Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality worldwide, highlighting the urgent need for advancements in risk assessment and management strategies. Although significant progress has been made recently, identifying and managing apparently healthy individuals at a higher risk of developing atherosclerosis and those with subclinical atherosclerosis still poses significant challenges. Traditional risk assessment tools have limitations in accurately predicting future events and fail to encompass the complexity of the atherosclerosis trajectory. In this review, we describe novel approaches in biomarkers, genetics, advanced imaging techniques, and artificial intelligence that have emerged to address this gap. Moreover, polygenic risk scores and imaging modalities such as coronary artery calcium scoring, and coronary computed tomography angiography offer promising avenues for enhancing primary cardiovascular risk stratification and personalised intervention strategies. On the other hand, interventions aiming against atherosclerosis development or promoting plaque regression have gained attention in primary ASCVD prevention. Therefore, the potential role of drugs like statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, omega-3 fatty acids, antihypertensive agents, as well as glucose-lowering and anti-inflammatory drugs are also discussed. Since findings regarding the efficacy of these interventions vary, further research is still required to elucidate their mechanisms of action, optimize treatment regimens, and determine their long-term effects on ASCVD outcomes. In conclusion, advancements in strategies addressing atherosclerosis prevention and plaque regression present promising avenues for enhancing primary ASCVD prevention through personalised approaches tailored to individual risk profiles. Nevertheless, ongoing research efforts are imperative to refine these strategies further and maximise their effectiveness in safeguarding cardiovascular health.

Cardiology Clinic Ankara Bilkent City Hospital Ankara Turkey

Cardiology Department Institute of Endocrinology and Metabolism Kyiv Ukraine

Cardiovascular Center Aalst OLV Clinic Aalst Belgium; Department of Prevention and Treatment of Emergency Conditions L T Malaya Therapy National Institute NAMSU Kharkiv Ukraine

Centre for Academic Primary Care School of Medicine University of Nottingham United Kingdom

Centre for Cardiovascular Medicine and Devices William Harvey Research Institute Queen Mary University of London London United Kingdom; Barts Interventional Group Barts Heart Centre St Bartholomew's Hospital London United Kingdom

Department of Clinical and Experimental Medicine University of Catania Catania Italy

Department of Endocrinology Tan Tock Seng Hospital Singapore

Department of Internal Medicine Faculty of Medicine Hacettepe University Ankara Turkey

Department of Internal Medicine Faculty of Medicine School of Health Sciences University of Ioannina Ioannina Greece

Department of Internal Medicine St Anne's University Hospital in Brno and Faculty of Medicine of Masaryk University Brno Czech Republic; Department of Physiology Faculty of Medicine Masaryk University Brno Czech Republic

Department of Laboratory Medicine Medical University of Vienna Vienna Austria

Department of Medicine and Surgery University of Perugia Italy

Department of Medicine University of Padova Italy

Department of Pharmacological and Biomolecular Sciences Rodolfo Paoletti Università Degli Studi di Milano Milan Italy

Division of Cardiology Department of Medicine Department of Physiology and Molecular Biology Institute UCLA Los Angeles CA USA

Division of Vascular and Endovascular Surgery Department of Medical Surgical and Health Sciences University of Trieste Trieste Italy

Genomics Medicine Unit Navarra Institute for Health Research IdiSNA Navarrabiomed Hospital Universitario de Navarra Pamplona Spain

Institute for Molecular Cardiovascular Research RWTH Aachen University 52074 Aachen Germany

Institute of Genetic Epidemiology Medical University of Innsbruck Innsbruck Austria

Internal Medicine Department Grigore T Popa University of Medicine and Pharmacy Iasi Romania

Laboratory of Cellular and Molecular Pathology of Cardiovascular System Petrovsky National Research Centre of Surgery Moscow Russia

Laboratory of Physiopharmacology University of Antwerp Antwerp Belgium

Nantes Université CNRS INSERM l'institut du Thorax Nantes France

Republican Specialized Scientific Practical Medical Center of Therapy and Medical Rehabilitation Tashkent Uzbekistan

Sumy State University Sumy Ukraine; Tallinn University of Technology Tallinn Estonia

The Hatter Cardiovascular Institute University College London London United Kingdom

Unidade 1 and D Grupo de Investigação Cardiovascular Departamento de Promoção da Saúde e Doenças Não Transmissíveis Instituto Nacional de Saúde Doutor Ricardo Jorge Lisboa Portugal; Universidade de Lisboa Faculdade de Ciências BioISI Biosystems and Integrative Sciences Institute Lisboa Portugal

Victor Babes University of Medicine and Pharmacy Timisoara Romania; Institute of Cardiovascular Diseases Timisoara Timisoara Romania

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