Circulating leptin is associated with serum uric acid level and its tubular reabsorption in a sample of adult middle-aged men.

PURPOSE: Leptin is associated with cardiovascular risk factors (e.g. hypertension, insulin resistance, kidney disease and excess body weight). Experimental studies showed that leptin might affect serum uric acid, by modulation of the uric acid excretion. However, there are few observational data on the relationship between leptin and uric acid in the general population. Therefore, the aim of the present study was to evaluate the relationship between leptin and uric acid and its excretion in a large middle-aged male general population. METHODS: A sample of 930 adult male individuals (mean age: 52 years) without therapy for high uric acid was included in the analysis (the Olivetti Heart Study). RESULTS: Uric acid was significantly and positively associated with blood pressure, BMI, waist circumference, insulin resistance, C-reactive protein and leptin (p < 0.01), while inversely with renal function (p = 0.01). The multivariate analysis confirmed the association between leptin and uric acid after adjustment for potential confounders (p < 0.01). After division for adiposity, this trend was confirmed separately for normal weight and excess body weight participants. Moreover, leptin was inversely associated with excretion of uric acid (p < 0.01), also in multivariate analysis (p = 0.03). CONCLUSION: The results of this study indicate a positive association between circulating leptin levels and uric acid, independently of potential confounders, both in normal and excess body weight men. Furthermore, an inverse association between leptin and uric acid excretion was detected.

Leptin levels predict the development of insulin resistance in a sample of adult men-The Olivetti Heart Study.

BACKGROUND AND AIMS: Leptin (LPT) is associated with unfavourable cardio-metabolic risk profile. Although a number of studies have found a positive association between LPT and insulin resistance (IR), no observational study has evaluated a prospective association to detect a predictive role of LPT in IR. Therefore, the aim of this study was to estimate the role of LPT on the incidence of IR in an 8-year follow-up of a sample of adult men (The Olivetti Heart Study). METHODS AND RESULTS: The study included 527 not diabetic men without IR (homeostasis model assessment - HOMA index < 2.77 UI) at baseline. Baseline LPT was significantly and positively associated with HOMA index, body mass index (BMI), waist circumference and blood pressure. At the end of the 8-year follow-up period, a positive and significant association was detected between baseline LPT and changes in HOMA index (r = 0.25, p < 0.01) and incidence of IR (OR: 2.6, 95%CI: 1.9-3.4). This trend was also confirmed after adjustment for potential confounders. In addition, the predictive value of LPT was found in subjects who had not experienced any weight increase over the years, and for normal weight and excess body weight participants, separately. CONCLUSIONS: The results of this prospective study suggest a predictive role of circulating LPT levels on a reduction of insulin sensitivity over time, independently of main potential confounders, in non-diabetic men without IR at baseline. In addition, in normal weight individuals, LPT levels were associated with development of IR.

Excess dietary sodium and inadequate potassium intake in Italy: results of the MINISAL study.

OBJECTIVE: As excess sodium and inadequate potassium intake are causally related to hypertension and cardiovascular disease, the MINISAL-GIRCSI Program aimed to provide reliable estimates of dietary sodium and potassium intake in representative samples of the Italian population. DESIGN AND METHODS: Random samples of adult population were collected from 12 Italian regions, including 1168 men and 1112 women aged 35-79 yrs. Electrolyte intake was estimated from 24 hour urine collections and creatinine was measured to estimate the accuracy of the collection. Anthropometric indices were measured with standardised procedures. RESULTS: The average sodium excretion was 189 mmol (or 10.9 g of salt/day) among men and 147 mmol (or 8.5 g) among women (range 27-472 and 36-471 mmol, respectively). Ninety-seven % of men and 87% of women had a consumption higher than the WHO recommended target of 5g/day. The 24 h average potassium excretion was 63 and 55 mmol, respectively (range 17-171 and 20-126 mmol), 96% of men and 99% of women having an intake lower than 100 mmol/day (European and American guideline recommendation). The mean sodium/potassium ratio was 3.1 and 2.8 respectively, i.e. over threefold greater than the desirable level of 0.85. The highest sodium intake was observed in Southern regions. Sodium and potassium excretion were both progressively higher the higher the BMI (p < 0.0001). CONCLUSIONS: These MINISAL preliminary results indicate that in all the Italian regions thus far surveyed dietary sodium intake was largely higher and potassium intake lower than the recommended intakes. They also highlight the critical association between overweight and excess salt intake.

Hyperleptinemia is associated with hypertension, systemic inflammation and insulin resistance in overweight but not in normal weight men.

BACKGROUND AND AIM: High leptin (LPT) is associated with high blood pressure (BP), insulin resistance and systemic inflammation but also excess body weight and adiposity. To disentangle these multiple relations, we analyzed BP, HOMA and circulating C-reactive protein concentration (hs-CRP) in white male adults with different LPT levels but similar age, body mass index (BMI) and body fat distribution. The novel aspect is the different statistical approach used to investigate the relation between LPT and the other alterations present in obesity. METHODS AND RESULTS: 972 Olivetti Heart Study participants were stratified according to the median LPT distribution (2.97 ng/ml) into low LPT (l-LPT) and high LPT (h-LPT). The two groups were then carefully matched for age and BMI. We identified two groups of 207 h-LPT and 207 l-LPT individuals with overlapping age, BMI and waist/hip ratio. The two groups had different BP (132.9 ± 16.2/85.7 ± 9.0 vs 128.7 ± 18.2/82.8 ± 9.8 mmHg, p = 0.014 for SBP and p = 0.002 for DBP) and prevalence of hypertension (57% vs 43%, p = 0.027). Upon separate evaluation of untreated individuals with BMI < 25 or BMI ≥ 25, within the latter subgroup h-LPT compared with l-LPT participants (n = 133 each group) had higher BP (p = 0.0001), HOMA index (p = 0.013), hs-CRP (p = 0.002) and heart rate (p = 0.008) despite similar age and BMI. By contrast, within the normal weight subgroup, h-LPT individuals did not differ from l-LPT (n = 37 each) for any of these variables. CONCLUSIONS: High LPT is associated with higher BP, HR, hs-CRP and HOMA index independently of BMI and fat distribution but only among overweight individuals.

High-circulating leptin levels are associated with greater risk of hypertension in men independently of body mass and insulin resistance: results of an eight-year follow-up study.

BACKGROUND: We previously reported a significant association between plasma leptin (LPT) concentration and blood pressure (BP), which was partly independent of serum insulin levels and insulin resistance. The aims of this study were to detect whether serum LPT levels predict the development of hypertension (HPT) in the 8-yr follow-up investigation of a sample of an adult male population (the Olivetti Heart Study), and to evaluate the role of body mass index (BMI) and insulin resistance in this putative association. PATIENTS AND METHODS: The study population was made up of 489 untreated normotensive subjects examined in 1994-1995 (age: 50.1 +/- 6.7 yr; BMI: 26.3 +/- 2.8 kg/m(2); BP: 120 +/- 10/78 +/- 6 mm Hg; and homeostatic model assessment index: 2.1 +/- 1.6). RESULTS: The HPT incidence over 8 yr was 35%. The participants with incident HPT had similar age but higher BMI (P < 0.001), serum LPT (P < 0.001), and BP (P < 0.01) at baseline. One sd positive difference in baseline serum LPT log was associated at univariate analysis with a 49% higher rate of HPT [95% confidence interval (CI) 22-83; P < 0.001]). In three different models of multivariable logistical regression analysis, LPT was respectively associated with a 41% greater risk to develop HPT (95% CI 15-74; P < 0.001) upon adjustment for age and baseline BP, with a 48% (95% CI 20-81) greater risk when adding the homeostatic assessment model index to the model, and with 33% greater risk (95% CI 6-67; P < 0.02) upon adjustment for BMI. CONCLUSIONS: In this sample of originally normotensive men, circulating LPT level was a significant predictor of the risk to develop HPT over 8 yr, independently of BMI and insulin resistance.

Altered renal sodium handling and hypertension in men carrying the glucagon receptor gene (Gly40Ser) variant.

A higher prevalence of hypertension has been associated with the G-->A/GT (Gly40Ser) polymorphism of the glucagon receptor gene (GCGR) in two population studies. As the mutated receptor is less responsive to glucagon, it has been speculated that the increased susceptibility to hypertension is due to deprivation of the recognized natriuretic effect of the hormone. To test this hypothesis we determined the frequency of the polymorphic variant and evaluated the segmental renal sodium handling by the clearances of uric acid and of exogenous lithium in the Olivetti Heart Study participants (n=971). The polymorphic variant was present only in heterozygous form in 37 individuals (3.8%). After controlling for age and body mass index, the carriers of the variant were twice more likely to be hypertensive and almost three times more likely to be on antihypertensive treatment at the time of examination. Compared to participants carrying the wild type, those carrying the Gly40Ser allele had higher serum uric acid and lower fractional excretion of uric acid and exogenous lithium, independently of age, body mass, and current pharmacological treatment. We conclude that the Gly40Ser polymorphism of the GCGR gene is associated with higher risk of hypertension and with enhanced proximal tubular sodium reabsorption, a factor possibly contributing to hypertension in this group.

Doxazosin and captopril in mildly hypercholesterolemic hypertensive patients. The Doxazosin-Captopril in Hypercholesterolemic Hypertensives Study.

The evidence linking hypertension and hypercholesterolemia is strong and has fueled research into possible adverse effects of some antihypertensive agents on serum lipid profile. This multicenter, open, parallel study compares the effects of doxazosin and captopril on blood pressure, serum lipid levels, and quality of life in 224 hypercholesterolemic hypertensive patients. Blood pressure was significantly reduced in both treatment groups (p < 0.001) and was normalized (standing diastolic pressure < or = 90 mm Hg) in 73% of the doxazosin patients and 67% of the captopril group. Serum total cholesterol level was favorably reduced by both doxazosin (from 238 to 223 mg/dl, p < 0.001) and captopril (from 245 to 233 mg/dl, p < 0.001), whereas high density lipoprotein cholesterol concentration increased only in the doxazosin group (from 33 to 36 mg/dl, p < 0.001). The calculated 10-year risk for the development of coronary heart disease was reduced significantly (p < 0.001) by 28% in the doxazosin group and by 19% in the captopril group. The quality of life evaluation showed beneficial changes in both treatment groups. As a result of proven antihypertensive efficacy and a lack of unfavorable effects on lipid parameters and health status measures, these findings support the use of both doxazosin and captopril as agents of first choice in the treatment of hypertensive patients with associated lipid abnormalities.

Relationship of the Trp64Arg polymorphism of the beta3-adrenoceptor gene to central adiposity and high blood pressure: interaction with age. Cross-sectional and longitudinal findings of the Olivetti Prospective Heart Study.

METHODS: The association of the Trp64Arg polymorphism of the beta3-adrenoceptor (beta3-AR) gene with high blood pressure, central adiposity and other features of the metabolic syndrome was investigated in a large unselected sample of a white male working population in Southern Italy (n = 979). RESULTS: In the whole population, subjects heterozygous for the Trp64Arg mutation (11.2%) were not different from the homozygous Trp64Trp for any of the variables investigated. However, upon stratification for age, among men in the upper tertile of age (> 53 years), the Trp64Arg genotype was associated with higher waist: hip ratio (0.992 +/- 0.021 versus 0.982 +/- 0.037, P< 0.05), serum uric acid (6.34 +/- 1.50 versus 5.75 +/- 1.30 micromol/l, P < 0.05) and systolic blood pressure (144.3 +/- 19.4 versus 136.9 +/- 18.9 mmHg, P< 0.05) compared with the wild-type homozygotes. Accordingly, in the same age group, the carriers of Trp64Arg genotype were more often in the upper tertile of abdominal adiposity (69.7 versus 43.7%, P< 0.02) and serum uric acid (56.3 versus 34.8%, P < 0.02) and were more often hypertensive (68.6 versus 57.6%, P< 0.058) than the Trp64Trp homozygotes. No such differences were observed in younger age groups. No association was found with fasting serum insulin and the homeostasis model assessment (HOMA) index of insulin resistance. Furthermore, in a subgroup of 457 men for whom retrospective 20-year follow-up data were available, the variant genotype was associated with a higher probability of developing overweight (44.7 versus 27.0%, P < 0.05) and a trend to higher blood pressure (52.6 versus 38.4%, P = 0.09) over 20 years. CONCLUSION: We conclude that the Trp64Arg variant of the beta3-AR receptor predicts a greater tendency to develop abdominal adiposity and high blood pressure with advancing age.

Factors affecting lipoprotein lipase in hypertensive patients.

Arterial hypertension is frequently associated with serum lipid abnormalities. Lipid metabolism can also be affected by antihypertensive treatment, possibly via an interference with lipoprotein lipase (LPL) activity. The aims of this study were to investigate the metabolic and hemodynamic factors that can interfere with plasma postheparin LPL activity in a sample of 13 patients with mild, uncomplicated arterial hypertension. The effects of vasodilator administration (prazosin and hydralazine) alone or in combination with a beta-blocker (propranolol) were also studied. A direct correlation between serum insulin levels and LPL activity was found during placebo treatment. This was confirmed by multiple regression analysis, which also showed a positive correlation of LPL activity with aortic flow velocity and plasma adrenaline (F significance = 0.0007, R2 = .905). Serum insulin was also directly correlated with cholesterol in high-density lipoproteins (HDLs) and in the HDL2 subfraction. A significant decrease in LPL activity was observed during the addition of propranolol to vasodilators as compared with vasodilators alone. A positive correlation was found between LPL and adrenaline changes induced by the combined treatment. These data suggest that LPL may play a role in the pathophysiologic connections between insulin action, the adrenergic nervous system (ANS), and lipid metabolism.

[The diaphragmatic relaxatio (author's transl)]. / La relaxatio diaframmatica.

The Authors briefly describe two cases of diaphragmatic relaxatio that they have seen and studied; then they make a revision of the literature about this uncommon disease. They speak about embryogenesis of the diaphragm and about nosology, etiopathogenesis, frequency (ages and sex) and phatological anatomy of this disease. In conclusion the Authors discuss in detail signs and symptoms, diagnosis and surgical treatment of diaphragmatic relaxatio.

[Occupational activity with risk of leptospirosis. Prevention and health surveillance]. / Rassegna delle attività lavorative a rischio d'infezione da leptospire. Prevenzione e sorveglianza sanitaria.

The analysis of the epidemiological studies carried out in Italy give us the idea for a very precise survey of the occupational leptospirosis. We have identified the occupational hazards and the precautionary measures. In Italy the first epidemiological data about human leptospirosis goes back to 1917. During following decades were highlighted several occupational forms of leptospirosis, specifically seasonal epidemics among rice-workers. Epidemiological studies carried out in Italy from 1950 to 1990 showed that leptospirosis was again widespread although precautionary measures and there was a probable spread of the "minor leptospirosis" at the same time of common cases of "major leptospirosis". The latest data issued by Ministry of the Health related years '94-'97 confirm the persistence of leptospirosis, for the most part in the north. However there is a problem of underestimate because many times human leptospirosis show itself with minor clinical forms. In the working environment is essential the function of the Medico Competente. He must avail himself of the precautionary measures for the biological risk specified in D.lgs 626/94.

[Retrospective study on the prevalence of latex allergic pathology in health personnel]. / Studio retrospecttivo sulla prevalenza di patologia allergica da latice negli operatori sanitari.

To evaluate the prevalence of latex sensitisation and latex-related symptoms, we performed a study on 837 hospital employees. All subjects were asked for medical and occupational history, and underwent Skin Prick Test (SPT) with latex and other airborne allergens. The results showed a prevalence of latex sensitisation of 6.1% and a prevalence of symptoms of 5.26%. The most frequent symptoms were oculorhinitis, dermatitis and asthma. The one-year retrospective evaluation showed, in a group of 767 hospital attendants selected by the whole population, an incidence of sensitisation of 0.26%; no new cases of latex-related symptomatology were observed. The improvement of symptoms was due to the reduction of the exposure to latex gloves. The results of the study confirm the importance of prevention strategies.

[Angiomyolipoma of the kidney]. / L'angiomiolipoma del rene.

The renal angiomyolipoma is a rare, benign, no epithelial neoplasm. It is frequently associated with tuberous sclerosis, above all in young patients. It may be under an asymptomatic form, especially if it deals of a small volume neoplasm, and sometimes it becomes evident only when it occurs an haemorrhagic complication. When we have a sure diagnosis and a small tumor, the treatment is preservative; on the contrary it is surgical either for big symptomatic neoplasms or haemorrhagic complications. The authors report a clinical case of renal angiomyolipoma in a pregnant patient, who had an haemorrhagic complication and was treated with nephrectomy.

Dietary sodium intake in a sample of adult male population in southern Italy: results of the Olivetti Heart Study.

BACKGROUND/OBJECTIVES: To assess dietary habitual sodium intake and the association between daily sodium intake and anthropometric indices, food habits and hypertension in the sample of adult male population participating in the Olivetti Heart Study. SUBJECTS/METHODS: The study population was composed of 940 men participating in the 2002-2004 follow-up examination of the Olivetti Heart Study. Blood pressure, anthropometric indices, biochemical parameters and sodium excretion in a 24-h urine collection were measured. The frequency of consumption of selected foods was estimated by a food frequency questionnaire (FFQ) capturing the previous year data. In a subgroup of the study population (n=138), the fractional excretion of sodium was estimated by endogenous lithium clearance. RESULTS: Dietary sodium intake estimated by 24 h urinary excretion was 203+/-70 mmol/day. Sodium excretion was significantly lower in treated hypertensive patients and higher in overweight/obese participants when compared with normotensive and normal-weight individuals, respectively. In addition, the inverse correlation detected in normal-weight individuals (r=-0.321; P<0.05) between fractional proximal tubular sodium reabsorption and dietary sodium intake was disrupted in overweight/obese individuals (r=0.058; P=NS). The independent determinants of 24 h urinary sodium excretion were body mass index (BMI), the occurrence of antihypertensive treatment, and frequency of consumption of pasta and cold cuts. CONCLUSIONS: Habitual salt intake in this sample of male adult population in southern Italy was well above the recommended amounts. A higher salt intake and an altered renal sodium handling were observed in overweight and obese participants. Sodium intake was only slightly reduced in hypertensive participants on pharmacological therapy.

[Heredity of twinning in families of monozygotic twins (author's transl)]. / Eredità della gemellazione in famiglie di gemelli monozigoti.

Whereas the existence of some genetic factor underlying the phenomenon of twinning is almost generally accepted with respect to DZ twins, no such agreement exists with respect to MZ twins. The possible existence of genetic factors underlying MZ twinning has been verified through an analysis of segregation in the sibships of MZ twins and in those of their parents, carried out on a sample of 57 MZ twin pairs (30 M and 27 F). Haldane's a priori method has been applied, considering the sample as obtained through a complete and through an incomplete ascertainment. The results may lead to cautiously confirm the hypothesis of some genetic conditioning of MZ twinning.

Endoscopic stenting of strictured bilio-enteric anastomosis.

The authors report on a case of neoplastic stricture of bilio-enteric anastomosis treated by endoscopic placement of two prosthesis. All endoscopic maneuvers were carried out through the afferent loop of hepatico-jejunostomy.

Evaluation of lipid metabolism during antihypertensive treatment with nicardipine sr.

The antihypertensive and metabolic effects of oral nicardipine SR 40 mg b.i.d. have been studied in 18 (15 m, 3 f; age 52.7 y) hypertensives with mild hypercholesterolaemia, treated for 3 months after a 2 week period on placebo. An iv Fat Tolerance Test (FTT) was also performed in 8 patients following placebo, treatment with acute nicardipine 20 mg and chronic administration of nicardipine SR. There was a significant fall in BP from 160/97 on placebo to 147/87 after 3 months on nicardipine SR with no change in heart rate. Blood lipids did not change significantly. The disappearance rate of the lipid emulsion in the ivFTT showed no significant change (K2 was 1.93%/min after placebo, 1.84 after nicardipine 20 mg and 1.71 after chronic treatment). The results suggest that nicardipine is an effective antihypertensive drug and that it is devoid of untoward effects on lipid metabolism.

Plasma leptin measurements in epidemiological investigation: comparison of two commonly used assays and estimate of regression dilution bias.

BACKGROUND AND AIM: As leptin is the object of intensive clinical research, we compared the radio-immunological assay (RIA) and enzyme-linked immunosorbent assay (ELISA) commercially available for measuring its plasma concentration in humans (Study 1), and sought to determine the power of a single plasma leptin measurement to characterise adequately a subject within a population on the basis of its intra- and inter-individual variations (Study 2). METHODS AND RESULTS: Study 1--Plasma leptin concentrations were determined by means of RIA and ELISA in a sample of 80 males. The measurements obtained using the two methods were closely correlated (r = 0.942), but the bias of the means was 21.1 +/- 73.5% (M +/- SD, p < 0.001) and indicated that the two assays were not in agreement with each other. As expected, there were strong statistical associations between plasma leptin and a number of anthropometric indices, but the slopes of the regression of leptin concentration was significantly steeper when measured by ELISA. Study 2--ELISA was used to measure plasma leptin concentrations in three different samples obtained from 12 males and 12 females at two-week intervals. The inter-individual variation in plasma leptin was much greater than its intra-individual variation (the ratio of intra-to inter-individual variance = 0.05 and 0.04 in males and females, respectively), thus suggesting that a single fasting measurement is sufficient to characterise an individual's plasma leptin level within a population. CONCLUSIONS: ELISA is at least as effective as RIA in measuring plasma leptin, and is fully suitable for epidemiological investigations. A single measurement made in the morning and under fasting conditions is sufficient to characterise an individual within a population.

Gly40Ser polymorphism of the glucagon receptor gene is associated with central adiposity in men.

OBJECTIVE: To study the association between the Gly40Ser polymorphism of the glucagon receptor gene (GCG-R) and central adiposity. RESEARCH METHODS AND PROCEDURES: Data from 985 working men (The Olivetti Heart Study) examined in 1994 were used in a cross-sectional design. A complete anthropometry was performed; body mass index and waist circumference were taken as measures of total and central adiposity, respectively. The GCG-R Gly40Ser polymorphism was characterized. Biochemical variables linked to energy metabolism were measured. RESULTS: The GCG-R Gly40Ser variant was present in 37 individuals only in heterozygous form and was significantly associated with anthropometric indices of central adiposity, accounting for age and body mass (odds ratio for waist circumference > 94 cm; 95% confidence interval: 3.14, 1.26 to 7.81), whereas no difference between the two groups was found with regard to biochemical indices of insulin resistance or plasma leptin levels. DISCUSSION: The Gly40Ser polymorphism of the GCG-R gene is associated with central adiposity independently from total body mass in men.