Search Results (229)

Background: Early initiation of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9-i) in patients with acute myocardial infarction (MI) may anticipate and maximize lipid-lowering benefit. Whether PCSK9 inhibition also exerts early anti-inflammatory effects in this setting remains unclear. This study aimed to evaluate the effects of early PCSK9-i administration on inflammatory markers and lipid parameters in patients with acute MI undergoing percutaneous coronary intervention (PCI). Methods: In this randomized, prospective, single-center, open-label trial, patients with acute MI undergoing PCI were randomly assigned to receive a single upstream 140 mg subcutaneous dose of evolocumab immediately before PCI, on top of oral lipid-lowering therapy (LLT) (n = 30), or oral LLT alone (control group; n = 30). Tumor necrosis factor-alpha (TNF-α), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), and lipoprotein(a) [Lp(a)] levels were measured at baseline and during the early post-intervention phase. Results: Baseline TNF-α values and lipid parameters were similar between the two groups. At 72 h after PCI, TNF-α levels were significantly lower in the evolocumab arm compared with controls (0.01 vs. 0.25 pg/mL; p = 0.025). Evolocumab was also associated with a greater relative reduction in LDL-C levels from baseline (−48% vs. −18%; p < 0.001) and apoB levels (−34% vs. −11%; p < 0.001). The proportion of patients achieving the LDL-C goal of <55 mg/dL at 72 h was higher in the evolocumab group than in controls (50% vs. 10%; p < 0.001). Lp(a) levels at 72 h were also lower with evolocumab (12 [10–33] vs. 28 [13.1–70] mg/dL; p = 0.032). Conclusions: In patients with acute MI undergoing PCI, upstream administration of a single evolocumab dose was associated with suppression of the early post-intervention increase in TNF-α levels, together with rapid reductions in LDL-C, apoB, and Lp(a). These findings suggest a potential modulation of the early inflammatory response by PCSK9 inhibition in addition to its lipid-lowering effects. Larger studies are needed to confirm these observations and to determine their clinical relevance. Full article

Cancer remains a major global health challenge, with persistent limitations in early diagnosis, metastatic disease control, and the achievement of durable therapeutic responses with acceptable toxicity. These challenges highlight the need for more precise biomarkers and more effective therapeutic strategies. Increasing evidence implicates dysregulated lipid metabolism as a central contributor to tumor development and progression. In recent years, proprotein convertase subtilisin/kexin type 9 (PCSK9), angiopoietin-like protein 3 (ANGPTL3), and cholesteryl ester transfer protein (CETP) have gained particular attention due to their roles in cholesterol homeostasis, oncogenic signaling, and immune modulation within the tumor microenvironment (TME). This narrative review evaluates the potential of these lipid-regulatory mediators as diagnostic biomarkers and therapeutic targets in oncology. The majority of available evidence derives from preclinical and epidemiological studies, with PCSK9 representing the most extensively investigated target. Findings are sometimes contradictory and strongly influenced by tumor type, disease stage, and biological context, which currently precludes the clinical applicability of these molecules as reliable biomarkers. Similar limitations apply to their translational potential as actionable therapeutic targets. Nevertheless, emerging preclinical evidence suggests that modulation of these glycoproteins may enhance the efficacy of chemotherapy, targeted therapies, and immunotherapy, including nanomedicine-based approaches. Of note, clinical research investigating the role of PCSK9 inhibition in oncology is currently ongoing, whereas comparable studies focusing on ANGPTL3 and CETP remain scarce. Overall, further mechanistic, translational, and prospective clinical investigations are warranted to elucidate the involvement of these lipid-regulatory proteins in cancer biology and to define their potential integration into future oncologic diagnostic and therapeutic strategies. Full article

Introduction/Objectives: Although contemporary cardiovascular guidelines endorse intensive low-density lipoprotein cholesterol (LDL-C) lowering and advanced lipid biomarkers for refined risk stratification, important gaps in knowledge and implementation persist. This study evaluated clinician familiarity with novel lipid-lowering therapies, approaches to residual cardiovascular risk, confidence in identifying familial hypercholesterolemia (FH), and perceived usefulness of digital decision-support tools. Methods: A multispecialty, cross-sectional online survey (October 2025) of physicians involved in dyslipidemia care was conducted. The questionnaire assessed familiarity, accessibility, and barriers regarding proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, inclisiran, and bempedoic acid; confidence and practice in managing complex populations and residual risk; confidence in detecting FH and expectations for lipoprotein(a) [Lp(a)]; and perceived value of digital decision-support and automated risk alerts. Descriptive statistics and chi-square tests were performed. Results: Ninety-five clinicians completed the survey, with the largest group (41.1%) being general practitioners. Of them, 20.0% reported familiarity with all three novel therapies, and 49.5% reported restricted access due to cost and reimbursement constraints. Overall confidence in managing dyslipidemia in complex populations was moderate. Of note, 31.6% did not routinely assess residual risk after achieving LDL-C targets. Among those who did, imaging-based evaluation of subclinical atherosclerosis was the most frequently selected approach, followed by Lp(a) and triglycerides, hs-CRP, and apoB. Confidence in recognizing FH was modest, and expectations regarding future Lp(a) testing differed across specialties. Most respondents endorsed integrated decision-support tools and automated risk-alert prompts. Conclusions: Implementation gaps persist in dyslipidemia care, while strong receptiveness to digital decision-support highlights an opportunity to align practice more closely with evidence-based recommendations. Full article

Background: Peripheral artery disease (PAD) is a manifestation of systemic atherosclerosis characterized by chronic inflammation, endothelial dysfunction, and high residual risk of major adverse cardiovascular events (MACEs) and major adverse limb events (MALEs). This review aimed to summarize the prognostic role of inflammatory biomarkers in PAD and to discuss their therapeutic implications. Methods: A comprehensive narrative review was performed using PubMed/MEDLINE, Scopus, Web of Science, and Cochrane Library, focusing mainly on English-language studies published in recent years. Randomized trials, observational studies, systematic reviews, and meta-analyses evaluating inflammatory biomarkers and anti-inflammatory or vasculoprotective therapies in PAD were included. Results: Both classical and emerging inflammatory biomarkers were associated with PAD severity and adverse outcomes. C-reactive protein, fibrinogen, interleukins, tumor necrosis factor-α, myeloperoxidase, galectin-3, and growth differentiation factor-15 showed prognostic value for MACEs, MALEs, restenosis, amputation, and mortality. Among newer indices, the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, C-reactive protein-to-albumin ratio, and HALP (Hemoglobin, Albumin, Lymphocyte, and Platelet) score appear especially promising for risk stratification. Anti-inflammatory and pleiotropic therapies, including canakinumab, colchicine, statins, and PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors, may help reduce residual inflammatory risk. Conclusions: Inflammatory biomarkers may improve prognostic stratification and support more personalized management in PAD. Their integration into clinical practice could enhance limb preservation and long-term cardiovascular outcomes. Full article

Background/Objectives: Emerging evidence suggests that alterations in lipid metabolism may play a contributing role in the pathogenesis of age-related macular degeneration (AMD). Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, a novel class of lipid-lowering agents, offer anti-inflammatory and antioxidant benefits, which may provide protective effects against AMD. We aimed to evaluate the risk of developing AMD among patients with atherosclerotic cardiovascular disease (ASCVD) who were newly treated with PCSK9 inhibitors compared with those receiving statins. Methods: This retrospective cohort study utilized data from the Global Collaborative Network within the TriNetX Research Network. Patients with ASCVD who were newly initiated on PCSK9 inhibitors or statins were identified and matched for age, sex, race, laboratory data, comorbidities, and concomitant medications. The primary outcomes were the hazard ratios (HRs) for developing AMD, dry AMD, and wet AMD. Propensity score matching (PSM) was used to adjust for baseline demographics and comorbidities. Results: After PSM, 50,102 patients were included in each group (PCSK9 inhibitor users vs. statin users). Compared to statin users, PCSK9 inhibitor users had significantly lower risks of AMD (HR, 0.81; 95% confidence interval [CI], 0.72–0.92) and dry AMD (HR, 0.78; 95% CI, 0.65–0.94), but not wet AMD (HR, 0.90; 95% CI, 0.70–1.16). Stratified and subgroup analyses showed reduced AMD risk among patients aged ≥65 years, White patients, female patients, and evolocumab users. Conclusions: In patients with ASCVD, compared with use of statins, use of PCSK9 inhibitors is associated with reduced risks of AMD and dry AMD, suggesting a potential novel strategy for managing a condition with limited therapeutic options. Full article

Background/Aim: Cardiovascular disease (CVD) represents a relevant global public health challenge with dyslipidemia as a major modifiable cardiovascular risk factor (CVRF). Recent advances have introduced injectable lipid-lowering therapies (LLT). Their clinical effectiveness in real-world practice seems to depend not only on pharmacological efficacy but also on patients’ acceptance, adherence, and persistence, influenced directly by perceived barriers and facilitators. The main objective of this scoping review is to map the barriers and facilitators related to the use of novel injectable LLTs among adult patients with dyslipidemia or CVD. Methods: This review was conducted in accordance with JBI methodology and reported according to Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for scoping reviews (PRISMA-ScR); pre-registration on Open Science Framework (OSF) was performed. A search was conducted in MEDLINE from PubMed, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL) from EBSCOhost, and Google Scholar up to June 2025. Eligible studies included qualitative, quantitative, mixed-methods, and review papers involving adult patients with dyslipidemia who reported experiences, perceptions or challenges related to the use of injectable LLT in any healthcare or community setting worldwide. Two reviewers independently screened studies, selected and extracted data. Results: Out of 665 records identified, 7 studies met the inclusion criteria. Patients’ adherence to injectable LLTs is shaped by psychological fears, prior negative experiences, and perceived efficacy. Satisfaction increases when patients feel supported and informed. Convenience, self-administration, and motivational meaning facilitate persistence. Organizational support and economic accessibility further influence uptake, highlighting that adherence depends on both patient experience and structural factors. Conclusions: Patient acceptance and persistence with injectable LLT depends on a complex interplay of emotional, clinical, organizational and economic factors, beyond pharmacological efficacy alone. Fear of injections, previous statin-related experiences, administrative complexity, and high costs remain major barriers, while shared decision-making, trust in healthcare providers, perceived efficacy, regimen convenience, and supportive structures act as strong facilitators. Addressing these challenges requires multidimensional and multidisciplinary strategies for policy makers and clinical managers. Full article

Background/Objectives: Cardiovasc{Citation}ular disease accounts for 50% of chronic kidney disease (CKD) mortality, yet fewer than 40% of patients achieve guideline LDL-cholesterol (LDL-C) targets on statins. Injectable lipid-lowering therapies (ILLTs)—PCSK9 inhibitors and inclisiran—offer 50–70% LDL-C reductions but lack comprehensive CKD-specific evidence synthesis. This systematic review evaluated ILLT efficacy, safety, and implementation across kidney function stages including dialysis. Methods: Following PROSPERO registration (CRD42024612594), we searched MEDLINE, Embase, Cochrane Library, CINAHL, and Google Scholar (1995–August 2025). Two reviewers independently screened studies using PICOS criteria: adults with CKD stages G3-G5, dialysis, or transplant recipients receiving injectable lipid therapies. Primary outcomes were LDL-C percentage change and major adverse cardiovascular events. Quality was assessed using NIH tools. Given heterogeneity, we performed narrative synthesis following SWiM guidance. Results: Eight studies (n = 28,013) met the criteria. The FOURIER trial demonstrated that evolocumab achieved 58–59% LDL-C reductions across kidney function strata (interaction p = 0.77) with preserved cardiovascular benefit (HR 0.82–0.89). Absolute risk reduction was greater in advanced CKD (2.5% vs. 1.7%), reflecting higher baseline rates. Pharmacokinetic studies showed no eGFR-exposure correlation requiring dose adjustment; evolocumab was not removed by haemodialysis. Inclisiran achieved a 67–80% PCSK9 reduction and a 35–58% LDL-C reduction across renal groups, with twice-yearly maintenance dosing. Both classes reduced non-HDL-C (45–50%), apoB (40–45%), and lipoprotein(a) (20–25%). Safety was favourable, with mild injection-site reactions (< 5%); no renal decline signals emerged. Conclusions: Evidence for injectable lipid-lowering therapies in CKD are driven largely by a single large post hoc subgroup analysis (FOURIER) and small phase 1–2 PK/PD studies, with minimal dialysis representation and no transplant data. These agents appear to provide substantial LDL-C reductions across CKD stages G3–G5 without dose adjustment, but cardiovascular and renal outcome data in advanced CKD and dialysis remain limited and should be interpreted cautiously. Full article

Background/Objectives: Prostate cancer (PCa) cells are known to heavily depend on lipids to support their growth. We hypothesized that hyperlipidemic factors, for which inhibitors are already available and used to treat cardiovascular disease, would be dysregulated in metastatic PCa (mPCa). The goal of this case-control study, including 35 men per group, was to compare the levels of PCSK9, ANGPTL3, Apo CIII, leptin, and the lipid profile in patients with mPCa versus localized Gleason 8/9 PCa (lPCa) and patients at risk of developing PCa (controls). Methods: Protein levels were assessed using ELISAs, while lipids were measured using the Roche Cobas analytical platform. Results: The following circulating analytes were higher in mPCa: triglycerides (in mmol/L; controls 1.7 ± 1.2, lPCa 1.5 ± 0.7, mPCa 2.3 ± 1.2, p = 0.0004), Apo CIII (in µg/mL; control 110.7 ± 55.7, lPCa 115.0 ± 57.64, mPCa 159.9 ± 96.7, p = 0.0179), ANGPTL3 (in ng/mL; controls 41.7 ± 20.0, lPCa 42.8 ± 24.1, mPCa 57.3 ± 26.9, p = 0.0390), and leptin (in ng/mL, controls 9.6 ± 9.1, lPCa 8.2 ± 7.9, mPCa 17.7 ± 17.8, p < 0.0001). Surprisingly, PCSK9 levels were negatively correlated with LDL in the entire cohort. Conclusions: In this cohort of men, whole-body lipid metabolic rewiring is a feature restricted to the metastatic phase of prostate cancer, suggesting it may play a significant role in the progression toward more aggressive cancer forms. Given the availability of drugs targeting ANGPTL3 and Apo CIII, the therapeutic potential of these drugs should be evaluated in metastatic PCa. Full article

Despite the availability of numerous lipid-lowering agents, the treatment of lipid disorders remains a public health challenge. A substantial portion of patients, especially those with severe dyslipidemia or familial hypercholesterolemia (FH), fail to achieve the LDL-C goal. The leading causes of suboptimal LDL-C control include underprescription and poor adherence; however, in rare cases, it may result from an unusual biological response to treatment. In the presented case, a 78-year-old female with a history of transient ischemic attack and myocardial infarction was diagnosed with a heterozygous variant of FH and true statin intolerance following trials of simvastatin, rosuvastatin and pitavastatin. Initially, inclisiran was added to ezetimibe, leading to an unexpected increase in LDL-C. Due to the patient’s refusal of another statin re-challenge and the unavailability of bempedoic acid, nutraceuticals were introduced. After 6 months, inclisiran was discontinued because only a 22% reduction in LDL-C was achieved, likely attributable to the nutraceutical’s effect. Another PCSK9 inhibitor, evolocumab, was subsequently initiated. Shortly after the treatment onset, the patient complained of paraesthesia in the upper extremities and discontinued therapy. LDL-C levels increased by 7% after one month of treatment with evolocumab. The patient refused treatment with lipid apheresis. Possible causes of poor response to PCSK9 inhibitors include elevated lipoprotein(a) and FH. Full article

Lipoprotein(a) [Lp(a)] is a low-density lipoprotein-like particle that contains a unique apolipoprotein(a) [apo(a)] component covalently bound to apolipoprotein B-100. Elevated levels of Lp(a) have been identified as a well-established and genetically determined risk factor for atherosclerotic cardiovascular disease, including coronary artery disease, stroke, and calcific aortic valve stenosis. In contrast to other lipids, Lp(a) concentrations are minimally influenced by lifestyle or traditional lipid-lowering therapies, emphasizing the necessity for novel treatment approaches. This narrative review summarizes current and emerging therapeutic strategies for reducing Lp(a) levels. Such strategies include traditional agents such as niacin and PCSK9 inhibitors, as well as innovative therapies such as antisense oligonucleotides, RNA interference-based molecules, and small-molecule inhibitors. The mechanisms of action of these agents, in addition to clinical trial data and their capacity to modify cardiovascular outcomes, are explored in further detail. Furthermore, the current status of clinical guidelines and the evolving role of Lp(a)-targeted therapies in cardiovascular risk stratification are reviewed. A particular emphasis is placed on therapies that are in the advanced stages of clinical development. These include late-phase outcome trials and orally administered agents, which have the potential to significantly impact future clinical practice. The integration of mechanistic data with ongoing and completed clinical studies has been undertaken in order to provide a comprehensive framework for understanding the therapeutic potential of Lp(a) in the context of cardiovascular prevention. Full article

PCSK9 is a gene associated with familial hypercholesterolemia and is involved in other biological processes such as apoptosis, autophagy, and inflammatory responses. This study aims to further validate whether PCSK9 inhibitors can improve diabetic cardiomyopathy and elucidate their mechanisms of action. This study utilized H9c2 cells and C57BL/6J mice to validate the efficacy of the PCSK9 inhibitor alirocumab through in vivo and in vitro experiments. In vitro, alirocumab was shown to enhance cell viability and reduce oxidative stress in H9c2 cells under high glucose stress. It can also decrease the expression levels of inflammatory reaction and mitochondrial apoptosis-related proteins. Through in vivo experiments, we demonstrated that alirocumab can reduce myocardial hypertrophy and improve cardiac function in diabetic cardiomyopathy mice. Meanwhile, alirocumab treatment increased mitochondrial size and quantity in the hearts of diabetic cardiomyopathy mice, promoted mitochondrial fusion, and reduced the number of damaged mitochondria. Alirocumab could also reduce the percentage of myocardial fibrosis and oxidative stress in mice. Finally, we found that alirocumab can improve cardiac function in diabetic cardiomyopathy through the ERK/p38 MAPK pathway. Our data demonstrate that the PCSK9 inhibitor alirocumab provides protective effects against diabetic cardiomyopathy, offering fundamental experimental support for its clinical application in this condition. Full article

Cholesterol acts as a metabolic cue that reshapes diverse signaling networks, including hedgehog and several sterol-regulated pathways orchestrated by key proteins, including sterol regulatory element-binding protein 2 (SREBP2), sterol O-acyltransferase 1 (SOAT1), Niemann–Pick type C1 (NPC1), and proprotein convertase subtilisin/kexin type 9 (PCSK9). Research over the past decade has highlighted cholesterol metabolism as a key modulator of cancer development and a promising therapeutic target. By integrating mechanistic and translational evidence, this review seeks to clarify how cholesterol metabolism interfaces with oncogenic signaling and set directions for future investigation. Accumulating preclinical and clinical data suggest that dysregulated cholesterol levels, often associated with high-fat diets, may contribute to tumorigenesis and malignant transformation. Implicated pathways, such as SREBP, NPC1, PCSK9, and SOAT1, orchestrate various processes of lipid metabolism, including cholesterol synthesis, esterification, receptor degradation, and transport, that harbor a tumorigenic environment and promote oncogenic processes. Additionally, these enzymes and corresponding pathways provide a promising direction for developing metabolism-oriented anticancer strategies. Cholesterol metabolism dysregulation serves as a major avenue for cancer signaling and growth, but studies also highlight key molecular mechanisms and targets for future treatments. Future studies should focus on expanding studies into further cancer types, investigating combination therapies, and developing novel inhibitors of key molecular targets. Full article

Thrombosis is a cardiovascular disease characterized by the pathological formation of a fibrin clot in blood vessels. Currently available fibrinolytic enzymes have some limitations, including severe side effects, high cost, short half-life, and low fibrin specificity. Proteins from microalgae and cyanobacteria have various biological effects and are emerging as promising sources for fibrinolytic enzymes. In this study, bioinformatics tools were used to evaluate the intrinsic disorder predisposition of microalgal fibrinolytic proteins, their capability to undergo liquid–liquid phase separation (LLPS), and the presence of disorder-based functional regions, and short linear motifs (SLiMs). Analysis revealed that these proteins are predominantly hydrophilic and exhibit acidic (pI 3.96–6.49) or basic (pI 8.05–11.0) isoelectric points. Most of them are expected to be moderately (61.4%) or highly disordered proteins (6.8%) and associated with LLPS, with nine proteins being predicted to behave as droplet drivers (i.e., being capable of spontaneous LLPS), and twenty-five proteins being expected to be droplet clients. These observations suggest that LLPS may be related to the regulation of the functionality of microalgal fibrinolytic proteins. The majority of these proteins belong to the blood coagulation inhibitor (disintegrin) 1 hit superfamily, which can inhibit fibrinogen binding to integrin receptors, preventing platelet aggregation. Furthermore, the SLiM-centered analysis indicated that the main motifs found in these proteins are MOD_GlcNHglycan and CLV_PCSK_SKI1_1, which can also play different roles in thrombolytic activity. Finally, Fisher and conservation analysis indicated that CLV_NRD_NRD_1, CLV_PCSK_FUR_1, CLV_PCSK_PC7_1, and MOD_Cter_Amidation motifs are enriched in intrinsically disordered regions (IDRs) of these proteins, showing significant conservation and suggesting compatibility with proteolytic activation and post-translational processing. These data provide important information regarding microalgal proteins with potential thrombolytic effects, which can be realized through protein–protein interactions mediated by SLiMs present in intrinsically disordered regions (IDRs). Additional analyses should be conducted to confirm these observations using experimental in vitro and in vivo approaches. Full article

Atherosclerosis is a chronic, multifactorial vascular disease and the leading global cause of cardiovascular morbidity. Its development reflects interconnected disturbances in lipid metabolism, endothelial function, inflammation, smooth muscle cell (SMC) phenotypic switching, and extracellular matrix remodeling. Genetic predisposition, including monogenic disorders such as familial hypercholesterolemia and polygenic risk variants, modulates disease susceptibility by altering lipid homeostasis as well as inflammatory and thrombotic pathways. Epigenetic regulators and noncoding RNAs, such as histone modifications, microRNAs, and long noncoding RNAs, further shape gene expression and link environmental cues to vascular pathology. Endothelial injury promotes lipoprotein retention and oxidation, triggering monocyte recruitment and macrophage-driven foam cell formation, cytokine secretion, and necrotic core development. Persistent inflammation, macrophage heterogeneity, and SMC plasticity collectively drive plaque growth and destabilization. Emerging insights into immune cell metabolism, intracellular signaling networks, and novel regulatory RNAs are expanding therapeutic possibilities beyond lipid-lowering. Current and evolving treatments include statins, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, anti-inflammatory agents targeting interleukin-1 beta (IL-1β) or NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3), and advanced approaches such as gene editing, siRNA, and nanoparticle-based delivery. Integrating multi-omics, biomarker-guided therapy, and precision medicine promises improved risk stratification and next-generation targeted interventions. This review summarizes recent molecular advances and highlights translational opportunities for enhancing atherosclerosis prevention and treatment. Full article

Atherosclerotic cardiovascular disease (ASCVD) persists as the foremost cause of global morbidity and mortality. Central to its pathogenesis, atherosclerosis emerges as a chronic inflammatory disorder fueled by the intricate interplay between dysregulated lipid metabolism and immune cell activation. Recent insights reveal that inflammatory cues within atherosclerotic plaques or ischemic tissues orchestrate metabolic reprogramming in immune cells, thereby modulating disease trajectories. While cholesterol-lowering agents such as statins and proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors have long been recognized for their lipid-modulating properties, accumulating evidence now underscores their pleiotropic anti-inflammatory effects mediated through immune cell modulation. For instance, recent clinical observations reveal that PCSK9 inhibitors not only substantially reduce low-density lipoprotein cholesterol (LDL-C) and triglycerides but also appear to reduce advanced glycoprotein signals, emerging composite biomarkers of systemic inflammation. This highlights a novel and more nuanced dimension of inflammation modulation by PCSK9 inhibitors, although current evidence remains limited and requires further confirmation. Moreover, this dual immune-metabolic influence reshapes our understanding of therapeutic mechanisms and calls for a reassessment of treatment paradigms in ASCVD management. Here, we present a synthesis of current findings that emphasize how both established and novel therapies transcend lipid-lowering to exert profound immunomodulatory actions, offering promising avenues to attenuate cardiovascular disease progression through integrated metabolic and inflammatory control. Full article