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BACKGROUND: The aldosterone synthase gene (CYP1B2) locus is a candidate region involved in the development of hypertension. OBJECTIVE: To study the relationship between the C-344T CYP1B2 polymorphism, plasma aldosterone, renin activity and blood pressure in a multi-ethnic population. DESIGN: Population-based, cross-sectional study of 1313 middle-aged men and women (456 white, 441 of African origin and 416 South Asian). Anthropometry, blood pressure, biochemistry, questionnaire data and timed urine collections were taken with standardized techniques. All were genotyped for the C-344T CYP11B2 polymorphism. RESULTS: The frequency of the C allele was significantly lower in people of African origin (0.21) than in white (0.46) and South Asian (0.43) (P < 0.001). After adjustment for age, sex and ethnicity the TT genotype was associated with 14% higher plasma aldosterone levels, 3.7 mmHg higher systolic and 2.1 mmHg higher diastolic blood pressure than CC (P for linear trend < 0.05). No significant interactions with age, sex, ethnicity, body mass index (BMI) and fractional excretion of sodium were found in the associations between genotype and both blood pressure and aldosterone levels. In a sub-sample of participants in which plasma renin activity was measured (n = 457), a significant excess of T alleles was found in those with a raised (>/= 750) aldosterone-to-renin ratio (ARR). CONCLUSION: In this multi-ethnic population, the C-344T CYP1B2 polymorphism is associated with blood pressure, plasma aldosterone levels and ARR. Although significant differences in allele frequencies were found between groups, ethnicity does not explain the results.

BACKGROUND: Because high circulating plasma leptin is associated with many features of the metabolic syndrome (MS), such as abdominal obesity, insulin resistance and high blood pressure (BP), we analysed the ability of plasma leptin concentration to predict the risk of developing MS in a prospective investigation of adult male participants of the Olivetti Heart Study (OHS). METHODS AND RESULTS: Three hundred and sixty out of 907 men participating in the 1994-95 and 2002-04 OHS examinations (mean age at baseline 50.4 years, range 25-73 years) were free of MS at first visit according to NCEP-ATP III criteria (modified for the lack of high-density lipoprotein cholesterol measurement at baseline). During an average follow-up period of 8 years, there were 52 incident cases of MS (14.5%) due, in particular, to a rise in the prevalence of high BP (+42.4%), abdominal obesity (+16.4%) and impaired fasting glucose (IFG, +6.1%). In multivariate analyses, a one standard deviation difference in baseline plasma leptin concentration was associated with a 1.58-fold greater risk of developing MS (95% confidence interval = 1.10-2.30, P = 0.016) accounting for age, waist circumference, homeostatic assessment model index, smoking, alcohol consumption and physical activity. In particular, plasma leptin was positively associated with the risk of developing high BP (0.006) and IFG (0.014), after adjustment for confounders. CONCLUSION: In this sample of an adult male population free of MS at baseline, circulating plasma leptin was a significant predictor of the risk of MS and, in particular, of its high BP and IFG components, independently of potential confounders.

OBJECTIVE To evaluate the incidence of hypertension and the rate of decline in renal function in a sample of 47 Olivetti Heart Study (OHS) participants whose blood pressure (BP) salt-sensitivity and renal tubular sodium handling had been assessed in 1987-88. METHODS During the 2002-04 OHS follow-up examination, medical history, physical examination and blood and urine sampling were performed in 36 of the 47 participants to the baseline study (age 60 +/- 6 years; average follow-up = 15.1 +/- 0.6 years). The renal length was measured in 23 participants by kidney ultrasonography. Based on the baseline salt-sensitivity evaluation, the subjects were classified into a lower salt-sensitivity (LSS, n = 20) and a higher salt-sensitivity group (HSS, n = 16). RESULTS In comparison with the LSS group, HSS participants had a significantly higher incidence of hypertension (87.5 versus 50.0%, P = 0.02), a higher glomerular filtration rate (median, first to fourth quartile: 81.9, 72.3-95.2 versus 72.3, 59.9-81.2 ml/min; P = 0.03) and greater kidney length (median, first to fourth quartile: 68.2, 63.3-72.1 versus 61.9, 58.7-62.7 mm/m of height; P = 0.003). The incidence of hypertension remained significantly higher in HSS individuals after adjustment for age, intercurrent changes in body mass index and baseline blood pressure on low sodium diet (P = 0.04). CONCLUSION Our findings indicate that individuals with higher BP salt-sensitivity have a higher rate of incident hypertension and suggest an altered renal tubular sodium handling involving a trend to increased glomerular filtration rate and blood pressure over time as a possible mechanism.

Objective To study the interaction between the C(-344)T CYP11B2 polymorphism and known determinants (age, body mass and dietary sodium) of blood pressure and plasma aldosterone. Design Cross-sectional and longitudinal (1980-1995) survey of male workers in southern Italy. Setting Medical centre of the Olivetti factories. Participants In 1995, the C(-344)T polymorphism was characterized in 811 untreated men. A subgroup of 280 participants already seen in 1980 was the object of longitudinal analysis. Main outcome measures Blood pressure, demographic, anthropometric and biochemical variables (serum and urinary electrolytes and plasma aldosterone) and frequency of the C(-344)T polymorphism. Results In the whole population, there was no difference among genotypes for any of the variables examined. However, multiple regression showed a significant interaction between age (but not body mass or sodium intake) and genotype with regard to systolic (P = 0.03) and diastolic (P= 0.02) pressure variability independently of covariates. Diastolic pressure increased linearly with age in carriers of the T allele (TT, P < 0.001 and TC, P = 0.005), but not in CC homozygotes (P= 0.848). In T carriers - but not in CC homozygotes - blood pressure and serum potassium increased and plasma aldosterone and serum sodium decreased across quintiles of age (P< 0.001 for all trends). In the longitudinal study, diastolic pressure increased significantly over time only in T carriers (TC+TT: +2.6 ± 0.6, versus CC: - 0.4 ± 1.5 mmHg, P= 0.04). Conclusion Inter-individual variation of blood pressure and plasma aldosterone is affected by the interaction of CYP11B2 C(-344)T polymorphism and ageing, thus supporting a role for this variant in mechanisms affecting blood pressure regulation.

Objective To examine whether hypertension predicts the incidence of kidney stone disease. Design Prospective cohort study (the Olivetti Prospective Heart Study). Setting The Olivetti factory in Southern Italy. Subjects Five hundred and three male workers, aged 21 - 68 years, with no evidence of kidney stone disease at baseline. Follow-up 8 years. Main outcome measures Anthropometry, blood pressure, biochemistry and history of kidney stone disease were evaluated at the baseline examination in 1987. Occurrence of kidney stone disease was evaluated again in 1994-1995. Hypertension was defined as systolic blood pressure > or = 160 or diastolic blood pressure, > or = 95 mmHg or both, or being on drug therapy for hypertension. Occurrence of kidney stone disease was defined as radiological or echographic evidence of calculi or documented passage of one or more stones. Results At baseline, 114/503 men (22.7%) had hypertension and 32 were on drug treatment. After 8 years, 52 (10.3%) incident cases of kidney stone disease were detected. The majority (n = 45) had a documented passage of one or more stones. The incidence of kidney stone disease was higher in hypertensive than in normotensive men (19/114 (16.7%) versus 33/389 (8.5%); P = 0.011). Hypertensive men had a greater risk of developing kidney stones than normotensive ones (RR 1.96; 95% confidence interval 1.16-3.32). The risk was unaffected by the exclusion of treated hypertensives (2.01; 1.13-3.59) and after adjustment for age (1.89; 1.12-3.18), body weight (1.78; 1.05-3.00) or height (2.00; 1.19-3.38). Conclusions Hypertension in middle-aged men is a significant predictor of kidney stone disease rather than a consequence of renal damage caused by the kidney stones.

INTRODUCTION:The aim of the study was to assess the age-specific, sex-specific, and region-specific average sodium and potassium intake and its association with anthropometric characteristics in a sample of the Italian adult hypertensive population. METHODS:A total of 1232 hypertensive patients were recruited consecutively by 47 centers recognized by the Italian Society of Hypertension. The enrolled participants were on stable antihypertensive treatment. Anthropometric indices, blood pressure, 24-h urinary sodium, and potassium excretion were measured and used as proxy for the average daily sodium and potassium intake. RESULTS:The average sodium intake was 172 mmol (or 10.1 g of salt/day) among men and 138 (or 8.1) among women, with no difference among geographical areas. Over 90% of men and 81% of women had a consumption higher than the recommended standard dietary intake of 5 g/day. The average potassium intake was 63 and 56 mmol, respectively in men and women, again without geographical differences, nearly 92% of men and 95% of women having an intake lower than the recommended intake (100 mmol/day or 3.9 g/day). There was a significant trend to a gradual decrease in sodium intake with age in both sexes (P

OBJECTIVES: Central adiposity, insulin resistance and hypertension are clearly interrelated but the mechanisms underlying this association have not been thoroughly elucidated. As renal sodium handling plays a central role in salt-sensitive forms of hypertension, we investigated the relation of renal tubular sodium handling to abdominal adiposity, blood pressure and insulin sensitivity. DESIGN: Population-based study. PARTICIPANTS: Five hundred and fifty-five untreated Olivetti male workers, aged 25-75 years. SETTING: Olivetti factory medical centers in Pozzuoli and Marcianise (Naples, Italy) MAIN OUTCOME MEASURES: Anthropometric indices, serum insulin, homeostatic model assessment index of insulin sensitivity, blood pressure, fractional excretions of uric acid and exogenous lithium (as markers of renal tubular sodium handling). RESULTS: In univariate analysis, measures of central adiposity (i.e. sagittal abdominal diameter and umbilical circumference) were directly correlated with serum insulin (P < 0.001) and blood pressure levels (P < 0.001) and inversely associated with the fractional excretions of uric acid and lithium (P = 0.01-0.001). In multiple linear regression analysis, the same anthropometric indices but not the measures of peripheral adiposity (arm circumference and tricipital skinfold thickness), were significant predictors of the fractional excretion of uric acid and lithium, independently of age, blood pressure and serum insulin levels (P = 0.01-0.001). CONCLUSIONS: Abdominal adiposity was associated with altered renal tubular sodium handling apart from insulin resistance and high blood pressure. The data indicate that men with prevalent abdominal adiposity have an enhanced rate of tubular sodium reabsorption, mainly at proximal sites. These findings provide a possible mechanistic link between central adiposity and salt-dependent hypertension.

International audience; BACKGROUND: Blood pressure control is of great importance in the prevention of cardiovascular events. AIM: To determine the prevalence, awareness, treatment and control of hypertension in healthy unrelated male-female pairs of European regions. METHODS: The dietary habit profile in European communities with different risk of myocardial infarction: the impact of migration as a model of gene-environment interaction (IMMIDIET) project was a cross-sectional study to investigate differences in the distribution of cardiovascular risk factors and dietary habits in healthy unrelated male-female pairs married or living together in European regions. Eight hundred and two unrelated male-female pairs were randomly recruited in Abruzzo (Italy), Limburg (Belgium) and south-west London (England). Blood pressure was measured using an automated device. Hypertension was defined as systolic blood pressure of at least 140 mmHg or diastolic blood pressure of at least 90 mmHg or current antihypertensive treatment. RESULTS: Overall, 24.4% of the population was hypertensive; among them, one-third was on antihypertensive treatment, but a significant proportion (56%) was unaware of the high blood pressure levels. Men were more often hypertensive than women (29.4 vs. 19.5%, P < 0.0001). Women were more often treated than men (49.8 vs. 28.9%, P < 0.0001). Women from south-west London showed blood pressure levels lower than those from Abruzzo and Limburg (P < 0.001 for both, adjusted for age, BMI and social status). No difference among countries was found in blood pressure levels in men. The adjusted prevalence of hypertension was 20.8% in south-west London, 23.6% in Limburg and 28.87% in Abruzzo (Abruzzo vs. south-west London P = 0.005). The prevalence of antihypertensive treatment was 43.5, 42.5 and 32.1% in Abruzzo, Limburg and south-west London, respectively. Out of those treated for hypertension, 42, 43 and 47.7% in Abruzzo, Limburg and south-west London, respectively, were well controlled. CONCLUSION: In communities of healthy unrelated male-female pairs from three different European regions, more than half of hypertensive patients appeared to have blood pressure levels not at target values. Interventions are required to optimize the use and effectiveness of antihypertensive drug therapy in these patients.

A controlled trial of the effect of low versus high calcium intake on blood pressure was performed in 15 patients with mild essential hypertension (supine blood pressure after a 1-month run-in period: 145.7 +/- 2.6/97.8 +/- 0.9 mmHg, mean +/- s.e.m.). After a 1-week baseline period on a standard calcium intake (900 mg/day, obtained by giving a 500-mg calcium tablet daily, in addition to a 400-mg calcium diet), the patients were randomly entered into a double-blind crossover study of 4-week low calcium intake (400 mg calcium diet plus two placebo tablets/day) and 4-week high calcium intake (1400 mg/day: 400-mg calcium diet plus two 500-mg calcium tablets/day). Compliance with the diets appeared to be satisfactory, based on the results of food record analysis. No significant blood pressure change was observed at the end of the low-compared to the high-calcium regimen. Serum ionized calcium was slightly, but not significantly lower, while 24-h urinary calcium excretion was significantly reduced during the low-calcium diet. No difference was found in urinary sodium and potassium excretion between the two study periods. We conclude that moderate modifications of oral calcium intake are not associated with changes in blood pressure within the time span of this study.

An increase in the polyunsaturated to saturated fatty acid ratio (P:S) in the diet has been reported to reduce blood pressure in man. We have investigated whether an increase in the percentage of saturated fatty acids in the typical Mediterranean diet would affect blood pressure in a sample of healthy rural population of southern Italy. Fifty-seven non-hospitalized normotensive volunteers (29 male, 28 female, aged 30-50 years) were studied. After a 2-week baseline period on their customary diet (P:S = 0.44), they underwent a 6-week isocaloric dietary intervention with a 70\% increase in energy from saturated fatty acids and a corresponding decrease in carbohydrate and mono-unsaturated fat (P:S = 0.23). Thereafter they returned to their usual diet and were followed-up for 6 more weeks (switch-back period). By the end of the intervention period, systolic pressure was increased by 2.6 mmHg in men (P less than 0.05) and by 4.8 mmHg in women (P less than 0.01). Diastolic pressure was not significantly increased, although a significant linear regression of the group average blood pressure over time was observed for both systolic (0.161 mmHg, P less than 0.01) and diastolic pressure (0.107 mmHg, P less than 0.01). After returning to their customary diet, blood pressure returned to baseline (-0.212 mmHg, P less than 0.05 systolic and -0.226 mmHg, P less than 0.01 diastolic). No significant change in body weight occurred throughout the study. These findings suggest that changes in the saturated fatty acid content of the diet with moderate change in the dietary P:S ratio can influence blood pressure to a significant extent.