Search Results (1,066)

Background/Objectives: Atrial fibrillation (AF) and heart failure (HF) frequently coexist, but later-pandemic data from Eastern Europe are limited. We evaluated their documented coexistence in patients hospitalized with COVID-19; the study was not designed to determine whether SARS-CoV-2 modifies the established AF–HF relationship. Methods: We retrospectively analysed 395 adults admitted with RT-PCR-confirmed SARS-CoV-2 infection between 1 September 2022 and 31 December 2024. AF was identified from the admission record, while HF was determined by an audited, rule-based review of cardiovascular free-text entries. A modified Poisson model with robust variance was the primary analysis and estimated adjusted prevalence ratios (aPRs) after adjustment for age, sex, body mass index, hypertension, ischaemic heart disease, pre-existing type 2 diabetes, chronic kidney disease, chronic obstructive pulmonary disease, smoking, and prior ischaemic stroke. Logistic regression and a restrictive NYHA-coded HF definition were sensitivity analyses. Results: AF was documented in 68 patients (17.2%), HF in 106 (26.8%), and both conditions in 26 (6.6%). HF prevalence was 38.2% among patients with AF and 24.5% among those without AF. AF was associated with documented HF in the primary model (aPR 1.51, 95% confidence interval 1.06–2.16; p = 0.022); age was also associated with HF (aPR 1.02 per year, 95% confidence interval 1.01–1.04; p = 0.010). Results were similar with the restrictive HF definition (aPR 1.54, 95% confidence interval 1.07–2.23) and logistic regression (adjusted odds ratio 1.89, 95% confidence interval 1.06–3.37). Exploratory mortality estimates were imprecise and were not used for prognostic inference. Conclusions: AF identified a subgroup with a higher prevalence of documented HF within this hospitalized COVID-19 cohort. The findings are best interpreted as evidence of cardiovascular and multimorbidity complexity, not as proof of a COVID-specific, temporal, or causal AF–HF effect. Full article

(1) Background: Whether spatial predictive patterns in non-communicable disease mortality persist after accounting for socio-demographic development and biomarkers remains understudied in East Africa. (2) Methods: This study used heterogeneous graph transformer (HGT) models and other techniques to model spatial patterns in cause- and sex/age-specific mortality (hypertensive heart disease [HHD], ischaemic heart disease [IHD], stroke, and diabetes), incorporating risk factors and socio-demographic development (SDI), using data from the Global Burden of Disease (GBD) study, 1990–2023, across Burundi, Kenya, Rwanda, Tanzania, and Uganda. (3) Results: HGT achieved higher performance than OLS spatial lag benchmarks (R² 0.948–0.970 vs. 0.194–0.376). Spatial predictive patterns were disease-specific. Stroke was the only disease with consistent positive spatial structure (SDI-only: 0.645%, 95% CI [0.380, 0.907]), with spatial structure strengthening after 2015. HHD exhibited severe and stable degradation (Risk-only: −137.892%, 95% CI [−181.908, −96.380]), driven by the interaction between metabolic risk covariates and geographic adjacency. Diabetes showed consistently severe degradation (SDI + Risk: −201.941%, 95% CI [−257.349, −150.082]). IHD patterns were weak and unstable. Sex disaggregation revealed stronger stroke spatial signals, indicating latent sex-specific patterns masked by aggregation. GBD measurement uncertainty contributed less than 0.025% of result variance, with model randomness dominating. (4) Conclusions: Spatial predictive patterns in NCD mortality in East Africa are disease-specific. Stroke shows emerging cross-border spatial structure after 2015, while HHD and diabetes reflect country-specific determinants. Sex-disaggregated graph construction reveals latent spatial heterogeneity invisible to aggregate models, supporting disease-specific, sex-stratified regional health strategies. Full article

Background: Arrhythmia recurrence after cryoballoon ablation remains a clinically relevant problem in atrial fibrillation (AF). However, factors associated with documented recurrence in low-risk patients without major comorbidities are not well defined. This study aimed to evaluate factors associated with documented arrhythmia recurrence after cryoballoon ablation in a highly selected low-risk AF population. Methods: This retrospective, single-center study included 153 eligible patients selected from an institutional cryoablation database after application of predefined exclusion criteria. Only patients with a CHA₂DS₂-VA (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke/transient ischemic attack/thromboembolism, vascular disease, and age 65–74 years) score ≤ 1 and without major comorbidities, including diabetes mellitus, hypertension, coronary artery disease, chronic kidney disease, cerebrovascular disease, and heart failure, were included. Recurrence was defined as electrocardiographically documented AF or atrial tachyarrhythmia after the 3-month blanking period over 1 year of follow-up; Holter-detected episodes were required to last ≥30 s. The primary multivariable model included sex, age, AF type, and absolute left atrial diameter; a sensitivity model replaced absolute left atrial diameter with left atrial diameter indexed to body surface area (BSA). Results: The study population included 70 women (45.8%) and 83 men (54.2%). Paroxysmal AF was present in 125 patients (81.7%), whereas 28 patients (18.3%) had persistent AF. Documented arrhythmia recurrence occurred in 40 patients (26.1%). Female sex was more frequent in the recurrence group than in the no-recurrence group (62.5% vs. 39.8%, p = 0.013). The complete-case primary multivariable model included 126 patients with 36 recurrence events. Female sex was associated with documented arrhythmia recurrence (odds ratio [OR] 2.69, 95% confidence interval [CI] 1.14–6.37; p = 0.024). The estimate for left atrial diameter was directionally positive but statistically uncertain (OR 1.086 per mm, 95% CI 0.989–1.192; p = 0.085). In the BSA-indexed sensitivity model (n = 123), the female-sex estimate was attenuated and statistically uncertain (OR 2.16, 95% CI 0.90–5.18; p = 0.084), while left atrial diameter/BSA was also statistically uncertain (OR 1.145 per mm/m², 95% CI 0.977–1.343; p = 0.095). Conclusions: In this selected low-risk cohort undergoing second-generation cryoballoon ablation, female sex was associated with clinically detected, electrocardiographically documented arrhythmia recurrence in the primary model under an intermittent rhythm-surveillance strategy based on scheduled 12-lead electrocardiograms (ECGs) and symptom-driven evaluations. However, the estimate was attenuated and statistically uncertain after indexing left atrial diameter to BSA. Given the retrospective, single-center design, non-systematic rhythm monitoring, and sensitivity of the sex estimate to body-size adjustment, these findings should be interpreted as hypothesis-generating. Full article

Background: Stroke survivors often present vascular risk factors (VRFs) that are increasingly recognized as contributing to neurodegenerative diseases such as Parkinson’s disease (PD). We examined the influence of VRFs on the risk of PD in stroke survivors. Methods: Using the Korean National Health Insurance Service database, we identified 284,799 individuals with new-onset stroke and followed them for the occurrence of PD. The diagnosis of PD was confirmed using the International Classification of Diseases (ICD-10) code G20 and the rare disease registration code (V124). Results: Cox proportional hazard analyses revealed that smoking (former: Hazard ratio [HR] = 0.80; current: HR = 0.66) and alcohol consumption (moderate: HR = 0.83; heavy: HR = 0.74) were associated with a lower risk of PD. Conversely, diabetes mellitus, especially with a duration ≥ 5 years, was associated with increased PD risk (HR = 1.38). Conclusions: These findings suggest that several VRFs are associated with subsequent PD risk in stroke survivors. Further studies are warranted to determine whether modification of these risk factors influences the development of PD. Full article

Background: Residential wood combustion (RWC) is a major local source of fine particulate matter (PM_2.5) in Nordic regions. We quantified the health impacts and economic costs of long-term exposure to PM_2.5 from RWC in Västerbotten County, northern Sweden. Methods: High-resolution annual mean concentrations of PM_2.5 from small-scale residential heating in 2023 were obtained from a national dispersion-modelling system. Population-weighted exposure was calculated by combining grid-level concentrations with home address coordinates for the resident population. Health impact assessment (HIA) followed the framework used in Nordic studies and the VALESOR project, applying a near-source PM_2.5–mortality exposure–response function with a relative risk of 1.26 per 10 µg/m³ for natural-cause mortality and VALESOR default functions for morbidity (ischaemic heart disease, stroke, COPD, lung cancer, type 2 diabetes, dementia, childhood asthma, cardiovascular hospital admissions). Attributable cases and years of life lost (YLL) were estimated, and the economic valuation used VALESOR unit costs for Sweden to derive central, low and high damage-cost estimates. Results: The population (n = 280,742)-weighted mean RWC-PM_2.5 exposure was 0.16 µg/m³ (interquartile range 0.10–0.21). This was associated with an estimated 30 years of life lost (YLL) per year from natural-cause mortality, plus incident morbidity of approximately 0.3 lung cancer cases, four childhood asthma cases, three COPD cases, three IHD events, one stroke, two dementia cases, one diabetes case and 0.8 cardiovascular hospital admissions annually. The total annual health-related cost attributable to RWC-PM_2.5 was about €7.0 million (95% uncertainty range €4.6–9.4 million), dominated by mortality and disutility costs. Conclusions: PM_2.5 concentrations from residential wood burning are associated with health impacts costing multi-million Euros in a Nordic region, supporting policies to reduce emissions from residential wood heating and to promote cleaner heating alternatives. Full article

The identification of valid biomarkers for ischemic stroke would greatly benefit not only diagnostic and prognostic assessment but also the development of new therapies. The development of omics technologies has made it possible to explore various perspectives of the pathophysiology of ischemic stroke, in particular genomics, transcriptomics, proteomics and metabolomics, and well-known clinical variables, such as hypertension, diabetes, heart diseases, and many others. Omics-based research has produced a mass of data evidencing candidate biomarkers at different stages in the disease process. However, further scientific evidence must be presented and affordable, and rapid detection techniques developed before these technologies can be usefully applied to the clinical setting of stroke. Here, we aim to provide stroke clinicians with an updated overview of the contribution of these emerging technologies in the individuation of diagnostic and prognostic biomarkers and the development of specifically targeted therapies. Cross-fertilization (translation and reverse translation) between preclinical and clinical research is of particular relevance in the identification of stroke biomarkers. We believe it is useful to provide, in parallel, an updated review of omics investigations using stroke rodent models. This review presents a detailed discussion of the state of the art, focusing on the strengths and limitations of the individual technologies and an outline of the promising, most recent results of both clinical and preclinical research in this field related to stroke. Full article

Background/Objectives: Personal listening devices (PLDs) have become ubiquitous in modern daily life, raising growing concerns about their cumulative impact on auditory health. This study examined the prevalence and patterns of PLD use and the independent predictors of perceived hearing handicap among Saudi adults. Methods: A nationwide cross-sectional survey was conducted between November 2025 and January 2026 among 2018 adults (aged 18 years or older) residing in Saudi Arabia. Participants completed a self-administered online questionnaire assessing sociodemographic characteristics, PLD usage patterns, and hearing handicap measured by the Revised Hearing Handicap Inventory (RHHI-18). Results: Participants had a mean age of 29 ± 12 years, 54.0% were female, and 93.9% were Saudi nationals. Earphones and headphones were used by 51.1% and 47.7% of participants, respectively, and 68.1% reported current use of at least one personal listening device. The mean RHHI-18 total score was 10 ± 18, and 23.0% of participants scored within the hearing handicap range (mild-to-moderate: 16.2%; significant: 6.8%). All PLD use categories were independently associated with higher RHHI-18 scores relative to non-use: headphones only (beta = 4.58; p < 0.001), earphones only (beta = 3.29; p = 0.002), and combined use (beta = 2.87; p = 0.005). Further independent correlates of higher RHHI-18 scores were stroke (beta = 21.51; p < 0.001), diabetes mellitus (beta = 8.64; p < 0.001), hypertension (beta = 4.84; p = 0.006), non-Saudi nationality (beta = 3.92; p = 0.014), male sex (beta = 3.09; p < 0.001), and older age (beta = 0.16; p = 0.002). Conclusions: PLD use is highly prevalent among Saudi adults and is independently associated with greater perceived hearing handicap. These findings support public health efforts promoting safe listening practices at the population level. Full article

Background/Objectives: Obesity and diabetes mellitus coexist, but the association of obesity with invasive management and in-hospital outcomes in acute myocardial infarction (AMI) complicated by cardiogenic shock is uncertain. We evaluated these associations among adults with diabetes mellitus. Methods: We performed a retrospective discharge-level analysis of the National Inpatient Sample for 2016–2021. Obesity was identified from ICD-10-CM codes. Survey-design logistic regression accounted for weights, strata, hospital clusters, and prespecified covariates. Results: The cohort comprised 19,399 discharges, representing 96,995 hospitalizations; 24.1% had obesity. Angiography and coronary artery bypass grafting (CABG) were more frequent with obesity, whereas percutaneous coronary intervention (PCI) was less frequent. After adjustment, obesity was associated with higher odds of angiography (adjusted odds ratio [aOR] 1.12, 95% confidence interval [CI] 1.03–1.21) and CABG (aOR 1.49, 95% CI 1.35–1.63), lower odds of PCI (aOR 0.90, 95% CI 0.84–0.97), and similar odds of circulatory support (aOR 1.00, 95% CI 0.93–1.07). Adjusted odds were lower for major adverse cardiovascular and cerebrovascular events (aOR 0.88, 95% CI 0.82–0.95), in-hospital mortality (aOR 0.90, 95% CI 0.83–0.98), acute ischemic stroke (aOR 0.78, 95% CI 0.64–0.95), and major bleeding (aOR 0.86, 95% CI 0.76–0.98). Procedure adjustment attenuated mortality and major bleeding. Conclusions: Obesity was associated with a different invasive-management pattern and lower adjusted odds of several short-term outcomes, consistent with an apparent in-hospital obesity paradox in this high-risk population. Full article

Non-communicable diseases (NCDs), including type 2 diabetes mellitus (DM), hypertension (HTA), obesity (OB), and cardiovascular disease (CVD), represent a major global health burden and disproportionately affect socially vulnerable populations. Small extracellular vesicles (EVs) are stable carriers of proteins and regulatory RNAs that may reflect endothelial dysfunction and cardiometabolic stress. This study explored plasma-derived EV-associated biomarkers in adults from La Guajira, Colombia, with emphasis on miR-126-3p, miR-21-5p, miR-92a-3p, and SNAIL. Anthropometric, clinical, and biochemical data were obtained from a cross-sectional cohort. Representative plasma samples were selected for EVs isolation by size-exclusion chromatography. Vesicles were characterized by nanoparticle tracking analysis, scanning transmission electron microscopy, protein quantification, Western blotting, and bead-based flow cytometry. Candidate miRNAs were identified by small RNA sequencing and validated by stem-loop RT-qPCR. Bioinformatic enrichment analyses were performed using miRNet 2.0 and KEGG pathway analysis. The epidemiological cohort showed a high cardiometabolic burden, with waist-to-height ratio (WHtR) and triglyceride-glucose (TyG) index emerging as key markers of central adiposity and metabolic dysfunction. Plasma-derived EVs displayed the expected nanoscale morphology and expressed canonical vesicle markers. Protein cargo analyses revealed EMT- and remodeling-associated proteins, including SNAIL and GAL-3. EV-associated miR-126-3p, miR-21-5p, and miR-92a-3p were enriched predominantly in hypertensive and hypertensive-diabetic groups. In an exploratory sub-cohort, CD31-positive EVs showed a trend toward increased expression in individuals with previous myocardial infarction or stroke (p = 0.057). KEGG enrichment analysis linked the identified miRNA signature to pathways involved in endothelial dysfunction, inflammation, vascular remodeling, apoptosis, and extracellular matrix organization. Plasma-derived EVs from individuals with cardiometabolic disorders carry molecular signatures consistent with endothelial stress and vascular remodeling. These findings identify miR-126-3p, miR-21-5p, miR-92a-3p, SNAIL, and CD31-positive EVs as exploratory candidate biomarkers that require validation in larger prospective cohorts. Full article

Background/Objectives: Recurrent urinary tract infection (rUTI) is common after menopause, but estrogen deficiency alone does not explain variation in recurrence, symptoms, and microbial profiles. This study aimed to synthesize evidence on the interactions among estrogen deficiency, urogenital microbial ecology, diabetes, obesity, microbial reservoirs, and anatomical, neurological, and functional modifiers of postmenopausal rUTI susceptibility. Methods: PubMed and Scopus were searched for original studies published from 1 January 2021 to 15 June 2026. A structured narrative synthesis included 62 original reports comprising clinical interventions, observational cohorts, microbiome and multi-omic studies, and cellular and animal experiments. Evidence was interpreted according to study design, population relevance, and biological directness. Results: Menopause was associated with reduced Lactobacillus dominance, higher vaginal pH, and altered vaginal or urinary communities, although findings were heterogeneous. Vaginal estrogen reduced recurrence and improved the local urogenital environment, but microbiome restoration is not established as its sole mechanism. Gut, rectal, vaginal, urinary, and bladder-wall reservoirs may contribute to persistence or repeated exposure. Diabetes was linked to dysbiosis and impaired urothelial defence, whereas obesity evidence remained less direct. Pelvic organ prolapse with incomplete emptying, elevated postvoid residual urine, age-related detrusor dysfunction, stroke, immobility, functional dependence, incontinence, and catheter exposure may further modify susceptibility. Conclusions: Postmenopausal rUTI is multifactorial. The urogenital microbiome–metabolic interface is a useful integrative framework, but not a validated causal or diagnostic model. Vaginal estrogen, urine culture, metabolic and bladder-function assessment, and antimicrobial stewardship remain the clinical foundation; microbiome-directed strategies require prospective validation. Full article

Background and Objectives: Despite the presence of atherosclerosis risk factors and symptoms associated with occlusive atherosclerotic cardiovascular disease (ASCVD), up to 30% of individuals do not present significant atherosclerotic lesions at the point of diagnostic evaluation. Those in whom ASCVD was ruled out once might be believed to be at low risk of future major cerebral and cardiac events (MACCEs). Despite this, they might still have some residual risk for MACCEs. Therefore, in the present study we aimed to evaluate risk factors for atherosclerosis progression to the stage of occlusive arterial disease in patients with cardiovascular risk factors but initially free from significant ASCVD. Materials and Methods: Between March 2012 and February 2014, a total of 686 consecutive patients presenting with clinical suspicion of significant coronary artery disease were evaluated. The actual status of atherosclerosis burden was verified in four major arterial territories (coronary, carotid, renal, lower limb arteries) with the use of angiography, computed tomography and ultrasonography. For the present study purpose, 188 (27.4%) patients were enrolled, in whom significant ASCVD (in any of the examined territories) was ruled out. In all patients, the incidence and severity of atherosclerotic risk factors, carotid intima–media complex thickness (CIMT) and carotid plaque presence were evaluated during first hospital admission. A ten-year follow-up period for a composite endpoint of MACCEs was included. Univariate and multivariate Cox proportional hazard analyses with the Simon–Makuch method for new-onset type 2 diabetes mellitus (T2DM) were performed for MACCEs. Results: MACCEs occurred in 30 (16%) of 188 patients, including 5 cardiovascular deaths, 19 non-fatal myocardial infarctions, and 6 non-fatal ischemic strokes, in a median of 48 (Q1; Q3: 25; 86) months. Univariate Cox proportional hazard analysis revealed that individuals who presented with baseline LDL cholesterol > 3.2 mmol/L, CIMT > 1 mm, carotid plaque, or experienced new-onset T2DM were predisposed to MACCE with hazard ratios (HRs) of 3.21 (p = 0.003), 3.82 (p = 0.001), 5.41 (p < 0.001), and 36.89 (p < 0.001), respectively. In multivariate Cox analysis, its associations with MACCEs were retained (HRs between 2.19 and 21.47), respectively. Conclusions: Our findings support the need for continued risk factor optimization despite the initial exclusion of obstructive ASCVD. In this study, we identified new-onset T2DM, initial LDL cholesterol, and the presence of subclinical atherosclerosis as risk factors for MACCEs. Full article

Historically framed as a behavioral addiction, gambling disorder (GD) has had its somatic dimension neglected by standard clinical evaluation. This is a narrative, hypothesis-generating review focusing on the somatic aspects of GD. Cross-sectional and prospective evidence increasingly shows a somatic phenotype distributed across four axes: cardiovascular (hypertension, angina, stroke, acute stress-induced cardiac events), metabolic (obesity, type 2 diabetes, chronic liver disease), sleep-related (insomnia, poor sleep quality, daytime sleepiness), and—as an emerging and insufficiently characterized dimension—neurological (clustering with seizures and frontal lobe epilepsy). Three candidate biological systems may translate this exposure into multi-system physiology: (i) a hyperreactive mesostriatal reward circuit hypothesized to sustain a behavioral cluster of smoking, hazardous alcohol use, low physical activity, and unhealthy diet; (ii) an integrated stress response postulated to shift from acute hyperreactivity to chronic basal cortisol blunting and reduced vagal tone; and (iii) putative alterations in peripheral neurotrophic signaling and frontal-callosal structure, marked by elevated peripheral brain-derived neurotrophic factor and by frontal-callosal white-matter alterations—with cumulative allostatic load serving as a conceptual integrating frame. We propose that GD can be a behaviorally driven systemic medical condition, warranting internal medicine involvement alongside addiction psychiatry. Within this framework, glucagon-like peptide-1 receptor agonists emerge as an exploratory therapeutic hypothesis warranting dedicated evaluation in GD, given their action on the mesolimbic reward substrate and phase 3 evidence in adjacent cardiometabolic, hepatic, and sleep conditions. Full article

Background: Autoimmune diseases (AIDs) are associated with increased cardiovascular risk. However, specific protein mediators linking AIDs to major adverse cardiovascular events (MACE) and cardiovascular death (CV death) remain unexplored. This study identifies proteomic mediators linking AIDs to MACE via high-dimensional mediation analysis in the UK Biobank. Methods: We used UK Biobank data with proteomic profiling by Olink platform. Participants with prevalent myocardial infarction (MI), stroke, and heart failure at baseline were excluded. AIDs were categorized into musculoskeletal (MSK), vasculitis, gastrointestinal (GI), neurologic, and rheumatic fever subsets. Fine–Gray models assessed associations between AIDs and MACE and CV death. Proteome-wide association studies identified proteins associated with both AIDs and cardiovascular outcomes. High-dimensional mediation analysis (HIMA) explored protein-mediated pathways. All models adjusted for age, sex, lipids, BMI, smoking, hypertension, diabetes, chronic kidney disease, atrial fibrillation, and coronary artery disease. Results: Among 400,633 participants (median follow-up 14.5 years, 44.8% male), AIDs were present in 28,754 (7.2%). All AID categories were associated with increased MACE (sHR: MSK 1.34, vasculitis 1.67, GI 1.20, neurologic 1.33, rheumatic fever 1.38; all p < 0.001). For CV death, MSK, vasculitis, and rheumatic fever showed increased risk (sHR 1.34, 1.78, 1.51; all p ≤ 0.004), but not GI or neurologic AIDs. In 43,599 participants with proteomic data, HIMA identified 66 and 32 unique potential mediators linking AIDs to MACE and CV death, respectively. Four proteins (Growth Differentiation Factor 15, Interleukin-15, urokinase plasminogen activator receptor, and Tenascin C) mediated the AID-MACE relationship across multiple AID categories. Growth Differentiation Factor 15 and Interleukin-15 were shared mediators for CV death. Conclusions: This proteomic analysis identifies specific proteins that may mediate the association between AIDs and adverse cardiovascular outcomes, offering mechanistic insights into immune-related cardiovascular risk. These findings are hypothesis-generating and require replication and validation before the identified proteins can be considered causal mediators or adopted for clinical risk stratification. Full article

Background/Objectives: Type 2 diabetes mellitus (DM) and carotid atherosclerosis are established risk factors for cardiovascular disease (CVD). However, their relative and combined prognostic significance in individuals without known CVD remains uncertain. This study aimed to evaluate the independent and combined associations of carotid plaques and DM with cardiovascular events and mortality in a high-cardiometabolic-risk primary prevention cohort. Methods: This prospective cohort study followed 6138 participants (3571 men [57%] and 2567 women [43%]; median age 53 years, IQR 48–58) enrolled in the Lithuanian High Cardiovascular Risk (LitHiR) primary prevention program from 2006 to 2023. All individuals underwent clinical assessment and carotid ultrasonography. Participants were stratified by DM status and the presence of carotid plaques. Associations with cardiovascular events, major adverse cardiovascular events (MACE, including non-fatal ischaemic stroke, non-fatal myocardial infarction, and cardiovascular death), and all-cause mortality were evaluated using Cox proportional hazards models. Results: During follow-up (median 6.5 years, IQR 4.5–9.0), 954 participants (16%) experienced composite cardiovascular events (MACE, including non-fatal ischaemic stroke, non-fatal myocardial infarction, and cardiovascular death). Bilateral carotid plaques were more common in individuals with cardiovascular events (23.3% vs. 19.4%; p = 0.007). Individuals with both DM and carotid plaques had the highest risk of MACE (HR = 1.696; 95% CI: 1.346–2.136; p < 0.001), myocardial infarction (MI; HR = 4.089; 95% CI: 1.590–10.516; p = 0.003), and all-cause mortality (HR = 1.802; p = 0.015). The presence of carotid plaques without DM was independently associated with increased risk of MACE (HR = 1.234; 95% CI: 1.062–1.433; p = 0.006) and MI (HR = 2.492; 95% CI: 1.176–5.278; p = 0.017), but not all-cause mortality (HR = 0.986; 95% CI: 0.689–1.413; p = 0.941). In contrast, DM without carotid plaques was not significantly associated with any outcome examined. Conclusions: In this high-cardiometabolic-risk primary prevention cohort, carotid plaques were independently and more strongly associated with cardiovascular outcomes than diabetes alone. Individuals with both carotid plaques and diabetes showed the highest observed risk of adverse cardiovascular events and all-cause mortality. These findings are associational and apply to a high-risk metabolic syndrome cohort; extrapolation to the general population requires further study. The results support the prognostic value of carotid plaque assessment as an adjunctive tool in cardiovascular risk evaluation. Full article

Diabetes Mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia resulting from the body’s inability to produce insulin or effectively respond to it. In this review, we summarize the cellular and molecular mechanisms involved in common clinical manifestations of DM, including neuropathy, retinopathy, nephropathy, sensorineural hearing loss, cardiovascular disease, stroke, immune dysfunction, and chronic wounds. Common pathways explored in these dysfunctions include the polyol pathway, formation of advanced glycation end products (AGEs) and their interaction with the receptor for advanced glycation end products (RAGE), mitochondrial dysfunctions leading to overproduction of reactive oxygen species (ROS), and the chronic state of inflammation and inflammatory cytokines. Furthermore, we explore current and developing treatments for DM, along with more targeted therapies for the clinical manifestations of DM. In summary, this review gives a comprehensive overview of the pathways involved in the clinical manifestations of DM, and how these pathways are targets for therapeutics and treatments. Full article