Cardiovascular diseases remain the leading cause of mortality and morbidity worldwide, with substantial impact in Italy. Cardiovascular prevention is a strategic priority, yet a significant gap persists between evidence-based guideline recommendations and their actual implementation in clinical practice. Artificial intelligence (AI), through machine learning and deep learning models, is emerging as a potentially transformative technology to bridge this gap, enabling more precise, dynamic, and personalized cardiovascular risk stratification compared with traditional risk scores. This review examines the most recent evidence on the application of AI in cardiovascular prevention, with a specific focus on risk stratification, early detection of subclinical disease, and identification of patients most likely to benefit from targeted interventions. It addresses the limitations of conventional risk scores and the contribution of emerging risk determinants, including digital biomarkers, genetic data, and wearable devices. It discusses the role of AI-enabled electrocardiography in the early detection of subclinical atrial fibrillation, left ventricular dysfunction, and coronary artery disease; the potential of opportunistic imaging (chest radiography, chest and coronary computed tomography, mammography) for subclinical atherosclerosis; and the integration of AI into clinical care pathways, electronic health records, clinical decision support systems, and telemonitoring networks. Overall, AI outlines the transition from a reactive cardiology model toward a predictive, proactive, and precision-based approach. Translation into routine clinical practice requires robust prospective evidence, randomized controlled trials, validation in heterogeneous populations, improved model interpretability, and adequate digital and regulatory infrastructures.
Simona Giubilato, Lucio Giuseppe Granata, Salvatore Massimo Petrina· Giornale italiano di cardiol...· 0 citations
Hypertension remains a major global health burden, and control rates remain suboptimal because of poor medication adherence and limitations of existing therapies, including escape within the renin–angiotensin–aldosterone system. Zilebesiran, a first-in-class, subcutaneously administered small interfering RNA therapeutic, represents a promising advance in hypertension management. Through N-acetylgalactosamine-mediated hepatic delivery, zilebesiran selectively silences angiotensinogen (AGT) messenger RNA, the transcript encoding the common precursor of all angiotensin peptides. This upstream intervention reduces AGT production and produces durable blood pressure lowering that can persist for up to 6 months after a single dose. This review summarizes the mechanism of action of zilebesiran, its pharmacokinetic and pharmacodynamic properties, and the available phase 1 and phase 2 clinical evidence, including the KARDIA program. We also place zilebesiran within the evolving antihypertensive landscape by comparing it with aldosterone synthase inhibitors, dual endothelin receptor antagonists, and brain aminopeptidase A inhibitors. Finally, we discuss translational challenges, including reversal strategies for emergency situations, monitoring considerations, and potential roles for personalized dosing. Early-phase and phase 2 trials show dose-dependent and durable reductions in serum AGT and blood pressure with infrequent dosing; however, long-term safety, cardiovascular outcome benefit, and generalizability in diverse high-risk populations remain to be established, and zilebesiran remains investigational while phase 3 outcome testing is underway.
M. Francese, Lucio Giuseppe Granata, A. Noor et al.· Life· 0 citations
Lipoprotein(a) [Lp(a)] has emerged as a major, genetically determined, contributor to residual cardiovascular risk. Accumulating evidence from epidemiological studies, human genetics, and Mendelian randomization has unequivocally established elevated Lp(a) as an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis (CAVS). Lp(a) consists of a low-density lipoprotein-like particle in which apolipoprotein(a) is covalently linked to apolipoprotein B100. This unique structure confers proatherogenic, pro-inflammatory, and antifibrinolytic properties, largely mediated by oxidized phospholipids and the structural homology of apolipoprotein(a) with plasminogen. Circulating Lp(a) concentrations are genetically determined and remain relatively stable throughout life with minimal influence from lifestyle interventions. Conventional lipid-lowering therapies have little or no meaningful effect on circulating Lp(a) concentrations, leaving an important component of residual cardiovascular risk unaddressed. In contrast, RNA-based therapeutics targeting hepatic LPA expression have demonstrated reductions in circulating Lp(a) of up to 80–90% and are currently being evaluated in phase 3 cardiovascular outcome trials. This narrative review summarizes the molecular biology, genetics, epidemiology, pathophysiological mechanisms, and clinical relevance of Lp(a), and critically examines current and emerging therapeutic strategies aimed at reducing Lp(a)-mediated cardiovascular risk.
Lucio Giuseppe Granata, Simona Giubilato, Francesca Campanella et al.· Frontiers in Medicine· 0 citations