Although low-density lipoprotein cholesterol (LDL-C) can now be effectively reduced, substantial residual risk of acute ischemic cardiovascular events persists. Lipoprotein(a) [Lp(a)] is an established causal risk factor for atherosclerotic cardiovascular disease (ASCVD), yet its mechanistic links to plaque vulnerability and their clinical implications remain incompletely understood. Clinical imaging studies have associated elevated Lp(a) with plaque progression and features of vulnerability, including lipid-rich necrotic cores, macrophage accumulation, and thin fibrous caps, suggesting that Lp(a)-associated risk may involve destabilization during plaque progression. This review draws on imaging and pathological evidence to examine the potential mechanisms underlying these associations and their implications for clinical risk stratification and preventive decision-making. The apolipoprotein(a) [apo(a)] component unique to Lp(a), together with the oxidized phospholipids (OxPL) it carries, may contribute to plaque vulnerability by sustaining vascular inflammation, promoting necrotic core expansion, and influencing fibrous cap stability and intraplaque neovascularization. Integrating circulating Lp(a) levels with plaque imaging features and baseline cardiovascular risk may help identify individuals at high risk in primary prevention and evaluate residual risk in secondary prevention, informing earlier or more intensive efforts to manage modifiable risk factors. Alongside established preventive measures, therapies aimed at lowering Lp(a) may provide an additional approach to reducing residual risk. In trials conducted to date, substantial reductions in Lp(a) have been observed with antisense oligonucleotides, small interfering RNAs, and oral small-molecule inhibitors; some agents have demonstrated sustained effects and favorable safety profiles. However, whether therapies targeting Lp(a) reduce cardiovascular event risk remains to be established through robust evidence from large cardiovascular outcome trials.

Background: Polydatin has shown anti-inflammatory, antioxidant, and cytoprotective effects in preclinical studies. Its development is limited by low oral bioavailability, extensive metabolism, and poorly defined tissue exposure. Objectives: This review summarizes the pharmacology and delivery systems of polydatin, distinguishes nano from non-nano formulations, and examines the evidence for improved exposure, tissue delivery, safety, and clinical translation. Methods: Relevant studies were identified through a structured PubMed search and assessed by formulation type, administration route, comparator, and reported endpoints. Results: Delivery strategies include liposomes, polymeric and polysaccharide nanoparticles, lipid-based formulations, inclusion complexes, solid-state systems, hydrogels, local matrices, and targeted systems. Only a few oral formulations have been compared directly with free polydatin using quantitative pharmacokinetic measurements. Many injectable and local studies report release, cellular uptake, fluorescence distribution, or pharmacodynamic effects, but these findings do not by themselves demonstrate improved bioavailability or drug-specific targeting. Evidence on repeat-dose toxicity, immunogenicity, carrier clearance, and manufacturing consistency remains limited. No clinical study of a polydatin nanocarrier was identified. Conclusions: Further development requires appropriate free-polydatin controls, measurement of polydatin and its metabolites, exposure–response analysis, fuller safety assessment, and reproducible product characterization.