[Inhalotherapy: Recommendations for Argentina 2021].

Last decades, a broad spectrum of inhaled devices (ID) had been developed to enhance efficacy and reduce adverse events. The correct use of IDs is a critical issue for controlling obstructive respiratory diseases. There is no recommendation on inhalation therapy in Argentina.

Efficacy and Safety of Text Messages Targeting Adherence to Cardiovascular Medications in Secondary Prevention: TXT2HEART Colombia Randomized Controlled Trial.

Background: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide, with a prevalence of approximately 100 million patients. There is evidence that antiplatelet agents and antihypertensive medications could reduce the risk of new vascular events in this population; however, treatment adherence is very low. An SMS text messaging intervention was recently developed based on behavior change techniques to increase adherence to pharmacological treatment among patients with a history of ASCVD.

Circulating Fatty Acids and Risk of Coronary Heart Disease and Stroke: Individual Participant Data Meta-Analysis in Up to 16 126 Participants.

Background We aimed at investigating the association of circulating fatty acids with coronary heart disease (CHD) and stroke risk. Methods and Results We conducted an individual-participant data meta-analysis of 5 UK-based cohorts and 1 matched case-control study. Fatty acids (ie, omega-3 docosahexaenoic acid, omega-6 linoleic acid, monounsaturated and saturated fatty acids) were measured at baseline using an automated high-throughput serum nuclear magnetic resonance metabolomics platform.

Improving the odds of drug development success through human genomics: modelling study.

Lack of efficacy in the intended disease indication is the major cause of clinical phase drug development failure. Explanations could include the poor external validity of pre-clinical (cell, tissue, and animal) models of human disease and the high false discovery rate (FDR) in preclinical science. FDR is related to the proportion of true relationships available for discovery (γ), and the type 1 (false-positive) and type 2 (false negative) error rates of the experiments designed to uncover them.

Metabolic Profiling of Adiponectin Levels in Adults: Mendelian Randomization Analysis.

Background: Adiponectin, a circulating adipocyte-derived protein, has insulin-sensitizing, anti-inflammatory, antiatherogenic, and cardiomyocyte-protective properties in animal models. However, the systemic effects of adiponectin in humans are unknown. Our aims were to define the metabolic profile associated with higher blood adiponectin concentration and investigate whether variation in adiponectin concentration affects the systemic metabolic profile.

Investigating associations between the built environment and physical activity among older people in 20 UK towns.

Background: Policy initiatives such as WHO Age Friendly Cities recognise the importance of the urban environment for improving health of older people, who have both low physical activity (PA) levels and greater dependence on local neighbourhoods. Previous research in this age group is limited and rarely uses objective measures of either PA or the environment.

Methods: We investigated the association between objectively measured PA (Actigraph GT3x accelerometers) and multiple dimensions of the built environment, using a cross-sectional multilevel linear regression analysis.

Are cardiovascular risk factors also associated with the incidence of atrial fibrillation? A systematic review and field synopsis of 23 factors in 32 population-based cohorts of 20 million participants.

Established primary prevention strategies of cardiovascular diseases are based on understanding of risk factors, but whether the same risk factors are associated with atrial fibrillation (AF) remains unclear. We conducted a systematic review and field synopsis of the associations of 23 cardiovascular risk factors and incident AF, which included 84 reports based on 28 consented and four electronic health record cohorts of 20,420,175 participants and 576,602 AF events. We identified 3-19 reports per risk factor and heterogeneity in AF definition, quality of reporting, and adjustment.

PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study.

Background: Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk.

Methods: In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores.

Optimising measurement of health-related characteristics of the built environment: Comparing data collected by foot-based street audits, virtual street audits and routine secondary data sources.

The role of the neighbourhood environment in influencing health behaviours continues to be an important topic in public health research and policy. Foot-based street audits, virtual street audits and secondary data sources are widespread data collection methods used to objectively measure the built environment in environment-health association studies. We compared these three methods using data collected in a nationally representative epidemiological study in 17 British towns to inform future development of research tools.

Efficacy and safety of ablation for people with non-paroxysmal atrial fibrillation.

Background: The optimal rhythm management strategy for people with non-paroxysmal (persistent or long-standing persistent) atrial fibrilation is currently not well defined. Antiarrhythmic drugs have been the mainstay of therapy. But recently, in people who have not responded to antiarrhythmic drugs, the use of ablation (catheter and surgical) has emerged as an alternative to maintain sinus rhythm to avoid long-term atrial fibrillation complications.

Natriuretic peptides and integrated risk assessment for cardiovascular disease: an individual-participant-data meta-analysis.

Background: Guidelines for primary prevention of cardiovascular diseases focus on prediction of coronary heart disease and stroke. We assessed whether or not measurement of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration could enable a more integrated approach than at present by predicting heart failure and enhancing coronary heart disease and stroke risk assessment.

Methods: In this individual-participant-data meta-analysis, we generated and harmonised individual-participant data from relevant prospective studies via both de-novo NT-proBNP concentration measurement of stored samples and collection of data from studies identified through a systematic search of the literature (PubMed, Scientific Citation Index Expanded, and Embase) for articles published up to Sept 4, 2014, using search terms related to natriuretic peptide family members and the primary outcomes, with no language restrictions.

Net clinical benefit of warfarin in individuals with atrial fibrillation across stroke risk and across primary and secondary care.

Objective: To investigate net clinical benefit (NCB) of warfarin in individuals with atrial fibrillation (AF) across stroke risk and across primary and secondary care.

Methods: We conducted a linked electronic health record cohort study of 70 206 individuals with initial record of diagnosis of AF in primary (n=29 568) or secondary care (n=40 638) in England (1998-2010). We defined stroke risk according to the CHADS-VASc score, and followed individuals over a median 2.

Marginal role for 53 common genetic variants in cardiovascular disease prediction.

Objective: We investigated discrimination and calibration of cardiovascular disease (CVD) risk scores when genotypic was added to phenotypic information. The potential of genetic information for those at intermediate risk by a phenotype-based risk score was assessed.

Methods: Data were from seven prospective studies including 11 851 individuals initially free of CVD or diabetes, with 1444 incident CVD events over 10 years' follow-up.

Mendelian Randomisation study of the influence of eGFR on coronary heart disease.

Impaired kidney function, as measured by reduced estimated glomerular filtration rate (eGFR), has been associated with increased risk of coronary heart disease (CHD) in observational studies, but it is unclear whether this association is causal or the result of confounding or reverse causation. In this study we applied Mendelian randomisation analysis using 17 genetic variants previously associated with eGFR to investigate the causal role of kidney function on CHD. We used 13,145 participants from the UCL-LSHTM-Edinburgh-Bristol (UCLEB) Consortium and 194,427 participants from the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis plus Coronary Artery Disease (CARDIoGRAMplusC4D) consortium.

Metabolic Characterization of a Rare Genetic Variation Within APOC3 and Its Lipoprotein Lipase-Independent Effects.

Background: Plasma triglyceride levels have been implicated in atherosclerosis and coronary heart disease. Apolipoprotein C-III (APOC3) plays a key role in the hydrolysis of triglyceride-rich lipoproteins to remnant particles by lipoprotein lipase (LPL) and their uptake by the liver. A rare variant in APOC3(rs138326449) has been associated with triglyceride, very low-density lipoprotein, and high-density lipoprotein levels, as well as risk of coronary heart disease.

Metabolomic Profiling of Statin Use and Genetic Inhibition of HMG-CoA Reductase.

Background: Statins are first-line therapy for cardiovascular disease prevention, but their systemic effects across lipoprotein subclasses, fatty acids, and circulating metabolites remain incompletely characterized.

Objectives: This study sought to determine the molecular effects of statin therapy on multiple metabolic pathways.

Methods: Metabolic profiles based on serum nuclear magnetic resonance metabolomics were quantified at 2 time points in 4 population-based cohorts from the United Kingdom and Finland (N = 5,590; 2.

Exome-wide analysis of rare coding variation identifies novel associations with COPD and airflow limitation in MOCS3, IFIT3 and SERPINA12.

Background: Several regions of the genome have shown to be associated with COPD in genome-wide association studies of common variants.

Objective: To determine rare and potentially functional single nucleotide polymorphisms (SNPs) associated with the risk of COPD and severity of airflow limitation.

Methods: 3226 current or former smokers of European ancestry with lung function measures indicative of Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 COPD or worse were genotyped using an exome array.

A qualitative geographical information systems approach to explore how older people over 70 years interact with and define their neighbourhood environment.

A growing body of literature explores the relationship between the built environment and health, and the methodological challenges of understanding these complex interactions across the lifecourse. The impact of the neighbourhood environment on health and behaviour amongst older adults has received less attention, despite this age group being potentially more vulnerable to barriers in their surrounding social and physical environment. A qualitative geographical information systems (QGIS) approach was taken to facilitate the understanding of how older people over 70 in 5 UK towns interact with their local neighbourhood.

Metabolite profiling and cardiovascular event risk: a prospective study of 3 population-based cohorts.

Background: High-throughput profiling of circulating metabolites may improve cardiovascular risk prediction over established risk factors.

Methods And Results: We applied quantitative nuclear magnetic resonance metabolomics to identify the biomarkers for incident cardiovascular disease during long-term follow-up. Biomarker discovery was conducted in the National Finnish FINRISK study (n=7256; 800 events).

Adherence to physical activity guidelines in older adults, using objectively measured physical activity in a population-based study.

Background: Physical activity (PA) levels in older adults decline with age. The prevalence and correlates of adherence to current UK PA guidelines in older adults has not been studied using objectively measured PA, which can examine precisely whether PA is carried out in bouts of specified length and intensity.

Methods: Free living men and women aged 70-93 years from 25 towns in the United Kingdom, participating in parallel on-going population based cohort studies were invited (by post) to wear a GT3x accelerometer over the hip for one week in 2010-12.

InterPregGen: genetic studies of pre-eclampsia in three continents.

Pre-eclampsia is a major cause of maternal and fetal mortality in pregnancy. The identification of genetic variants which predispose to pre-eclampsia demands large DNA collections from affected mothers and babies and controls, with reliable supporting phenotypic data. The InterPregGen study has assembled a consortium of researchers from Europe, Central Asia and South America with the aim of elucidating the genetic architecture of pre-eclampsia.

Genetic prediction of quantitative lipid traits: comparing shrinkage models to gene scores.

Accurate genetic prediction of quantitative traits related to complex disease risk would have potential clinical impact, so investigation of statistical methodology to improve predictive performance is important. We compare a simple approach of polygenic scores using top ranking single nucleotide polymorphisms (SNPs) to a set of shrinkage models, namely Ridge Regression, Lasso and Hyper-Lasso. These penalised regression methods analyse all genotyped SNPs simultaneously, potentially including much larger sets of SNPs in the models, not only those with the smallest P values.

Gene-centric association signals for haemostasis and thrombosis traits identified with the HumanCVD BeadChip.

Coagulation phenotypes show strong intercorrelations, affect cardiovascular disease risk and are influenced by genetic variants. The objective of this study was to search for novel genetic variants influencing the following coagulation phenotypes: factor VII levels, fibrinogen levels, plasma viscosity and platelet count. We genotyped the British Women's Heart and Health Study (n=3,445) and the Whitehall II study (n=5,059) using the Illumina HumanCVD BeadArray to investigate genetic associations and pleiotropy.