Gianvincenzo Barba

Potassium intake, stroke, and cardiovascular disease a meta-analysis of prospective studies.

Objective To assess the relation between the level of habitual salt intake and stroke or total cardiovascular disease outcome. Design Systematic review and meta-analysis of prospective studies published 1966-2008. Data sources Medline (1966-2008), Embase (from 1988), AMED (from 1985), CINAHL (from 1982), Psychinfo (from 1985), and the Cochrane Library. Review methods For each study, relative risks and 95% confidence intervals were extracted and pooled with a random effect model, weighting for the inverse of the variance. Heterogeneity, publication bias, subgroup, and meta-regression analyses were performed. Criteria for inclusion were prospective adult population study, assessment of salt intake as baseline exposure, assessment of either stroke or total cardiovascular disease as outcome, follow-up of at least three years, indication of number of participants exposed and number of events across different salt intake categories. Results There were 19 independent cohort samples from 13 studies, with 177 025 participants (follow-up 3.5-19 years) and over 11 000 vascular events. Higher salt intake was associated with greater risk of stroke (pooled relative risk 1.23, 95% confidence interval 1.06 to 1.43; P=0.007) and cardiovascular disease (1.14, 0.99 to 1.32; P=0.07), with no significant evidence of publication bias. For cardiovascular disease, sensitivity analysis showed that the exclusion of a single study led to a pooled estimate of 1.17 (1.02 to 1.34; P=0.02). The associations observed were greater the larger the difference in sodium intake and the longer the follow-up. Conclusions High salt intake is associated with significantly increased risk of stroke and total cardiovascular disease. Because of imprecision in measurement of salt intake, these effect sizes are likely to be underestimated. These results support the role of a substantial population reduction in salt intake for the prevention of cardiovascular disease.

Genetic Variation in the Renin–Angiotensin System and Abdominal Adiposity in Men: The Olivetti Prospective Heart Study

Context Angiotensinogen (AGT), angiotensin-converting enzyme (ACE), and angiotensin II receptor type I (AT2R1) are expressed in adipose tissue, but their role in obesity is unknown. Common polymorphisms involve the ACE gene on chromosome 17 (ACE I/D), the AGT gene on chromosome 1, and the AT2R1 receptor gene on chromosome 3. Contribution Among 959 adult Italian men, DD homozygosity in the ACE gene was associated with overweight (odds ratio, 1.82 [95% CI, 1.16 to 2.87]) and abdominal obesity (odds ratio, 1.76 [CI, 1.06 to 2.90]) compared with the genotypes I/D and II. It was also associated with increases in weight over 20 years. Polymorphisms of AGT and AT2R1 were unrelated to measures of body size. Implications These results suggest that the reninangiotensin system plays a role in the development of obesity. The Editors Human obesity is caused by the interaction of genetic predisposition and many environmental and lifestyle factors (1). Although the chromosomal location of a few putative major genes for human obesity has been identified (2-5), the presence of a greater number of minor genes involved in the process of adipogenesis or in the regulation of adipocyte metabolism probably engenders susceptibility to obesity (6). Polymorphism in several obesity candidate genes has been the subject of intensive investigation, but little attention has been paid to the genes encoding for components of the reninangiotensin system. The products of these genes (angiotensinogen [AGT], angiotensin-converting enzyme [ACE], and angiotensin II type 1 [AT2R1] and type II [AT2R2] receptors) are expressed in the adipose tissue in animal models as well as in humans (7-10). Recent experimental studies suggest that adipose tissue in the reninangiotensin system plays a role in adipocyte growth and differentiation through angiotensin II (11, 12). In addition, epidemiologic studies have reported associations between AGT plasma levels (13, 14), plasma renin activity (15, 16), plasma ACE activity (17), and body mass index (BMI). We investigated the relationship of overweight, obesity, and body fat distribution to three common polymorphisms of the reninangiotensin system: intron 16 of the ACE gene on chromosome 17 (18), the M235T polymorphism of the AGT gene in exon 2 on chromosome 1 (19), and the A-to-C polymorphism in the 3-untranslated region at nucleotide 1166 of the AT2R1 gene on chromosome 3 (20). Because the reninangiotensin system plays a fundamental role in blood pressure regulation and in vascular and cardiac modifications, these polymorphisms have been studied with regard to hypertension and cardiovascular disease. Associations have been reported between the AGT M235T and the AT2R1 A1166C variants and hypertension (19-24), as well as among ACE I/D polymorphism, insulin sensitivity (25-27), and the risk for coronary heart and cerebrovascular disease (28, 29). In adult men who attended the 19941995 follow-up examination of the Olivetti Prospective Heart Study, we examined associations between these polymorphic variants and overweight or obesity, body fat distribution, and related metabolic and hemodynamic variables. We also reported longitudinal findings for a subset of participants who were first examined in 1975 and had been followed for 20 years. Methods Study Sample and Procedures We used the DNA bank and the database of the Olivetti Prospective Heart Study, an epidemiologic investigation of cardiovascular risk factors in men working at the Olivetti factories in southern Italy. The procedures of the Olivetti Prospective Heart Study, which began in 1975, have been described in detail elsewhere (30). Between May 1994 and December 1995, we examined 1075 men 25 to 75 years of age. The participants were seen in the morning, after fasting, in a quiet room at the medical center of the Olivetti factories in Pozzuoli and Marcianise, suburbs of Naples, Italy. We obtained anthropometric measurements, performed blood tests, and administered a fixed-sequence questionnaire that assessed demographic information and medical history. Genotyping of the three polymorphisms of the reninangiotensin system was possible in 959 participants. A group of 457 men seen at the 19941995 follow-up visit of the Olivetti Prospective Heart Study had also been examined in 1975; of these, 143 reported being under dietary restriction for various reasons at follow-up examination. Since the Olivetti Prospective Heart Study aims to evaluate spontaneous changes in body mass and blood pressure, this subgroup was excluded from the main analysis. The local ethics committee approved the study protocol, and participants gave informed consent. Anthropometric Measurements Body weight and height were measured on a standard beam-balance scale with an attached ruler. Body weight was measured to the nearest 0.1 kg, and height was measured to the nearest 1 cm; participants wore light indoor clothing and no shoes. Body mass index was calculated as weight in kilograms divided by the square of the height in meters. At the 19941995 examination, but not at the 1975 examination, waist and arm circumferences were also measured. Waist circumference was measured at the umbilicus level as participants stood erect with abdomens relaxed, arms at their sides, and feet together. After the acromion was marked with each participants arm flexed at a 90-degree angle, arm circumference was measured at the midpoint between the acromion and the olecranon with the arm relaxed and hanging just away from the side of the body. The measurements were obtained to the nearest 0.1 cm with a flexible plastic measuring tape. Overweight was defined as a BMI greater than or equal to 27 kg/m2, obesity was defined as a BMI greater than or equal to 30 kg/m2, and abdominal adiposity was defined as a waist circumference greater than 1.00 m. Blood Pressure Measurement Blood pressure was measured after the participant had been sitting upright for at least 10 minutes. Systolic and diastolic (phase V) blood pressure was measured three 2 minutes apart with a random-zero sphygmomanometer (Gelman Hawksley Ltd., Sussex, United Kingdom). The first reading for each type of pressure was discarded, and the average of the second two readings was recorded. Hypertension was defined as a systolic blood pressure 140 mm Hg or greater, a diastolic blood pressure 90 mm Hg or greater, or both, or as current use of antihypertensive drugs. Biochemical Assays After blood pressure was measured, a fasting venous blood sample was taken in the seated position without stasis. The blood specimens were immediately subjected to centrifugation and stored at 70 C until analyzed. Glucose levels were measured by using an automated method (Cobas-Mira, Roche, Italy), and serum insulin concentration was measured by using radioimmunoassay (Insuline Lisophase, Technogenetics, Milan, Italy). Insulin resistance was estimated by homeostasis model assessment using the following formula, as described by Matthews and colleagues (31): fasting serum insulin level (U/mL) fasting serum glucose level (mmol/L)/22.5. Gene Polymorphisms in the ReninAngiotensin System Genomic DNA was isolated from leukocytes with a nonenzymatic, salting-out procedure (32). The ACE I/D polymorphism in intron 16 was typed by using the method of Rigat and associates (33). To address the possibility of mistyping ID heterozygotes as DD homozygotes because of the preferential amplification of the smaller D allele, all samples typed as DD homozygotes were subjected to a second, independent polymerase chain reaction with a primer pair that permits amplification only in the presence of the I allele; this was done by using the method described by Lindpaintner and coworkers (34). The T235 allele of the ATG gene was detected by using the method of Russ and colleagues (35), and the A1166C polymorphism of the AT2R1 gene was tested as described elsewhere (36). Allelic frequencies were estimated by using gene counting, and genotype distribution was tested for HardyWeinberg equilibrium by using chi-square analysis. Statistical Analysis Analysis of variance was used to evaluate differences in quantitative variables according to genotype; analysis of covariance was performed to account for confounders. A nonparametric test (KruskalWallis) was used for variables that were not normally distributed. The interaction between the effects of gene polymorphism and age on the anthropometric indexes and blood pressure was tested by using multiple linear regression analysis. The association of categorical variables with gene polymorphisms was tested by using logistic regression analysis and is expressed as odds ratios and 95% CIs. Results are expressed as the mean SD or as the mean SE, as specified. Two-sided P values and 95% CIs were used to test the statistical significance of between-group differences. Statistical analysis was performed by using SPSS statistical software, version 10.0 (SPSS, Inc., Chicago, Illinois). Role of the Funding Source The funding source had no role in the collection, analysis, or interpretation of the data or in the decision to submit the paper for publication. Results Table 1 summarizes the main characteristics of the participants of the Olivetti Prospective Heart Study at the 19941995 examination. Nine hundred fifty-nine participants were tested for ACE, AGT, and AT2R1 polymorphism. For the ACE I/D polymorphism, 40% (n = 385) had the DD genotype, 45% (n = 431) had the ID genotype, and 15% (n = 143) had the II genotype. For the AGT polymorphism, 31% (n = 297) had the M235M genotype, 48% (n = 460) had the M235T genotype, and 21% (n = 202) had the T235T genotype. For the AT2R1 polymorphism, 54% (n = 518) had the A1166A genotype, 39% (n = 377) had the A1166C genotype, and 7% (n = 64) had the C1166C genotype. All three polymorphisms were in HardyWeinberg equilibrium, showing that the study sample excluded selection pressure for the genotypes under investigation. Table 1. Characteristics of

Inverse association between body mass and frequency of milk consumption in children

Recent studies have shown an inverse association between the level of dietary Ca, particularly from dairy sources, and body weight in adults; there is, however, a paucity of data regarding this relationship in children. We therefore investigated this issue in 1087 children who underwent body weight and height measurement during a survey on childhood obesity. Lifestyle and dietary habits were investigated by a questionnaire. After excluding children who were following a dietary regimen for any reason, 884 children (M:F 451:433; age 7.5 (sd 2.1) years) were selected. Milk consumption was pooled into four frequency categories: poor (< or =1/week; n 125), moderate (>1 but < or =5-6/week; n 133), regular (1/d; n 408) and high (> or =2/d; n 218). The frequency of consumption of milk was inversely and significantly associated (t=-2.964, P=0.003) with age- and sex-specific BMI z-scores by linear regression analysis, controlling for sex, age, physical activity, birth weight and parental overweight and education. The statistical association remained significant (t=-2.831, P=0.005) after the inclusion of children consuming only skimmed milk (n 91). Milk consumption was still significantly and inversely associated with BMI z score (t=-2.791, P=0.005) in the whole-milk consumers when controlling for age and the frequency of consumption of various foods; this association was no longer significant (P=0.21) when children consuming skimmed milk were included in the analysis. This is the first report showing a significant inverse association between frequency of milk consumption and body mass in children. Regardless of the mechanisms involved, our results might encourage further research on this issue and might have important implications for the prevention of obesity.

Potassium Intake, Stroke, and Cardiovascular Disease

OBJECTIVES The objective of this study was to assess the relation between the level of habitual potassium intake and the incidence of cardiovascular disease (CVD). BACKGROUND Prospective cohort studies have evaluated the relationship between habitual potassium intake and incidence of vascular disease, but their results have not been not entirely consistent. METHODS We performed a systematic search for prospective studies published, without language restrictions (1966 to December 2009). Criteria for inclusion were prospective adult population study, assessment of baseline potassium intake, assessment of vascular events as outcome, and follow-up of at least 4 years. For each study, relative risks (RRs) and 95% confidence intervals (CIs) were extracted and pooled using a random-effect model, weighted for the inverse of the variance. Heterogeneity, publication bias, subgroup, and meta-regression analyses were performed. RESULTS Eleven studies were identified, providing 15 cohort samples that included 247,510 male and female participants (follow-up 5 to 19 years), 7,066 strokes, 3,058 coronary heart disease (CHD) events, and 2,497 total CVD events. Potassium intake was assessed by 24-h dietary recall (n = 2), food frequency questionnaire (n = 6), or 24-h urinary excretion (n = 3). In the pooled analysis, a 1.64-g (42 mmol) per day higher potassium intake was associated with a 21% lower risk of stroke (RR: 0.79; 95% CI: 0.68 to 0.90; p = 0.0007), with a trend toward lower risk of CHD and total CVD that attained statistical significance after the exclusion of a single cohort, based on sensitivity analysis (RR: 0.93; 95% CI: 0.87 to 0.99; p = 0.03 and RR: 0.74; 95% CI: 0.60 to 0.91; p = 0.0037). CONCLUSIONS Higher dietary potassium intake is associated with lower rates of stroke and might also reduce the risk of CHD and total CVD. These results support recommendations for higher consumption of potassium-rich foods to prevent vascular diseases.

Physical fitness reference standards in European children: the IDEFICS study

Background/Objectives:A low fitness status during childhood and adolescence is associated with important health-related outcomes, such as increased future risk for obesity and cardiovascular diseases, impaired skeletal health, reduced quality of life and poor mental health. Fitness reference values for adolescents from different countries have been published, but there is a scarcity of reference values for pre-pubertal children in Europe, using harmonised measures of fitness in the literature. The IDEFICS study offers a good opportunity to establish normative values of a large set of fitness components from eight European countries using common and well-standardised methods in a large sample of children. Therefore, the aim of this study is to report sex- and age-specific fitness reference standards in European children.Subjects/Methods:Children (10 302) aged 6–10.9 years (50.7% girls) were examined. The test battery included: the flamingo balance test, back-saver sit-and-reach test (flexibility), handgrip strength test, standing long jump test (lower-limb explosive strength) and 40-m sprint test (speed). Moreover, cardiorespiratory fitness was assessed by a 20-m shuttle run test. Percentile curves for the 1st, 3rd, 10th, 25th, 50th, 75th, 90th, 97th and 99th percentiles were calculated using the General Additive Model for Location Scale and Shape (GAMLSS).Results:Our results show that boys performed better than girls in speed, lower- and upper-limb strength and cardiorespiratory fitness, and girls performed better in balance and flexibility. Older children performed better than younger children, except for cardiorespiratory fitness in boys and flexibility in girls.Conclusions:Our results provide for the first time sex- and age-specific physical fitness reference standards in European children aged 6–10.9 years.

Altered renal sodium handling in men with abdominal adiposity: a link to hypertension.

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.

Abnormalities of renal sodium handling in the metabolic syndrome. Results of the Olivetti Heart Study.

Objective The mechanisms underlying high blood pressure in the framework of metabolic syndrome (MS) are not clarified: we thus analyzed the relationship of MS and its components to renal tubular sodium handling among participants of the Olivetti Heart Study, an epidemiological investigation of a representative sample of adult white male population in southern Italy. Methods Proximal (FPRNa) and distal (FDRNa) fractional sodium reabsorption were estimated by the clearance of exogenous lithium in 702 participants aged 25–75 years examined in 1994–1995. Blood pressure and relevant anthropometric and biochemical variables were also measured. The diagnosis of MS was based on modified National Cholesterol Education Program (NCEP)-Adult Treatment Panel III (ATP III) criteria. Results FPRNa, but not FDRNa, was directly associated with body mass index (BMI), waist circumference, diastolic pressure, serum triglyceride and uric acid, independently of age and of antihypertensive treatment. After adjustment for age, FPRNa, but not FDRNa, was significantly greater in individuals with MS, as compared to those without [77.6% (95% confidence interval = 76.7–80.1) versus 74.4% (73.7–75.1), P < 0.001]. A similar difference was observed after the exclusion of participants on current antihypertensive treatment (P = 0.018). In untreated individuals, a significant interaction was observed between obesity and insulin resistance as related to FPRNa (P = 0.002): the highest age-adjusted levels of FPRNa were detected in obese hypertensive and obese insulin-resistant participants. Conclusion In this sample of an adult male population, MS was associated with an increased rate of FPRNa. This finding is relevant to the pathophysiology of MS and possibly to the prevention of its cardiovascular and renal consequences.

Moderate alcohol use and health: a consensus document.

AIMS The aim of this consensus paper is to review the available evidence on the association between moderate alcohol use, health and disease and to provide a working document to the scientific and health professional communities. DATA SYNTHESIS In healthy adults and in the elderly, spontaneous consumption of alcoholic beverages within 30 g ethanol/d for men and 15 g/d for women is to be considered acceptable and do not deserve intervention by the primary care physician or the health professional in charge. Patients with increased risk for specific diseases, for example, women with familiar history of breast cancer, or subjects with familiar history of early cardiovascular disease, or cardiovascular patients should discuss with their physician their drinking habits. No abstainer should be advised to drink for health reasons. Alcohol use must be discouraged in specific physiological or personal situations or in selected age classes (children and adolescents, pregnant and lactating women and recovering alcoholics). Moreover, the possible interactions between alcohol and acute or chronic drug use must be discussed with the primary care physician. CONCLUSIONS The choice to consume alcohol should be based on individual considerations, taking into account the influence on health and diet, the risk of alcoholism and abuse, the effect on behaviour and other factors that may vary with age and lifestyle. Moderation in drinking and development of an associated lifestyle culture should be fostered.

Socioeconomic factors and childhood overweight in Europe: results from the multi-centre IDEFICS study.

What is already known about this subject Overweight and obesity can be linked to different parental socioeconomic factors already in very young children. In Western developed countries, the association of childhood overweight and obesity and parental socioeconomic status shows a negative gradient. Ambiguous results have been obtained regarding the association between socioeconomic factors and childhood overweight and obesity in different countries and over time.

The IDEFICS community-oriented intervention programme: a new model for childhood obesity prevention in Europe?

Background and objectives:The European Union—as well as other parts of the world—faces a major challenge of increasing incidence of overweight/obesity. In particular, the increase in childhood obesity gives rise to a strong imperative for immediate action. Yet, little is known about the effectiveness of community interventions, and further research in this field is needed. There is, however, a growing consensus that such research should start from the paradigm that the current living environments tend to counteract healthy lifestyles. Questioning these environments thoroughly can help to develop new pathways for sustainable health-promoting communities. Against this background, the IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) study developed and implemented innovative community-oriented intervention programmes for obesity prevention and healthy lifestyle primarily in children aged 2–10 years in eight European countries: Sweden, Estonia, Germany, Belgium, Hungary, Italy, Spain and Cyprus.Materials and methods:The IDEFICS community-oriented intervention study mobilised an integrated set of interventional efforts at different levels of society, with the aim of facilitating the adoption of a healthy obesity-preventing lifestyle. The overall programme has been composed of 10 modules: three at community level, six at school level and one for parents. The main focus was on diet, physical activity and stress-coping capacity. The sphere of action encompassed both children and their (grand) parents, schools, local public authorities and influential stakeholders in the community. All materials for the interventions were centrally developed and culturally adapted.Results:So far, the following has been achieved: focus group research, literature review and expert consultations were done in an early phase as a basis for the development of the intervention modules. The intervention mapping protocol was followed as guide for structuring the intervention research. The overall intervention programmes duration was 2 years, but a longer-term follow-up programme is under development.Conclusions:This large-scale European effort is expected to contribute significantly to the understanding of this major public health challenge.