Phosducin rs12402521 polymorphism predicts development of hypertension in young subjects with overweight or obesity.

BACKGROUND AND AIMS: The G-protein regulator phosducin has been shown to be associated with stress-dependent blood pressure, but whether obesity is a modulator of the relationship between phosducin and risk of hypertension is unknown. We studied the effect of two phosducin polymorphisms on risk of hypertension in 273 overweight or obese (Ov-Ob) young-to-middle-age participants from the HARVEST and 287 normal weight (NW) participants. METHODS AND RESULTS: Genotyping of phosducin SNPs rs12402521 and rs6672836 was performed by real time PCR. For rs12402521, 64.6% of the participants were homozygous for the G allele, 27.9% heterozygous, and 7.5% homozygous for the A allele. During 7.7 years of follow-up, 339 subjects developed hypertension. In a Cox multivariable model, carriers of the A allele had a 1.28 (95% CI,1.00-1.63, p = 0.046) increased risk of hypertension. However, increased incidence of hypertension associated with A allele (AA + AG, 79% and GG, 59%, p = 0.001) was observed only among Ov-Ob individuals with a hazard ratio of 1.60 (95% CI, 1.13-2.21, p = 0.007) whereas in NW subjects the incidence of hypertension did not differ by genotype (56% in both groups). In the whole cohort, there was a significant interaction of phosducin genotype with body mass index on the risk of hypertension (p = 0.012). For SNP rs6672836 no association was found with incident hypertension. No haplotype effect was detected on the risk of hypertension. CONCLUSION: These data suggest that phosducin rs12402521 polymorphism is an important genetic predictor of obesity-related hypertension. In Ov-Ob carriers of the A allele aggressive nonpharmacological measures should be implemented.

Effects of physical exercise on clinic and 24-hour ambulatory blood pressure in young subjects with mild hypertension.

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.

Reproducibility of heart rate measured in the clinic and with 24-hour intermittent recorders.

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.

Structural abnormalities and not diastolic dysfunction are the earliest left ventricular changes in hypertension. HARVEST Study Group.

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.

Target-organ damage in stage I hypertensive subjects with white coat and sustained hypertension: results from the HARVEST study.

Controversy remains on whether white coat hypertension is a benign clinical condition or carries an increased risk of target-organ damage. Nine hundred forty-two stage I hypertensive subjects enrolled in the HARVEST trial underwent 24-hour ambulatory blood pressure monitoring and urine collection for albumin measurement. Reliable echocardiographic data were obtained in 722 subjects. White coat hypertensive subjects were defined on the basis of three different partition values: mean daytime blood pressure <130/90 mm Hg, <135/85 mm Hg, or <140/90 mm Hg. Ninety-five normotensive subjects with similar age and sex distribution were studied as controls. With all threshold levels, left ventricular mass index and wall thicknesses were greater in the sustained hypertensive subjects than in the white coat hypertensive subjects, also when these differences were adjusted for blood pressure readings taken in the office. Relative wall thickness was similar in the two hypertensive groups. All echocardiographic dimensional data were greater in the white coat hypertensive subjects than in the normotensive subjects. Urinary albumin and the prevalence of microalbuminuria were also greater in the sustained hypertensive subjects than in the white coat hypertensive subjects. No significant differences in urinary albumin were found between the white coat hypertensive and the normotensive subjects. These results show that within a population of subjects with stage I hypertension, subjects with white coat hypertension have a smaller degree of hypertensive complications than those with sustained hypertension, irrespective of their blood pressure levels taken in the office. However, in comparison with normotensive subjects, white coat hypertensive subjects seem to be at greater risk. Cardiac involvement seems to precede glomerular damage in the early stage of hypertension.

Target organ damage and ambulatory blood pressure in stage I hypertension. The Hypertension and Ambulatory Recording Venetia Study.

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.

Encephalocele: experimental model. Morphogenesis, pathogenesis and clinical correlations discussion.

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.

[4 years using clozapine in community psychiatry]. / Quatre ans d'utilisation de la clozapine en psychiatrie de secteur.

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.

Relationship of plasma renin activity with caffeine intake and physical training in mild hypertensive men. HARVEST Study Group.

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.

Relationship between albumin excretion rate, ambulatory blood pressure and left ventricular hypertrophy in mild hypertension.

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.

Factors affecting ambulatory blood pressure reproducibility. Results of the HARVEST Trial. Hypertension and Ambulatory Recording Venetia Study.

To assess the reproducibility of ambulatory blood pressure, we recorded 24-hour blood pressure twice 3 months apart in 508 hypertensive subjects participating in the HARVEST trial using a noninvasive technique. Blood pressure was measured every 10 minutes during the daytime and 30 minutes during the nighttime. Reproducibility was better for ambulatory than for office blood pressure. It was greater for 24-hour than for daytime blood pressure and lowest for nighttime blood pressure. The reproducibility of blood pressure variability (standard deviation) was poorer than that of the average values. A small but significant decrease in average daytime blood pressure (-0.8/-1.0 mm Hg) and virtually no change in nighttime blood pressure (+0.5/+0.1 mm Hg) were observed at repeat recording. Reducing the sampling rate by 50% caused only a small impairment of the reproducibility indexes of both the average values and variability. Blood pressure reduction was greater during the first and last hours of the recordings, indicating an effect of the hospital environment on the between-monitoring difference. Changes in body weight (-0.7 kg, P = .006, at repeat recording) were related to those of 24-hour diastolic blood pressure (P < .05). In conclusion, patient reaction to medical environment and changes of body weight seem to account for most of the change in 24-hour blood pressure that occurs over a 3-month period.

[Pordenone study: HDL-cholesterol and obesity indexes in the young]. / Studio di Pordenone: HDL-colesterolo e indici di obesità nei giovani.

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.

Açäo da cypermetrina sobre Haematobia irritans (mosca-do-chifre) parasitando bovinos / Action of cypermetrina on Haematobia irritans (horn fly) sponging bovines

Em um rebanho de bovinos da raça Nelore parasitados com Haematobia irritans, foram separados e identificados dois lotes, sendo um deles pulverizado com uma soluçäo de cypermetrina a 0,01//e o outro deixado como testemunha. O grupo tratado ficou protegido de maneira eficiente por mais de 30 dias, ou seja, 69 moscas em média, no 40§ dia, contra a média de 131 do grupo-testemunha, em que pese a alta precipitaçäo pluviométrica no período do experimento, que, sem dúvida, carreou boa parte do princípio ativo no pêlo dos animais

[The Pordenone study on the precursors of atherosclosis in childhood. A 10-year follow-up. Cigarette smoking]. / Studio di Pordenone sui precursori dell'aterosclerosi nell'infanzia. Follow-up dopo dieci anni. Il fumo di sigaretta.

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.

[Results of diet treatment in 100 adult obese patients after 1-year follow-up]. / Risultati del trattamento dietetico in cento pazienti adulti obesi dopo un anno di "follow-up".

One hundred overweight adult patients were subjected to a hypocaloric diet with periodic controls during a one year observation period. During the first 4 months, 98% of the patients adhered to the dietary regimen, with an initial mean percentage loss of body weight of 9.3% for the females and 8.9% for the males. The weight loss was more conspicuous during the first two months of the diet therapy and in patients with an initially higher BMI. With time, the rate of drop-out from the diet therapy increased, which resulted in a follow-up of 49% and 87% of cases at 6 and 12 months respectively, with no significant differences between the two sexes. The drop-out phenomenon resulted to be more frequent in patients with an initially lower BMI.

Familial hypercholesterolemia and HLA antigens.

Hereditary factors play an important role in the etiology and progression of coronary heart disease (CHD), most probably by causing the appearance and the levels of its risk factors. To investigate if there is a correlation between familial hypercholesterolemia and HLA system antigens, 25 subjects of 7 families with familial hypercholesterolemia were compared with 14 normocholesterolemic related subjects. Compared to normocholesterolemic kindreds, the familial hypercholesterolemic subjects have a significant increased HLA-Bw35 antigen and a lack of HLA-A1. Therefore, the correlation found with some HLA system phenotypes improves our knowledge about familial hypercholesterolemia and aids in the identification of subjects affected with this disorder of lipid metabolism, which is one of the most important CHD risk factors.