Impact of the Health Gym Program on hospital admissions for stroke in the state of Pernambuco, Brazil

This study aimed to evaluate the impact of the Health Gym Program (HGP) on hospital admissions for stroke in the state of Pernambuco, Brazil. This policy impact evaluation used a quasi-experimental approach consisting of a difference-in-differences estimator, weighted by propensity score matching to deal with potential confounding variables. The study comprised socioeconomic, demographic, and epidemiological data from official Brazilian databases from 2010 to 2019. The treatment group was composed of the 134 municipalities that implemented the HGP since 2011. The 51 municipalities that did not were allocated to the comparison group. The nearest neighbor algorithm (N5) was used to pair treatment and comparison group municipalities and create the weights to evaluate the average treatment effect on the treated (ATT) in the difference-in-differences estimator. In 2010, 2,771 people were hospitalized for stroke (0.51% of all hospitalizations) and in 2019, 11,542 (2%). Municipalities that implemented the HGP had 18.37% fewer hospitalizations than their counterparts in the comparison group. The program’s impact in reducing hospitalization rates was incrementally greater among men (ATT: -0.1932) and those aged 71 to 80 years (ATT: -0.1911). All results were statistically significant at the 5% level. The HGP reduced hospitalization for stroke in several population groups, but primarily in those whose underlying prevalence of stroke is highest, reinforcing the importance of public investments in health promotion policies designed to encourage lifestyle changes.Resumo: O estudo teve como objetivo avaliar o impacto do Programa Academia da Saúde (PAS) nas internações hospitalares por acidente vascular cerebral (AVC) no Estado de Pernambuco, Brasil. Esta avaliação de impacto das políticas utilizou uma abordagem quase-experimental que consiste em um estimador de diferença-em-diferenças, ponderado pelo pareamento por escore de propensão para lidar com possíveis fatores de confusão. O estudo foi composto por dados socioeconômicos, demográficos e epidemiológicos de bases de dados oficiais brasileiras entre os anos de 2010 e 2019. O grupo de tratamento foi composto pelos 134 municípios que implantaram o PAS a partir de 2011, e os 51 municípios que não implantaram foram alocados no grupo de comparação. O algoritmo do vizinho mais próximo (N5) foi utilizado para emparelhar os municípios tratados e comparar aos municípios do grupo controle, criando os pesos que foram utilizados para avaliar o efeito médio do tratamento sobre o tratado (ATT) no estimador de diferença- -em-diferenças. Houve 2.771 internações por AVC em 2010 (0,51% de todas as internações) e 11.542 (2%) em 2019. Os municípios que implementaram o PAS tiveram 18,37% menos internações em comparação com seus homólogos no grupo de comparação. O impacto do programa na redução das taxas de internação foi maior entre os homens (ATT: -0,1932) e naqueles com idade entre 71 e 80 anos (ATT: -0,1911). Todos os resultados foram estatisticamente significativos em um nível de 5%. O PAS reduziu a hospitalização por AVC em vários grupos populacionais, mas principalmente naqueles em que a prevalência subjacente de AVC é mais alta, reforçando a importância dos investimentos públicos em políticas de promoção da saúde destinadas a estimular mudanças nos estilos de vida. Avaliação de Programas e Projetos de Saúde; Doença Crônica; Promoção da Saúde; Pontuação de Propensão; Acidente Vascular CerebralResumen: El objetivo de este trabajo es evaluar el impacto del Programa Academia de la Salud (PAS) en los ingresos hospitalarios por accidente cerebrovascular (ACV) en el estado de Pernambuco, Brasil. Esta evaluación del impacto de la política utilizó un enfoque cuasi-experimental que consiste en un estimador de diferencias en diferencias, ponderado por el emparejamiento de puntuación de propensión para hacer frente a posibles factores de confusión. El estudio incluyó datos socioeconómicos, demográficos y epidemiológicos de bases de datos oficiales brasileñas de 2010 a 2019. El grupo de tratamiento se compuso de los 134 municipios que implementaron el PAS a partir de 2011 y los 51 municipios que no lo hicieron se asignaron al grupo de comparación. Se utilizó el algoritmo del vecino más próximo (N5) para emparejar los municipios tratados y los del grupo de comparación y crear las ponderaciones que se emplearon para evaluar el efecto medio del tratamiento sobre los tratados (ATT) en el estimador de diferencias en diferencias. Hubo 2.771 hospitalizaciones por ACV en 2010 (0,51% de todas las hospitalizaciones) y 11.542 (2%) en 2019. Los municipios que aplicaron el PAS tuvieron un 18,37% menos de hospitalizaciones en comparación con sus homólogos del grupo de comparación. El impacto del programa en la reducción de las tasas de hospitalización fue gradualmente mayor entre los hombres (ATT: -0,1932) y entre las personas de 71 a 80 años (ATT: -0,1911). Todos los resultados fueron estadísticamente significativos al nivel del 5%. El PAS redujo la hospitalización por ACV en varios grupos de población, pero principalmente en aquellos en los que la prevalencia subyacente de ACV es mayor, lo que refuerza la importancia de las inversiones públicas en políticas de promoción de la salud diseñadas para impulsar cambios en los estilos de vida. Evaluación de Programas y Proyectos de Salud; Enfermedad Crónica; Promoción de la Salud; Puntaje de Propensión; Accidente CerebrovascularPernambuco State Foundation for the Support of Science and Technology (FACEPE), and the Brazilian National Research Council (CNPq)

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

A saturated map of common genetic variants associated with human height

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes(1). Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel(2)) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.

BACKGROUND: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. RESULTS: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. CONCLUSIONS: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk

A saturated map of common genetic variants associated with human height.

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries

Consumo alimentar, estado nutricional e nível de atividade física em comunidade universitária brasileira

OBJETIVO: Este estudo teve como objetivo avaliar a variabilidade e a frequência do consumo alimentar, o estado nutricional e o nível de atividade física em uma comunidade universitária brasileira. MÉTODOS: A amostra constitui-se de 303 voluntários (130 homens e 173 mulheres) pertencentes à comunidade universitária do interior de São Paulo e avaliada por meio da disponibilização pela Internet do Questionário de Frequência Alimentar do International Physical Activity Questionaire e por meio da coleta da descrição autorreferida do peso e da altura. Foi realizada análise descritiva dos dados, análise de frequência alimentar e teste do coeficiente de correlação de Spearman. RESULTADOS: Foram observados inadequação dos hábitos alimentares, sobrepeso e obesidade na amostra estudada. As correlações entre os grupos alimentares apresentaram valores de magnitude maiores no grupo de mulheres que se alimentam de forma mais adequada do que os homens, mas não foram observadas diferenças entre os sexos no nível de atividade física. Não houve correlação significativa entre grupos de alimentos consumidos, índice de massa corporal e nível de atividade física em ambos os sexos. CONCLUSÃO: A comunidade universitária estudada apresentou baixo consumo de frutas, legumes e verduras, bem como consumo insuficiente de alimentos do grupo de cereais e leguminosas

A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids.

A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology