Genome-wide association analysis of blood-pressure traits in African-ancestry individuals reveals common associated genes in African and non-African populations.

High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease (CVD) in African Americans than in any other United States ethnic group. Several small African-ancestry (AA) BP genome-wide association studies (GWASs) have been published, but their findings have failed to replicate to date. We report on a large AA BP GWAS meta-analysis that includes 29,378 individuals from 19 discovery cohorts and subsequent replication in additional samples of AA (n = 10,386), European ancestry (EA) (n = 69,395), and East Asian ancestry (n = 19,601). Five loci (EVX1-HOXA, ULK4, RSPO3, PLEKHG1, and SOX6) reached genome-wide significance (p < 1.0 × 10(-8)) for either systolic or diastolic BP in a transethnic meta-analysis after correction for multiple testing. Three of these BP loci (EVX1-HOXA, RSPO3, and PLEKHG1) lack previous associations with BP. We also identified one independent signal in a known BP locus (SOX6) and provide evidence for fine mapping in four additional validated BP loci. We also demonstrate that validated EA BP GWAS loci, considered jointly, show significant effects in AA samples. Consequently, these findings suggest that BP loci might have universal effects across studied populations, demonstrating that multiethnic samples are an essential component in identifying, fine mapping, and understanding their trait variability.

Glomerular hyperfiltration and increased proximal sodium reabsorption in subjects with type 2 diabetes or impaired fasting glucose in a population of the African region.

BACKGROUND. Glomerular hyperfiltration (GHF) is a well-recognized early renal alteration in diabetic patients. As the prevalence of GHF is largely unknown in populations in the African region with respect to normal fasting glucose (NFG), impaired fasting glucose (IFG) and type 2 diabetes [diabetes mellitus (DM)], we conducted a cross-sectional study in the Seychelles islands among families including at least one member with hypertension. METHODS. The glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and proximal tubular sodium reabsorption were measured using inulin, p-aminohippurate (PAH) and endogenous lithium clearance, respectively. Twenty-four-hour urine was collected on the preceding day. RESULTS. Of the 363 participants (mean age 44.7 years), 6.6% had IFG, 9.9% had DM and 63.3% had hypertension. The prevalence of GHF, defined as a GFR >140 ml/min, was 17.2%, 29.2% and 52.8% in NFG, IFG and DM, respectively (P trend <0.001). Compared to NFG, the adjusted odds ratio for GHF was 1.99 [95% confidence interval (CI) 0.73-5.44] for IFG and 5.88 (2.39-14.45) for DM. Lithium clearance and fractional excretion of lithium were lower in DM and IFG than NFG (P < 0.001). CONCLUSION. In this population of African descent, subjects with impaired fasting glucose or type 2 diabetes had a high prevalence of GHF and enhanced proximal sodium reabsorption. These findings provide further insight on the elevated incidence of nephropathy reported among African diabetic individuals.

Marked association between obesity and glomerular hyperfiltration: a cross-sectional study in an African population.

BACKGROUND: Obesity and African American ethnicity are established independent risk factors for the development of chronic kidney disease. No data exist about the association between obesity and renal hemodynamics in the African region. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 301 nondiabetic participants (97 lean, 108 overweight, and 96 obese) of African descent with a positive family history of hypertension from the Seychelles islands. PREDICTOR: Body mass index (BMI). OUTCOMES: Glomerular hyperfiltration, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and filtration fraction. MEASUREMENTS: GFR and ERPF were measured using inulin and para-aminohippurate clearances, respectively. Participants' baseline demographics, laboratory data, and blood pressure were measured using standard techniques. RESULTS: The prevalence of glomerular hyperfiltration (defined as GFR >or=140 mL/min) increased across BMI categories (7.2%, 14.8%, and 27.1% for lean, overweight, and obese participants, respectively; P < 0.001). Higher BMI was associated with higher median GFR (99, 110, and 117 mL/min for lean, overweight, and obese participants, respectively; P < 0.001), ERPF (424, 462, and 477 mL/min, respectively; P = 0.01), and filtration fraction (0.23, 0.24, and 0.25; P < 0.001). Multivariate analyses adjusting for age, sex, blood pressure, fasting glucose level, and urinary sodium excretion and accounting for familial correlations confirmed the associations between high BMI (>25 kg/m(2)) and increased GFR, ERPF, and filtration fraction. No association between BMI categories and GFR was found with adjustment for body surface area. LIMITATIONS: Participants had a positive family history of hypertension. CONCLUSION: Overweight and obesity are associated with increased GFR, ERPF, and filtration fraction and a high prevalence of glomerular hyperfiltration in nondiabetic individuals of African descent. The absence of associations between BMI categories and GFR indexed for body surface area raises questions regarding the appropriateness of indexing GFR for body surface area in overweight populations.

Risk factors of stroke mortality in the African region: a cohort study

Background: Population-based cohort studies of risk factors of stroke are scarce in developing countries and none has been done in the African region. We conducted a longitudinal study in the Seychelles (Indian Ocean, east of Kenya), a middle-income island state where the majority of the population is of African descent. Such data in Africa are important for international comparison and for advocacy in the region. Methods: Three examination surveys of cardiovascular risk factors were performed in independent samples representative of the general population aged 25-64 in 1989, 1994 and 2004 (n=1081, 1067, and 1255, respectively). Baseline risk factors data were linked with cause-specific mortality from vital statistics up to May 2007 (all deaths are medically certified in the Seychelles and kept in an electronic database). We considered stroke (any type) as a cause of death if the diagnosis was reported in any of the 4 fields in the death certificates for underlying and concomitant causes of death. Results. Among the 2479 persons aged 35-64 at baseline, 280 died including 56 with stroke during follow up (maximum: 18.2 years; mean: 10.2 years). In this age range, age-adjusted mortality rates (/100'000/year) were 969 for all cause and 187 for stroke; age-adjusted prevalence of high blood pressure (≥140/90 mmHg) was 48%. In multivariate Cox survival time regression, stroke mortality was increased by 18% and 35% for a 10-mmHg increase in systolic, respectively diastolic BP (p<0.001). Stroke mortality was also associated with age, smoking ≥5 cigarettes vs. no smoking (HR: 2.4; 95% CI: 1.2-4.8) and diabetes (HR: 1.9; 1.02-3.6) but not with sex, LDL-cholesterol intake, alcohol intake and professional occupation. Conclusion. This first population-based cohort study in the African region demonstrates high mortality rates from stroke in middle-aged adults and confirms associations with high BP and other risk factors. This emphasizes the importance of reducing BP and other modifiable risk factors in high risk individuals and in the general population as a main strategy to reduce the burden of stroke.

Randomized controlled trial of interventions for young people at ultra-high risk of psychosis: study design and baseline characteristics.

OBJECTIVE: Intervention during the pre-psychotic period of illness holds the potential of delaying or even preventing the onset of a full-threshold disorder, or at least of reducing the impact of such a disorder if it does develop. The first step in realizing this aim was achieved more than 10 years ago with the development and validation of criteria for the identification of young people at ultra-high risk (UHR) of psychosis. Results of three clinical trials have been published that provide mixed support for the effectiveness of psychological and pharmacological interventions in preventing the onset of psychotic disorder. METHOD: The present paper describes a fourth study that has now been undertaken in which young people who met UHR criteria were randomized to one of three treatment groups: cognitive therapy plus risperidone (CogTher + Risp: n = 43); cognitive therapy plus placebo (CogTher + Placebo: n = 44); and supportive counselling + placebo (Supp + Placebo; n = 28). A fourth group of young people who did not agree to randomization were also followed up (monitoring: n = 78). Baseline characteristics of participants are provided. RESULTS AND CONCLUSION: The present study improves on the previous studies because treatment was provided for 12 months and the independent contributions of psychological and pharmacological treatments in preventing transition to psychosis in the UHR cohort and on levels of psychopathology and functioning can be directly compared. Issues associated with recruitment and randomization are discussed.

Psychiatric co-morbidities and cardiovascular risk factors in people with lifetime history of epilepsy of an urban community.

OBJECTIVES: Depression has been consistently reported in people with epilepsy. Several studies also suggest a higher burden of cardiovascular diseases. We therefore analysed psychosocial co-morbidity and cardiovascular risk factors in patients with a lifetime history of epilepsy in the PsyCoLaus study, a Swiss urban population-based assessment of mental health and cardiovascular risk factors in adults aged between 35 and 66 years. PATIENTS AND METHODS: Among 3719 participants in the PsyCoLaus study, we retrospectively identified those reporting at least 2 unprovoked seizures, defined as epilepsy. These subjects were compared to all others regarding psychiatric, social, and cardiovascular risk factors data using uni- and multivariable assessments. RESULTS: A significant higher need for social help (p<0.001) represented the only independent difference between 43 subjects with a history of epilepsy and 3676 controls, while a higher prevalence of psychiatric co-morbidities (p=0.015) and a lower prevalent marital status (p=0.01) were only significant on univariate analyses. Depression and cardio-vascular risk factors, as well as educational level and employment, were similar among the groups. CONCLUSIONS: This analysis confirms an increased prevalence of psychosocial burden in subjects with a lifetime history of epilepsy; conversely, we did not find a higher cardiovascular risk. The specific urban and geographical location of our cohort and the age span of the studied population may account for the differences from previous studies.

Patients âgés admis aux urgences suite à une chute: que faire [Older people admitted to the emergency department after a fall: what to do?].

Falls in older people are frequent. Falls may lead to serious injuries and are associated with greater morbidity, mortality, and reduced overall functioning in the older population. Evidences exist regarding the beneficial effects of fall prevention programs. However, these interventions are rarely implemented in our health system. Older people admitted to the emergency department after a fall should get careful attention in order to initiate specific interventions to prevent new falls. This article provides a clinical assessment strategy to evaluate older persons after a fall and proposes an algorithm for discharge planning decision.

Potential impact of single-risk-factor versus total risk management for the prevention of cardiovascular events in Seychelles.

OBJECTIVE: To assess the prevalence of cardiovascular (CV) risk factors in Seychelles, a middle-income African country, and compare the cost-effectiveness of single-risk-factor management (treating individuals with arterial blood pressure >/= 140/90 mmHg and/or total serum cholesterol >/= 6.2 mmol/l) with that of management based on total CV risk (treating individuals with a total CV risk >/= 10% or >/= 20%).METHODS: CV risk factor prevalence and a CV risk prediction chart for Africa were used to estimate the 10-year risk of suffering a fatal or non-fatal CV event among individuals aged 40-64 years. These figures were used to compare single-risk-factor management with total risk management in terms of the number of people requiring treatment to avert one CV event and the number of events potentially averted over 10 years. Treatment for patients with high total CV risk (>/= 20%) was assumed to consist of a fixed-dose combination of several drugs (polypill). Cost analyses were limited to medication.FINDINGS: A total CV risk of >/= 10% and >/= 20% was found among 10.8% and 5.1% of individuals, respectively. With single-risk-factor management, 60% of adults would need to be treated and 157 cardiovascular events per 100 000 population would be averted per year, as opposed to 5% of adults and 92 events with total CV risk management. Management based on high total CV risk optimizes the balance between the number requiring treatment and the number of CV events averted.CONCLUSION: Total CV risk management is much more cost-effective than single-risk-factor management. These findings are relevant for all countries, but especially for those economically and demographically similar to Seychelles.