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Objective: The association of short-term blood pressure (BP) variability (BPV) with cardiovascular events (CVEs) is controversial. Aim of this study was to investigate whether BPV measured as weighted 24-h SD was associated with CVE in a prospective cohort study of young patients screened for stage 1 hypertension., Methods: We performed 24-h ambulatory BP monitoring in 1206 participants aged 33.1 ± 8.5 years, untreated at baseline examination. Participants were divided into two categories with low (<12.8 mmHg) or high (≥12.8 mmHg) SBPV. Hazard ratios for CVE associated with BPV expressed either as continuous or categorical variable were computed from multivariable Cox models., Results: During 15.4 ± 7.4 years of follow-up there were 69 fatal and nonfatal CVE. In multivariable Cox models, high SBPV was an independent predictors of CVE [2.75 (1.65-4.58); P = 0.0001] and of coronary events [3.84 (2.01-7.35), P < 0.0001]. Inclusion in the model of development of hypertension requiring treatment during the follow-up, did not reduce the strength of the associations. Addition of SBPV to fully adjusted models had significant impact on risk reclassification and integrated discrimination (relative integrated discrimination improvement for BPV as continuous variable: 13.5%, P = 0.045, and for BPV as categorical variable: 26.6%, P = 0.001). When the coefficient of variation was used as BPV metric similar results were obtained. Of note, in all Cox models average 24-h BP was no longer an independent predictor of outcome after BPV was included., Conclusion: Short-term BPV adds to the risk stratification for cardiovascular events in young-to-middle-age patients screened for stage 1 hypertension over and above traditional 24-h ambulatory monitoring indexes.

Background: Glomerular hyperfiltration predicts development of nephropathy in hypertension but the factors responsible for increased glomerular filtration rate (GFR) are not well known. Aim of this study was to examine which clinical variables influence GFR in the early stage of hypertension., Methods: Participants were 1,106 young-to-middle-age hypertensive adults with creatinine clearance >60 ml/min/1.73 m(2). Clinic and ambulatory blood pressures (BPs) were measured and the difference between clinic and 24-h systolic BP was defined as the white-coat effect (WCE). In 606 participants, 24-h urinary epinephrine and norepinephrine were also measured. Glomerular hyperfiltration, defined as a GFR ≥150 ml/min/1.73 m(2), was present in 201 subjects., Results: Patients' mean age was 33.1 ± 8.5 years and office BP was 146 ± 10.5/94 ± 5.0 mm Hg. In multivariable linear regression, significant predictors of GFR were younger age (P < 0.0001), male gender (P < 0.0001), 24-h systolic BP (P = 0.0001), body mass (P < 0.0001), WCE (P = 0.02), log-epinephrine (P = 0.01), and coffee use (P < 0.01). In a logistic model, independent predictors of glomerular hyperfiltration were obesity (odds ratio, 95% confidence interval = 6.1, 3.8-9.8), male gender (2.9, 1.8-4.9), age <33 years (2.1, 1.5-3.1), ambulatory hypertension (2.0, 1.4-3.0), WCE >15 mm Hg (1.6, 1.1-2.3), heavy coffee use (2.0, 1.1-3.8), and epinephrine >25 mcg/24 h (1.9, 1.2-3.1)., Conclusions: The novel finding of this study is that hyper-reactivity to stress, as determined by urinary epinephrine level and WCE, and coffee use contribute to determining glomerular hyperfiltration in the early stage of hypertension. Our data may help to identify a subset of patients with glomerular hyperfiltration, who may be at increased risk of chronic kidney disease and may benefit from antihypertensive treatment.

Background/aims: Predictors of microalbuminuria in the early stage of hypertension are not well known. We did a prospective study to investigate whether glomerular hyperfiltration assessed from serum cystatin C predicts development of microalbuminuria in hypertension., Methods: We assessed 101 treatment-naive subjects screened for stage 1 hypertension and followed-up for a median 3.1 years. Cystatin C was measured at entry and glomerular filtration rate was estimated using the Hoek formula (CystGFR). Urinary albumin and ambulatory blood pressure were measured at entry and during the follow-up., Results: Subjects in the top CystGFR tertile (>115 ml/min/1.73 m(2)) were leaner (p = 0.002) and developed microalbuminuria more frequently (p = 0.02) than the rest of the group. In univariate Cox regression, CystGFR was associated with future microalbuminuria (hazard ratio, 1.06, 95% confidence interval (CI), 1.02-1.10, p = 0.001). After controlling for baseline albumin excretion rate and several confounders, CystGFR remained a significant predictor of microalbuminuria development (hazard ratio, 1.19, 95% CI, 1.03-1.37, p = 0.019). The association between future microalbuminuria and creatinine clearance or glomerular filtration rate estimated with the Cockroft-Gault or the Modification of Diet in Renal Disease formula did not attain the level of statistical significance in this sample., Conclusions: The present findings indicate that CystGFR is more sensitive than creatinine clearance or estimated glomerular filtration rate for predicting microalbuminuria development in the early stage of hypertension and confirm that hyperfiltration precedes microalbuminuria in this clinical entity., ((c) 2009 S. Karger AG, Basel.)

Objective: Microalbuminuria (MA) is a marker of adverse outcome in hypertension. The aim of this study was to investigate the association of MA with cardiovascular risk factors and glomerular hyperfiltration in the early stage of hypertension and to assess its predictive value for the development of sustained hypertension requiring antihypertensive treatment., Design and Participants: We studied 1041 young stage 1 hypertensive subjects. Study variables were 24-h ambulatory blood pressure and heart rate, anthropometric measures, metabolic variables, creatinine clearance and lifestyle factors analyzed as a function of ascending urinary albumin measured from 24-h collections. Subjects were followed until they developed sustained hypertension and were eligible for antihypertensive medication according to current guidelines., Setting: Seventeen outpatient clinics in Italy., Results: Eighty-five percent of the subjects were normoalbuminuric, 9% had borderline MA, and 6% had overt MA. No between-group differences were found for age, body mass index, heart rate, lifestyle factors and biochemistry in both genders. Creatinine clearance was greater in the subjects with overt MA and borderline MA than in the normoalbuminuric subjects (P = 0.003 and 0.011, respectively). In a two-way ANCOVA, microalbuminuric subjects both with hyperfiltration (P < 0.001) and with normal filtration (P = 0.04) had higher 24-h systolic blood pressure than subjects with normoalbuminuria and normal filtration. In a Cox analysis, neither MA nor hyperfiltration were significant predictors of development of sustained hypertension., Conclusion: MA is not associated with an adverse metabolic risk profile in the early stage of hypertension. MA is associated with greater hemodynamic load and with glomerular hyperfiltration in this clinical setting, but does not help in predicting those subjects destined to develop sustained hypertension requiring antihypertensive therapy.

Background: The aim of the study was to assess the effect of physical activity on 24-hr ambulatory blood pressure (ABPM) and office blood pressure (BP) in 572 male subjects with borderline to mild hypertension from the HARVEST study., Methods: Subjects were 18 to 45 years old with diastolic BP of 90-99 mmHg and/or systolic BP of 140-159 mmHg. They never took any anti-hypertensive therapy. All subjects underwent physical examination, office BP measurement and two 24-hr ambulatory BP monitorings performed three months apart. Subjects were classified as non exercisers, group 1 (n=331), mild exercisers, group 2 (n=192) and heavy exercisers, group 3 (n=49). During the three months of follow-up subjects maintained the same physical activity habits. There was no difference in smoking and alcohol consumption between the 3 groups. As the groups differed significantly in age and body mass index data were adjusted for these confounders., Results: At baseline office and ambulatory systolic BP were similar in the 3 groups, while diastolic BP was proportional to the level of physical activity although the difference was significant only between the group of non-exercisers and mild exercisers. Heart rate (HR) was always inversely related to the intensity of exercise. After three months follow-up office systolic BP was similar among the three groups and diastolic BP slightly decreased in the exercisers (group 1 vs group 3 p=0.02, group 2 vs group 3 p=0.04). At ABPM the group of heavy exercisers showed a significant decrease in daytime systolic BP (135.4plus minus0.6 vs 134plus minus0.8 vs 132.2plus minus1.6 mmHg; group 1 vs group 3 p<0.05) and the difference between systolic ambulatory BP at the 3rd month and at baseline, showed an additional significant decrease according to exercise intensity (24-hr systolic BP group 1 vs group 3 p=0.001, group 2 vs group 3 p=0.004; daytime systolic BP group 1 vs group 3 p=0.0009, group 2 vs group 3 p=0.004; night-time systolic BP group 1 vs group 3 p=0.02, group 2 vs group 3 p=0.02). No changes in ambulatory diastolic BP were observed., Conclusions: In conclusion, physical activity has a positive effect in lowering BP attenuating the risk of hypertension in young subjects with borderline hypertension. The anti-hypertensive effect of physical activity persisted after three months and the group of exercisers had an additional reduction in systolic BP detected by ABPM. To obtain accurate information on chronic levels of arterial pressure over time 24-hr ambulatory BP should be preferred to traditional casual readings.

This study was undertaken to assess the reproducibility of office versus ambulatory heart rates in 839 hypertensive subjects participating in the Hypertension and Ambulatory Recording Venetia Study (HARVEST). A 24-hour heart rate was recorded twice; this procedure was repeated three months later. Reproducibility was better for ambulatory than for office measurement, and was greater for 24-hour than for daytime heart rate, and lowest for night-time heart rate. Reproducibility of office heart rate was impaired above 85 bpm, and was poorer in subjects with more severe office hypertension. A small but significant decrease in average daytime (-1 bpm, P < 0.0001) and virtually no change in night-time heart rate (-0.3 bpm, NS) were observed at repeat recording. Heart rate reproducibility indices were related to the extent of the heart rate and blood pressure white-coat effect, but did not vary according to age, gender, body mass index, day-night blood pressure difference, or alcohol or tobacco use. Results indicate that heart rate recorded over the 24 hours has a better reproducibility than office heart rate, and could thus be a better prognostic indicator than traditional measurement of resting heart rate in the hospital setting.

It has been claimed that diastolic dysfunction is the earliest cardiac abnormality in hypertension, preceding the development of left ventricular (LV) structural abnormalities. To detect early signs of hypertensive cardiac involvement 722 subjects (533 men and 189 women), 18-45 years old, with stage I hypertension, were studied by M-mode and Doppler echocardiography. Blood pressure was measured by 24-h ambulatory monitoring. Ninety-five normotensive individuals of similar age and gender distributions were studied as controls. Significant, though modest, changes of LV mass and geometry were found in the participants in comparison with the normotensive controls. The increment was +10.4 g/m2 for LV mass index, +1.8 mm for LV wall thickness, and +0.032 for relative wall thickness. A slight increase in atrial filling peak velocity was found in the hypertensive subjects at Doppler analysis of transmitral flow, but the ratio of early to atrial velocity of LV diastolic filling did not differ between the two groups. In multiple regression analyses, which included age, body mass index, heart rate, smoking, and physical activity, 24-h mean blood pressure emerged as a significant predictor of LV mass index (men, P = .003; women, P = .04) and wall thickness (men, P = .03; women, P = .004) in the hypertensive subjects, whereas no index of diastolic filling was significantly associated with ambulatory blood pressure in either gender. The present data indicate that changes in LV anatomy are the earliest signs of hypertensive cardiac involvement. Left ventricular filling is affected only marginally in the initial phase of hypertension.

RESEARCH OBJECT: This study intends to consider an encephalocele experimental model, obtained in embryonate eggs, treated in a post-neurulation phase with chemical teratogens. This study intends to point out possibility that pathogenic process, which have determined a malformation, is referable to an original defect of embryonic cranial coatings development and that neurulation defect is secondary., Experimental Plan: Chick and duck embryonate eggs have been used. They have been inoculated in their development phase with known chemical teratogens, as Dintoina and Blue Trypan. A controlling group has been inoculated with physiological solution and, then, it has been followed till the hatching. The experimental group has been undergone to artificial hatching, according to prearranged conditions and it has been analysed during different phases of its development., Measures: Four cranioencephalic malformations have been obtained: three cases of encephalocele and one case of exencephalia. The individual pathological compounds have been studied under the morphological and histopathological profile. The skull base dimensions have been taken and then compared with the controlling group ones., Conclusions: In the light of experimental data, some considerations have been undertaken considering the pathogenetic hypothesis findable in medical literature, stressing the possibility that encephalocele may be arranged as a post-neurulation defect and that, for taxonomic aims, it has to fit in a different group within cranial disraphims.

According to recent international guidelines the decision on whether to treat young subjects during the early phase of hypertension should be based not only on their office blood pressure but also on their ambulatory blood pressure and whether target organ damage has occurred. Few data on the prevalence of hypertensive complications in young subjects with mild hypertension are available. In the Hypertension and Ambulatory Recording Venetia Study (HARVEST), a multicenter trial conducted in northeast Italy, the percentage of young borderline-to-mild hypertensive subjects with echocardiographic left ventricular hypertrophy was 4.5% and the percentage with concentric remodeling was 4%. Clear differences in cardiac size and geometric adjustment to ambulatory systolic pressure between the two sexes were found. The impact of blood pressure on the walls of the left ventricle and on the left ventricular mass was remarkable in women but weak in men. The assessment of left ventricular systolic function confirmed that many young mild hypertensive subjects have an increased ejective performance. The left ventricular contractility evaluated by midwall measurement was, however, found to be depressed in 9.2% of the HARVEST participants. Their left ventricular diastolic function was similar to that of 50 normotensive controls. The prevalence of microalbuminuria [albumin excretion rate (AER) > 30 mg/24 h) was 6.1%, only slightly higher than that found by other authors among normotensive subjects and much lower than that observed among patients with more severe hypertension. For our stage I hypertensives, however, the AER was correlated to the 24 h blood pressure with high statistical significance, whereas we found no relationship between the AER and left ventricular mass index either for all of the subjects taken together or for the men and women considered separately. The results suggest that renal and cardiac involvement do not occur in parallel during the initial phase of hypertension.

This study report clinical experience of Clozapine treatment in 48 chronic schizophrenic patients. At the study time, 35 patients are still under this treatment while 13 patients have stopped it. These two populations and their differences are presented. Clozapine experience is positive as testifies quality of life and social situation improvement in numerous cases.

Unlabelled: To study the relationship between plasma renin activity (PRA) and coffee consumption, cigarette smoking, alcohol intake and physical activity habits., Setting: The multicentre HARVEST trial, involving 17 Hospital Centres in Northeast Italy., Subjects: 351 borderline to mild hypertensive men (mean age +/- SEM 22.7 +/- 0.47 years), never treated for hypertension., Interventions: Office and 24-hour blood pressure measurement, supine and standing PRA levels, and urinary catecholamines output., Main Outcome Measures: PRA levels according to coffee intake and physical activity status., Results: Coffee intake showed a major effect on PRA. Supine PRA levels were 40% higher in the subjects abstaining from coffee (n = 94) than in the coffee drinkers and was similar in the moderate (n = 223) and heavy (n = 34) drinkers. A weaker negative association was found between coffee use and PRA on standing. Office and whole-day blood pressure and heart rate, and urinary catecholamines did not differ according to coffee intake. Supine PRA was lower in the subjects performing regular physical activity than in the inactive subjects. Office and whole-day diastolic blood pressure and heart rate, and urinary norepinephrine were lower in the active than in the sedentary men. No relationship was found between PRA measured either in the supine or the upright posture and tobacco or alcohol use. In a multiple linear regression model supine PRA was negatively correlated with age, coffee consumption and physical activity habits., Conclusions: Chronic coffee intake and physical training showed an inverse relationship with PRA in mild hypertensive men, while tobacco and alcohol use were unrelated to PRA.

Objective: To study the relationship of urinary albumin excretion to ambulatory blood pressure and other cardiovascular risk factors in borderline to mild hypertension., Patients and Methods: We studied 779 patients with borderline to mild hypertension (mean +/- SEM age 33 +/- 0.3 years; mean +/- SEM office blood pressure 146 +/- 0.4/94 +/- 0.2 mmHg) at 17 hypertension clinics in northeast Italy. Office and 24-h blood pressures were recorded with simultaneous urine collection for albumin measurement. In 510 subjects, left ventricular mass was measured by echocardiography., Results: Subjects with overt (> or = 30 mg/24 h) and borderline (16-29 mg/24 h) microalbuminuria had similar 24-h blood pressure levels, higher than those in the subjects without microalbuminuria. In the univariate and multiple regression analyses the albumin excretion rate was closely correlated with 24-h systolic blood pressure and not related to age, body mass index, metabolic parameters, lifestyle factor and degree of left ventricular hypertrophy., Conclusions: Borderline values of urinary albumin excretion (16-29 mg/24 h) may be clinically relevant in subjects with borderline to mild hypertension. Renal and cardiac damage do not develop in parallel in the initial phases of hypertension.

Background: In 1987, ten years after the first observation, we performed the follow-up of the subjects included in the "Pordenone Study on the precursors of atherosclerosis in childhood"., Methods: The anthropometric, biologic and anamnestic indicators of coronary risk were evaluated. The W.H.O. protocol was always used. 439 (90%) subjects underwent reexamination, (234 males and 205 females between 18 and 26 years). HDL cholesterol, tricipital and subscapular skinfold thickness, weight and height were evaluated. The aim of our study was to find possible correlations between obesity indexes and HDL cholesterol values., Results: We found that HDL cholesterol levels are lower in males compared to females and that differences exist below and over the 80 degrees percentile of BMI. Obese subjects have lower HDL cholesterol levels in both sexes. Females with android obesity (subjects with subscapular skinfold thickness values over 80 degrees percentile) had low HDL cholesterol values., Conclusions: Because of this inverse correlation between HDL cholesterol and coronary risk, and because young obese generally have low HDL cholesterol levels, we believe that the study of coronary risk factors is also useful starting from this age in overweight subjects. This will be useful for preventive purposes. Particular attention must be given to young girls with android obesity.

We have studied smoking habit in the sample enrolled in the ten year follow-up of the "Pordenone Study on the Precursors of Atherosclerosis in Childhood". The response rate at ten year follow-up was very high (about 90%). Prevalence of smoking is 45.1% among males and 25.6% among females. Males and females aged 23 present a prevalence of smokers higher than the other groups while the group aged 26 smoke less. Males began to smoke at 16.4 years, females at 16.7. Mean daily consumption is 12.6 cigarettes among males, and 5.0 among females. Juvenile experimentation with cigarettes and juvenile smoking habit are strong predictors to smoke ten years later; while parental smoking behaviour is not so influential. Therefore we conclude that smoking habit acquired in youngs has a high probability to be maintained in adults, remarking the importance of planning a preventive intervention as early as possible.