Search Results (1,148)

Background and Objectives: Obesity, heart failure (HF), and atherosclerosis have common pathways, including chronic inflammation, immune cells activation, and metabolic disturbances. These pathways often coexist and overlap, increasing cardiometabolic risk. Growth differentiation factor 15 (GDF-15) is an emerging cytokine linked to inflammation, oxidative stress, and metabolic dysregulation, which are common pathways between heart failure, obesity and atherosclerosis. Beyond its established prognostic value in cardiovascular diseases (CVD) and HF, recent evidence suggests that GDF-15 may also reflect subclinical atherosclerosis, potentially improving early risk stratification in obese and HF populations. The aim of this review is to synthesize current evidence on the association between GDF-15 and markers of subclinical atherosclerosis, and to evaluate whether GDF-15 may serve as an integrative biomarker reflecting shared cardiometabolic pathways. Materials and Methods: We conducted a systematic review following PRISMA recommendations registered by CRD420251267457 number on PROSPERO. PubMed, Embase, Scopus, and Web of Science were searched for human studies evaluating the correlation between markers of subclinical atherosclerosis and GDF-15 concentration. We excluded the studies not published in English, not involving human participants, and not meeting the inclusion criteria. We assessed the risk of bias using the Joanna Briggs Institute appraisal tool. Due to the heterogeneity of studies, a narrative synthesis was performed. Result: The review included 18 studies, which evaluated the association between GDF-15 and subclinical atherosclerosis markers, such as intima media thickness, coronary artery calcium score, ankle-brachial index, and atherosclerotic plaques. Studies included patients with metabolic disorders, chronic inflammatory diseases, HIV cohorts, and general population samples. Most of the studies reported that GDF-15 levels were associated with greater atherosclerotic burden; however, results were frequently influenced by confounders. Methodological limitations, such as limited or highly specified samples, cross-sectional designs, variability in atherosclerotic-imaging technique, and inconsistent adjustment for confounders, restrict generalization of the results. Conclusions: Current evidence supports GDF-15 as a biomarker integrating inflammatory and metabolic stress signals, indirectly linking obesity, HF and subclinical atherosclerosis. While current data supports its prognostic relevance, further studies are needed to confirm its clinical utility in routine assessment and preventive cardiovascular care. Full article

Current pharmacotherapies against atherosclerotic cardiovascular disease are associated with considerable residual risk, together with various adverse side effects. Nutraceuticals, such as resveratrol (RSV), with excellent safety profile, represent promising alternatives and potential treatment. However, the full spectrum of anti-atherogenic actions regulated by RSV and the underlying molecular mechanisms remain poorly understood. The objective of this study therefore was to investigate the impact of RSV on key atherosclerosis-associated processes in monocytes, macrophages, endothelial cells, and smooth muscle cells in vitro, as well as in LDL receptor-deficient mice fed a high-fat diet in vivo. RSV produced beneficial changes in the plasma lipid profile and peripheral blood lymphoid cells in vivo. RSV also attenuated plaque inflammation by decreasing macrophage and T cell content and enhanced markers of plaque stability, with increased levels of smooth muscle cells and collagen content. In vitro, RSV inhibited chemokine-driven monocyte migration, inflammasome activation, matrix metalloproteinase activity, pro-inflammatory gene expression, reactive oxygen species production, and smooth muscle cell invasion. RNA-sequencing of the thoracic aorta revealed key genes and pathways mediating the antioxidant, anti-inflammatory and plaque-stabilising activities of RSV. These studies provide novel mechanistic insights on the anti-atherogenic actions of RSV and support further evaluation in human clinical trials. Full article

Metformin, the most widely prescribed oral antihyperglycemic agent, is established as the first-line therapy for type 2 diabetes mellitus (T2DM) owing to its efficacy, affordability, and safety. Increasing evidence indicates that its benefits extend beyond glycemic control, encompassing cardiovascular protection and diabetes prevention in individuals at elevated cardiometabolic risk. Mechanistic studies demonstrate that metformin exerts pleiotropic effects through activation of AMP-activated protein kinase, modulation of the gut microbiota, inhibition of pro-inflammatory and oxidative stress pathways, and improvements in endothelial function, lipid metabolism, and insulin sensitivity. These actions address core drivers of atherosclerosis and metabolic dysfunction, many of which occur independently of glucose lowering. In patients with T2DM, the cardiovascular benefits of metformin are well recognized, including reductions in all-cause mortality and cardiovascular events. In individuals without diabetes but at high cardiovascular risk—such as those with prediabetes, obesity, or metabolic syndrome—evidence is more limited, as most data are derived from subgroup analyses or trials with surrogate endpoints. Nonetheless, consistent signals suggest that metformin may delay the progression from prediabetes to overt diabetes and potentially confer vascular protection, particularly in carefully selected high-risk populations. Clinical trials and meta-analyses have demonstrated that metformin reduces incident diabetes by approximately one quarter in high-risk adults, with stronger effects observed in younger, overweight individuals, women with prior gestational diabetes, and those treated for longer durations. However, uncertainties remain regarding its long-term cost-effectiveness, optimal dosing strategies, and cardiovascular benefits in non-diabetic populations. The ongoing VA-IMPACT trial (NCT02915198) is expected to clarify whether metformin reduces major cardiovascular events in prediabetic patients with atherosclerotic disease. Taken together, metformin represents more than an antidiabetic drug. Its pleiotropic mechanisms, favorable safety profile, and low cost support its potential integration into broader cardiometabolic prevention strategies, including primary prevention. Expanding its role beyond diabetes management may offer a cost-effective, widely accessible intervention with significant public health impact. Full article

Background/Objectives: Cardiovascular diseases are the leading cause of death worldwide. The preventive efforts to reduce the burden are crucial. Primary causes of cardiovascular diseases include lipid disorders. The variety of available medications influences cardiovascular risk and allows for improvement. However, discontinuation or infrequent initiation of lipid-lowering therapies remains a problem. This study aimed to investigate predictors of lipid-lowering therapy escalation. Methods: 431 patients with known concentrations of Lipoprotein (a) (Lp (a)) acquired as part of routine cardiovascular risk assessment from the HELPE-R registry, hospitalised in the University Clinical Hospital in Białystok were included in this study. Escalation of treatment was defined as the initiation of any form of lowering therapy or an increase in the potency or dose of statins. The analysis of the influence of various factors on the decision about escalation was performed. Results: The median age was 69.00 years. The escalation of therapy occurred in 48.49% of patients. Not reaching the LDL-C goal was the strongest predictor of escalation (OR: 9.177). The other factors increasing the probability of escalation included acute coronary syndrome (OR: 3.913), prediabetes (OR: 2.372), chronic coronary syndrome (OR: 2.217), dyslipidemia (OR: 2.354), hypertension (OR: 1.734), carotid artery stenosis (OR: 1.625), and obesity (OR: 1.543). There was no effect of past MI and stroke on the escalation of lipid profile. Lp (a) did not affect the escalation. Conclusions: The decision about escalation of lipid-lowering therapy is mainly influenced by classical risk factors and established atherosclerotic disease. Lp (a) did not affect the escalation, despite growing interest among medical practitioners. Full article

Low-density lipoprotein cholesterol (LDL-C) has traditionally been the primary biomarker used to assess cardiovascular risk. However, a substantial proportion of cardiovascular events occur in individuals with LDL-C levels within the normal range, highlighting the need for additional risk markers. Lipoprotein(a) [Lp(a)] has emerged as an independent and genetically determined cardiovascular risk factor that is not adequately captured by conventional lipid profiling. Elevated Lp(a) levels are associated with an increased risk of atherosclerotic cardiovascular disease, including coronary artery disease, ischemic stroke, and calcific aortic valve stenosis, and appear to be particularly relevant in the context of premature cardiovascular events. The pathogenicity of Lp(a) is driven by distinct mechanisms that extend beyond cholesterol transport. These include pro-atherogenic, pro-inflammatory, and pro-thrombotic effects mediated largely by oxidized phospholipids carried by the particle and by the structural properties of apolipoprotein(a), which interfere with fibrinolysis. Despite its strong and stable genetic determination, Lp(a) remains underrecognized and inconsistently measured in clinical practice, partly due to historical limitations in assay standardization and reporting. This minireview summarizes current knowledge on the pathophysiological mechanisms underlying elevated Lp(a), discusses its clinical implications for cardiovascular risk assessment, and highlights the importance of standardized Lp(a) measurement in routine practice, particularly in light of emerging Lp(a)-targeted therapies. Full article

Background/objectives: Chronic degenerative complications of diabetes, such as atherosclerotic cardiovascular disease and chronic kidney disease, contribute to an increased morbimortality in patients with type 2 diabetes (T2D), and thus, a multifactorial approach becomes essential. Among the classes of antihyperglycemic agents with beneficial pleiotropic cardiorenal effects, the glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have proven to reduce the risk of major adverse cardiovascular (CV) and renal events. This study aims to assess the impact of treatment with GLP-1 RA on CV risk factors, insulin sensitivity, and renal function in Romanian patients with T2D. Methods: In an observational retrospective study, 150 patients with T2D were evaluated at the start of therapy with a GLP-1 RA and then after 6 and 12 months. Results: After 12 months of treatment, 59.3% of patients succeeded in achieving weight loss of over 5% of their initial weight, and 24.7% of patients achieved weight loss of over 10% of their initial weight, with the most significant decrease being measured in the first 6 months. HbA1c has shown a similar profile, with a significant reduction in the first 6 months of treatment, continued at a slower rate in the following 6 months. Additionally, the lipid profile, blood pressure values, and uric acid values, alongside the triglyceride/high-density lipoprotein cholesterol (TG/HDLc) ratio and the triglyceride–glucose (TyG) index have improved in these T2D patients treated with GLP-1 RA, while their eGFR decrease was slower than the one expected for similar populations without such a pharmacologic agent in their regimen. Conclusions: Treatment with GLP-1 RA in patients with T2D is associated with an improved cardiovascular–kidney–metabolic risk profile, ameliorated glycemic control, reduced weight, lower insulin resistance, and slower kidney disease progression. Full article

Residual cardiovascular risk remains a major challenge in coronary artery disease, even after optimal lipid-lowering and anti-inflammatory therapy. Beyond classical risk factors, persistent low-grade inflammation and fibrotic remodeling contribute to adverse outcomes that current treatments fail to fully prevent. Growing evidence highlights the glyco-inflammatory axis—the interplay between protein glycosylation-dependent signaling and inflammation—as an underappreciated contributor to residual atherosclerotic risk, largely because current therapeutic strategies do not directly target glycan-mediated mechanisms. Within this framework, Galectin-3 (Gal-3), a β-galactoside-binding lectin, has emerged as a key molecular hub linking metabolic stress, lysosomal dysfunction, and vascular remodeling. By recognizing specific glycan motifs on immune and stromal cells, Gal-3 orchestrates macrophage activation, endothelial dysfunction, and extracellular matrix deposition, thereby amplifying chronic inflammation and fibrosis. Elevated circulating Gal-3 levels are associated with plaque vulnerability and major adverse cardiovascular events, independent of lipid or C-reactive protein levels. Experimental Gal-3 inhibition reduces inflammation and fibrosis in preclinical models, supporting its therapeutic potential. This review integrates mechanistic, translational, and clinical evidence to propose Gal-3 as a missing link between intracellular stress responses and extracellular fibro-inflammatory remodeling. Targeting the Gal-3-mediated glyco-inflammatory axis may represent a novel strategy to overcome residual cardiovascular risk and achieve comprehensive vascular protection in the post-statin era. Full article

Background: Intracranial atherosclerotic disease (ICAD) remains a major global cause of ischemic stroke—particularly in Asian, Black, and Hispanic populations—and is characterized by high recurrence rates despite advances in intensive medical management. Objectives: This review synthesizes current evidence on surgical and endovascular approaches for ICAD, including extracranial–intracranial bypass, encephaloduroarteriosynangiosis, angioplasty, and hybrid revascularization strategies. Methods: We performed a structured narrative literature search of PubMed and Scopus. Searches were conducted up to 1 October 2025 using combinations of subject headings and keywords, including “intracranial atherosclerotic disease”, “ICAD”, “intracranial stenosis”, “bypass”, “encephaloduroarteriosynangiosis”, “angioplasty”, “stenting”, “revascularization”, and “stroke”. We also scanned reference lists of key articles and relevant reviews. Non-English language articles were excluded. Results: While randomized trials such as SAMMPRIS, VISSIT, and CASSISS reaffirm intensive medical management as first-line therapy, emerging data suggest that surgical revascularization may benefit select patients with hemodynamic compromise refractory to medical therapy. Recent studies incorporating physiologic imaging—such as PET, SPECT, and perfusion MRI—have refined patient selection, reducing perioperative risk and improving long-term outcomes. Innovations in indirect revascularization, hybrid procedures, and intraoperative imaging continue to expand therapeutic possibilities. However, evidence remains heterogeneous, underscoring the need for well-powered randomized trials integrating modern surgical techniques, objective hemodynamic endpoints, and AI-enhanced imaging analytics. Conclusions: While intensive medical management remains the first-line standard of care, select patients with refractory, hemodynamically significant ICAD may benefit from direct, indirect, or hybrid surgical revascularization. Future directions emphasize personalized, physiology-based management frameworks that combine medical, surgical, and technological advances to optimize stroke prevention and long-term vascular outcomes in ICAD. Full article

Background and Objectives: Acute type A aortic dissection (ATAAD) remains a life-threatening condition requiring prompt surgical management. Over the last decades, improvements in diagnosis, surgical techniques, and perioperative care have influenced patient characteristics and outcomes. This study analyzes temporal trends in the clinical profiles and results of patients surgically treated for acute type A aortic dissection (ATAAD) in a Northern Italian region over a fifteen-year period. Materials and Methods: All consecutive patients undergoing emergency surgery for acute Stanford type A aortic dissection or acute intramural hematoma (IMH) between January 2010 and December 2024 were retrospectively reviewed. Patients with chronic penetrating atherosclerotic ulcer or traumatic etiology were excluded. Demographic, clinical, and perioperative variables were analyzed to assess temporal changes. Trends were evaluated using linear regression and Cochran–Armitage tests for trend. Results: A total of 427 patients underwent surgery for AAD during the study period. The proportion of patients presenting with preoperative intubation significantly decreased over time (p for trend < 0.05), as did the incidence of preoperative shock (p for trend < 0.001). Conversely, the mean EuroSCORE showed a non-significant increase over the years. No significant differences were observed in age or other baseline parameters. A non-significant but progressive increase in female representation was observed over time (p = 0.064). Given this observation, a sex-based subanalysis was performed: women were significantly older (p < 0.001) and presented with higher EuroSCORE values (p < 0.001) compared to men, yet postoperative mortality was similar between sexes. This finding contrasts with recent reports suggesting worse outcomes among female patients. Conclusions: Over fifteen years, patients undergoing surgery for acute type A aortic dissection have shown decreasing rates of preoperative critical conditions, reflecting earlier diagnosis and improved management. Despite higher operative risk scores, women demonstrated comparable short-term survival to men within our regional program. Multivariable analysis showed that sex was dependently associated with in-hospital mortality. Full article

Background: Coronary artery disease (CAD) is a multifactorial atherosclerotic disorder. Silicon (Si) is a trace mineral with potential antioxidant, anti-inflammatory, and lipid-modulating effects, but its clinical relevance in cardiovascular disease remains unclear. This study evaluated whether hair Si concentration—reflecting long-term exposure—is associated with CAD severity, clinical phenotype, risk factors, and systemic inflammation. Methods: A total of 130 patients with angiographically confirmed CAD (N = 36, 28% women) who met the inclusion criteria were enrolled. Disease severity was quantified using the Coronary Artery Surgery Study Score (CASSS) and SYNTAX score. Hair Si concentration was determined by inductively coupled plasma optical emission spectrometry (ICP-OES). Associations with demographic, clinical, biochemical, and inflammatory parameters were analyzed using non-parametric tests and multivariable ordinal logistic regression. Results: Median hair Si concentration was 21.3 ppm (range: 0.7–211.0). Hair Si levels showed no significant differences across CAD severity assessed by CASSS (H = 2.51; p = 0.47) or SYNTAX score (r = 0.079; p = 0.37). Similarly, no differences were observed between patients with stable angina and those presenting with acute coronary syndrome (p = 0.57) or between individuals with and without prior myocardial infarction. Hair Si concentration was unrelated to age, BMI, cardiovascular risk factors, lipid profile, or systemic inflammatory indices (all p > 0.2). Conclusions: Hair silicon concentration was not associated with CAD severity, phenotype, or systemic inflammation, suggesting that long-term Si exposure is metabolically neutral in advanced atherosclerosis. Unlike other minerals, silicon appears unlikely to serve as a diagnostic or prognostic biomarker in CAD, although its relevance may be confined to early vascular remodeling and primary prevention. Full article

Background: Interleukin-6 (IL-6) is a key inflammatory cytokine implicated in atherosclerotic plaque progression and carotid vulnerability. Although elevated IL-6 levels have been linked to cerebrovascular risk, its prognostic value in patients undergoing carotid endarterectomy (CEA) remains undefined. This systematic review aimed to investigate the available evidence on the relationship between IL-6 levels, surgical outcomes and mechanistic evidence in CEA patients. Materials and Methods: The review followed the PRISMA statement and AMSTAR-2 critical appraisal guidelines, with the protocol registered on PROSPERO (CRD420251120023). PubMed/MEDLINE, Scopus, and Web of Science were systematically searched up to July 2025 using the terms “interleukin-6” and “carotid endarterectomy”. Original studies in humans assessing IL-6 in relation to clinical outcomes after CEA or mechanistic evidence were included without language or date restrictions. Study quality was evaluated using the Cochrane Risk of Bias 2 and NHLBI tools, and evidence certainty was appraised using the GRADE framework. Given the heterogeneity of studies, only a qualitative synthesis was performed. Results: From 1232 records identified, 13 studies encompassing 1396 patients met the inclusion criteria. Most were prospective observational cohorts, with a mean participant age of 68.52 years and 81.16% male predominance. Perioperative stroke and mortality rates were uniformly low (≤2%), consistent with contemporary registry data. Across studies, elevated IL-6 levels—whether systemic or plaque-derived—were consistently associated with symptomatic carotid disease, plaque vulnerability, and adverse long-term outcomes. However, not all studies presented quantitative data on IL-6 levels, limiting the ability to draw definitive prognostic conclusions. Conclusions: Current evidence supports a mechanistic link between IL-6–mediated inflammation and carotid plaque instability, yet robust clinical validation in surgical populations is lacking. Future large-scale, prospective studies incorporating IL-6 measurement are warranted to establish its prognostic utility, guide anti-inflammatory therapeutic strategies, and refine postoperative risk stratification in patients undergoing CEA. Full article

Background/Objectives: Cardiovascular diseases continue to be the foremost global cause of morbidity and mortality, representing about 40% of all causes of death. Atherosclerotic cardiovascular disease is the most common and clinically important type of these, occurring when cholesterol accumulates over time in the artery intima, which induces an inflammatory process that leads to the production of atherosclerotic plaques. Nowadays, lipid profile alterations and high/very high cardiovascular risk can be observed in more and more patients. Combination therapy, which includes high-intensity statins, ezetimibe, bempedoic acid, and PCSK9-targeted medicines, can lower LDL-C by more than 80%, which is far more than the 50% that statin monotherapy usually achieves. Thus, novel lipid-lowering therapies are needed, as current agents—though effective in reducing cardiovascular events—leave considerable residual risk in many patients. Methods: The aim of our study was to evaluate the cost-effectiveness of Inclisiran and its association with standard of care for the prevention of cardiovascular events across multiple international settings, in articles that reported quality-adjusted life years gained and cost-effectiveness metrics. Results: Our findings suggest that the cost-effectiveness of Inclisiran is highly context-dependent, shaped by local pricing, population risk, and system-level capacity. While Inclisiran demonstrates potential economic value in high-income settings or among high-risk patients, its widespread adoption for primary prevention appears unjustified under current conditions. Conclusions: Policymakers should consider risk-based targeting, price renegotiation, and performance-based reimbursement models to improve the value proposition of such interventions. Full article

Coronary artery disease remains a significant global health challenge, driven by a multifactorial pathophysiology, including immunological activation. The identification and management of potential risk factors are crucial for improving prevention opportunities. In this study, the role of novel, innate immune system response markers, such as podoplanin 38, in atherosclerosis was investigated. A total of 150 consecutive patients (87 (58%) male; median age of 68 (61–76) years) with chronic coronary symptoms (anginal equivalent, e.g., exertional dyspnea) who underwent clinical evaluation and de novo coronary angiography for a prospective single-center analysis were included. Demographic and clinical data, combined with echocardiographic and coronary angiography results, were analyzed in conjunction with laboratory results from admission, including serum podoplanin (PDPN) concentrations. Serum PDPN concentrations were significantly lower in the coronary artery disease group (238 (174–360) pg/mL) compared to the control group (428 (207–1381) pg/mL, p = 0.002). A negative correlation was observed between PDPN and the number of involved coronary arteries in the atherosclerotic process (R = −0.27, p < 0.01). In diabetic populations, glycemic hemoglobin (Hb1Ac) is correlated with the podoplanin concentration (r = −0.51, p = 0.001). A correlation between PDPN and the left ventricular ejection fraction was noted in both the control (r = 0.33, p < 0.01) and CAD groups (r = 0.37, p < 0.001). Podoplanin (PDPN) can be considered a novel marker for coronary atherosclerosis. Low serum podoplanin concentrations characterized patients with coronary artery disease. Full article

Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes in younger women without typical atherosclerotic risk factors. Its distinct pathophysiology and vessel fragility create unique challenges for revascularization. Conservative management is preferred when hemodynamics and coronary flow permit, but selected cases necessitate intervention, primarily percutaneous coronary intervention (PCI). Despite growing insights into SCAD pathomechanics—the “outside-in” and “inside-out” hypotheses—and the central role of intracoronary imaging (OCT/IVUS), optimal device strategies remain under-researched. The present review covers contemporary SCAD-PCI pitfalls and limitations, expanding to the mechanistic underpinnings and procedural applications of drug-coated balloons (DCB) and bioresorbable scaffolds (BRS) as “leave-nothing-behind” alternatives. Both approaches have advantages and drawbacks but are attractive in selected scenarios: DCB delivers antiproliferative therapy without permanent caging, and BRS provides temporary scaffolding (amenable to overlap when required) with the potential to restore biomechanics/vasomotion after resorption. Acknowledging that definitive evidence is lacking and current data are largely observational, the review finally sets future research priorities including head-to-head trials of different DCB types and evaluation of next-generation, thinner-strut, predictably resorbing BRS. The overarching question is whether—and how—these modalities can be integrated into standardized, imaging-guided interventional algorithms for SCAD. Full article

Background: Cardiovascular disease (CVD), driven primarily by atherosclerosis, is a major cause of morbidity and mortality among cancer patients. This study aims to evaluate the diagnostic value of [⁶⁸Ga]Ga-FAPI-PET as a novel molecular imaging tool for atherosclerosis, compared with established, non-specific [¹⁸F]FDG. Methods: We retrospectively analyzed twenty patients with bladder cancer who underwent [⁶⁸Ga]Ga-FAPI positron-emission tomography/magnetic resonance (PET/MR) and [¹⁸F]FDG positron emission tomography/computed tomography (PET/CT) at staging. The target-to-background ratio (TBRs) of both tracers were assessed along six arterial segments, and uptake patterns were compared between the two radiotracers. Additionally, associations between the intensity of PET-active lesions and certain CVD risk factors, as well as the intake of acetylsalicylic acid (ASA), were evaluated. Results: [⁶⁸Ga]Ga-FAPI detects significantly more active arterial PET lesions and shows significantly higher uptake than [¹⁸F]FDG in the per-lesion analysis (TBR_FAPI: 1.7 ± 0.5 vs. TBR_FDG: 1.4 ± 0.2; difference 19%; p < 0.001) and in the patient-based analysis (TBR_FAPI: 1.7 ± 0.4 vs. TBR_FDG: 1.4 ± 0.2; difference 19%; p = 0.018). Arterial hypertension (p < 0.001), dyslipidemia (p < 0.001), and particularly type 2 diabetes mellitus (p < 0.001; difference 34%), were significantly associated with elevated [⁶⁸Ga]Ga-FAPI expression compared to [¹⁸F]FDG uptake. ASA therapy was associated with a significant reduction in arterial [⁶⁸Ga]Ga-FAPI expression than [¹⁸F]FDG (p = 0.02). Conclusions: [⁶⁸Ga]Ga-FAPI-PET imaging, demonstrating superior detection of atherosclerotic activity compared to [¹⁸F]FDG, might be a promising molecular imaging marker for atherosclerosis. Full article