Increased glucocorticoid metabolism in diabetic kidney disease.

AIMS: Glomerular damage indicated by proteinuria is a main symptom in diabetic nephropathy. Mineralocorticoid receptor (MR) antagonists (MRAs) are beneficial irrespective of aldosterone availability. Thus, we hypothesized an alternatively activated MR to promote glomerular damage in proteinuric diabetic nephropathy. Specifically, we aimed first to demonstrate the presence of steroid hormones serving as alternative MR targets in type II diabetic patients with proteinuric kidney disease, second whether MR selectivity was modified, third to characterize MR and glucocorticoid receptor (GR) expression and activity in glomerular cell types exposed to eu- and hyperglycemic conditions, fourth to characterize the pro-fibrotic potential of primary human renal mesangial cells (HRMC) upon stimulation with aldosterone and cortisol, and fifth to specify the involvement of the MR and/or GR in pro-fibrotic signaling. MATERIALS AND METHODS: Urinary steroid hormone profiles of patients with diabetic kidney disease were analyzed by gas chromatography-mass spectrometry and compared to an age and gender matched healthy control group taken out of a population study. In both cohorts, the activity of the MR pre-receptor enzyme 11ß-hydroxysteroid dehydrogenase type 2 (HSD11B2), which inactivates cortisol to prevent it from binding to the MR, was assessed to define a change in MR selectivity. Expression of HSD11B2, MR and GR was quantified in HRMC and primary human renal glomerular endothelial cells (HRGEC). Activity of MR and GR was explored in HRMC by measuring the MR/GR down-stream signal SGK1 and the pro-fibrotic genes TGFB1, FN1 and COL1A1 in normal and high glucose conditions with the MR/GR agonists aldosterone/cortisol and the MR/GR antagonists spironolactone/RU486. RESULTS: Patients with diabetic kidney disease excreted more tetrahydroaldosterone than the control group reaching significance in men. The excretion of MR-agonistic steroid hormones was only increased for 18-hydroxytetrahydrocorticosterone in diabetic women. The excretion of most glucocorticoids was higher in the diabetic cohort. Higher apparent systemic HSD11B2 activity suggested less activation of the MR by cortisol in diabetic patients. Both cell types, HRMC and HRGEC, lacked expression of HSD11B2. Hyperglycemic conditions did not change MR and GR expression and activity. Stimulation with both aldosterone and cortisol promoted upregulation of pro-fibrotic genes in HRMC. This effect of MR and/or GR activation was more pronounced in high glucose conditions and partially inhibited by MRAs and GR antagonists. CONCLUSIONS: In patients with diabetic kidney disease alternative MR activation is conceivable as cortisol and cortisone metabolites are increased. Systemic availability of active metabolites is counteracted via an increased HSD11B2 activity. As this cortisol deactivation is absent in HRMC and HRGEC, cortisol binding to the MR is enabled. Both, cortisol and aldosterone stimulation led to an increased expression of pro-fibrotic genes in HRMC. This mechanism was related to the MR as well as the GR and more marked in high glucose conditions linking the benefit of MRAs in diabetic kidney disease to these findings.

Clinical Profiles and Factors Associated with a Low Sodium Intake in the Population: An Analysis of the Swiss Survey on Salt.

As a part of the salt controversy, it has been suggested that people with a low sodium intake have an increased risk of cardiovascular events. However, there is no clear explanation for this increased risk. We examined the socio-demographic, clinical profile, and behavioral factors associated with a low sodium intake in the Swiss subjects who participated in the Swiss Survey on Salt. Only 13.3% of the Swiss population eat less than 5 g of salt daily and among them 78.2% are women. Subjects with a low sodium intake eat and drink less as reflected by lower intakes of proteins, potassium, and calcium and a smaller urine volume. In addition, a low blood pressure, a normal body mass index, a low prevalence of obesity, a low serum uric acid, and less alcohol and cigarette consumption characterized this group, suggesting a rather low cardiovascular risk profile. Being single and doing most of the cooking at home are associated with a low intake of sodium, as well as a less frequent consumption of meat and fish when eating less than 5 g salt per day. However, the awareness of the effects of salt on health and cardiovascular risk, health concerns, and physical activity are similar in subjects eating more or less salt. In conclusion, we could not evidence clinical or behavioral factors that could significantly increase the risk of developing cardiovascular events in low salt eaters.

Uranium exposure of the Swiss population based on 24-hour urinary excretion.

AIM OF THE STUDY: Important regional differences in uranium exposure exist because of varying uranium concentrations in soil, water and food. Comprehensive data on the exposure of the general population to uranium is, however, scarce. Based on the 24-hour urinary excretion, the uranium exposure of the adult Swiss population was assessed in relation to age, sex, place of residence, body mass index (BMI), smoking habit and type of drinking water, as well as risk factors in relation to kidney impairment and indicators of a possible renal dysfunction. METHODS: Uranium was quantified in 24-hour urine from a nationwide population-based sample (n = 1393). The ratio 238U/233U was measured for isotope dilution calibration with a sector field inductively coupled plasma mass spectrometer (HR-ICP-MS). RESULTS: Overall median and 95th percentile were 15 and 67 ng/24 h, respectively. The place of residence significantly influenced urinary uranium excretion. However, most of the highest urinary uranium excretion levels could not be associated to areas known for their elevated uranium concentrations in the drinking water. Sources other than the local drinking water (e.g., bottled water) might be important, too. Gender as well as albumin excretion also had a significant effect on uranium excretion. The latter was, however, strongly dependent on the presence of diabetes mellitus. No association was found for age, BMI, smoking habit or the other examined kidney related variables. CONCLUSIONS: On the basis of uranium exposure, assessed via 24-hour urinary uranium excretion, and current knowledge of the toxicity of naturally occurring uranium, a substantial corresponding health risk for the general adult population is unlikely. However, as long as no specific sensitive biomarker for the biological impact of low-dose chronic uranium exposure has been identified and validated, assessing subtle health impact of such exposure will remain difficult.

Sex and Body Mass Index Modify the Association Between Leptin and Sodium Excretion: A Cross-sectional Study in an African Population.

BACKGROUND: Renal sodium handling could be a potential mediator linking adipokines to hypertension. The aim of the study was to assess the relationship of leptin with urinary sodium excretion and proximal sodium reabsorption in humans. METHODS: This cross-sectional study was conducted on participants of hypertensive families from the Seychelles Island. A split urine (daytime and nighttime) collection and plasma leptin were measured. Endogenous lithium clearance was used to assess proximal sodium reabsorption. Mixed multiple linear regression tests adjusted for confounding factors were used. RESULTS: Three hundred and sixty-five participants (57% women) were included in this analysis. Leptin and adiponectin were higher in women (P < 0.001). Leptin was associated positively with daytime (coefficient [c]: 0.16, standard deviation (SD): 0.03, P < 0.001), nighttime urinary sodium excretion (c: 0.17, SD: 0.04), P < 0.01), daytime lithium clearance (c: 0.40, SD: 0.08, P < 0.001), and nighttime lithium clearance (c: 0.39, SD: 0.10, P < 0.001) after adjusting for sex. The association was lost or mitigated only when BMI was introduced in the model. When BMI was categorized in normal vs. overweight participant, leptin was associated with daytime and nighttime sodium excretion rates (c: 0.14, SD: 0.05, P = 0.011 and c: 0.22, SD: 0.07, P = 0.002, respectively) only in overweight participants. CONCLUSION: Leptin is associated positively with daytime and nighttime sodium excretion and lithium clearance suggesting a natriuretic rather than a sodium retaining effect of leptin. Sex and body mass index (BMI) are major confounders in this association. These results highlight the importance of sex and obesity in our understanding of the relationships between leptin, blood pressure, and renal sodium handling.

Effects of short- and long-term exposures to particulate matter on inflammatory marker levels in the general population.

The effect of particulate matter (PM) on health increases with exposure duration but the change from short to longer term is not well studied. We examined the exposure to PM smaller 10 µm (PM10) from short to longer duration and their associations with levels of inflammatory markers in the population-based CoLaus cohort in Lausanne, Switzerland. Baseline and follow-up CoLaus data were used to study the associations between PM10 exposure and inflammatory markers, including the high-sensitivity C-reactive protein (CRP), as well as interleukin 1-beta (IL-1ß), interleukin 6 (IL-6), and tumor-necrosis-factor alpha (TNF-α) using mixed models. Exposure was determined for each participant's home address from hourly air quality simulations at a 5-m resolution. Short-term exposure intervals were 1 day, 1 week, and 1 month prior to the hospital visit (blood withdrawal); long-term exposure intervals were 3 and 6 months prior to the visit. In most time windows, IL-6, IL-1ß, and TNF-α were positively associated with PM10. No significant associations were identified for CRP. Adjusted associations with long-term exposures were stronger and more significant than those for short-term exposures. In stratified models, gender, age, smoking status, and hypertension only led to small modifications in effect estimates, though a few of the estimates for IL-6 and TNF-α became non-significant. In this general adult cohort exposed to relatively low average PM10 levels, clear associations with markers of systemic inflammation were observed. Longer duration of elevated exposure was associated with an exacerbated inflammatory response. This may partially explain the elevated disease risk observed with chronic PM10 exposure. It also suggests that reducing prolonged episodes of high PM exposure may be a strategy to reduce inflammatory risk.

Socioeconomic status, non-communicable disease risk factors, and walking speed in older adults: multi-cohort population based study.

OBJECTIVE: To assess the association of low socioeconomic status and risk factors for non-communicable diseases (diabetes, high alcohol intake, high blood pressure, obesity, physical inactivity, smoking) with loss of physical functioning at older ages. DESIGN: Multi-cohort population based study. SETTING: 37 cohort studies from 24 countries in Europe, the United States, Latin America, Africa, and Asia, 1990-2017. PARTICIPANTS: 109 107 men and women aged 45-90 years. MAIN OUTCOME MEASURE: Physical functioning assessed using the walking speed test, a valid index of overall functional capacity. Years of functioning lost was computed as a metric to quantify the difference in walking speed between those exposed and unexposed to low socioeconomic status and risk factors. RESULTS: According to mixed model estimations, men aged 60 and of low socioeconomic status had the same walking speed as men aged 66.6 of high socioeconomic status (years of functioning lost 6.6 years, 95% confidence interval 5.0 to 9.4). The years of functioning lost for women were 4.6 (3.6 to 6.2). In men and women, respectively, 5.7 (4.4 to 8.1) and 5.4 (4.3 to 7.3) years of functioning were lost by age 60 due to insufficient physical activity, 5.1 (3.9 to 7.0) and 7.5 (6.1 to 9.5) due to obesity, 2.3 (1.6 to 3.4) and 3.0 (2.3 to 4.0) due to hypertension, 5.6 (4.2 to 8.0) and 6.3 (4.9 to 8.4) due to diabetes, and 3.0 (2.2 to 4.3) and 0.7 (0.1 to 1.5) due to tobacco use. In analyses restricted to high income countries, the number of years of functioning lost attributable to low socioeconomic status by age 60 was 8.0 (5.7 to 13.1) for men and 5.4 (4.0 to 8.0) for women, whereas in low and middle income countries it was 2.6 (0.2 to 6.8) for men and 2.7 (1.0 to 5.5) for women. Within high income countries, the number of years of functioning lost attributable to low socioeconomic status by age 60 was greater in the United States than in Europe. Physical functioning continued to decline as a function of unfavourable risk factors between ages 60 and 85. Years of functioning lost were greater than years of life lost due to low socioeconomic status and non-communicable disease risk factors. CONCLUSIONS: The independent association between socioeconomic status and physical functioning in old age is comparable in strength and consistency with those for established non-communicable disease risk factors. The results of this study suggest that tackling all these risk factors might substantially increase life years spent in good physical functioning.

Association of 24-Hour Blood Pressure With Urinary Sodium Excretion in Healthy Adults.

BACKGROUND: While the positive relationship between urinary sodium excretion and blood pressure (BP) is well established for middle-aged to elderly individuals using office BP, data are limited for younger individuals and ambulatory BP measurements. METHODS: Our analysis included 2,899 individuals aged 18 to 90 years from 2 population-based studies (GAPP, Swiss Kidney Project on Genes in Hypertension [SKIPOGH]). Participants with prevalent cardiovascular disease, diabetes, or on BP-lowering treatment were excluded. In SKIPOGH, 24-hour urinary sodium excretion was used as a measure of sodium intake, while in GAPP it was calculated from fasting morning urinary samples using the Kawasaki formula. Multivariable linear regression models were used to assess the relationships of 24-hour urinary salt excretion with office and ambulatory BP measurements. RESULTS: Mean age, ambulatory BP, sodium excretion, and estimated glomerular filtration rate in GAPP and SKIPOGH were 35 and 44 years, 123/78 and 118/77 mm Hg, 4.2 and 3.3 g/d, and 110 and 99 ml/min/1.73 m2, respectively. A weak linear association was observed between 24-hour ambulatory systolic BP and urinary sodium excretion (ß (95% confidence interval [CI]) per 1 g increase in sodium excretion (0.33 % (0.09; 0.57); P = 0.008). No significant relationships were observed for 24-hour ambulatory diastolic BP (ß (95% CI) (0.13 % (-0.15; 0.40) P = 0.37). When repeating the analyses in different age groups, all BP indices appeared to have stronger relationships in the older age groups (>40 years). CONCLUSIONS: In these large cohorts of healthy adults, urinary sodium excretion was only weakly associated with systolic 24-hour ambulatory BP.

Urinary Cadmium Excretion Is Associated With Increased Synthesis of Cortico- and Sex Steroids in a Population Study.

Context: Urinary cadmium (Cd) excretion is associated with cancer and cardiovascular morbidity. A potential mechanism could be disturbance of steroidogenesis in gonads and adrenal glands. Objective: We tested whether urinary excretion of Cd is correlated with that of cortico- and sex steroid metabolites in the general adult population. Setting: The Swiss Kidney Project on Genes in Hypertension is a multicentric, family-based population study. Measures: Urinary excretions of steroid hormone metabolites and Cd were measured with separate day and night collections. Associations were analyzed by mixed linear models. Results: Urinary Cd and testosterone excretions in men were significantly correlated (respective day and night ß values [standard error (SE)], 1.378 [0.242], P < 0.0005; and 1.440 [0.333], P < 0.0005), but not in women [0.333(0.257), P = 0.2; and 0.674 (0.361), P = 0.06]. Urinary Cd and cortisol excretions were positively associated in both sexes [day: ß = 0.475 (SE, 0.157), P = 0.0025, and 0.877 (SE, 0.194), P < 0.0005, respectively; night: ß = 0.875 (SE, 0.253), P < 0.0005 and 1.183 (SE, 0.277), P = 0.00002, respectively]. Cd excretion was correlated with mineralocorticoid metabolites excretion, except tetrahydroaldosterone, in both sexes (P < 0.01). There was an independent effect of Cd on sex hormone and corticosteroid synthesis and an interdependent effect on gluco- and mineralcorticoid production. Conclusion: Our findings provide evidence for a global stimulating effect on steroid synthesis already at low-dose Cd exposure. These findings might explain the association of Cd with diseases such as steroid-sensitive cancers or metabolic disorders.

Major Differences in Diet across Three Linguistic Regions of Switzerland: Results from the First National Nutrition Survey menuCH.

Switzerland is a multilingual country located between Germany, France and Italy, which differ by dietary habits and related outcomes. We explored differences in food consumption as well as compliance to the Swiss food-based dietary guidelines (FBDG) across the German-, French-, and Italian-speaking regions. The 2014-2015 nationwide cross-sectional survey was conducted among a stratified random sample of 2057 adults aged 18 to 75 years. Trained dietitians assessed food consumption via two non-consecutive 24-h dietary recalls using the international validated software GloboDiet®. Recorded foods and beverages were classified into six groups and 31 subgroups relevant for assessing compliance to the FBDG (Swiss Food Pyramid). Usual daily intake distributions were modelled and weighted for sampling design, non-response, weekdays and season. Participation rate was 38%. Significant differences across regions were observed in 18 of 31 food subgroups (p ≤ 0.01). Weighted mean daily intakes in the German-, French- and Italian-speaking regions were, respectively, 245 g, 155 g, 140 g for soft drinks, 273 g, 214 g, 135 g for coffee, 127 g, 72 g, 109 g for milk, 32 g, 45 g, 43 g for red meat, 18 g, 29 g, 34 g for fish/seafood, 8.1 g, 6.4 g, 3.7 g for butter, and 206 g, 214 g, 168 g for vegetables. The seven FBDGs were followed by <1% of the population. Four in 10 participants met ≥3 FBDG. Eighteen percent of participants ate ≥5 portions of fruit and vegetables a day, without regional differences. Food consumption substantially differed across the three linguistic regions of Switzerland. Adherence to FBDG was uniformly low. This highlights the potential influence of culture on diet. Nutritional education along with public health interventions are needed and may be most efficient if regionally targeted.

A population-based approach to assess the heritability and distribution of renal handling of electrolytes.

The handling of electrolytes by the kidney is essential for homeostasis. However, the heritability of these processes, the first step in gene discovery, is poorly known. To help clarify this, we estimated the heritability of serum concentration, urinary excretion, renal clearance, and fractional excretion of sodium, potassium, magnesium, calcium, phosphate, and chloride in a population-based study. Nuclear families were randomly selected from the general population in Lausanne, Geneva, and Bern, Switzerland, and urine collected over 24-hour periods. We used the ASSOC program (S.A.G.E.) to estimate narrow sense heritability, including sex, age, body mass index, and study center as covariates in the model. The 1128 participants, from 273 families, had a mean age of 47 years, body mass index of 25.0 kg/m2, and an estimated glomerular filtration rate (CKD-EPI) of 98 mL/min/1.73 m2. The heritability of serum concentration was highest for calcium, 37% and lowest for sodium, 13%. The heritability of 24-hour urine clearances, excretions, and fractional excretions ranged from 15%, 10%, and 16%, respectively, for potassium to 45%, 44%, and 51%, respectively, for calcium. All probability values were significant. The heritability for phosphate-related phenotypes was lower than that for calcium. Thus, the serum and urine concentrations as well as urinary excretion and renal handling of electrolytes are heritable in the general adult population. The phenotypic variance attributable to additive genetic factors was variable and was higher for calcium. These results pave the way for identifying genetic variants involved in electrolyte homeostasis in the general population.

Bayesian association scan reveals loci associated with human lifespan and linked biomarkers.

The enormous variation in human lifespan is in part due to a myriad of sequence variants, only a few of which have been revealed to date. Since many life-shortening events are related to diseases, we developed a Mendelian randomization-based method combining 58 disease-related GWA studies to derive longevity priors for all HapMap SNPs. A Bayesian association scan, informed by these priors, for parental age of death in the UK Biobank study (n=116,279) revealed 16 independent SNPs with significant Bayes factor at a 5% false discovery rate (FDR). Eleven of them replicate (5% FDR) in five independent longevity studies combined; all but three are depleted of the life-shortening alleles in older Biobank participants. Further analysis revealed that brain expression levels of nearby genes (RBM6, SULT1A1 and CHRNA5) might be causally implicated in longevity. Gene expression and caloric restriction experiments in model organisms confirm the conserved role for RBM6 and SULT1A1 in modulating lifespan.

Geriatric Patient Safety Indicators Based on Linked Administrative Health Data to Assess Anticoagulant-Related Thromboembolic and Hemorrhagic Adverse Events in Older Inpatients: A Study Proposal.

BACKGROUND: Frail older people with multiple interacting conditions, polypharmacy, and complex care needs are particularly exposed to health care-related adverse events. Among these, anticoagulant-related thromboembolic and hemorrhagic events are particularly frequent and serious in older inpatients. The growing use of anticoagulants in this population and their substantial risk of toxicity and inefficacy have therefore become an important patient safety and public health concern worldwide. Anticoagulant-related adverse events and the quality of anticoagulation management should thus be routinely assessed to improve patient safety in vulnerable older inpatients. OBJECTIVE: This project aims to develop and validate a set of outcome and process indicators based on linked administrative health data (ie, insurance claims data linked to hospital discharge data) assessing older inpatient safety related to anticoagulation in both Switzerland and France, and enabling comparisons across time and among hospitals, health territories, and countries. Geriatric patient safety indicators (GPSIs) will assess anticoagulant-related adverse events. Geriatric quality indicators (GQIs) will evaluate the management of anticoagulants for the prevention and treatment of arterial or venous thromboembolism in older inpatients. METHODS: GPSIs will measure cumulative incidences of thromboembolic and bleeding adverse events based on hospital discharge data linked to insurance claims data. Using linked administrative health data will improve GPSI risk adjustment on patients' conditions that are present at admission and will capture in-hospital and postdischarge adverse events. GQIs will estimate the proportion of index hospital stays resulting in recommended anticoagulation at discharge and up to various time frames based on the same electronic health data. The GPSI and GQI development and validation process will comprise 6 stages: (1) selection and specification of candidate indicators, (2) definition of administrative data-based algorithms, (3) empirical measurement of indicators using linked administrative health data, (4) validation of indicators, (5) analyses of geographic and temporal variations for reliable and valid indicators, and (6) data visualization. RESULTS: Study populations will consist of 166,670 Swiss and 5,902,037 French residents aged 65 years and older admitted to an acute care hospital at least once during the 2012-2014 period and insured for at least 1 year before admission and 1 year after discharge. We will extract Swiss data from the Helsana Group data warehouse and French data from the national health insurance information system (SNIIR-AM). The study has been approved by Swiss and French ethics committees and regulatory organizations for data protection. CONCLUSIONS: Validated GPSIs and GQIs should help support and drive quality and safety improvement in older inpatients, inform health care stakeholders, and enable international comparisons. We discuss several limitations relating to the representativeness of study populations, accuracy of administrative health data, methods used for GPSI criterion validity assessment, and potential confounding bias in comparisons based on GQIs, and we address these limitations to strengthen study feasibility and validity.

Associations of sodium, potassium and protein intake with blood pressure and hypertension in Switzerland.

BACKGROUND: Nutritional factors play an important role in the regulation of blood pressure and in the development of hypertension. In this analysis, we explored the associations of 24-hour urinary Na+, K+ and urea excretion with blood pressure levels and the risk of hypertension in the Swiss population, taking regional linguistic differences into account. METHODS: The Swiss Survey on Salt is a population based cross-sectional study that included 1336 subjects from the three main linguistic regions (French, German and Italian) of Switzerland. Blood pressure was measured with a validated oscillometric Omron HEM 907 device. Hypertension was defined as current antihypertensive treatment or a mean systolic blood pressure >140 mm Hg and/or diastolic >90 mm Hg, based on eight blood pressure measurements performed at two visits. Na+, K+ and urea excretion were assessed in 24-hour urine collections. We use multiple logistic/linear regressions to explore the associations of urine Na+, K+ and urea with blood pressure / hypertension, taking into account potential confounders and effect modifiers. RESULTS: The prevalence of hypertension was 30%, 26% and 17% in the German-, French- and Italian- speaking regions respectively, (p-value across regions <0.001). In the Swiss adult population, besides age, sex, and body mass index, urinary Na+ excretion was positively associated with systolic blood pressure and hypertension. Urinary K+ excretion tended to be negatively associated with blood pressure but this was not significant (p = 0.08). Hypertensive people had a higher 24-hour urinary Na+/K+ ratio than normotensive people (p = 0.003). Urinary urea excretion was associated with neither blood pressure nor hypertension. Participants from the German-speaking region had a higher likelihood of having a high systolic blood pressure. CONCLUSIONS: We confirm a high prevalence of elevated blood pressure in Swiss adults, including regional differences. In Switzerland, urinary Na+ excretion is associated positively with blood pressure and hypertension, independently of urinary K+ and urea excretion. The observed differences in blood pressure levels across linguistic regions are independent of the urinary Na+, K+ and urea excretion.

Trends in prevalence, awareness, treatment and control of high blood pressure in the Seychelles between 1989 and 2013.

BACKGROUND: Limited data are available in the African region on trends in blood pressure (BP) and awareness, treatment and control rates. OBJECTIVE: We examined trends in these indicators for a 25-year period in the Seychelles, a rapidly developing small island state in the African region. METHODS: Population-based surveys of adults aged 25-64 years were performed in 1989, 1994, 2004 and 2013 using nearly identical methods for all surveys. BP was based on the average of the second and third readings. Data were age-standardized. RESULTS: Between 1989 and 2013, mean SBP decreased in older adults (but increased in younger adults) and mean DBP decreased in all age categories, despite a marked secular increase in mean BMI. At age 25-64 years, the proportions with BP at least 140/90 mmHg decreased from 44%/33% (men/women) in 1989 to 37%/22% in 2013. The proportions of persons aware of having high BP (among those with BP ≥ 140/90 or treatment) increased from 40%/63% (men/women) in 1989 to 65%/80% in 2013; the proportions under treatment (among aware) increased from 37%/49% to 64%/78%; and the proportions with controlled BP (among treated) increased from 10%/16% to 34%/61%. Awareness was associated with female sex, age, obesity and diabetes; treatment with age, obesity, low alcohol consumption and diabetes; and control with female sex, age and high socio-economic status. In 2013, the main classes of antihypertensive medications were used in similar proportions, and 64.5% received at least two medications. CONCLUSION: The prevalence of high BP (≥140/90 mmHg) decreased over time, which paralleled improved detection and control of hypertension. The identified associated factors should be considered when strengthening BP control programs.

Building leadership capacity to prevent and control noncommunicable diseases: evaluation of an international short-term training program for program managers from low- and middle-income countries.

OBJECTIVES: To assess the impact of a 1-week training seminar jointly developed and conducted by the World Health Organization and the University Institute of Social and Preventive Medicine of Lausanne targeting senior policy-makers in low- and middle-income countries on public health aspects of noncommunicable diseases (NCDs). METHODS: A short qualitative questionnaire was emailed to all participants to one of the nine seminars organized between 2010 and 2015. RESULTS: From the 195 participants from 96 different countries, 122 (63%) completed the questionnaire. Among them, 87% reported that the seminar made a positive contribution to their professional development and 48% said it helped strengthening their national NCD program. All respondents remained directly or indirectly involved in NCD work. A frequent suggestion was that similar seminars are developed in their region or country. CONCLUSIONS: The evaluation strongly suggests that this short-term seminar had positive impact on both participants' personal development and the organization they worked for. There is a demand for organizing similar seminars at regional/country levels to support NCD prevention and control programs.

Performance of targeted screening for the identification of hypertension in children.

Targeted screening of hypertension in childhood might be more efficient than universal screening. We estimated the sensitivity, specificity, negative and positive predictive values of combined parental history of hypertension and overweight/obesity for the diagnosis of hypertension in 5207 children aged 10-14 years. Children had hypertension if they had sustained elevated blood pressure over three separate visits. The prevalence of hypertension was 2.2%. 14% of children were overweight or obese, 20% had a positive history of hypertension in at least one parent and 30% had either or both conditions. Targeted screening of hypertension to children with either overweight/obesity or with hypertensive parents limits the proportion of children (30%) to screen and identifies up to 65% of all hypertensive cases.

Interventions promoting healthy eating as a tool for reducing social inequalities in diet in low- and middle-income countries: a systematic review.

INTRODUCTION: Diet is a major risk factor for non-communicable diseases (NCDs) and is also strongly patterned by socioeconomic factors. Whether interventions promoting healthy eating reduce social inequalities in diet in low- and middle-income countries (LMICs) remains uncertain. This paper aims to summarize current evidence on interventions promoting healthy eating in LMICs, and to establish whether they reduce social inequalities in diet. METHODS: Systematic review of cross-sectional or quasi-experimental studies (pre- and post-assessment of interventions) in Pubmed, Scielo and Google Scholar databases, including adults in LMICs, assessing at least one outcome of healthy eating and showing results stratified by socioeconomic status. RESULTS: Seven intervention studies including healthy eating promotion, conducted in seven LMICs (Brazil, Chile, Colombia, Iran, Panama, Trinidad and Tobago, and Tunisia), met our inclusion criteria. To promote healthy eating, all interventions used nutrition education and three of them combined nutrition education with improved acces to foods or social support. Interventions targeted mostly women and varied widely regarding communication tools and duration of the nutrition education sessions. Most interventions used printed material, media use or face-to-face training and lasted from 6 weeks to 5 years. Four interventions targeted disadvantaged populations, and three targeted the entire population. In three out of four interventions targeting disadvantaged populations, healthy eating outcomes were improved suggesting they were likely to reduce social inequalities in diet. All interventions directed to the entire population showed improved healthy eating outcomes in all social strata, and were considered as having no impact on social inequalities in diet. CONCLUSION: In LMICs, agentic interventions promoting healthy eating reduced social inequalities in diet when specifically targeting disadvantaged populations. Further research should assess the impact on social inequalities in diet of a combination of agentic and structural approaches in interventions promoting healthy eating.

Relation of 24-hour urinary caffeine and caffeine metabolite excretions with self-reported consumption of coffee and other caffeinated beverages in the general population.

BACKGROUND: Caffeine intake is generally estimated by self-reported consumption, but it remains unclear how well self-report associates with metabolite urinary excretion. We investigated the associations of self-reported consumption of caffeinated drinks with urinary excretion of caffeine and its major metabolites in an adult population. METHODS: We used data from the population-based Swiss Kidney Project on Genes in Hypertension (SKIPOGH) study. Consumption of caffeinated coffee, decaffeinated coffee and other caffeinated beverages was assessed by self-administered questionnaire. Quantification of caffeine, paraxanthine, theobromine and theophylline was performed by ultra-high performance liquid chromatography tandem mass spectrometry in 24-h urine. Association of reported consumption of caffeinated drinks with urinary caffeine derived metabolites was determined by quantile regression. We then explored the association between urinary metabolite excretion and dichotomized weekly consumption frequency of caffeinated coffee, with Receiver Operator Characteristic (ROC) analysis. RESULTS: In the present analysis, we included 598 individuals (52% women, mean age =46 ± 17 years). Self-reported caffeinated coffee intake was positively associated with 24-h urinary excretions of paraxanthine, theophylline and caffeine (p < 0.001), whereas reported intakes of decaffeinated coffee and other caffeinated beverages showed no association. In ROC analysis, optimal discrimination between individuals consuming less than one caffeinated coffee/week, vs. at least one coffee, was obtained for 24-h urinary paraxanthine (Area Under Curve (AUC) = 0.868, 95% Confidence Interval (CI) [0.830;0.906]), with slightly lower performance for theophylline and caffeine, whereas theobromine did not allow any discrimination. CONCLUSION: Our results suggest that reported consumption of caffeinated coffee is positively associated with 24-h urinary excretion of caffeine, paraxanthine, and theophylline, and may be used as a marker of caffeine intake for epidemiological studies.

Fibroblast growth factor 23 and markers of mineral metabolism in individuals with preserved renal function.

Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that regulates phosphate homeostasis. Circulating FGF23 is elevated in chronic kidney disease (CKD) and independently associated with poor renal and cardiovascular outcomes and mortality. Because the study of FGF23 in individuals with normal renal function has received little attention, we examined in a large, population-based study of 1128 participants the associations of FGF23 with markers of mineral metabolism and renal function. The median estimated glomerular filtration rate (eGFR) of the cohort was 105 ml/min per 1.73 m(2), and the median plasma FGF23 was 78.5 RU/ml. FGF23 increased and plasma 1,25-dihydroxyvitamin D3 decreased significantly below an eGFR threshold of 102 and 99 ml/min per 1.73 m(2), respectively. In contrast, plasma parathyroid hormone increased continuously with decreasing eGFR and was first significantly elevated at an eGFR of 126 ml/min per 1.73 m(2). On multivariable analysis adjusting for sex, age, body mass index, and GFR, FGF23 was negatively associated with 1,25-dihydroxyvitamin D3, and urinary absolute and fractional calcium excretion but not with serum calcium or parathyroid hormone. We found a positive association of FGF23 with plasma phosphate, but no association with urinary absolute or fractional phosphate excretion and, unexpectedly, a positive association with tubular maximum phosphate reabsorption/GFR. Thus, in the absence of CKD, parathyroid hormone increases earlier than FGF23 when the eGFR decreases. The increase in FGF23 occurs at a higher eGFR threshold than previously reported and is closely associated with a decrease in 1,25-dihydroxyvitamin D3. We speculate that the main demonstrable effect of FGF23 in the setting of preserved renal function is suppression of 1,25-dihydroxyvitamin D3 rather than stimulation of renal phosphate excretion.