Search Results (595)

Ischemic heart disease is currently diagnosed mainly through cardiac computed tomography (CT) angiography and functional testing, both of which detect only advanced arterial macrocalcification, at a stage when treatment can merely slow disease progression rather than reverse it. Yet, macrocalcification represents the end product of a much earlier molecular process, which is microcalcification. This process is driven by smooth muscle cell and macrophage apoptosis, matrix vesicle release, and osteogenic phenotypic transitions within the arterial intima, occurring years to decades before mineral deposits become visible on CT. [¹⁸F]Sodium fluoride (NaF) positron emission tomography (PET) exploits fluoride binding at accessible hydroxyapatite surfaces to detect increased tracer uptake associated with active mineral deposition, including mineralization occurring at a microscopic scale below the direct spatial resolution of clinical PET. Studies demonstrate that anti-atherosclerotic interventions, including statins, and tissue-nonspecific alkaline phosphatase inhibition can suppress NaF uptake even when CT-based calcium scores remain unchanged or continue to rise, a dissociation now also observed in human trials of statins and PCSK9 inhibitors. This review traces the cellular and histological basis of arterial calcification, outlines the principles and limitations of NaF-PET imaging, and evaluates its emerging role—supported by artificial intelligence-based quantification—as a tool for monitoring targeted anti-atherosclerotic treatment. Full article

Background: Population aging is driving a convergent rise in three disorders historically managed in isolation: cardiovascular disease, neurocognitive decline, and osteoporotic bone loss. Mechanistic data indicate that these systems are coupled through shared regulators of calcium trafficking, inflammation resolution, vascular integrity, and inflammaging. On this basis, a “Heart–Brain–Bone” axis has been proposed; it should be understood as an integrative conceptual framework that organizes evidence drawn from three separate studies, not as a validated physiological entity with agreed diagnostic criteria or demonstrated modifiability. Three lipid-soluble nutrients—long-chain omega-3 polyunsaturated fatty acids (EPA/DHA), vitamin D3 (cholecalciferol), and vitamin K2 (menaquinone-7 [MK-7])—act on overlapping nodes of this network. Methods: We performed a structured narrative review. PubMed/MEDLINE, Embase, the Cochrane Library, and Web of Science were searched from database inception to 25 June 2026 using predefined term blocks for each nutrient, each organ domain, and each candidate mechanism, and the search was updated on 7 August 2026. Records were screened against prespecified inclusion and exclusion criteria by two authors independently, with disagreements resolved by a third. The strength of evidence for each nutrient–organ relationship was graded with an explicitly defined four-level scheme ((−) to (+++)) applied separately to preclinical, observational, randomized and meta-analytic evidence. Results: Vitamin K2-dependent gamma-carboxylation of matrix Gla protein (MGP) and osteocalcin has been proposed to influence whether calcium is incorporated into the bone matrix or deposited in the arterial wall, offering a candidate mechanistic account of the “calcium paradox” associated with isolated vitamin D3 supplementation; EPA/DHA-derived specialized pro-resolving mediators may support resolution of endothelial and neuronal inflammation; and bone-, vascular- and brain-derived signals (osteocalcin, FGF23, the neurovascular unit) interconnect the three organs. These mechanisms are biologically plausible but remain insufficiently confirmed in humans. The clinical evidence is heterogeneous, formulation- and population-dependent, and comprises positive, neutral and null results: cardiovascular omega-3 trials are discordant (REDUCE-IT, which used icosapent ethyl [an EPA ethyl ester], positive; VITAL/STRENGTH/ASCEND null, predominantly in lower-risk or replete cohorts); cognitive trials are largely null or subgroup-dependent (MAPT, DO-HEALTH, VITAL); and MK-7 improves surrogate bone and calcification biomarkers and slowed coronary artery calcification in one recent randomized imaging trial (VitaK-CAC), whereas combined MK-7 plus vitamin D3 did not slow aortic valve or coronary calcification in AVADEC and MK-7 did not reduce bone loss in early menopausal women. Recognized safety signals include a dose-dependent increase in atrial fibrillation with high-dose omega-3, adverse skeletal effects of high-dose or bolus vitamin D, and clinically relevant interference of even low-dose MK-7 with vitamin K antagonist therapy. Conclusions: No adequately powered randomized trial has demonstrated that the combination of long-chain omega-3, vitamin D3 and MK-7 is superior to its individual components or to placebo for any clinical endpoint. The combined regimen is therefore mechanistically rational and hypothesis-generating rather than clinically established; benefit appears most plausible in individuals with elevated risk or demonstrable nutritional insufficiency, and least in replete, low-risk populations. Findings should be interpreted within a broader healthy-aging context that includes lifestyle and psychosocial factors. Adequately powered factorial randomized controlled trials stratified by baseline Omega-3 index, 25(OH)D and vitamin K status, with prespecified mechanistic biomarkers and hard endpoints, are required. Full article

Atherosclerosis remains the principal underlying cause of myocardial infarction, ischemic stroke and peripheral artery disease, and its progression reflects a complex interplay between lipid accumulation, endothelial dysfunction, chronic vascular inflammation and maladaptive remodeling of the arterial wall. The Notch signaling pathway, an evolutionarily conserved juxtacrine communication system, has emerged as a central regulator of every cell type implicated in atherogenesis, including endothelial cells, vascular smooth muscle cells, monocytes/macrophages and T lymphocytes. Depending on the receptor–ligand pairing, the hemodynamic context and the cellular compartment involved, Notch signaling can be either atheroprotective or atherogenic, a duality that has complicated efforts to translate mechanistic insight into therapy. This review summarizes current knowledge of the molecular architecture of the Notch pathway in the vasculature, dissects its cell type-specific and stage-specific contributions to atherosclerotic plaque initiation, progression, calcification and destabilization, and critically appraises pharmacological strategies designed to modulate Notch activity, including γ-secretase inhibitors, ligand- and receptor-directed monoclonal antibodies, soluble decoy receptors, microRNA-based approaches and drug repurposing strategies such as statins. Particular attention is paid to the cardiovascular toxicities that have emerged from oncology trials of Notch pathway inhibitors, which illustrate both the pharmacological tractability and the narrow therapeutic window of this pathway. We conclude that Notch-directed therapy for atherosclerosis is mechanistically well justified but will require cell type-selective and context-selective delivery strategies to be clinically viable. Full article

Cardiovascular toxicity associated with anti-tumor therapies is garnering increased attention. Anti-tumor therapies may elevate the risk of acute coronary syndrome, particularly in patients with underlying subclinical atherosclerosis. In this context, a 58-year-old female patient with HER2-positive breast cancer experienced an acute ST-segment elevation myocardial infarction following chemotherapy, dual HER2-targeted therapy, and radiotherapy to the left breast. Prior to the initiation of anti-tumor treatment, chest-computed tomography had identified coronary artery calcification. Angiographic evaluation revealed subtotal occlusion of the middle segment of the left circumflex artery extending to the first obtuse marginal branch, accompanied by multivessel coronary atherosclerotic lesions. Coronary blood flow was restored following emergency interventional treatment. This case indicates that multimodal anti-tumor therapy may facilitate the progression of coronary atherosclerosis, thereby elevating the risk of acute coronary events. Full article

Coronary artery calcification (CAC) is a hallmark of advanced atherosclerosis and a major determinant of procedural complexity during percutaneous coronary intervention (PCI). Once considered a passive consequence of vascular degeneration, CAC is now recognized as an active, highly regulated process driven by inflammation, oxidative stress, extracellular vesicle release, osteogenic differentiation of vascular smooth muscle cells, and biomechanical remodeling. These mechanisms generate a spectrum of calcific phenotypes, ranging from microcalcifications and sheet calcium to nodular calcium and calcified nodules. Calcified nodules represent an advanced fibrocalcific plaque phenotype characterized by fractured calcific plates, luminal calcium protrusion, surface disruption, and variable thrombus formation. They can be characterized using intravascular ultrasound (IVUS), optical coherence tomography (OCT), and hybrid near-infrared spectroscopy–IVUS imaging, and are associated with coronary thrombosis, stent underexpansion, restenosis, target lesion failure, and the need for advanced calcium-modification strategies. A structured literature search of PubMed/MEDLINE, Web of Science Core Collection, and Scopus identified 83 publications published between 2020 and 2026 for inclusion in the narrative synthesis. This narrative review summarizes the biological and biomechaniclam mechanisms of coronary calcification and calcified nodule formation, compares multimodality intravascular imaging criteria, and discusses contemporary imaging-guided PCI strategies, including balloon-based modification, rotational and orbital atherectomy, excimer laser coronary atherectomy, intravascular lithotripsy, and hybrid approaches. By integrating pathobiology, intravascular imaging criteria, and lesion-specific PCI strategies, this review provides a clinically oriented framework for the assessment and management of calcified nodules. Future directions include standardized imaging definitions, prospectively validated morphology-guided treatment algorithms, and computational and artificial intelligence-assisted plaque characterization. Full article

Lipoprotein(a) (Lp(a)) is an elusive yet powerful cardiovascular risk factor, largely independent of LDL cholesterol. Elevated Lp(a) increases the risk of coronary artery disease, stroke, peripheral arterial disease, calcific aortic valve disease, heart failure, and abdominal aortic aneurysm. The challenge is that conventional lipid-lowering therapies have minimal impact on Lp(a), leaving patients with substantial residual risk. While observational and genetic studies generally support Lp(a) as a driver of cardiovascular events, results are not entirely consistent, and risk may differ between primary and secondary prevention. Novel therapies—including antisense oligonucleotides, siRNA therapeutics, CETP inhibitors, and experimental gene-editing approaches—show promising potential, reducing Lp(a) levels by up to 90%. Ongoing phase III trials will clarify whether these reductions translate into meaningful decreases in cardiovascular morbidity and mortality. This review critically examines the current evidence, highlights gaps in knowledge, and discusses emerging therapeutic strategies, emphasizing the need for individualized risk assessment. Lp(a) may soon shift from a “silent threat” to a precise, actionable target in cardiovascular prevention. Full article

Background: Chronic kidney disease–mineral and bone disorder contributes to vascular calcification in kidney transplant recipients. However, the relationship between circulating bone turnover markers, Gla-rich protein (GRP), pelvic arterial calcification, and post-transplant outcomes remains uncertain. Methods: In this prospective single-centre study, 79 kidney transplant recipients underwent pre-transplant assessment of serum calcium, phosphate, alkaline phosphatase, parathyroid hormone, osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANKL), and GRP. Pelvic arterial calcification was quantified using a validated CT-based scoring system. Associations between biomarkers, pelvic calcification severity, graft function, graft survival, patient survival, and major adverse cardiovascular events were evaluated. Results: Serum calcium was associated with serum creatinine (p = 0.039), and serum phosphate was associated with MAG-3 clearance (p = 0.009). OPG concentrations were significantly higher in patients receiving haemodialysis than in those receiving peritoneal dialysis (p = 0.021). No significant associations were observed between pelvic arterial calcification severity and circulating OPG, RANKL, or GRP concentrations. Furthermore, in univariable Cox proportional hazards models, none of the investigated biomarkers was significantly associated with graft or patient survival. Conclusions: Circulating OPG, RANKL, and GRP were not associated with pelvic arterial calcification, graft or patient survival. Larger multicentre studies with longer follow-up are warranted to clarify the prognostic value of these biomarkers. Full article

Background/Objectives: A novel CT dynamic angiographic imaging (CT-DAI) analytic algorithm was evaluated against the clinical gold standard for fractional flow reserve (FFR) measurement in patients with coronary artery disease (CAD) characterized by diffuse dense calcification and previous stent implantation. Methods: This retrospective feasibility study included 24 coronary arteries in 16 patients (age 69.9 ± 8.9 years, 11 males) with CAD who underwent dynamic CT myocardial perfusion scanning using a dual-source CT scanner after intravenous infusion of adenosine triphosphate. The included patients had analyzable proximal and distal coronary artery segments adjacent to the stenosis in the myocardial perfusion images and had corresponding invasive catheter-based FFR measurements for that stenosis. An in-house software based on the CT-DAI algorithm was used to compute FFR using the coronary time-enhancement curves sampled across the stenosis from stress myocardial CT perfusion images. The CT-DAI derived FFR values were then compared to the corresponding catheter-based FFR values. A coronary stenosis was considered functionally significant for FFR values below 0.8. Results: The mean axial length and calcium score of the coronary stenoses were 47.9 mm and 1911.63 Agatston Units, respectively. Eight coronary arteries received stents from previous treatments. The CT-DAI derived FFR values (0.822 ± 0.143) showed an excellent linear correlation (R = 0.974) with and were indifferent from the invasive FFR values (0.826 ± 0.147, p = 0.537), resulting in 100% per-vessel and per-patient sensitivity and specificity for the detection of functionally significant coronary stenosis. Bland–Altman analysis revealed a minimal mean difference in FFR measurements (0.004) between the two modalities with the lower and upper limits of agreement at −0.061 and 0.069, respectively. Conclusions: The findings suggest that CT-DAI can derive FFR for the coronary arteries with heavy calcification and stents from dynamic myocardial CT perfusion images. Full article

Background: Erectile dysfunction and cardiovascular disease share common pathophysiological mechanisms, yet little is known about the postmortem cardiac profile of men with detectable sildenafil use. This study investigated whether postmortem sildenafil positivity is associated with acute or chronic cardiac pathological findings in men who died of ischemic heart disease. Methods: In a sample of 154 male decedents who died of ischemic heart disease, postmortem cardiac and toxicological findings in 77 sildenafil-positive cases were compared with those of age-matched controls. Heart weight z-scores were calculated based on 27,645 reference autopsies. Multivariable logistic regression analyses were performed to identify independent associations. Results: No significant differences were observed between groups regarding acute ischemic pathologies. However, chronic cardiac findings were more prevalent in the sildenafil-positive group, including coronary artery disease (96.1% vs. 85.7%; p = 0.025), congestive heart failure (40.3% vs. 24.7%; p = 0.039), prior coronary artery bypass grafting (24.7% vs. 11.7%; p = 0.037), increased heart weight (547.7 gr vs. 507.5 gr; p = 0.037) and z-score (+1.63 vs. 1.08; p = 0.040), and coronary calcification (88.3% vs. 74.0%; p = 0.023). After adjustment for cardiovascular comorbidities, only coronary calcification remained independently associated (adjusted OR: 2.586; 95% CI: 1.076–6.215; p = 0.034). Conclusions: Sildenafil-positive cases showed no excess of acute ischemic pathology. However, sildenafil-positive cases had a greater burden of chronic cardiac pathology, particularly coronary calcification. These findings are consistent with the proposed role of coronary artery calcification as a surrogate marker of erectile dysfunction and cardiovascular disease. They also underscore the importance of cardiovascular risk assessment in sildenafil users and support a cautious approach in individuals with poor cardiac reserve. Full article

Lipoprotein(a) (Lp(a)) is increasingly recognized as a genetically determined and clinically relevant contributor to residual cardiovascular risk. Through pro-atherogenic, pro-inflammatory, pro-thrombotic, and pro-calcific mechanisms, Lp(a) appears to play a significant role in both coronary artery disease and aortic valve disease. In patients undergoing percutaneous coronary intervention, elevated Lp(a) has been associated with worse long-term outcomes, including recurrent ischemic events, repeat revascularization, and in-stent restenosis, even in the setting of controlled low-density lipoprotein cholesterol. In parallel, experimental, genetic, and clinical data support a role for Lp(a) in the initiation and progression of calcific aortic stenosis, while its prognostic significance after transcatheter aortic valve interventions remains less clearly defined. Current guidelines now recognize Lp(a) as a relevant risk-enhancing factor, and emerging targeted therapies are achieving substantial reductions in circulating levels. Overall, Lp(a) should be regarded as both a meaningful biomarker and a promising therapeutic target, although ongoing outcome trials are needed to determine whether selective Lp(a) lowering translates into clinical benefit across interventional cardiovascular settings. The aim of this narrative review is to provide a single, comprehensive account of lipoprotein(a) [Lp(a)] in interventional cardiology, following this lipoprotein from its biology and pathophysiology through to its clinical impact and to the therapies that are now reaching the clinic, with a specific focus on the two most frequent catheter-based procedures in which it may carry prognostic weight: percutaneous coronary intervention (PCI) and transcatheter aortic valve implantation (TAVI). PCI and TAVI are deliberately addressed within the same review since they share a common upstream biology: Lp(a) contributes both to the atherosclerotic process that underlies coronary disease and to the calcific process that underlies aortic valve disease, and the corresponding patient populations overlap considerably in everyday interventional practice. Covering them together offers the interventional cardiologist a single, practical reference on how a patient with elevated Lp(a) may be approached in both scenarios. Full article

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a systemic metabolic disorder associated with an elevated risk of cardiovascular disease. Mac-2 binding protein glycosylation isomer (M2BPGi), a noninvasive serum biomarker of hepatic fibrosis, has also been linked to adverse metabolic and cardiovascular outcomes. However, the association between serum M2BPGi levels and subclinical coronary atherosclerosis in individuals with MASLD remains unclear. We investigated the association between serum M2BPGi levels and coronary artery calcium score (CACS), an established imaging marker of subclinical atherosclerosis, in individuals with MASLD. Methods: This retrospective cross-sectional study included 6514 adults with MASLD who underwent health screening examinations between 2020 and 2025. Participants were categorized into quartiles according to serum M2BPGi levels: Q1 (<0.48), Q2 (0.48–0.61), Q3 (0.62–0.80), and Q4 (≥0.81). Coronary artery calcification (CAC) was defined as CACS > 0. Multivariable logistic regression analysis was performed after adjustment for age, sex, smoking status, liver enzymes, adiposity, dysglycemia, blood pressure, and lipid profile. Multivariable ordinal logistic regression analysis was additionally performed to evaluate the association between M2BPGi levels and CAC severity. Results: The prevalence of CAC increased progressively across M2BPGi quartiles (39.4%, 45.3%, 48.5%, and 57.4% for Q1–Q4, respectively; p < 0.001). In multivariable logistic regression analysis, participants in the highest M2BPGi quartile had significantly higher odds of CAC presence than those in the lowest quartile (OR, 1.32; 95% CI, 1.10–1.58; p = 0.0035). Higher M2BPGi quartiles were also independently associated with greater CAC severity in multivariable ordinal logistic regression analysis (OR, 1.33; 95% CI, 1.13–1.57; p = 0.0007 for Q4 vs. Q1). Conclusions: Higher serum M2BPGi levels were independently associated with both the presence and severity of CAC in individuals with MASLD. These findings suggest that M2BPGi may serve as a potential biomarker for identifying individuals with MASLD at increased risk of subclinical atherosclerosis and may complement conventional cardiovascular risk assessment. Full article

Background: Coronary artery bypass grafting (CABG) is the standard revascularization procedure, and the left internal mammary artery (LIMA) is the most widely used conduit owing to its long-term patency and favorable impact on survival. Although fibrosis and calcification are comparatively infrequent in internal mammary artery (IMA) grafts, progressive remodeling may still compromise patency. Tumor necrosis factor-α (TNF-α) is a pro-inflammatory cytokine implicated in vascular remodeling and calcification, whereas L-arginine, a precursor of nitric oxide, may exert vasoprotective effects. Aim: To investigate the effects of ex vivo TNF-α and combined TNF-α plus L-arginine treatment on the morphology, calcification, elemental composition, and biomechanical properties of human LIMA grafts. Patients and Methods: LIMA graft segments from 18 male CABG patients were allocated to one control group (G0) and two ex vivo treatment groups. Grafts were assessed using hematoxylin and eosin and Masson’s Trichrome staining under brightfield microscopy, using Alizarin Red S fluorescence staining to measure calcification, and by scanning electron microscopy with energy-dispersive spectroscopy (SEM/EDS) to assess ultrastructure and elemental composition. Scanning acoustic microscopy (SAM) was used to derive acoustic impedance as a label-free index of tissue stiffness. Results: TNF-α treatment was associated with increased acoustic impedance, consistent with graft stiffening, together with greater calcification signatures, whereas combined TNF-α and L-arginine treatment shifted impedance toward control-like values and showed more organized tissue architectures with reduced calcification. Conclusions: In this preliminary ex vivo model, L-arginine attenuated TNF-α-associated remodeling and stiffening of LIMA grafts, suggesting a potential role in supporting graft durability; larger, statistically powered studies with molecular validation are required to confirm these findings. Full article

Cardiovascular and vascular diseases remain major causes of morbidity and mortality worldwide, despite substantial advances in prevention, diagnosis, and treatment. In recent years, cardiovascular imaging has moved beyond the traditional assessment of anatomy and morphology toward a multidimensional evaluation of function, tissue composition, haemodynamics, inflammation, and individualized risk. This evolution has been driven by technological progress in echocardiography, cardiovascular magnetic resonance, computed tomography, nuclear imaging, intravascular imaging, and point-of-care ultrasound, together with the rapid development of artificial intelligence, radiomics, and predictive analytics. Advanced echocardiographic techniques, including contrast stress echocardiography and emerging methods for myocardial scar detection, may improve functional and prognostic assessment in patients with suspected or established coronary artery disease. Cardiac magnetic resonance, through tissue mapping, late gadolinium enhancement, and 4D flow imaging, provides unique information on myocardial fibrosis, perfusion, ventricular remodelling, and vascular haemodynamics. Computed tomography, particularly with the introduction of photon-counting technology, is expanding the non-invasive characterization of coronary plaques, vascular calcification, and thromboembolic disease. Hybrid imaging with PET/CT and PET/MR offers additional insight into vascular inflammation, myocardial metabolism, and active disease processes. At the same time, intravascular ultrasound, optical coherence tomography, and augmented-reality-supported imaging are refining interventional guidance, while point-of-care ultrasound is broadening access to rapid bedside cardiovascular and vascular assessment. The integration of imaging findings with circulating biomarkers, clinical scores, lipid profiles, coagulation parameters, and machine-learning models represents a promising strategy for personalized risk stratification, particularly in complex conditions such as coronary artery disease, venous thromboembolism, pulmonary embolism, and bleeding risk during antithrombotic therapy. This review summarizes current advances in cardiovascular imaging, discusses their translational implications, and highlights future directions for integrating imaging, artificial intelligence, and precision medicine into daily clinical practice. Full article

Coronary artery calcification (CAC) is a pressing issue in cardiology. Mesenchymal stem cells (MSCs) derived from epicardial adipose tissue (EAT) may serve as a source of osteoblasts in the cardiovascular system. This study aimed to evaluate and compare the immunophenotype, proliferation, and osteogenic potential of EAT-MSCs from patients with coronary artery disease (CAD) and those with aortic stenosis (AS). The immunophenotype of MSCs was analyzed based on key markers: CD105, CD90, CD73, CD31, CD34, CD45, HLA-DR. Cell proliferation was assessed by the doubling time of the population and the specific growth rate of the cultures. The osteogenic potential was evaluated by the expression levels of the RUNX2, SPP1, ALPL, and BGLAP genes using PCR, as well as the protein levels in supernatants via ELISA. Qualitative detection of osteogenic proteins in cells by immunofluorescence staining. The intensity of extracellular matrix mineralization was measured using photometric methods. CD73 expression in EAT-MSCs from CAD patients was nearly 50% lower than in EAT-MSC cultures from AS patients. Following osteogenic induction, EAT-MSCs from CAD patients showed increased expression of osteogenic marker genes and their corresponding proteins. The intensity of extracellular matrix mineralization by osteoblasts derived from EAT-MSCs of CAD patients was higher than in the comparison group. EAT-MSCs from CAD patients with coronary calcification demonstrated reduced CD73 expression in culture and enhanced osteogenic potential compared to patients without coronary artery involvement. Full article

Background: Micro- and nanoplastics (MNPs) are emerging contaminants increasingly detected in human tissues and biological fluids. Their presence in blood, vascular tissues, thrombi, and atherosclerotic plaques raises concern about their possible association with cardiovascular disease. This systematic review synthesized evidence on associations between MNPs and cardiovascular pathology. Methods: A systematic search was conducted in October 2025 in PubMed, Scopus, Web of Science, and Embase according to PRISMA guidelines and a PICOS-based strategy. Original human studies from the last 10 years were eligible. Fourteen studies were included. Due to methodological heterogeneity, a narrative synthesis was performed. Risk of bias was assessed using ROBINS-E, and certainty of evidence was evaluated using a GRADE-informed approach. Results: MNPs were detected in multiple cardiovascular-related matrices. Included studies suggested possible associations with major adverse cardiovascular events, acute coronary syndrome, myocardial infarction, arterial stenosis, vascular calcification, thromboembolic disease, hypertension, inflammatory markers, coagulation-related parameters, and lipid profiles. However, the certainty of evidence was very low, and most studies had a high or very high risk of bias. Conclusions: Current evidence suggests a possible association between MNPs and cardiovascular pathology, but causality remains unproven. Larger prospective studies using standardized detection protocols, rigorous contamination control, and adjustment for confounders are needed. Full article