Search Results (1,265)

Background: Familial hypercholesterolemia (FH) continues to be underrecognized and inadequately treated. We aimed to investigate the current status of FH diagnosis and treatment in South Korea. Methods: Patients from two tertiary hospitals in South Korea between 2010 and 2023 with either a diagnosis of FH (ICD-10 code: E7800), had LDLR, APOB, or PCSK9 mutations, or had low-density lipoprotein cholesterol (LDL-C) levels exceeding 325 mg/dL were considered for inclusion. Demographic and laboratory characteristics as well as pharmacologic treatment patterns were assessed. Results: A total of 148 patients were retrospectively identified. The mean age at diagnosis was 49.3 years, and 33 (22.3%) had a history of established atherosclerotic cardiovascular disease (ASCVD). The majority of patients were diagnosed in the cardiology or endocrinology departments. The LDL-C level at enrollment was 247 ± 98 mg/dL (conversion to treatment-naïve LDL-C: 343 ± 141 mg/dL), which decreased to 122 ± 60 mg/dL after one year, achieving guideline-recommended target levels in 11.5%. A high proportion of patients were treated with statins (80.2%) and ezetimibe (64.9%), but the use of proprotein convertase subtilisin/kexin type 9 inhibitors was low (11.7%). Patients diagnosed after 2020 achieved significantly lower LDL-C levels at one year compared to those diagnosed between 2020 and 2019 (107 ± 50 vs. 152 ± 68 mg/dL, p = 0.003). Two ischemic strokes and two myocardial infarctions occurred during a median follow-up of 25.3 months. Conclusions: FH is frequently diagnosed late after the onset of clinical ASCVD and is undertreated, although recent trends show improvement. Our results again underline the need for proper screening and identification of patients with FH. Full article

Atherosclerosis, a major contributor to vascular damage and plaque formation, is brought on by cellular senescence and chronic inflammation. A crucial matter that emerges is the classification of the disease in order to understand the pathogenic mechanisms before treatment. Given that oxidative stress, DNA damage, and inflammation contribute to cellular senescence, an increase in pro-inflammatory factors is detected in the atherosclerotic plaque, which exacerbates its instability while impeding vascular repair. This study emphasizes the importance of pathways such as Nrf2, ICAM-1, and p38 MAPK/p16^INK4A in the development of atherosclerosis. It also underscores the potential of senescence-targeting interventions to complement the conventional treatments for atherosclerosis. The study promotes using senolytic approaches that may serve as effective adjuncts to conventional pharmacological treatments for atherosclerosis. Particularly, quercetin, a flavonoid, demonstrates a potential action as senolytic agent by mitigating macrophage senescence, improving lipid profiles, and reducing plaque size of up to 56% in experimental models. This review article advocates for integrating senolytic approaches, including nutraceuticals like quercetin and combination therapies, to improve cardiovascular health and age-related vascular disorders. Full article

Scarce evidence exists on the impact of ozone (O₃) on atherosclerotic cardiovascular disease (ASCVD) morbidity in tropical urban settings, and whether temperature modifies this effect remains unclear. To bridge this gap, we assessed the association between ambient O₃ and ASCVD outpatient visits, and the potential effect modification by temperature, in Haikou, China. A time-series analysis was performed on data from 163,348 daily hospital outpatient visits for ASCVD collected between 1 January 2020 and 31 December 2022. The association between O₃ exposure and daily visits was evaluated with an over-dispersed Poisson generalized additive model (GAM), and the modifying effect of temperature was scrutinized using a nonparametric bivariate response surface model. A 10 μg/m³ increment in the daily maximum 8 h average concentration of O₃ was associated with a 1.35% (95% CI: 0.63, 2.07) increase in ASCVD outpatient visits at lag0. Stratified analyses revealed that the association between O₃ and ASCVD visits was only significant during the warm season, with stronger effects observed above 30 °C, peaking at 34 °C (lag06). The combined exposure to high temperature and O₃ concentrations significantly amplified ASCVD outpatient visits. Ambient O₃ exposure was associated with increased ASCVD outpatient visits in the tropical city, and this risk was enhanced under high temperatures. These results highlighted the importance of considering temperature interaction in O₃-related risk assessments. Full article

Background and Objectives: Cardiovascular–kidney–metabolic (CKM) syndrome reflects the interconnection between metabolic risk factors, chronic kidney disease (CKD), and cardiovascular disease (CVD). Despite increasing awareness, population-based data on CKM syndrome are limited, particularly in Europe. This study assessed the prevalence of CKM syndrome and the use of renal and cardiac biomarkers in Lithuania. Materials and Methods: Health records of 923,329 adults aged ≥40 years from the national Electronic Health Services and Cooperation Infrastructure Information System were analyzed. CKM-associated conditions (prediabetes/type 2 diabetes, obesity, CKD) and cardiovascular outcomes (atherosclerotic CVD, peripheral vascular disease, stroke, heart failure, atrial fibrillation) were identified. CKM stages were defined as stage 0 (no CKM conditions), stages 1–3 (at least one CKM condition), and stage 4 (at least one CVD diagnosis). The use of estimated glomerular filtration rate (eGFR), albumin-to-creatinine ratio (ACR) and N-terminal pro–B-type natriuretic peptide (NT-proBNP) testing was evaluated. Results: Overall, 34.8% of adults met criteria for stage 4 CKM syndrome, and 23.4% were classified as stage 1–3. Obesity (21.2%) and type 2 diabetes (17.2%) were the most common CKM-associated conditions. Heart failure (25.4%) and atrial fibrillation (14.0%) were the most common cardiovascular outcomes, with ≥2 CVD diagnoses present in 15.4% of patients. Among stage 1–3 patients, eGFR, ACR, and NT-proBNP were measured in 53.5%, 9.0%, and 4.9%, respectively. Conclusions: A third of Lithuanian adults aged ≥40 years had stage 4 CKM syndrome. The underuse of biomarker testing highlights missed opportunities for early detection. Broader implementation of biomarker testing and integrated care is warranted to slow progression of CKM syndrome and reduce cardiovascular risk. Full article

Background/Objectives: Metabolic dysfunction–associated steatotic liver disease (MASLD) is closely linked to atherosclerotic cardiovascular disease (ASCVD), but the prognostic value of liver fibrosis and gut–liver axis alterations remains uncertain. Methods: We conducted a prospective, observational study in two tertiary centers (in Romania and Italy) and compared the outcomes with different tests available for fibrosis (FibroTest in Romania or acoustic radiation force impulse (ARFI) elastography in Italy) and intestinal permeability (IP) (by fecal zonulin in Romania or lactulose/mannitol ratio in Italy). Liver steatosis was confirmed at ultrasonography. Analyses followed a within-cohort strategy. Ten-year ASCVD categories were summarized separately per cohort, and within-cohort associations with elevated ASCVD risk (≥7.5%) were explored using univariate logistic regression with age-adjusted two-parameter checks. A pooled robustness analysis (n = 132) was then performed using multivariable logistic regression models for intermediate–high ASCVD risk (≥7.5%), adjusted for age (per 5 years), waist circumference (per 5 cm), total cholesterol (per 10 mg/dL), diabetes, and hypertension. A higher threshold (≥20%) yielded the same qualitative interpretation. Results: ASCVD was computable for 52 Romanian (low 78.8%, borderline 5.8%, intermediate 7.7%, high 7.7%) and 80 Italian participants (low 80.0%, borderline 6.2%, intermediate 12.5%, high 1.2%). In both cohorts, age was associated with higher ASCVD. Fibrosis severity (FibroTest or ARFI) and IP (zonulin or LA/MA) showed no associations with ASCVD. In pooled adjusted models, neither significant fibrosis nor high intestinal permeability was independently associated with ASCVD, whereas age and cardiometabolic comorbidities remained the dominant correlates. Conclusions: Across both cohorts, 10-year ASCVD risk was mainly determined by age and major cardiometabolic comorbidities. Neither liver fibrosis nor intestinal permeability contributed additional prognostic value in this setting, regardless of the assessment method. These data support prioritizing aggressive metabolic risk management and call for harmonized, longitudinal studies to clarify gut–liver contributions to cardiovascular outcomes. Full article

Background: Coronary disease (CAD) is a multifactorial complex pathology characterized by excessive inflammatory activation and oxidative stress. Amino acids are among the potential biomarkers for cardiovascular pathology. The analysis aimed to investigate the possible relationship between proteomic profiling and coronary artery disease risk as novel markers of CAD. Methods: Patients with similar demographic and clinical profiles, including the prevalence of comorbidities such as arterial hypertension, dyslipidemia, and diabetes mellitus, were divided into two groups based on the results of their coronary angiograms. Serum amino acid levels were measured using liquid chromatography–tandem mass spectrometry. Results: Patients with significant coronary atherosclerosis confirmed in coronary angiograms were characterized by higher levels of circulating cystine, threonine, methionine, and proline. The number of involved coronary arteries in atherosclerotic processes revealed a correlation with circulating levels of threonine, methionine, and proline, not cystine. The multivariable logistic regression analysis for any significant coronary artery disease prediction revealed higher values of circulating threonine as a possible risk factor. Thereafter, a subanalysis was conducted to examine the relationship between amino acid levels and atherosclerotic risk in specific coronary arteries. The multivariate analysis revealed cystine and proline as potential risk factors for atherosclerosis of the left descending artery (LAD). Higher values of threonine were identified as a possible risk factor for atherosclerotic plaque location in the circumflex artery in multivariate regression analysis. Proline circulating levels were found to be prognostic for right coronary artery disease. Conclusions: Elevated circulating levels of amino acids, including cystine, threonine, methionine, and proline, were observed in patients with significant coronary artery disease in our exploratory pilot study. The high circulating amino acid levels can be predictive of coronary artery disease in our multivariate models. Full article

Cardiovascular diseases (CVDs), including coronary artery disease (CAD), are the main causes of mortality and morbidity worldwide. The pathophysiology of CAD includes atherosclerosis, a chronic process leading to atherosclerotic plaque development. Clinical manifestations could be chronic, such as in the chronic coronary syndrome (CCS) scenario, or acute, such as acute coronary syndrome (ACS). The risk of subsequent cardiovascular (CV) events depends on the risk category defined by international guidelines. In particular, patients who have experienced a CV event requiring percutaneous coronary intervention (PCI) remain at heightened residual risk for subsequent events, despite advancements in standard-of-care strategies. Therefore, comprehensive residual risk management is essential in this population to mitigate ischemic risk. Secondary prevention includes different targets of treatments—hypertension, dyslipidemia, diabetes mellitus, body weight control, smoking habit reduction, and healthy lifestyle promotion. Nevertheless, there is a critical, unmet need for therapeutic strategies for this high-risk population. Growing evidence shows that atherogenic lipids and vascular inflammation drive residual risk after PCI, despite guideline-directed therapy. This review summarizes more recent evidence about secondary prevention focusing on optimal medical therapy (OMT), targeting lipids and inflammation for patients undergoing PCI. Full article

Programmed cell death (PCD), a regulated cell death (RCD) subtype essential for physiological homeostasis, encompasses distinct mechanisms including apoptosis, necroptosis, autophagy, ferroptosis, cuproptosis, and pyroptosis. This evolutionarily conserved process critically regulates disease pathogenesis across degenerative disorders, malignancies, fungal infections, and vascular calcification (VC). VC manifests as pathological calcium deposition in cardiovascular tissues, impairing vascular elasticity and hemodynamics. These structural alterations elevate risks of atherosclerotic events, cerebrovascular accidents, and peripheral vascular dysfunction, while concomitantly inducing vital organ hypoperfusion and cardiac overload that predispose individuals to myocardial ischemia, left ventricular hypertrophy, and heart failure. Despite advances in delineating associated signaling networks, the molecular etiology of VC remains elusive, and effective therapeutic interventions are currently lacking. While systematically examining the pathophysiological contributions of both established and novel PCD mechanisms to VC progression, this review incorporates a discussion of cuproptosis as a novel form of PCD, which may serve as a target for atherosclerosis treatment. The inclusion of cuproptosis, alongside other PCD modalities, allows for a more integrated and updated perspective on the complex regulatory networks governing VC. Our objective is to synthesize the current understanding of how these diverse PCD pathways, both classical and emerging, collectively contribute to the disease pathogenesis and to explore the broader therapeutic potential of targeting PCD in VC. Full article

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated significant benefits in cardiovascular outcomes trials, but their effect on atherosclerotic plaques remains unclear. This review aims to summarize the current evidence on the impact of SGLT2i on atherogenesis. Methods: A systematic search was conducted across PubMed, Embase, Scopus, Web of Science, and Google Scholar databases up to August 2025. Preclinical and clinical studies on the effect of SGLT2i on atherogenesis and atherosclerotic plaque extent and phenotype were included. Results: A total of 27 studies were included. Twenty-four studies examined in vitro and animal models of atherosclerosis exposed to SGLT2i, while three studies focused on the effects of SGLT2i on coronary plaques in patients with ischemic heart disease. SGLT2is modulate atherogenesis through multiple mechanisms: prevention and reversal of endothelial dysfunction, reduction in monocyte recruitment and promotion of anti-inflammatory macrophage polarization. Additionally, SGLT2is reduce inflammation and inhibit vascular calcification. Through these mechanisms, SGLT2is decrease plaque burden in both diabetic and non-diabetic atherosclerosis models. Furthermore, they reduce lipid content and macrophages accumulation while increasing fibrous cap thickness, thereby contributing to plaque stabilization. Conclusions: Preclinical and clinical evidence suggest that SGLT2is modulate every step of the atherogenic process, reduce atherosclerotic burden and promote coronary plaque stabilization. Full article

Sarcopenic obesity (SO) is a syndrome characterized by a gradual reduction in skeletal muscle mass, strength, and function coupled with excessive fat accumulation, which considerably increases the risk of metabolic disorders and atherosclerotic cardiovascular disease. Owing to its extensive influence on the health of elderly individuals and distinct pathophysiological mechanisms, SO should be considered an independent clinical condition. Atherosclerosis, the fundamental pathophysiological underpinning of atherosclerotic cardiovascular disease, has garnered increased interest because of its association with SO. Existing research indicates that SO may synergistically promote atherosclerosis development through multiple pathways, including hormonal dysregulation, adipo-myokine imbalance, insulin resistance, chronic low-grade inflammation, and lipid metabolic abnormalities. The current literature gaps predominantly encompass the absence of standardized diagnostic criteria for SO, inconsistent results in studies investigating the relationship between SO and atherosclerosis, and inadequate causal validation. Studies indicate associations between SO and carotid atherosclerosis, coronary atherosclerosis, arterial stiffness, and 10-year atherosclerotic cardiovascular disease risk; however, conclusions remain inconsistent, and most studies are cross-sectional. Additionally, this field has insufficient focus on peripheral atherosclerosis, such as in the lower extremities. Moreover, the pathophysiological mechanisms remain unclear. A complex vicious cycle potentially exists among decreased muscle mass and function, fat accumulation, and atherosclerosis, a relationship that has not received sufficient attention. Therefore, this review aims to integrate existing evidence, summarize advances in diagnostic criteria for SO, review the epidemiological association between sarcopenic obesity and atherosclerosis, and analyze the reasons for heterogeneity in conclusions. It further explores potential pathophysiological mechanisms, delving into the vicious cycle among declining muscle mass and function, fat accumulation, and atherosclerosis. Finally, this review proposes future research directions, including diagnostic standardization, in-depth mechanism exploration, conducting prospective cohort studies to validate causal relationships, and developing intervention targets for SO–Atherosclerosis comorbidity. Full article

Dyslipidemia is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD). Abnormal maternal lipid profiles in pregnancy are associated with pregnancy complications including preeclampsia, gestational diabetes, and pre-term delivery as well as increased ASCVD risk for both mother and child. Dyslipidemia management remains a central tenet for atherosclerotic cardiovascular disease prevention for women who are thinking about becoming pregnant or are already pregnant. Effective individualized guidance and multidisciplinary lifestyle/dietary strategies, along with targeted pharmacological interventions, are required for the successful management of lipid disorders in pregnancy in order to optimize outcomes. This review discusses the physiological changes occurring in lipid metabolism during pregnancy and provides an overview of the current strategies for managing dyslipidemia during pregnancy, with a special focus on consideration of pharmacological therapy. Full article

Cardiovascular morbidity and mortality rise precipitously during the 6th–9th decades of life, identifying aging as a critical risk factor. Simultaneously, older individuals are susceptible to severe viral infection, raising the question whether shared mechanisms exist that predispose to both cardiovascular disease (CVD) and failing anti-viral immunity. The aging process causes steady decline in immune fitness (immune aging), which undermines the ability to generate protective anti-viral immune responses. Paradoxically, the aging immune system supports unopposed inflammatory pathways (inflammaging), which exacerbates tissue inflammation in CVD, specifically atherosclerosis. Here, we review the current evidence of how innate and adaptive immune aging promotes tissue-destructive inflammation in atherosclerosis while failing to fight viral infections. Further, we consider how these two disease processes mutually influence each other. We propose that mounting an effective anti-viral response induces off-target bystander activation and exhausts immune cells, ultimately exacerbating CVD. Additionally, we explore how atherosclerotic CVD impacts innate immunity through epigenetic modification of hematopoietic precursors and metabolically conditioning immune cells, leading to a dysfunctional immune system that accelerates plaque inflammation while simultaneously impairing host defense. Full article

High-density lipoprotein (HDL) metabolism depends on several key factors, including ATP-binding cassette (ABC) transporters such as ABCA1 and ABCG1. These transporters are essential for maintaining cholesterol homeostasis by mediating the efflux of cellular lipids and promoting HDL formation and maturation. Dysfunction in these pathways compromises HDL biogenesis, leading to lipid accumulation in macrophages and peripheral cells. Together with oxidized low-density lipoproteins (LDLs), these alterations promote foam cell formation, atherosclerotic plaque development, and the progression of cardiovascular and metabolic diseases. Oxidative stress plays a central role in disturbing lipid balance and impairing ABC transporter activity. Unlike previous reviews that have mainly summarized mechanisms of oxidative regulation, this work integrates recent molecular findings to propose a unifying framework in which oxidative stress sequentially disrupts ABCA1 and ABCG1 function, thereby altering HDL metabolism. Moreover, it highlights emerging pharmacological strategies aimed at restoring cholesterol homeostasis and mitigating oxidative damage, contributing to the prevention of cardiovascular and metabolic disorders. Full article

Background: High-throughput metabolomics studies have promoted the discovery of candidate biomarkers linked to atherosclerosis (AS). This narrative systematic review summarises metabolomics studies conducted in (1) individuals with subclinical AS (assessed by imaging techniques such as carotid intimal media thickness, IMT, and coronary artery calcium, CAC), (2) patients with established atherosclerotic plaques, and (3) individuals with AS risk factors. Methods: The systematic search was conducted in the PubMed database according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The inclusion criteria were as follows: (i) publication date between 2009 and 2024; (ii) identification of potential biomarkers for AS in subjects with a diagnosis of AS or with one or more traits characteristic of the disease (i.e., CAC or IMT); (iii) identification of potential AS biomarkers in subjects with atherogenic clinical conditions (i.e., Down’s syndrome, DS, polycystic ovarian syndrome, PCOS, and systemic lupus erythematosus, SLE); (iv) metabolomic studies; and (iv) studies in human samples. Exclusion criteria comprised the following: (i) studies on lipid metabolic diseases unrelated to AS, (ii) “omics” results not derived from metabolomics, (iii) reviews and studies in animal models or cell cultures, and (iv) systematic reviews and meta-analyses. Of 90 eligible studies screened, 24 met the inclusion criteria. Results: Across subclinical and overt AS, consistent disturbances were observed in amino acid, lipid, and carbohydrate metabolism. Altered profiles included branched-chain amino acids (BCAAs), aromatic amino acids (AACs) and derivatives (e.g., kynurenine–tryptophan pathway), bile acids (BAs), androgenic steroids, short-chain fatty acids (FAs)/ketone intermediates (e.g., acetate, 3-hydroxybutyrate, 3-HB), and Krebs cycle intermediates (e.g., citrate). Several metabolites (e.g., glutamine, lactate, 3-HB, phosphatidylcholines, PCs/lysophosphatidylcholines, lyso-PCs) showed reproducible associations with vascular phenotypes (IMT/CAC) and/or clinical AS. Conclusions: The identification of low-weight metabolites altered in both subclinical and overt AS suggests their potential as candidate biomarkers for early AS diagnosis. Given the steady increase in deaths from cardiovascular disease, a manifestation of advanced AS, this finding could have significant clinical relevance. Full article

Atherosclerosis is a widespread cardiovascular disease characterized by retention of atherogenic lipoproteins in the arterial wall and the onset of subclinical vascular inflammation; the development of atherosclerotic plaques; eventual narrowing of the arterial lumen and/or plaque disruption; and subsequent manifestation with stable ischemia or acute atherothrombotic events. Numerous cell types are implicated in atherogenesis. Monocytes/macrophages are considered pivotal participants in this complex process. They play a crucial role in the onset and augmentation of inflammation and greatly contribute to atherosclerotic plaque growth and destabilization. However, monocytes/macrophages are also essential for the resolution of inflammation and the stabilization of atherosclerotic lesions. In this regard, studies of the function of monocytes/macrophages in relation to this disease are of considerable interest to researchers, as the results can help to design new drugs aimed at preventing the development of atherosclerosis and its complications. This review presents current data on the classification and functions of monocytes/macrophages; discusses current hypotheses regarding the involvement of monocytes/macrophages in atherogenesis; and highlights existing gaps in evidence. This review is primarily aimed at readers with a background in clinical medicine who are interested in the involvement of monocytes/macrophages in atherogenesis. Full article