Andreana Foresta’s research while affiliated with Mario Negri Institute for Pharmacological Research and other places

Peripheral artery disease (PAD) remains underdiagnosed in patients with coronary artery disease (CAD) and barriers persist to measure screening PAD in routine clinical practice. We assessed the prevalence of PAD in patients with CAD in Italian primary care setting using an easy automatic instrument to measure ankle brachial pressure index (ABI). A multicenter, observational study was conducted with 32 General Practitioners (GPs). Prevalence of PAD was calculated dividing the number of patients with abnormal ABI value, or with symptoms associated with PAD or history of lower limb revascularization procedures, over the total number of patients included in the study. Incidence of major CV clinical events and all-cause death was also evaluated at 12 months in both CAD and CAD + PAD groups. In total, 713 CAD patients were included in the study, 148 (20.8%) patients had also PAD, asymptomatic in nearly 15% of them (106). The 35.4% of patients had ABI value ≤ 0.9 and 46.0% > 1.3 ABI. A significantly higher incidence of major CV events and all-cause death was seen in patients with PAD than in those without. Over 80% of patients received the therapy for secondary CV prevention and difference was seen between groups. Our findings showed that the use of an easy automatic instrument to measure ABI, easily managed by nurses, allowed to detect PAD in a relevant proportion of CAD patients who otherwise would not have been recognized. This encourages performing PAD screening in primary care setting to optimize the management of major CV risk factors associated with PAD. NCTumber: NCT03921905

Background Childhood obesity has become a significant public health concern over the past 2 decades, posing multifactorial challenges, including modifiable factors like dietary habits, physical activity, screen time, and sleeping habits. Prevention efforts require a comprehensive approach comprising educational interventions, collaboration among multidisciplinary teams, and community engagement. Since schools play a central role in children's lives, they are the ideal setting for promoting healthy habits. Objective The LIVELY (Multidimensional School-Based and Family-Involved Interventions to Promote a Healthy and Sustainable Lifestyle) study will assess the prevalence of overweight and obesity in primary school children and identify contributing factors within families. Additionally, it aims to implement and evaluate a multidimensional, multidisciplinary intervention to foster a sustainable and healthy lifestyle, ultimately working toward preventing obesity in school-aged children. Methods During the school year, each class will be individually involved in a multidimensional educational intervention covering the topics of healthy, sustainable nutrition and lifestyle. Children will also participate in a multimedia lab where they will create an animated cartoon. The lectures will engage them through various methods, including direct instructions, games, and drawing activities, to stimulate and enhance their learning and involvement. Results Data collection began in October 2023 and will last until the end of October 2024. A sample of 227 children from 14 classes was included in the study. The mean age was 8.9 (SD 1.2) years, and 48% (n=110) were males. Among the overall sample, 18.1% (n=41; 95% CI 13.7%-23.7%) were overweight, while 5.3% (n=12; 95% CI 3%-9%) had obesity. Males had a higher prevalence of obesity than females (9.1%, n=10 vs 1.7%, n=3, P=.03, respectively). Otherwise, the prevalence of central obesity was similar between the two (P=.329). Data analysis and the presentation of the complete results will be available after the end of 2024. Conclusions The study could lead to the structuring of an educational intervention model in school settings aimed at preventing childhood obesity. Moreover, it could help raise awareness of childhood obesity and help prevent this public health issue. Trial Registration ClinicalTrials.gov NCT05966051; https://clinicaltrials.gov/study/NCT05966051 International Registered Report Identifier (IRRID) DERR1-10.2196/57509

BACKGROUND Childhood obesity has become a significant public health concern over the past 2 decades, posing multifactorial challenges, including modifiable factors like dietary habits, physical activity, screen time, and sleeping habits. Prevention efforts require a comprehensive approach comprising educational interventions, collaboration among multidisciplinary teams, and community engagement. Since schools play a central role in children's lives, they are the ideal setting for promoting healthy habits. OBJECTIVE The LIVELY (Multidimensional School-Based and Family-Involved Interventions to Promote a Healthy and Sustainable Lifestyle) study will assess the prevalence of overweight and obesity in primary school children and identify contributing factors within families. Additionally, it aims to implement and evaluate a multidimensional, multidisciplinary intervention to foster a sustainable and healthy lifestyle, ultimately working toward preventing obesity in school-aged children. METHODS During the school year, each class will be individually involved in a multidimensional educational intervention covering the topics of healthy, sustainable nutrition and lifestyle. Children will also participate in a multimedia lab where they will create an animated cartoon. The lectures will engage them through various methods, including direct instructions, games, and drawing activities, to stimulate and enhance their learning and involvement. RESULTS Data collection began in October 2023 and will last until the end of October 2024. A sample of 227 children from 14 classes was included in the study. The mean age was 8.9 (SD 1.2) years, and 48% (n=110) were males. Among the overall sample, 18.1% (n=41; 95% CI 13.7%-23.7%) were overweight, while 5.3% (n=12; 95% CI 3%-9%) had obesity. Males had a higher prevalence of obesity than females (9.1%, n=10 vs 1.7%, n=3, P =.03, respectively). Otherwise, the prevalence of central obesity was similar between the two ( P=. 329). Data analysis and the presentation of the complete results will be available after the end of 2024. CONCLUSIONS The study could lead to the structuring of an educational intervention model in school settings aimed at preventing childhood obesity. Moreover, it could help raise awareness of childhood obesity and help prevent this public health issue. CLINICALTRIAL ClinicalTrials.gov NCT05966051; https://clinicaltrials.gov/study/NCT05966051 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/57509

The unfavorable effect of proton pump inhibitors (PPIs) on cardiovascular (CV) outcomes and mortality was reported in the general population. We investigated the impact of PPIs on CV outcomes and total mortality in older people with diabetes mellitus (DM) for whom evidence is missing. Using administrative health databases of the Lombardy Region, we analyzed the risk of myocardial infarction (MI), ischemic stroke and total mortality in individuals with DM (≥65 years of age) exposed to PPIs in 2015 and followed up to 2021. The outcomes were analyzed using a multivariable-adjusted Cox proportional hazards model to compute hazard ratios (HRs) with 95% confidence intervals (CIs). HRs between PPI users and non-users were also estimated in selected subgroups. A sensitivity analysis was also performed in a 1:1 propensity score matching population. A total of 284,068 patients were included in the analysis (49.4% PPI users, 50.6% non-PPI users). A higher prevalence of comorbidities and medications was reported in PPI users as compared with non-users. During a median follow-up of 6.7 years, the use of PPIs was associated with a higher risk for ischemic stroke (HR 1.14, 95% CI 95% 1.08–1.20), MI (HR 1.36, 95% CI 1.31–1.41) and total mortality (HR 1.24, 95% CI 1.22–1.26). These risks were higher in PPI users regardless of the PPI type. Among sexes, previous CV diseases, and insulin subgroups, the use of PPIs was correlated with a statistically significant increased risk of ischemic stroke in men, in individuals without a history of CV disease, and in those who were not treated with insulin. A significantly higher risk of MI was associated with PPIs for all subgroups, as well as for total mortality, with the exception of patients with a previous history of CV diseases. The sensitivity analysis confirmed the results of the unmatched cohort. Our findings confirmed an increased risk of CV events and all-cause mortality in a large population of older adults with DM exposed to PPIs. This could have an important impact on public health and costs for National Health Service, therefore a regular assessment of PPI appropriateness is recommended, particularly in this population.

Background Despite all the progress in the management of acute COVID-19, it is still not clear why some people continue to experience symptoms after recovery. Using data from a self-administered online survey, we assessed the prevalence and predictors of post-acute COVID-19 in an unselected population followed by GPs. Methods Patients ≥18 years with a confirmed COVID-19 diagnosis were included. The survey collected information on demographics, risk factors, COVID-19 course and symptomatology. Fatigue and Quality of Life questionnaires were also administered. Descriptive statistics were used to describe patients’ characteristics, stratified as acute and post-acute COVID-19. Logistic regression models were used to assess the association between clinical characteristics and post-acute COVID-19. Results A total of 1108 surveys were analyzed. Nearly 29% of patients reported post-acute COVID-19. The more persistent symptoms were fatigue, memory and concentration impairment. Adjusted Odds Ratio (OR) showed a significantly higher probability of post-acute COVID-19 for women compared to men (OR 1.9, 95% CI 1.4-2.5), for age >50 years than ≤50 years (OR 1.6, 95% CI 1.2-2.2), for BMI > 25 compared to BMI ≤ 25 (OR 1.6, 95% CI 1.1-2.1) and those with autoimmune diseases, compared to those without (OR 1.8 95% CI 1.1-2.9). In addition, a significant association was found with COVID-19 hospitalization, anxiety and allergies. We found that post-acute COVID-19 patients showed a higher fatigue and a worst quality of life. Conclusions These findings suggest the need for tailored personalized strategies to improve the management of patients with post-acute COVID-19.

Background COVID-19 has been associated with a higher risk of post-acute complications. Our aim was to analyze and compare post-acute cardiovascular complications of COVID-19 survivors of the first and second/third pandemic waves in Lombardy, in both hospitalized and non-hospitalized COVID-19 patients. Methods and results We included adults aged ≥40 years infected during the first and second/third waves of COVID-19 pandemic. The follow-up initiated 30 days after COVID-19 diagnosis and continued up to 9 months. Hazard ratios (HRs) and 95% confidence intervals (CIs) of the post-acute cardiovascular outcomes were calculated against an inverse probability treatment weighted control group. Subgroup analysis were performed by age classes, sex, previous cardiovascular disease and stratified by COVID-19 hospitalization status to explore the impact of COVID-19 severity on outcomes. Compared to the control group, COVID-19 patients had an increased risk of hospitalization for any cardiovascular complications (HR 1st wave 1.53 95% CI: 1.38–1.69; HR 2nd/3rd wave 1.25 95% CI: 1.19–1.31) and for individual cardiovascular outcomes, although HRs were higher in COVID-19 group from the 1st pandemic wave. The results were confirmed in the subgroup analyses. Of note, the risk for any cardiovascular disease was also evident even among individuals who were not hospitalized during the acute phase of the infection. Conclusion Our results provide evidence that COVID-19 is a risk factor for post-acute cardiovascular complications among different pandemic waves regardless of COVID-19 severity, age, sex and a history of cardiovascular diseases. Care strategies of people with COVID-19 should include cardiac monitoring.

Ursodeoxycholic acid (UDCA), an off‐patent drug used to treat liver disease, is able to block SARS‐CoV‐2 entry into the cells downregulating ACE2 expression, a promising strategy to protect against infection. In this light, John et al. have recently demonstrated that in patients with cirrhosis, UDCA exposure was associated with both a decrease in SARS‐CoV‐2 infection and a reduction in COVID‐19 severity confirming previous data published by Brevini et al. To investigate the impact of UDCA treatment in SARS‐CoV‐2 infection and COVID‐19 outcomes in an unselected population of COVID‐19 patients we used the administrative databases from Lombardy (Northern Italy), the first region of Western world to experience a rapid increase in the number of COVID‐19 cases and related deaths and the most populated Italian region. The analysis included patients from the 1st and 2nd pandemic waves, were wild‐type and alfa variant were predominant. This article is protected by copyright. All rights reserved

Introduction Prevention of cardiovascular disease (CVD) is of key importance in reducing morbidity, disability and mortality worldwide. Observational studies suggest that digital health interventions can be an effective strategy to reduce cardiovascular (CV) risk. However, evidence from large randomised clinical trials is lacking. Methods and analysis The CV-PREVITAL study is a multicentre, prospective, randomised, controlled, open-label interventional trial designed to compare the effectiveness of an educational and motivational mobile health (mHealth) intervention versus usual care in reducing CV risk. The intervention aims at improving diet, physical activity, sleep quality, psycho-behavioural aspects, as well as promoting smoking cessation and adherence to pharmacological treatment for CV risk factors. The trial aims to enrol approximately 80 000 subjects without overt CVDs referring to general practitioners’ offices, community pharmacies or clinics of Scientific Institute for Research, Hospitalization and Health Care (Italian acronym IRCCS) affiliated with the Italian Cardiology Network. All participants are evaluated at baseline and after 12 months to assess the effectiveness of the intervention on short-term endpoints, namely improvement in CV risk score and reduction of major CV risk factors. Beyond the funded life of the study, a long-term (7 years) follow-up is also planned to assess the effectiveness of the intervention on the incidence of major adverse CV events. A series of ancillary studies designed to evaluate the effect of the mHealth intervention on additional risk biomarkers are also performed. Ethics and dissemination This study received ethics approval from the ethics committee of the coordinating centre (Monzino Cardiology Center; R1256/20-CCM 1319) and from all other relevant IRBs and ethics committees. Findings are disseminated through scientific meetings and peer-reviewed journals and via social media. Partners are informed about the study’s course and findings through regular meetings. Trial registration number NCT05339841 .

Aims: To describe glucose-lowering drugs prescribing pattern in a large population of older diabetics from 2010 to 2021. Methods: Using linkable administrative health databases, we included patients aged 65-90 years treated with glucose-lowering drugs. Prevalence rate of drugs was collected within each study year. A stratified analysis by gender, age and coexistence of cardiovascular disease (CVD) was conducted. Results: A total of 251 737 and 308 372 patients were identified in 2010 and 2021, respectively. Use of metformin (68.4% to 76.6%), DPP-4i (1.6% to 18.4%), GLP-1-RA (0.4% to 10.2%), SGLT2i (0.6% to 11.1%) increased, while sulfonylureas (53.6% to 20.7%) and glinides (10.5% to 3.5%) decreased over time. Metformin, glitazones, GLP1-RA, SGLT2i and DPP4i (except for 2021) usage decreased with aging, in contrast to sulfonylureas, glinides and insulin. The coexistence of CVD was associated with a higher prescription of glinides, insulin, DPP-4i, GLP1-RA and SGLT2i, particularly in 2021. Conclusions: We found a significant increase in the prescriptions of GLP-1 RA and SGLT2i in older diabetics, mainly in those with CVD. However, drugs without CV benefits including sulfonylureas and DPP-4i continued to be highly prescribed in older patients. There is still room to improve the management in this population according to recommendations.

Purpose: It has been reported that dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have a role in modulation of inflammation associated with coronavirus disease 2019 (COVID-19). This study assessed the effect of these drug classes on COVID-19-related outcomes. Methods: Using a COVID-19 linkable administrative database, we selected patients aged ≥40 years with at least 2 prescriptions of DPP-4i, GLP-1 RA, or SGLT-2i or any other antihyperglycemic drug and a diagnosis of COVID-19 from February 15, 2020, to March 15, 2021. Adjusted odds ratios (ORs) with 95% CIs were used to calculate the association between treatments and all-cause and in-hospital mortality and COVID-19-related hospitalization. A sensitivity analysis was performed by using inverse probability treatment weighting. Findings: Overall, 32,853 subjects were included in the analysis. Multivariable models showed a reduction of the risk for COVID-19 outcomes for users of DPP-4i, GLP-1 RA, and SGLT-2i compared with nonusers, although statistical significance was reached only in DPP-4i users for total mortality (OR, 0.89; 95% CI, 0.82-0.97). The sensitivity analysis confirmed the main results reaching a significant reduction for hospital admission in GLP-1 RA users and in-hospital mortality in SGLT-2i users compared with nonusers. Implications: This study found a beneficial effect in the risk reduction of COVID-19 total mortality in DPP-4i users compared with nonusers. A positive trend was also observed in users of GLP-1 RA and SGLT-2i compared with nonusers. Randomized clinical trials are needed to confirm the effect of these drug classes as potential therapy for the treatment of COVID-19.