Translational longevity medicine: a Swiss perspective in an ageing country.

Breakthroughs in medical research in the last century have led to a significant extension of the human lifespan, resulting in a shift towards an elderly population worldwide. Due to the ongoing progress of global development towards elevated standards of living, this study specifically examines Switzerland as a representative nation to explore the socioeconomic and healthcare ramifications associated with an ageing population, thereby highlighting the tangible impact experienced in this context. Beyond the exhaustion of pension funds and medical budgets, by reviewing the literature and analysing publicly available data, we observe a "Swiss Japanification". Old age is associated with late-life comorbidities and an increasing proportion of time spent in poor health. To address these problems, a paradigm shift in medical practice is needed to improve health rather than respond to existing diseases. Basic ageing research is gaining momentum to be translated into therapeutic interventions and provides machine learning tools driving longevity medicine. We propose that research focus on closing the translational gap between the molecular mechanisms of ageing and a more prevention-based medicine, which would help people age better and prevent late-life chronic diseases.

Clinical practice guidelines for cardiovascular disease: how is depression addressed? Protocol for a systematic review.

INTRODUCTION: Depression frequently affects patients with cardiovascular disease (CVD). When these conditions co-occur, outcomes such as quality of life and life expectancy worsen. In everyday practice, this specific and prevalent disease-disease interaction complicates patient management. Clinical practice guidelines (CPGs) aim to provide the best available advice for clinical decision-making to improve patient care. This study will aim to evaluate how CPGs specifically address depression in patients with CVD, and whether they provide any operational guidance for screening and management of depression in the primary care and outpatient setting. METHODS AND ANALYSIS: We will conduct a systematic review of CPGs on CVD management published from 2012 to 2023. A broad literature search for guidelines will be performed through electronic medical databases, grey literature search tools, and websites of national and professional medical organisations.Based on the inclusion criteria, two independent reviewers will evaluate eligible guidelines for screening and management recommendations on depression in patients with CVD. Additional points to be evaluated will be any mention of drug-drug or drug-disease interactions, other aspects of specific relevance to treating physicians, as well as general information on mental health. We will assess the quality of CPGs with a recommendation regarding depression in CVD patients using the Appraisal of Guidelines for Research and Evaluation II. ETHICS AND DISSEMINATION: As this systematic review is based on available published data, ethics approval and consent are not applicable. Our intent is that our results will be published in a peer-reviewed journal, presented at international scientific meetings, and distributed to healthcare providers. PROSPERO REGISTRATION NUMBER: CRD42022384152.

[A He(art) museum for an existential rebirth after a myocardial infarction]. / HeART museum : soigner son cœur au musée après un infarctus du myocarde.

Rebuilding one's life after a myocardial infarction requires mobilizing each and every resource available during a difficult period. Medical treatments, physical training and patient education (PE) help to initiate this process. Associating healthcare with art and culture is known to favour an existential « rebirth ¼ and positive biological effects. Since 2019, we propose an initiation to museotherapy (museum in health) to patients in our cardiac rehabilitation program. This article summarizes the evidence about museotherapy benefits in cardiovascular diseases and describes the experience gathered by the cardiology service of the HUG since museotherapy was initiated in 2019.

Reconstruire sa vie, une santé et une identité acceptables après un infarctus du myocarde nécessite de mobiliser toutes ses ressources dans un moment perturbé. Traitements médicamenteux, réentraînement physique et éducation thérapeutique du patient (ETP) engagent ce processus. On sait de longue date qu'incorporer l'art et la culture aux soins favorise une « renaissance ¼ existentielle et des effets biologiques positifs. Depuis 2019, nous proposons aux patients une initiation à la muséothérapie intégrée à notre programme de réadaptation cardiovasculaire (RCV) ambulatoire. Cet article a pour but de résumer les évidences concernant les bénéfices de la muséothérapie dans les maladies cardiovasculaires et de décrire l'expérience débutée en 2019 par le Service de cardiologie des HUG dans ce domaine.

[Long-lasting LDL-C lowering: silence at last]. / Une baisse du cholestérol LDL de longue durée : enfin le silence.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is responsible for the degradation of the LDL-receptor. Inclisiran is a new synthetic interfering ribonucleic acid (siRNA) lowers LDL-cholesterol (LDL-C) levels in the blood by using RNA silencing technology to reduce the production of PCSK9. Inclisiran administered subcutaneously at 0 and 3 months, and then every 6 months has been shown to reduce LDL-C by approximately 50 % in patients at high and very-high cardiovascular risk, or with a diagnosis of familial hypercholesterolemia, but also in patients intolerant to statins. New data are expected, in particular with cardiovascular clinical endpoints, as well as safety for use in adolescents.

La proprotéine convertase subtilisine/kexine de type 9 (PCSK9) est responsable de la dégradation du LDL (Low Density Lipoprotein)-récepteur. L'inclisiran est un nouveau petit ARN interférent synthétique qui baisse les taux de LDL-cholestérol (LDL-C) circulant en utilisant la technologie de silençage ARN pour réduire la production de PCSK9. Administré par voie sous-cutanée à 0 et 3 mois, puis tous les 6 mois, l'inclisiran a démontré une réduction du LDL-C d'environ 50 % chez des patients à haut et très haut risque cardiovasculaire ou avec un diagnostic d'hypercholestérolémie familiale, mais aussi chez des patients intolérants aux statines. De nouvelles données sont attendues, notamment sur les critères de jugement cliniques cardiovasculaires, ainsi que la sécurité d'emploi chez les adolescents.

Design of the randomized, placebo-controlled evolocumab for early reduction of LDL-cholesterol levels in patients with acute coronary syndromes (EVOPACS) trial.

Statins lower low-density lipoprotein cholesterol (LDL-C) and improve clinical outcomes in patients with atherosclerotic cardiovascular disease (CVD). Patients with acute coronary syndromes (ACS) often do not achieve LDL-C targets despite potent statin treatment, and have a particularly high risk of early recurrent events. Evolocumab, a proprotein convertase subtilisin/kexin type (PCSK9)-inhibitor resulting in rapid, marked LDL-C reduction, has been studied in hypercholesterolemic subjects without CVD and stabilized patients with CVD; the feasibility, safety, and efficacy of this treatment initiated in the acute phase of ACS remain unknown. We report the design of evolocumab for early reduction of LDL-cholesterol levels in patients with ACS (EVOPACS), a phase-3, multicenter, randomized, double-blind, placebo-controlled trial to assess the feasibility, safety, and LDL-C-lowering efficacy of evolocumab on top of atorvastatin 40 mg in patients with ACS. The primary endpoint is percent change in LDL-C from baseline to 8 weeks. Secondary endpoints are adverse events and serious adverse events. Against a background of beneficial cardiovascular effects of statins beyond LDL-C lowering and in view of preclinical evidence of similar effects of PCSK9 inhibition, the study will also address a variety of exploratory endpoints including the change in C-reactive protein and other inflammatory biomarkers; platelet reactivity; and occurrence of contrast-induced acute kidney injury and myocardial injury in patients undergoing cardiac catheterization. An intracoronary imaging sub-study will investigate the change from baseline in the lipid core burden index in non-culprit lesions, as assessed by serial near-infrared spectroscopy. Recruitment began in January 2018 and enrollment of 308 patients is planned.

Use and role of monoclonal antibodies and other biologics in preventive cardiology.

Biotechnological advances now enable the design of fully human antibodies to target specific antigens in a growing number of diseases. Monoclonal antibodies (mAbs) differ from traditional small chemical molecules in several ways: (1) biological production ‒ they are grown in and extracted from cell cultures; (2) specificity ‒ they demonstrate high target specificity, with a low risk of drug-drug interactions; (3) administration ‒ they are delivered parenterally (intravenously or subcutaneously); (4) dosage interval ‒ their extended half-lives generally allow for spaced dosing (from weekly to monthly). In cardiology, fully human mAbs directed against proprotein convertase subtilisin / kexin type 9 (PCSK9) have shown to be effective in reducing low-density lipoprotein cholesterol (LDL-C) in phase II clinical trials among patients with familial hypercholesterolaemia (FH). PCSK9 inhibitors have just received approval for the treatment of FH and clinical atherosclerotic disease, and patients not at target under maximally tolerated statin therapy or intolerant to statins. Large-scale phase III trials are currently assessing the role of PCSK9 inhibitors in the secondary prevention setting for patients with acute coronary syndromes (ACS) and poorly controlled LDL-C under evidence-based therapies. Another area currently under investigation for fully human mAbs in secondary prevention is their potential ability to inhibit inflammatory pathways. In this context, canakinumab, a specific mAb inhibiting interleukin-1ß (IL-1ß), has already received approval for the treatment of systemic juvenile idiopathic arthritis. The canakinumab anti-inflammatory thrombosis outcomes trial (CANTOS) is an ongoing trial assessing whether inhibition of IL-1ß could reduce the occurrence of cardiovascular adverse events in 17,200 patients with ACS and with defined persisting inflammation.