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High leptin levels are associated with an unfavorable cardiometabolic risk profile. A number of studies found a positive association between leptin and vascular damage, but to date, no observational study has evaluated a potential predictive role of leptin for arterial stiffening. Therefore, the aim of this study was to estimate the role of leptin in the incidence of arterial stiffening (pulse pressure >60 mmHg) and changes in pulse pressure in an 8-year follow-up of a sample of adult men (The Olivetti Heart Study). The analysis included 460 men without baseline arterial stiffening and antihypertensive treatment at baseline and at follow-up (age: 50.0 years, BMI: 26.5 kg/m 2 ). At the end of the follow-up period, the incidence of arterial stiffening was 8%. Baseline leptin was significantly greater in the group that developed arterial stiffening and was significantly correlated with pulse pressure changes over time ( p  < 0.05). According to the median plasma leptin distribution of the whole population, the sample was stratified into two groups: one with leptin levels above the median and the other with leptin levels below the median. Those who had baseline leptin levels above the median had a greater risk of developing arterial stiffening (odds ratio: 2.5, p  < 0.05) and a greater increase in pulse pressure over time (beta: 2.1, p  < 0.05), also after adjustment for confounders. The results of this prospective study indicate a predictive role of circulating leptin levels for vascular damage, independent of body weight and blood pressure.

Purpose The World Health Organization recommends reduction of salt intake to < 5 g/day and the use of iodized salt to prevent iodine deficiency states. A high prevalence of excess salt consumption and an inadequate iodine intake has been previously shown in an Italian pediatric population. It was appropriate, therefore, to analyse in the same population the relationship occurring between salt consumption and iodine intake. Methods The study population was made of 1270 children and adolescents. Estimates of salt consumption and iodine intake were obtained by measuring 24 h urinary sodium and iodine excretion. Results The iodine intake increased gradually across quartiles of salt consumption independently of sex, age and body weight ( p  < 0.001). Median iodine intake met the European Food Safety Authority adequacy level only in teenagers in the highest quartile of salt consumption (salt intake > 10.2 g/day). We estimated that approximately 65–73% of the total iodine intake was derived from food and 27–35% from iodized salt and that iodized salt made actually only 20% of the total salt intake. Conclusion In this pediatric population, in face of an elevated average salt consumption, the use of iodized salt was still insufficient to ensure an adequate iodine intake, in particular among teenagers. In the perspective of a progressive reduction of total salt intake, the health institutions should continue to support iodoprophylaxis, in the context of the national strategies for salt reduction. In order for these policies to be successful, in addition to educational campaigns, it is needed that the prescriptions contained in the current legislation on iodoprophylaxis are made compelling through specific enforcement measures for all the involved stakeholders.

Hypertension is the leading cause of death in developed countries and reduction of salt intake is recommended as a key preventive measure. To assess the dietary sodium and potassium intakes in a national sample of Italian children and adolescents and to examine their relationships with BMI and blood pressure (BP) in the framework of the MINISAL survey, a program supported by the Italian Ministry of Health. The study population included 1424 healthy subjects (766 boys, 658 girls) aged 6-18 years (mean age: 10.1±2.9) who were consecutively recruited in participating National Health Service centers in 10 Italian regions. Electrolyte intake was estimated from 24 hour urine collections tested for completeness by the concomitant measurement of creatinine content. Anthropometric indices and BP were measured with standardized procedures. The average estimated sodium intake was 129 mmol (7.4 g of salt) per day among boys and 117 mmol (6.7 g of salt) among girls. Ninety-three percent of the boys and 89% of the girls had a consumption higher than the recommended age-specific standard dietary target. The estimated average daily potassium intakes were 39 mmol (1.53 g) and 36 mmol (1.40 g), respectively, over 96% of the boys and 98% of the girls having a potassium intake lower than the recommended adequate intake. The mean sodium/potassium ratio was similar among boys and girls (3.5 and 3.4, respectively) and over 3-fold greater than the desirable level. Sodium intake was directly related to age, body mass and BP in the whole population. The Italian pediatric population is characterized by excessive sodium and deficient potassium intake. These data suggest that future campaigns should focus on children and adolescents as a major target in the framework of a population strategy of cardiovascular prevention.

Renal tubular sodium (Na) handling plays a key role in blood pressure (BP) regulation. Several cross-sectional studies reported a positive association between higher proximal tubule fractional reabsorption of Na and BP, but no prospective investigation has been reported of this possible association. Hence, the purpose of this study was to estimate the predictive role of renal Na handling on the risk of incident hypertension and the changes in BP occurring in the 8-year follow-up observation of a sample of initially normotensive men (The Olivetti Heart Study). The study included 294 untreated normotensive non-diabetic men with normal renal function examined twice (1994-95 and 2002-04). Renal tubular Na handling was estimated by exogenous lithium clearance. Fractional reabsorption of Na in proximal and distal tubules was calculated and included in the analysis. At baseline, there was no association between BP and either proximal or distal fractional reabsorption of Na. At the end of the 8-year follow-up, direct associations were observed between baseline proximal (but not distal) Na fractional reabsorption and the changes occurred in systolic and diastolic BP over time (+2.79 and +1.53 mmHg, respectively, per 1SD difference in proximal Na-FR; p<0.01). Also multivariable analysis showed a direct association between baseline proximal Na fractional reabsorption and risk of incident hypertension, independently of potential confounders (OR: 1.34, 95%CI:1.06-1.70). The results of this prospective investigation strongly suggest a causal relationship between an enhanced rate of Na reabsorption in the proximal tubule and the risk of incident hypertension in initially normotensive men.

The renin-angiotensin system is involved in adipocyte growth and differentiation and possibly in adipose tissue metabolism. To investigate the association of polymorphism in the angiotensin-converting enzyme (ACE) I/D gene, angiotensinogen M235T gene, and angiotensin II type 1 receptor A1166C gene with body mass index, body fat pattern, and obesity-associated hypertension. Cross-sectional longitudinal study. The Olivetti factories in Marcianise and Pozzuoli, suburbs of Naples, Italy. 959 adult men, 25 to 75 years of age. Renin-angiotensin system polymorphism, anthropometric indexes, blood pressure, and serum glucose and insulin levels. No association was detected between angiotensinogen or angiotensin II type 1 receptor gene polymorphism and anthropometric indexes or blood pressure. For ACE I/D polymorphism, significant age-genotype interaction was detected on cross-sectional observation; the relation of body mass index, waist circumference, and diastolic blood pressure to age was significantly greater in persons with the DD genotype than in those with the ID or II genotype. Overweight and abdominal adiposity were more common in men with the DD genotype, particularly among older participants (51.1% vs. 36.5% and 33.1% vs. 22.0%, respectively). Odds ratios were 1.82 (95% CI, 1.16 to 2.87) for overweight and 1.76 (CI, 1.06 to 2.90) for abdominal adiposity. Among 314 untreated men first examined 20 years earlier, those with the DD genotype had greater age-adjusted weight gain (1.45 kg [CI, 0.12 to 2.78 kg]) and change in diastolic blood pressure (2.83 mm Hg [CI, 0.39 to 5.28 mm Hg]). The relative risk for overweight was 2.34 (CI, 1.32 to 4.15) among participants with the DD genotype versus those with the ID or II genotype. The ACE I/D polymorphism was a significant predictor of overweight and abdominal adiposity in men. DD homozygosity was associated with larger increases in body weight and blood pressure in aging persons, as well as with higher incidence of overweight.

Plasma potassium concentration (PK) is tightly regulated. Insulin is known to favor potassium entry into cells. But how potassium leaves the cells later on is not often considered. Previous studies in rats showed that glucagon infusion increased urinary potassium excretion dose‐dependently and reversibly. This prompted us to investigate the possible influence of glucagon on potassium handling in humans. We took advantage of the Gly40Ser mutation of the glucagon receptor (GR) that results in a partial loss of function of the GR. In the Olivetti cohort (male workers), 25 subjects who carried this mutation were matched 1:4 to 100 noncarriers for age and weight. Estimated osmolarity of serum and 24‐h urine (Sosm and Uosm, respectively) was calculated from the concentrations of the main solutes: [(Na+K)*2 + urea (+glucose for serum)]. Transtubular potassium gradient (TTKG), reflecting the intensity of K secretion in the distal nephron, was calculated as [(urine K/serum K)(Uosm/Sosm)]. There was no significant difference in serum K, or 24‐h urine urea, Na and K excretion rates. But urine K concentration was significantly lower in carriers than in noncarriers. Means (interquartile range): 38 (34–43) versus 47 (43–51) mmol/L, P = 0.030. TTKG was also significantly lower in carriers: 4.2 (3.9–4.6) versus 5.0 (4.7–5.2), P = 0.015. This difference remained statistically significant after adjustments for serum insulin and 24‐h Na and urea excretions. These results in humans suggest that glucagon stimulates K secretion in the distal nephron. Thus, in conjunction with insulin, glucagon may also participate in K homeostasis by promoting renal K excretion. Plasma potassium concentration is tightly regulated. Insulin is known to favor potassium entry into cells. But how potassium leaves the cells later on is not often considered. In rats, glucagon was shown to increase significantly, dose‐dependently, and reversibly urinary potassium excretion. The present study shows, in a human cohort, that subjects carrying a mutation of the glucagon receptor that induces a partial loss of function, exhibit a reduced urinary potassium concentration and a reduced TTKG, an index of potassium secretion in the collecting duct. These results suggest that glucagon, in conjunction with insulin, may participate in potassium homeostasis by its influence on urinary potassium excretion.

A number of evidence showed an emerging role of leptin on immune system, involving inflammation, and innate and adaptive immunity. Few observational studies have evaluated the relationship between leptin and immunity, albeit with low statistical power and methodological differences. Therefore, the aim of this study was to evaluate the potential role of leptin on the immunity, expressed as white blood cells (WBC)—and its subpopulations, by comprehensive multivariate models in a sample of adult men. A cross-sectional evaluation of a general population comprised 939 subjects participating in the Olivetti Heart Study, with available leptin levels and WBC—and its subpopulations. WBC were significantly and positively associated with leptin, C-reactive protein and HOMA index (p < 0.05), but not with age and anthropometric indices (p > 0.05). The multivariate analysis confirmed the association between leptin and WBC, after accounting for main confounders (p < 0.05). Additional analysis on WBC subpopulations showed a positive and significant correlation between leptin and lymphocytes, monocytes and eosinophils (p < 0.05), but not with neutrophils and basophils (p > 0.05). After stratification by body weight, the positive and significant association between leptin and WBC—and its subpopulations—was found in excess body weight participants. The results of this study indicate a direct relationship between leptin levels and WBC—and its subpopulations—in excess body weight participants. These results support the hypothesis that leptin has modulatory functions on immunity and role in the pathophysiology of immune-related diseases, in particular in those associated with excess body weight.

Leptin (LPT) is associated with a number of cardiovascular risk factors, such as high blood pressure (BP), insulin resistance and excess in body weight. Some studies find an unfavorable cross-sectional association between LPT and renal disease, in particular in patients with already known kidney dysfunction. There are few data on the relationship between LPT and changes in renal function over time in subjects without evidence of kidney dysfunction. Hence, the aim of this study is to estimate the predictive role of LPT on the decline in renal function occurring in an 8-year follow-up observation of a sample of adult apparently healthy men (The Olivetti Heart Study). The study includes 319 untreated normotensive and nondiabetic men without clinical evidence of renal dysfunction (creatinine clearance-CrCl > 60 mL/min/1.73 m2) at baseline. At baseline, LPT is significantly and positively associated with BMI, abdominal circumference, BP and Homa index, no relationship is found with CrCl. At the end of the 8-year follow-up, a significant association is detected between baseline LPT and changes occurring in BP. Moreover, an inverse correlation with changes in CrCl is found (r = − 0.12). This unfavorable relationship between baseline LPT and decline in renal function is also confirmed in the multivariate analyses, after adjustment for all potential confounders (R2 = 0.42, p < 0.01). The results of this prospective investigation suggest a predictive role of circulating LPT levels on decline in renal function over time, independently of main potential confounders, in normotensive and nondiabetic men with normal renal function at baseline.

Since the Italian iodoprophylaxis strategy is based on the use of iodized salt, we assessed the relationship between dietary salt consumption and iodine intake in the Italian adult population. We estimated the relative contribution given by the use of iodized salt and by the iodine introduced by foods to the total iodine intake. The study population included 2219 adults aged 25–79 years (1138 men and 1081 women) from all Italian regions, participating to the Osservatorio Epidemiologico Cardiovascolare/Health Examination Survey 2008–2012 (OEC/HES), and examined for sodium and iodine intake in the framework of the MINISAL-GIRCSI Programme. Dietary sodium and total iodine intake were assessed by the measurement of 24 h urinary excretion, while the EPIC questionnaire was used to evaluate the iodine intake from food. Sodium and iodine intake were significantly and directly associated, upon accounting for age, sex, and BMI (Spearman rho = 0.298; p < 0.001). The iodine intake increased gradually across quintiles of salt consumption in both men and women (p < 0.001). The European Food Safety Authority (EFSA) adequacy level for iodine intake was met by men, but not women, only in the highest quintile of salt consumption. We estimated that approximately 57% of the iodine intake is derived from food and 43% from salt. Iodized salt contributed 24% of the total salt intake, including both discretionary and non-discretionary salt consumption. In conclusion, in this random sample of the Italian general adult population examined in 2008–2012, the total iodine intake secured by iodized salt and the iodine provision by food was insufficient to meet the EFSA adequate iodine intake.

Monitoring the population iodine status is essential for iodine deficiency eradication. This study assessed the average dietary iodine intake and the iodine status of a random sample of the Italian general adult population. The study population included 2378 adults aged 35–79 years (1229 men and 1149 women) from all 20 Italian regions, participating in the Osservatorio Epidemiologico Cardiovascolare/Health Examination Survey 2008–2012 (OEC/HES), and were examined for iodine intake in the framework of the MINISAL-GIRCSI Programme. Dietary iodine intake was assessed by the measurement of 24 h urinary iodine excretion. The median daily iodine intake of the whole population was lower (96 µg/d, interquartile range 51–165) than the daily adequate iodine intake according to both EFSA and WHO recommendation (150 µg/d), with a significantly lower value among women (85 µg/d) compared with men (111 µg/d). Iodine intake diminished with age and increased with BMI (body mass index) in male but not in female participants, without achieving the adequate intake in any sex, age, or BMI category. In this random sample of Italian general adult population examined in 2008–2012, iodine intake still remained lower than the recommended values despite the implementation of a strategy of iodoprophylaxis based on salt iodization in 2005. These data represent a valuable reference for future monitoring of iodine status in our country.