h mean BP (24-MBP) (beta = 0.27; P = 0.008) and 24-h pulse pressure (24-h PP) (beta = 0.23; P = 0.02) were associated with LVM, in the subset of younger hypertensives only 24-h MBP (beta = 0.21; P = 0.009) was related to LVM, independent of other covariates. The relations observed between 24-h PP and LVM in the entire study population and in the patients older than 50 years lost statistical significance when the effect of 24-h systolic blood pressure (24-h SBP) was taken into account, in a multiple regression model in which 24-h MBP was replaced by 24-h SBP. Our findings seem to suggest that the association of PP with LVM in middle-aged hypertensives may partially explain the increased cardiovascular risk, documented in subjects with high PP. However, this relation is not independent, but is mediated by SBP.

[25 years old woman with nocturia]. / Donna di 25 anni con nicturia.

A 25 years old lady presented to our outpatient clinic complaining nicturia, polyuria and polydipsia. On the basis of clinical assessment and the results of a simple test, a diagnosis of Nephrogenic Diabetes Insipidus (NDI) was made. The diagnosis of NDI is often missed, and appropriate treatment therefore delayed, with severe consequences especially in elderly and bed restricted people.

Relationships between 24 h blood pressure load and target organ damage in patients with mild-to-moderate essential hypertension.

OBJECTIVE: To analyse the relationships between 24 h blood pressure load (the percentage of systolic/diastolic blood pressures exceeding 140/90 mmHg while awake and 120/80 mmHg during sleep) and some indices of hypertensive target organ involvement, independently of the mean level of 24 h blood pressure. METHODS: One hundred and thirty patients with mild-to-moderate hypertension underwent 24 h ambulatory blood pressure monitoring, ocular fundus examination, microalbuminuria assay and two-dimensional guided M-mode echocardiography. The study population was divided into subsets according to the systolic and diastolic 24 h blood pressure load values predicted from the regression equation relating 24 h blood pressure load to 24 h mean blood pressure. The subjects with an observed load above this predicted value were included in the higher blood pressure load groups, the remaining ones being included in the lower groups. RESULTS: Relative myocardial wall thickness and total peripheral resistance were greater, and mid-wall fractional shortening, end-systolic stress-corrected mid-wall fractional shortening and cardiac index lower, in the subjects with a higher systolic blood pressure load. Moreover, the stroke index:pulse pressure ratio was reduced, and a greater prevalence of hypertensive retinopathy was observed in the higher systolic load group. On the contrary, no statistically significant difference was found for any of the cardiac, renal and funduscopic parameters examined when the two groups with a higher and lower 24 h diastolic blood pressure load were compared. CONCLUSIONS: Our results seem to suggest that, in mild-to-moderate arterial hypertension, a high 24 h systolic blood pressure load may be associated, independently of the average level of 24 h systolic ambulatory blood pressure, with an adverse cardiovascular risk profile.

Insulin, renin-aldosterone system and blood pressure in obese people.

OBJECTIVE: To evaluate the relationship between insulin, the renin-aldosterone system and blood pressure in obese subjects. DESIGN AND METHODS: A cross sectional study of a group of severely obese normotensive subjects who were surgical candidates (n=39; mean BMI: 47.8+/-1.4) and a group of hypertensive patients (n=57; mean BMI: 28.0+/-0.7) twenty-nine of whom had BMI>27. All subjects were studied after 15 days on a balanced diet. Insulin, plasma renin activity and aldosterone were measured. RESULTS: Fasting insulin, plasma renin activity and aldosterone were higher in severely obese normotensive subjects than in hypertensive subjects (respectively 32.3+/-3.0 vs 13.1+/-1.0 mU/l, P=0.0001; 1.34+/-0.22 vs 0.88+/-0.12 ng/ml/h, P=0.04; 137.2+/-16.2 vs 87.9+/-12.1 pg/ml, P=0.015). Insulin was related to BMI and to aldosterone both in normotensive and in hypertensive patients. CONCLUSION: Hyperinsulinemia itself does not determine hypertension; in some people it could play a vasodilator role in opposition to the renin-aldosterone system.

Sympathetic activity and blood pressure pattern in autosomal dominant polycystic kidney disease hypertensives.

To study the potential role of sympathetic activity in the pathogenesis of arterial hypertension associated with autosomal dominant polycystic kidney disease (ADPKD) and to analyze its relationship with 24-hour blood pressure pattern, plasma catecholamines and 24-hour ambulatory blood pressure monitoring were evaluated in 30 ADPKD hypertensive patients (of which 17 without and 13 with renal failure) and in 50 essential hypertensives. The groups were matched for sex, body mass index, known duration of hypertension, and clinic blood pressure. Plasma catecholamines, determined in resting position, were higher in ADPKD patients without renal failure than in essential hypertensives. Nighttime diastolic blood pressure was higher and the percentage day-night difference in mean blood pressure was lower in hypertensives with ADPKD compared to patients with essential hypertension. Blood pressure was significantly correlated with plasma noradrenaline in ADPKD patients, independently of renal function. No significant differences were observed between ADPKD patients with and without renal failure, with respect to plasma catecholamines, 24-hour daytime and nighttime ambulatory blood pressures and the percentage day-night difference in mean blood pressure.

Insulin, sodium-lithium countertransport, and microalbuminuria in hypertensive patients.

Both microalbuminuria (>0.290 nmol/min [20 microg/min]) and high sodium-lithium countertransport (SLC) in diabetic or hypertensive humans are predictive of overt nephropathy and more aggressive cardiovascular complications, perhaps induced by insulin resistance. To analyze the relationships between microalbuminuria, SLC, microalbuminuria, and insulin in essential hypertension, we studied 90 hypertensive white patients, 25 of whom had microalbuminuria and 32 of whom were healthy. When urine sampling was completed for albuminuria determination, SLC was measured; all patients then underwent standard (75 g) oral glucose load to measure basal (0 minutes) and 2-hour glucose and insulin serum levels. Glucose-insulin ratio was used as insulin sensitivity index (ISI). In both hypertensive patients with normal microalbuminuria and those with pathological microalbuminuria, plasma insulin at 120 minutes was significantly higher than in control subjects. When the patients with pathological microalbuminuria were divided into thirds on the basis of their microalbuminuria, in the lower third, we found statistically significant less fasting insulin and higher basal ISI. SLC was higher in hypertensives than normotensives and, among hypertensives, higher in the subgroup with elevated microalbuminuria. In hypertensives, we found a weak but significant correlation between SLC and microalbuminuria, independent of insulin or ISI. The prevalence of high value of SLC (> or =0.383 mmol x L-1 x h-1) was significantly lower in hypertensives with normal rather than abnormal urinary albumin excretion. Our results indicate that in nondiabetic hypertensive whites, higher microalbuminuria is accompanied by signs of insulin resistance; moreover, a link exists between SLC and microalbuminuria, both predictive of aggressive complications of hypertension.

In vivo relationship between insulin and endothelin role of insulin-resistance.

Since endothelin production is stimulated in vitro by insulin, we performed this study to evaluate in vivo the relationships between endothelin and insulin plasma levels during a glucose load. We studied 28 subjects; 17 with normal glucose tolerance (NGT) and 11 with impaired glucose tolerance (IGT). Ten of the subjects in this study were normotensive and 18 with mild to moderate hypertension. Age, sex and body mass index were comparable among the groups. After a 2-week period of washout they underwent an oral glucose tolerance test; blood was drawn at 0 (basal), 90 and 120 min after the load for determination of glucose, insulin, C-peptide of insulin and endothelin-1 and -2. Basal endothelin in all the subjects under study was correlated with basal insulin; moreover it was negatively related with the glucose:insulin ratio that has been considered as an insulin-sensitivity index and positively with the insulin:C-peptide ratio as hepatic insulin-resistance index. The relationship between basal endothelin and insulin values was also found in each glucose tolerance group. At 120 min after the glucose load, mean plasma values of endothelin were significantly higher (6.66 +/- 1.31 vs 4.17 +/- 0.61 pmol/L); moreover, the per cent increase of endothelin at 120 min was positively related to the per cent increase of insulin. Between the normotensive and hypertensive groups there were no significant differences in studied endothelin parameters. Our results appear to confirm that, even in vivo, insulin modulates circulating endothelin levels.

Microalbuminuria, renal dysfunction and cardiovascular complication in essential hypertension.

OBJECTIVE: To evaluate the prevalence of microalbuminuria (albumin excretion rate, AER) in a wide hypertensive population, and to evaluate any relationship with cardiovascular damage and renal dysfunction. DESIGN: A transversal study. SUBJECTS AND METHODS: In 383 hospitalized Caucasian essential hypertensives (198 men, 185 women) of mean age 44 +/- 0.5 years and mean clinic blood pressure 170.3 +/- 0.95/ 103.4 +/- 0.47 mmHg, metabolic parameters, serum creatinine level (Cs), creatinine clearance rate (Ccs), 24 AER and plasma renin activity (PRA) were measured. Furthermore, each patient underwent 24 h ambulatory blood pressure monitoring (ABPM) and echocardiography to measure left ventricular mass, which was indexed both by body surface area to obtain left ventricular mass index (LVMI) and by height to obtain the left ventricular mass indexed for height (LVMH). By Doppler echocardiography, the diastolic compliance by early:late peak filling velocity ratio was analysed. The fundus oculi was also observed. Three subsets of hypertensives were obtained by dividing the 383 essential hypertensives on the basis of their AER: < or = 11 (group A), 11 < or = 20 (group B) and > 20 micrograms/min (group C). MAIN OUTCOME MEASURES: Microalbuminuria, creatinine clearance, PRA, ABPM, LVMI, LVMH, early:late peak filling velocity ratio, hypertensive retinopathy. RESULTS: Among the 383 essential hypertensives, AER was < 11 micrograms/min in 55% of the patients (group A), 18% had AER in the range 11-20 micrograms/min (group B) and 27% had AER > 20 micrograms/min (group C). In the entire essential hypertensive population the prevalence of left ventricular hypertrophy was 44.39% and hypertensive retinopathy was observed in 54.83%. Moreover, AER significantly correlated with clinic systolic blood pressure (SBP) and diastolic blood pressure (DBP), with 24 SBP and DBP and with 24 h daytime and night-time mean blood pressure (MBP). AER was correlated also with LVMH and creatinine clearance. The analysis of the three subsets revealed no differences in age, body mass index, serum creatinine level and PRA. Group C in comparison with group A showed higher values of clinic SBP, 24 h SBP, DBP and MBP, and of daytime and night-time MBP. Furthermore, in group C, LVMI and LVMH were significantly greater than in group A, with a prevalence of left ventricular hypertrophy of 55% in the former group. Group C showed a prevalence of hypertensive retinopathy of 69% whereas in group A the prevalence was 48%. In group C, AER was significantly correlated with serum creatinine level. CONCLUSIONS: The transversal phase of our research, performed in a homogeneous population of Caucasian essential hypertensives with no metabolic disturbances, confirms the relationship between blood pressure pattern and early glomerular changes in essential hypertensives without overt proteinuria. Furthermore, these results emphasize the role of microalbuminuria as a marker of early cardiac, renal and retinal structural and functional changes in essential hypertension. The longitudinal study, which is in progress, will confirm the prognostic value of microalbuminuria in essential hypertension.

Insulin-like growth factor 1 and pressure load in hypertensive patients.

To verify the effect of a pressure load on the production of Insulin-like Growth Factor 1 (IGF1) in essential hypertensives, we studied 15 patients and 8 normotensive controls before and during orthostatism. Upright standing was characterized both in normals and in hypertensives by significant higher rate-pressure product [RPP = systolic blood pressure (mm Hg) x heart rate (beats/min)]. Proportional increases of RPP were significantly related to IGF1 values at the end of orthostatism and to proportional increases of IGF1 in hypertensive group but not in normotensive one. Our results confirm that IGF1 plasma levels in hypertensive patients are related to pressure load.