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.

Aims: A polygenic risk score (PRS) has the potential to improve individual atherosclerotic cardiovascular disease (ASCVD) risk assessment. To determine whether a PRS combined with two clinical risk scores, the Systematic COronary Risk Evaluation 2 (SCORE2) and the Pooled Cohort Equation (PCE) improves the prediction of ASCVD. Methods and results: Using a population-based European prospective cohort, with 6733 participants at the baseline (2003–2006), the PRS presenting the best predictive accuracy was combined with SCORE2 and PCE to assess their joint performances for predicting ASCVD Discrimination, calibration, Cox proportional hazard regression, and net reclassification index were assessed. : 4218 subjects (53% women; median age, 53.4 years), with 363 prevalent and incident ASCVD, were used to compare four PRSs. The metaGRS_CAD PRS presented the best predictive capacity (AUROC = 0.77) and was used in the following analyses. 3383 subjects (median follow-up of 14.4 years), with 190 first-incident ASCVD, were employed to test ASCVD risk prediction. The changes in C statistic between SCORE2 and PCE models and those combining metaGRS_CAD with SCORE2 and PCE were 0.008 (95% CI, −0.00008–0.02, P = 0.05) and 0.007 (95% CI, 0.005–0.01, P = 0.03), respectively. Reclassification was improved for people at clinically determined intermediate-risk for both clinical scores [NRI of 9.6% (95% CI, 0.3–18.8) and 12.0% (95% CI, 1.5–22.6) for SCORE2 and PCE, respectively]. Conclusion: Combining a PRS with clinical risk scores significantly improved the reclassification of risk for incident ASCVD for subjects in the clinically determined intermediate-risk category. Introducing PRSs in clinical practice may refine cardiovascular prevention for subgroups of patients in whom prevention strategies are uncertain.

Caffeine 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.

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 asNCT04439383. RISE has the potential to optimize VTE risk stratification, and thus to improve the quality of care of medically hospitalized patients.

Background: Association between cannabis use and development of atherosclerotic cardiovascular disease (ASCVD) is inconsistent and challenging to interpret, given existing study limitations. Methods: Sixty five independent single-nucleotide polymorphisms (SNPs), obtained from a genome-wide association study on lifetime cannabis use, were employed as genetic instruments to estimate the effects of genetically indexed cannabis use on risk of coronary artery disease (CAD) and acute ischemic stroke (IS) using a two-sample Mendelian randomization (MR) approach. Summary statistics on CAD (CARDIoGRAMplusC4D; 60,801 cases and 123,504 controls) and IS (MEGASTROKE; 34,217 cases and 406,111 controls) were obtained separately. A comprehensive review of the observational literature on cannabis use and CAD or IS was also performed and contrasted with MR results. Results: There was no causal effect of cannabis use on the risk of CAD (odds ratio (OR) per ever-users vs. never-users 0.93; 95% confidence interval (CI), 0.83 to 1.03) or IS (OR 1.05; 95%CI, 0.93 to 1.19). Sensitivity analyses yielded similar results, and no heterogeneity and directional pleiotropy was observed. Our meta-analysis of observational studies showed no significant association between ever use of cannabis with risk of CAD (k = 6 studies; OR_pooled = 1.23, 95%CI 0.78 to 1.69), nor with IS (k = 6 studies; OR_pooled = 1.22, 95%CI 0.95 to 1.50). Conclusion: Using a genetic approach approximating a clinical trial does not provide evidence consistent with a causal effect of genetic predisposition to cannabis use on CAD or IS development. Further studies are needed to replicate our findinds, an to investigate more precisely the risk of ASCVD in relation to the quantity, type, route of administration, or the age at exposure to cannabis.

Aims: External validation of the new 10-year PREVENT risk score for atherosclerotic cardiovascular disease (ASCVD) is important to assess its potential clinical applicability in Switzerland and to highlight its influence in preventive treatment eligibility. Methods and results: This study, which was not used in the development process of PREVENT, included 5064 individuals from a prospective Swiss cohort, aged 40 or older, without pre-existing ASCVD, and with complete data for risk score calculation. Main outcomes were adjudicated ASCVD events, including fatal and non-fatal myocardial infarction and strokes. The performances of the PREVENT score were assessed overall, and stratified by gender and age groups (<70 vs. ≥70 years), and compared with SCORE2 and the Pooled Cohort Equation (PCE) scores. Among 4356 participants followed from 2009 to 2012 over a median of 9 years, 224 experienced a first incident of ASCVD. The PREVENT cardiovascular risk prediction model demonstrated adequate discrimination performance, correctly identifying 76% of concordant pairs [C-Index, 95% Confidence Interval (CI) 0.73 to 0.79]. The model's calibration performances suggest systematic underestimation (Observed/Expected ratio 1.45, 95% CI 1.44–1.46), especially in women and those under 70 years old, yet it maintained positive clinical utility across all subgroups, particularly at the 7.5% threshold, which is the lower limit of the intermediate-risk category in clinical practice. However, PREVENT did not improve predictive performance when compared with SCORE2 and PCE. Conclusion: Our study confirmed the PREVENT model demonstrated adequate discrimination and calibration capabilities, along with significant clinical utility, particularly at intermediate-risk thresholds. However, it did not outperform the established models, SCORE2 or PCE. Additionally, PREVENT may systematically underestimate risk, which could raise concerns about the underprescription of preventive treatments.