Comparison of the European and U.S. guidelines for lipid-lowering therapy in primary prevention of cardiovascular disease

AIMS: Population-wide impacts of new guidelines in the primary prevention of atherosclerotic cardiovascular disease (ASCVD) should be explored in independent cohorts. Assess and compare the lipid-lowering therapy eligibility and predictive classification performance of 2016 and 2021 European Society of Cardiology (ESC), 2019 American Heart Association/American College of Cardiology (AHA/ACC), and 2022 US Preventive Services Task Force (USPSTF) guidelines. METHODS AND RESULTS: Participants from the CoLaus|PsyCoLaus study, without ASCVD and not taking lipid-lowering therapy at baseline. Derivation of 10-year risk for ASCVD using Systematic COronary Risk Evaluation (SCORE1), SCORE2 [including SCORE2-Older Persons (SCORE2-OP)], and pooled cohort equation. Computation of the number of people eligible for lipid-lowering therapy based on each guideline and assessment of discrimination and calibration metrics of the risk models using first incident ASCVD as an outcome. Among 4,092 individuals, 158 (3.9%) experienced an incident ASCVD during a median follow-up of 9 years (interquartile range, 1.1). Lipid-lowering therapy was recommended or considered in 40.2% (95% confidence interval, 38.2-42.2), 26.4% (24.6-28.2), 28.6% (26.7-30.5), and 22.6% (20.9-24.4) of women and in 62.1% (59.8-64.3), 58.7% (56.4-61.0), 52.6% (50.3-54.9), and 48.4% (46.1-50.7) of men according to the 2016 ESC, 2021 ESC, 2019 AHA/ACC, and 2022 USPSTF guidelines, respectively. 43.3 and 46.7% of women facing an incident ASCVD were not eligible for lipid-lowering therapy at baseline according to the 2021 ESC and 2022 USPSTF, compared with 21.7 and 38.3% using the 2016 ESC and 2019 AHA/ACC, respectively. CONCLUSION: Both the 2022 USPSTF and 2021 ESC guidelines particularly reduced lipid-lowering therapy eligibility in women. Nearly half of women who faced an incident ASCVD were not eligible for lipid-lowering therapy

Weight loss directly influences intermediate-term remission of diabetes mellitus after bariatric surgery: a retrospective case-control study

Contexte et Enjeux L'obésité est, de nos jours, un enjeux majeur de santé publique. C'est une maladie multifactorielle complexe avec de nombreuses comorbidités associées telles que le diabète de type 2 (DT2), l'hypertension (HTA) ou la dyslipidémie. La chirurgie bariatrique, notamment le bypass gastrique en Y selon Roux (RYBG) est un traitement accepté depuis 1991 pour l'obésité morbide avec un profil risque/bénéfice favorable. L'approche chirurgicale permet en effet, comparée à la prise en charge médicale seule, une perte de poids moyenne de 60-75 0/0 de l'excès de poids. Cela améliore également significativement et rapidement, voire parfois guérit, les comorbidités métaboliques responsables de la mortalité liée à l'obésité. En effet, des taux de rémission d'environ 70 0/0, 60 0/0 et 40 0/0, ont été rapportés jusqu'à 7 ans après un RYGB pour le D T 2, la dyslipidémie et l'HTA respectivement. Les mécanismes sous-jacents à l'amélioration des paramètres métaboliques après la chirurgie bariatrique, notamment le RYGB, ne sont pas encore clairement identifiés.Cette étude vise à mieux définir le rôle direct de la perte de poids dans les améliorations métaboliques après RYGB. Conclusion et Perspective En comparant des sujets ayant perdu beaucoup de poids après un RYGB avec des sujets ayant perdu moins de poids suite à cette même procédure, nous mettons en évidence une association statitstiquement significative entre l'importante de la perte de poids et la résolution du diabète 2 ans après l'intervention. Une analyse de régression linéaire multiple a également permis d'affirmer une association statistiquement significative entre l'importance de la perte de poids et l'amélioration de toutes comorbidités métaboliques confondues. Ces résultats soulignent l'importance de la perte de poids dans les avantages de cette procédure et la probable influence directe d'une diminution de la masse grasse, en plus des changements hormonaux induits par le bypass, dans l'amélioration des paramètres métaboliques. Nous savons qu'il y a une tendance à reprendre du poids sur le long terme (10 ans et plus) après la chirurgie bariatrique. Le maintien de la perte de poids obtenue nécessite donc un suivi et un investissement de longue durée, ce que nos résultats viennent appuyer. En effet, cette perte de poids, permet de diminuer l'obésité en tant que telle, mais également des comorbidités métaboliques telles que le diabète, lourdes de conséquences économiques et médicales

Cerebrospinal and Brain Proteins Implicated in Neuropsychiatric and Risk Factor Traits: Evidence from Mendelian Randomization

Neuropsychiatric disorders present a global health challenge, necessitating an understanding of their molecular mechanisms for therapeutic development. Using Mendelian randomization (MR) analysis, this study explored associations between genetically predicted levels of 173 proteins in cerebrospinal fluid (CSF) and 25 in the brain with 14 neuropsychiatric disorders and risk factors. Follow-up analyses assessed consistency across plasma protein levels and gene expression in various brain regions. Proteins were instrumented using tissue-specific genetic variants, and colocalization analysis confirmed unbiased gene variants. Consistent MR and colocalization evidence revealed that lower cortical expression of low-density lipoprotein receptor-related protein 8, coupled higher abundance in the CSF and plasma, associated with lower fluid intelligence scores and decreased bipolar disorder risk. Additionally, elevated apolipoprotein-E2 and hepatocyte growth factor-like protein in the CSF and brain were related to reduced leisure screen time and lower odds of physical activity, respectively. Furthermore, elevated CSF soluble tyrosine-protein kinase receptor 1 level increased liability to attention deficit hyperactivity disorder and schizophrenia alongside lower fluid intelligence scores. This research provides genetic evidence supporting novel tissue-specific proteomic targets for neuropsychiatric disorders and their risk factors. Further exploration is necessary to understand the underlying biological mechanisms and assess their potential for therapeutic intervention

Caffeine Intake, Plasma Caffeine Level, and Kidney Function: A Mendelian Randomization Study.

Peer reviewed: TruePublication status: PublishedCaffeine is a psychoactive substance widely consumed worldwide, mainly via sources such as coffee and tea. The effects of caffeine on kidney function remain unclear. We leveraged the genetic variants in the CYP1A2 and AHR genes via the two-sample Mendelian randomization (MR) framework to estimate the association of genetically predicted plasma caffeine and caffeine intake on kidney traits. Genetic association summary statistics on plasma caffeine levels and caffeine intake were taken from genome-wide association study (GWAS) meta-analyses of 9876 and of >47,000 European ancestry individuals, respectively. Genetically predicted plasma caffeine levels were associated with a decrease in estimated glomerular filtration rate (eGFR) measured using either creatinine or cystatin C. In contrast, genetically predicted caffeine intake was associated with an increase in eGFR and a low risk of chronic kidney disease. The discrepancy is likely attributable to faster metabolizers of caffeine consuming more caffeine-containing beverages to achieve the same pharmacological effect. Further research is needed to distinguish whether the observed effects on kidney function are driven by the harmful effects of higher plasma caffeine levels or the protective effects of greater intake of caffeine-containing beverages, particularly given the widespread use of drinks containing caffeine and the increasing burden of kidney disease

Genetic investigation into the broad health implications of caffeine: evidence from phenome-wide, proteome-wide and metabolome-wide Mendelian randomization

Acknowledgements: The authors thank the study participants that contributed the data used in this study.Abstract Background Caffeine is one of the most utilized drugs in the world, yet its clinical effects are not fully understood. Circulating caffeine levels are influenced by the interplay between consumption behaviour and metabolism. This study aimed to investigate the effects of circulating caffeine levels by considering genetically predicted variation in caffeine metabolism. Methods Leveraging genetic variants related to caffeine metabolism that affect its circulating levels, we investigated the clinical effects of plasma caffeine in a phenome-wide association study (PheWAS). We validated novel findings using a two-sample Mendelian randomization framework and explored the potential mechanisms underlying these effects in proteome-wide and metabolome-wide Mendelian randomization. Results Higher levels of genetically predicted circulating caffeine among caffeine consumers were associated with a lower risk of obesity (odds ratio (OR) per standard deviation increase in caffeine = 0.97, 95% confidence interval (CI) CI: 0.95—0.98, p = 2.47 × 10−4), osteoarthrosis (OR = 0.97, 95% CI: 0.96—0.98, P=1.10 × 10−8) and osteoarthritis (OR: 0.97, 95% CI: 0.96 to 0.98, P = 1.09 × 10−6). Approximately one third of the protective effect of plasma caffeine on osteoarthritis risk was estimated to be mediated through lower bodyweight. Proteomic and metabolomic perturbations indicated lower chronic inflammation, improved lipid profiles, and altered protein and glycogen metabolism as potential biological mechanisms underlying these effects. Conclusions We report novel evidence suggesting that long-term increases in circulating caffeine may reduce bodyweight and the risk of osteoarthrosis and osteoarthritis. We confirm prior genetic evidence of a protective effect of plasma caffeine on risk of overweight and obesity. Further clinical study is warranted to understand the translational relevance of these findings before clinical practice or lifestyle interventions related to caffeine consumption are introduced. </jats:sec

Genetic investigation into the broad health implications of caffeine: evidence from phenome-wide, proteome-wide and metabolome-wide Mendelian randomization

Abstract Background Caffeine is one of the most utilized drugs in the world, yet its clinical effects are not fully understood. Circulating caffeine levels are influenced by the interplay between consumption behaviour and metabolism. This study aimed to investigate the effects of circulating caffeine levels by considering genetically predicted variation in caffeine metabolism. Methods Leveraging genetic variants related to caffeine metabolism that affect its circulating levels, we investigated the clinical effects of plasma caffeine in a phenome-wide association study (PheWAS). We validated novel findings using a two-sample Mendelian randomization framework and explored the potential mechanisms underlying these effects in proteome-wide and metabolome-wide Mendelian randomization. Results Higher levels of genetically predicted circulating caffeine among caffeine consumers were associated with a lower risk of obesity (odds ratio (OR) per standard deviation increase in caffeine = 0.97, 95% confidence interval (CI) CI: 0.95—0.98, p = 2.47 × 10−4), osteoarthrosis (OR = 0.97, 95% CI: 0.96—0.98, P=1.10 × 10−8) and osteoarthritis (OR: 0.97, 95% CI: 0.96 to 0.98, P = 1.09 × 10−6). Approximately one third of the protective effect of plasma caffeine on osteoarthritis risk was estimated to be mediated through lower bodyweight. Proteomic and metabolomic perturbations indicated lower chronic inflammation, improved lipid profiles, and altered protein and glycogen metabolism as potential biological mechanisms underlying these effects. Conclusions We report novel evidence suggesting that long-term increases in circulating caffeine may reduce bodyweight and the risk of osteoarthrosis and osteoarthritis. We confirm prior genetic evidence of a protective effect of plasma caffeine on risk of overweight and obesity. Further clinical study is warranted to understand the translational relevance of these findings before clinical practice or lifestyle interventions related to caffeine consumption are introduced

Associations of genetic and infectious risk factors with coronary heart disease

Coronary heart disease (CHD) is one of the most pressing health problems of our time and a major cause of preventable death. CHD results from complex interactions between genetic and environmental factors. Using multiplex serological testing for persistent or frequently recurring infections and genome-wide analysis in a prospective population study, we delineate the respective and combined influences of genetic variation, infections, and low-grade inflammation on the risk of incident CHD. Study participants are enrolled in the CoLaus|PsyCoLaus study, a longitudinal, population-based cohort with baseline assessments from 2003 through 2008 and follow-up visits every 5 years. We analyzed a subgroup of 3459 individuals with available genome-wide genotyping data and immunoglobulin G levels for 22 persistent or frequently recurring pathogens. All reported CHD events were evaluated by a panel of specialists. We identified independent associations with incident CHD using univariable and multivariable stepwise Cox proportional hazards regression analyses. Of the 3459 study participants, 210 (6.07%) had at least one CHD event during the 12 years of follow-up. Multivariable stepwise Cox regression analysis, adjusted for known cardiovascular risk factors, socioeconomic status, and statin intake, revealed that high polygenic risk (hazard ratio [HR] 1.31, 95% CI 1.10-1.56, p=2.64 x 10(-3)) and infection with Fusobacterium nucleatum (HR 1.63, 95% CI 1.08-2.45, p=1.99 x 10(-2)) were independently associated with incident CHD. In a prospective, population-based cohort, high polygenic risk and infection with F. nucleatum have a small, yet independent impact on CHD risk.GR-F

Additional file 1 of Genetic investigation into the broad health implications of caffeine: evidence from phenome-wide, proteome-wide and metabolome-wide Mendelian randomization

Additional file 1: Table S1. Phenome-wide association estimates per standard deviation unit increase in standardized plasma caffeine level genetic risk score. Table S2. Mendelian randomization estimates for the association of one standard deviation unit increase in genetically predicted plasma caffeine with plasma metabolite levels and ratios

Risk stratification for hospital-acquired venous thromboembolism in medical patients (RISE): Protocol for a prospective cohort study

Background: Hospital-acquired venous thromboembolism (VTE) is one of the leading preventable causes of in-hospital mortality. However, its risk assessment in medically ill inpatients is complicated due to the patients' heterogeneity and complexity of currently available risk assessment models (RAMs). The simplified Geneva score provides simplicity but has not yet been prospectively validated. Immobility is an important predictor for VTE in RAMs, but its definition is inconsistent and based on subjective assessment by nurses or physicians. In this study, we aim to prospectively validate the simplified Geneva score and to examine the predictive performance of a novel and objective definition of in-hospital immobilization using accelerometry. Methods and analysis: RISE is a multicenter prospective cohort study. The goal is to recruit 1350 adult inpatients admitted for medical illness in three Swiss tertiary care hospitals. We collect data on demographics, comorbidities, VTE risk and thromboprophylaxis. Mobility from admission to discharge is objectively measured using a wrist-worn accelerometer. Participants are followed for 90 days for the occurrence of symptomatic VTE (primary outcome). Secondary outcomes are the occurrence of clinically relevant bleeding, and mortality. The evolution of autonomy in the activities of daily living, the length of stay, and the occurrence of readmission are also recorded. Time-dependent area under the curve, sensitivity, specificity, and positive and negative predictive values are calculated for each RAM (i.e. the simplified and original Geneva score, Padua, and IMPROVE score) with and without the objective mobility measures to assess their accuracy in predicting hospital-acquired VTE at 90 days. Ethics and expected impact: The ethics committee approved the protocol and the study was registered on ClinicalTrials.gov as NCT04439383. RISE has the potential to optimize VTE risk stratification, and thus to improve the quality of care of medically hospitalized patients.</p