Search Results (7,658)

Background/Objectives: Traditionally, risk stratification in heart failure with reduced ejection fraction (HFrEF) patients has been a static process. This study aims to identify clinical predictors and causes of mortality at different stages of the disease, distinguishing between early mortality (≤1 year) and late mortality (>1 year), as well as cardiovascular and non-cardiovascular causes. Methods: This is an observational, longitudinal study of a cohort of 1510 patients with HFrEF followed up in a specialist heart failure unit between 2011 and 2023. Patients were categorized into three groups: alive (n = 1093), early mortality (n = 55) and late mortality (n = 362). Multivariate Cox regression models were used to identify mortality independent predictors in each period. Results: During the first year, cardiovascular and non-cardiovascular mortality showed a relatively balanced distribution, with a slight predominance of non-cardiovascular causes (52.8%). Progression of heart failure remained the leading individual cause of early death (38.2%). Independent predictors of early cardiovascular death included ischemic etiology (HR 2.78; 95% CI: 1.20–6.40; p = 0.01), NYHA functional class (HR 4.38; 95% CI: 2.18–8.81; p < 0.001) and renal function (HR 0.60; 95% CI: 0.44–0.84; p = 0.002). In contrast, late mortality (>1 year) was predominantly due to non-cardiovascular causes (59.7%), notably cancer (24.3%) and infections (7.5%). Late all-cause mortality was independently associated with age (HR 1.35; 95% CI: 1.17–1.56; p < 0.001), hypertension (HR 1.38; 95% CI: 1.06–1.81; p = 0.015) and ischemic etiology (HR 1.45; 95% CI: 1.16–1.80; p < 0.001). In the follow-up, the improvement of left ventricular ejection fraction (LVEF) emerged as a protective factor against long-term all-cause mortality (HR 0.77; 95% CI: 0.63–0.94; p = 0.01) and, even more markedly, against late cardiovascular mortality (HR 0.47; 95% CI: 0.33–0.66; p < 0.001), whereas baseline LVEF at diagnosis lacked significant predictive value in either model. Conclusions: Mortality in HFrEF is a dynamic process. Early survival is determined by hemodynamic stability, renal function and functional severity, whilst late survival is predominantly driven by non-cardiovascular comorbidities, biological aging, and ventricular remodeling trajectory. The improvement of LVEF during follow-up is a more reliable prognostic marker than the baseline measurement, suggesting that clinical management should shift from early pharmacological optimization towards a multidisciplinary approach focused on long-term non-cardiovascular risk. Full article

Hyperlipidemia (HL) is a major metabolic disorder and a critical risk factor for cardiovascular diseases, closely associated with oxidative stress, inflammation, and disrupted cholesterol homeostasis. Freeze-dried Poecilobdella manillensis powder (FDPMP), a traditional medicinal product, has shown therapeutic potential against hyperlipidemia; however, its underlying mechanisms remain largely unclear. In this study, HL was induced in ApoE⁻/⁻ mice by feeding a high-fat diet (HFD) for eight weeks, during which FDPMP or simvastatin (positive control) was orally administered daily. Concurrently, an in vitro foam cell model was established by exposing RAW264.7 macrophages to oxidized low-density lipoprotein (ox-LDL, 80 μg/mL) for 24 h, with FDPMP pretreatment applied 30 min prior to ox-LDL stimulation. Following intervention, serum lipid profiles, hepatic oxidative stress markers, histopathological changes, and cholesterol metabolism-related gene and protein expression were systematically evaluated. FDPMP administration significantly improved serum lipid profiles by reducing triglycerides, total cholesterol, and low-density lipoprotein cholesterol, while increasing high-density lipoprotein cholesterol levels. Additionally, FDPMP alleviated histopathological damage in the liver, kidney, and heart, enhanced antioxidant enzyme activities, and attenuated oxidative stress. Untargeted metabolomic analysis revealed that FDPMP markedly modulated key metabolic pathways, including choline metabolism, glycerophospholipid metabolism, and arachidonic acid metabolism. Mechanistically, FDPMP restored cholesterol homeostasis through dual regulation of cholesterol metabolism, characterized by upregulation of cholesterol 7α-hydroxylase (CYP7A1) to promote bile acid-mediated cholesterol excretion, alongside downregulation of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and synthase (HMGCS1) to inhibit cholesterol biosynthesis. In vitro, FDPMP effectively suppressed ox-LDL-induced foam cell formation, reduced intracellular lipid accumulation, and mitigated oxidative stress in macrophages. Collectively, these findings demonstrate that FDPMP ameliorates hyperlipidemia through coordinated regulation of cholesterol synthesis and excretion, coupled with systemic metabolic reprogramming and antioxidative effects. This study provides mechanistic insights supporting FDPMP as a promising natural therapeutic candidate for hyperlipidemia and related metabolic disorders. Full article

Background: Elevated levels of lipoprotein(a) [Lp(a)] are an independent risk factor for the development of atherosclerotic cardiovascular disease (ASCVD). However, there is only limited data investigating the role of elevated Lp(a) levels in patients with patent foramen ovale (PFO)-associated embolic stroke of undetermined source (ESUS). Methods: We included 266 patients with PFO-associated ESUS who underwent percutaneous PFO closure and had Lp(a) measurements available. These patients were matched according to age, sex and previously documented statin treatment to 947 hospital controls without stroke. Results: Median age was 51 years (IQR 43–59) and 40% were female. Median Lp(a) levels were higher in cases (24 IQR 12–88 nmol/L) than in controls (21 IQR 7–75 nmol/L; p = 0.003). This association appeared more pronounced in men than in women. In males, patients with Lp(a) in the second tertile had an odds ratio (OR) of 1.64 (95% CI, 1.03–2.62) and patients with Lp(a) in the third tertile had an odds ratio of 2.18 (95% CI 1.38–3.44) independent of age, statin use, HbA1c and eGFR. In contrast, in females the second (OR 2.08 [95% CI 1.22–3.54]) but not the third tertile (OR 0.88 [95% CI 0.49–1.59]) of Lp(a) was associated with case status. Conclusions: In this retrospective matched case–control study, higher Lp(a) concentrations were associated with case status in a selected cohort of patients with PFO-associated ESUS, particularly in men. These findings should be considered hypothesis-generating and require confirmation in prospective studies with more representative comparison cohorts. Full article

Diabetic cardiomyopathy (DCM) is a cardiac condition characterized by various structural and functional abnormalities that are associated with diabetes mellitus. Its development involves multiple factors, among which endothelial dysfunction plays a significant role. To fully describe the relationship between DCM and endothelial dysfunction, we conducted a literature search across several databases, including PubMed, Web of Science, and EMBASE. Our review of DCM research focused on understanding its mechanisms, exploring the methods used to diagnose it, and potential treatment options. Although researchers have made significant progress in DCM diagnosis and treatment in recent years, considerable challenges persist as well. Artificial intelligence (AI)-based multimodal approaches may provide new opportunities for cardiovascular risk stratification and early DCM screening, but DCM-specific models still require external validation before clinical implementation. Regarding treatment options, emerging evidence suggests potential benefits of medications that enhance mitochondrial function and antioxidant properties, as well as anti-inflammatory therapies and lifestyle modifications. Future research should focus on combining different relevant data types, such as genetic and molecular information, to improve the AI tools utilized in medical environments. This study aims to identify novel markers for diagnosing DCM and to devise tailored treatment approaches. These advancements have the potential to improve the prognosis of DCM patients and enhance the identification and management of this condition. Full article

Background: Heart failure (HF) represents the final common pathway of diverse cardiovascular disorders, including coronary artery disease, primary myocardial pathology, and abnormalities of cardiac conduction. These conditions arise from an interplay of genetic, environmental, and psychosocial influences, making it essential to understand these determinants to improve risk prediction and prevention. Multiple biological pathways of inflammation, fibrosis, coagulation, oxidative stress, lipid dysregulation, endothelial dysfunction, and metabolic disturbances are shaped by inherited susceptibility and modifiable exposures. Together, these mechanisms drive HF development and progression, though their relative contributions vary across populations. Methods: PubMed and Google Scholar were searched for clinical, biomedical, and interdisciplinary studies published between 1 January 2000, and 31 December 2025. Keywords included “Asian,” “adult,” “India,” “heart failure,” “risk assessment,” “prognosis,” and “predictive value.” Studies were included if they focused on South Asian Indian adults, with priority given to original research, systematic reviews, and meta-analyses. Pediatric studies and those centered on other ethnic groups were excluded. Results: Among South Asian Indians, cardiovascular disease burden remains disproportionately high compared with Western populations. Unique genetic architecture, environmental exposures, and sociocultural factors appear to contribute to earlier onset and more aggressive disease. Identifying population-specific genetic variants, clarifying psychosocial influences, and addressing environmental risks may help reduce these disparities. Conclusions: This qualitative review highlights key gaps in current knowledge. A deeper understanding of these determinants could refine HF risk stratification, guide targeted prevention strategies, and reduce the growing cardiovascular burden in South Asian Indians. There is an urgent need for South Asian specific HF risk prediction models. Full article

Background/Objectives: A body shape index (ABSI) has been proposed as an anthropometric measure reflecting abdominal body shape beyond body mass index (BMI). However, its relative cross-sectional discriminative ability compared with conventional anthropometric measures and surrogate markers of insulin resistance for prevalent diabetes and cardiovascular disease (CVD) remains poorly characterized in Korean adults. Methods: This cross-sectional study included 11,448 Korean adults aged 18–64 years from the 2019–2021 Korean National Health and Nutrition Examination Survey (KNHANES). Using receiver operating characteristic (ROC) curve analyses, we compared the discriminative ability of ABSI with BMI, waist circumference, waist-to-height ratio, homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride-to-HDL cholesterol ratio (TG/HDL-C), and the triglyceride–glucose index (TyG) for prevalent diabetes and CVD. Multivariable logistic regression analyses assessed associations after adjustment for demographic and socioeconomic factors. Results: ABSI showed the highest ROC-AUC for both prevalent diabetes (74%) and CVD (74%) among the compared indices. In multivariable-adjusted analyses, individuals in the very high ABSI risk group had higher odds of prevalent CVD (OR, 3.75; 95% CI, 1.60–8.78) than those in the very low-risk group. Among individuals with diabetes, the odds of comorbid CVD were also higher in the very high ABSI group (OR, 3.38; 95% CI, 2.26–5.07). Similar patterns appeared in obesity-subgroup analyses. Conclusions: ABSI showed greater discriminative ability for prevalent diabetes and CVD than several conventional measures and insulin-resistance markers, supporting its potential utility as a simple marker of cardiometabolic disease burden. Prospective studies are needed to determine its prognostic value. Full article

Background: Carfilzomib, a second-generation proteasome inhibitor, is widely used in multiple myeloma (MM) treatment but has been associated with cardiovascular adverse events (CVAEs). Real-world data evaluating the incidence and risk factors are limited. Methods: We conducted a multicenter retrospective cohort study of 385 adult MM patients treated with carfilzomib between January 2020 and August 2024 at three U.S. institutions. The primary objective of this study was to determine the incidence of carfilzomib-associated CVAEs. The secondary objectives included the identification of risk factors, characterization of cardiovascular events, and time-to-onset analysis. Results: Carfilzomib-associated CVAEs occurred in 25 patients (6.5%). The median time to event was 114 days. Heart failure was the most common manifestation (86%), followed by arrhythmias (32%) and acute coronary syndromes (8%). Patients with baseline heart failure had a significantly increased risk of CVAEs (HR 1.61, p = 0.042), whereas arrhythmias showed a trend toward significance. Traditional cardiovascular risk factors were not independently associated with an increased risk. CVAEs were associated with numerically inferior overall survival (45.7 vs. 97.3 months; HR 1.316, 95% CI 0.728–2.377, p = 0.361). Partial recovery of the left ventricular ejection fraction was observed following treatment discontinuation. Conclusion: Carfilzomib-associated CVAEs were infrequent but clinically meaningful in this multicenter cohort. These findings support consideration of a risk-adapted cardio-oncology approach, particularly in patients with pre-existing cardiac dysfunction, where closer surveillance and early intervention may help mitigate clinically significant cardiotoxicity. Full article

Metabolic syndrome (MetS) is a complex multisystem disorder characterized by insulin resistance, central obesity, dyslipidemia, hypertension, and chronic low-grade inflammation, all of which substantially increase the risk of type 2 diabetes mellitus and cardiovascular disease. The aim of this narrative review is to examine the role of vitamin D in the pathophysiology of MetS from a multisystem perspective. Specifically, it synthesizes current evidence on the molecular mechanisms through which vitamin D may influence inter-organ communication, insulin resistance, adipose tissue dysfunction, hepatic metabolism, skeletal muscle function, chronic inflammation, oxidative stress, and mitochondrial homeostasis, highlighting its potential contribution to the prevention and management of MetS. Current evidence indicates that MetS should not be regarded merely as a cluster of isolated metabolic abnormalities but rather as a disorder characterized by disrupted molecular signaling and impaired communication among metabolically active organs. In this context, experimental and preclinical evidence suggests that vitamin D, through activation of the vitamin D receptor (VDR), modulates key signaling pathways, including AMP-activated protein kinase (AMPK), the mechanistic target of rapamycin (mTOR), nuclear factor kappa B (NF-κB), and peroxisome proliferator-activated receptor gamma (PPAR-γ), thereby influencing insulin sensitivity, inflammation, oxidative stress, mitochondrial function, and metabolic homeostasis. Nevertheless, clinical evidence remains heterogeneous due, in part, to the lack of consensus regarding serum 25-hydroxyvitamin D thresholds for defining vitamin D status, as well as differences in baseline vitamin D concentrations, supplementation regimens, study populations, and methodological designs. Overall, the available evidence suggests that vitamin D should be considered an adjunct to lifestyle-based interventions rather than a stand-alone therapeutic strategy. Future research is warranted to clarify its clinical utility in the prevention and management of MetS. Full article

High-sensitivity cardiac troponin has made the diagnosis of myocardial infarction (MI) faster and more precise, but it does not measure the broader biological vulnerability that often determines the outcome after an acute coronary syndrome (ACS). Growth differentiation factor-15 (GDF-15) is induced by ischemic stress, inflammation, oxidative injury, renal dysfunction, metabolic disease, and ageing. This biology explains its appeal in ACS, but also its diagnostic limitation: GDF-15 is not cardiac-specific and should not be used as an alternative to electrocardiography and high-sensitivity troponin algorithms for early MI diagnosis. Its better supported role is prognostic. Across emergency department chest pain cohorts, non-ST elevation MI, ST elevation MI, post-ACS trial populations, and serial biomarker studies, higher GDF-15 concentrations are most consistently associated with all-cause mortality, cardiovascular mortality, heart failure, and major bleeding, while associations with recurrent ischemic events alone are less specific. The key unresolved issue is incremental clinical value. GDF-15 may improve discrimination and reclassification beyond clinical predictors, troponin, natriuretic peptides, renal function and GRACE or GRACE 2.0 in selected settings, but statistical association is not equivalent to clinical utility. Its possible role in bleeding risk estimation and antithrombotic benefit–risk assessment is clinically important, especially after the PLATO biomarker analyses, yet routine GDF-15-guided dual antiplatelet therapy decisions remain unsupported. Future implementation requires validated thresholds, calibration, decision curve evidence, health economic evaluation, and trials in which GDF-15-guided management changes care and improves outcomes. Full article

Background: Sodium–glucose co-transporter-2 (SGLT-2) inhibitors are widely prescribed for type 2 diabetes mellitus (T2DM) because of their cardiovascular and renoprotective benefits. However, their use is associated with euglycemic diabetic ketoacidosis (EDKA), a rare but potentially life-threatening complication characterized by severe ketoacidosis despite relatively normal blood glucose levels. Failure to discontinue SGLT-2 inhibitors before surgery, as recommended in current guidelines, together with perioperative fasting and surgical stress, increases the risk of EDKA. Diagnostic complexity is compounded when concurrent postoperative surgical complications provide an alternative explanation for persistent metabolic acidosis. Methods: A 71-year-old man with T2DM receiving uninterrupted empagliflozin underwent direct lateral interbody fusion under general anesthesia. On postoperative day 2, he developed severe high anion-gap metabolic acidosis (pH 7.204, HCO₃⁻ 10.1 mEq/L) with near-normal blood glucose levels (178 mg/dL). Pneumoperitoneum identified on imaging was attributed to Hemovac drain-related peritoneal injury, and emergent laparoscopic exploration was performed under a working diagnosis of surgical sepsis. Although surgical source control was successfully achieved, severe metabolic acidosis persisted postoperatively (pH 7.275). Euglycemic diabetic ketoacidosis is an uncommon diabetic complication associated with several perioperative risk factors, including prolonged fasting and surgical stress. Subsequent serum ketone analysis demonstrated markedly elevated beta-hydroxybutyrate levels (4.8 mmol/L), confirming co-existing EDKA. Results: Following empagliflozin discontinuation, targeted treatment with concurrent insulin–dextrose infusion resulted in complete resolution of acid-base imbalance within five days. Conclusions: A concurrent surgical complication appeared to mask EDKA and contributed to a delay in its recognition. In patients receiving SGLT-2 inhibitors, metabolic acidosis that persists after an apparent surgical cause has been addressed should prompt measurement of serum ketones, irrespective of the blood glucose concentration. Structured perioperative protocols for SGLT-2 inhibitor management and postoperative ketone surveillance may help to prevent similar events. Full article

Introduction: Sarcopenia and frailty are emerging independent risk factors for cardiovascular disease. Sarcopenia represents a decline in function associated with reduced muscle mass. Frailty, defined as a phenotype or the multiple stress model, is associated with weakness and a decline in organ reserve with vulnerability to disease. Frailty and sarcopenia may overlap and have shared clinical risk factors including age and malnutrition. Methods: We performed a literature review of published studies on frailty and sarcopenia with respect to cardiovascular risk factors and body composition. Results: Studies demonstrated that obese sarcopenic or obese frail subjects had a higher prevalence of cardiovascular risk factors such as hypertension, diabetes mellitus, dyslipidaemia, smoking and sedentary lifestyle, which was highly associated with cardiovascular disease. On the other hand, anorexic malnourished frail participants with unintentional weight loss or sarcopenic subjects without obesity had a low prevalence of cardiovascular risk factors, which was less associated with cardiovascular disease. Conclusions: Obesity appears to play a crucial role in mediating the cardiovascular risk of both sarcopenic and frail patients. Full article

Objectives: Coronary artery disease (CAD) remains a leading cause of morbidity and mortality worldwide, yet population-specific evidence regarding the contribution of MIA3 genetic variation in Middle Eastern populations remains limited. This study investigated the association of the MIA3 rs17465637 polymorphism with CAD susceptibility and its relationship with lipid-related phenotypes in a Saudi population. Methods: A case–control study was conducted between June 2020 and August 2022, including 200 patients with angiographically confirmed CAD and 200 age- and sex-matched healthy Saudi controls. Genotyping of rs17465637 was performed using a TaqMan real-time polymerase chain reaction assay. Genotype distributions were evaluated using chi-square analysis under multiple inheritance models. Multivariable logistic regression was subsequently performed to estimate adjusted odds ratios after controlling age, BMI, smoking, physical inactivity, systolic BP, diastolic BP, blood glucose, triglycerides, total cholesterol, LDL-C, and HDL-C. Associations between rs17465637 genotypes and serum lipid parameters were also examined. Results: Genotype frequencies of rs17465637 differed modestly between cases and controls; however, unadjusted comparisons under codominant, dominant, recessive, and allelic inheritance models did not reach statistical significance, and none remained significant after Bonferroni correction. In contrast, multivariable logistic regression demonstrated an independent association between the rs17465637 C allele and CAD after adjustment for conventional cardiovascular risk factors. In genotype–phenotype analyses, carriers of the C allele exhibited higher association with low-density lipoprotein cholesterol concentrations and less favorable lipid profiles than AA homozygotes, supporting a relationship between the variant and lipid metabolism. These findings are consistent with a potential contribution of rs17465637 to CAD susceptibility through lipid-related pathways. Conclusions: Although unadjusted genotype comparisons were not statistically significant after correction for multiple testing, multivariable analysis provides evidence supporting an independent association between the MIA3 rs17465637 variant and CAD susceptibility in this Saudi cohort. The observed associations with adverse lipid profiles further provide evidence linking this specific locus to the molecular mechanisms underlying cardiovascular disease. Replication in larger, multi-center studies incorporating genome-wide ancestry-informative markers and functional investigations is warranted to further minimize the possibility of residual population stratification, confirming these findings and clarifying the biological mechanisms underlying this association. Full article

Background: Non-group 1 pulmonary hypertension, also known as secondary pulmonary hypertension (SPH), is predominantly observed among females. However, there is a significant lack of data concerning factors associated with hospitalization among patients diagnosed with SPH. This study aims to provide clinicians with vital insights for the identification of high-risk groups and for the more effective management of contributory risk factors within the female population affected by SPH. Methods: Using the 2019 National Inpatient Sample, we identified female admissions with SPH (n = 648,190), accounting for 3.8% of the total 17,236,228 female admissions. An Artificial Neural Network (ANN) analysis was conducted to evaluate predictive factors. We randomly allocated 3,319,543 patients into training and testing datasets at a ratio of 70:30, comprising 2,323,696 (70%) for training and 995,847 (30%) for testing, to calibrate and validate the performance of the ANN algorithm. Model performance was assessed by comparing misclassification rates between training and testing sets and by the area under the receiver operating characteristic curve (AUC); only internal validation was performed. Results: Females hospitalized with SPH were generally of older age, with a median of 75 years compared to 58 years, and more frequently identified as White (67.7% versus 65.5%) or Black (20.5% versus 15.5%) relative to those without SPH. They also demonstrated a higher prevalence of most atherosclerotic cardiovascular disease (ASCVD) risk factors or their equivalents, including complicated hypertension (50.6% versus 17.8%), diabetes with chronic complications (30.6% versus 13.7%), and hyperlipidemia (50.8% versus 29.2%), as well as other comorbidities such as COPD (43.4% versus 20.2%) and CKD (43.3% versus 14.0%), and exhibited increased all-cause mortality (4.5% versus 1.8%) (p < 0.001). Our ANN model achieved an AUC of 0.823, indicating good predictive capability. The rates of incorrect predictions were comparable in both the testing and training cohorts, at 3.8% each. The factors most strongly associated with a coded SPH diagnosis included age at admission, complicated hypertension, chronic kidney disease, chronic obstructive pulmonary disease, uncomplicated hypertension, prior VTE, race, arthropathies, and AIDS. Conclusions: Our ANN model identified demographic and comorbidity factors associated with a coded SPH diagnosis among hospitalized females, with good discrimination (AUC = 0.823). Because the model classifies the presence of an existing diagnosis rather than predicting future hospitalization, and was validated only internally, external and prospective validation is required before clinical application. Once validated, these factors could support individualized, sex-specific risk stratification for high-risk female populations, consistent with the goals of personalized medicine. Full article

Background/Objectives: Albuminuria is an important marker of kidney and cardiovascular risk in adults with type 2 diabetes mellitus (T2DM). Regional data from Mexico remain limited among patients with preserved estimated glomerular filtration rate (eGFR) and no previous diagnosis of diabetic kidney disease. This study aimed to describe albuminuria categories observed at a single screening assessment and to explore clinical factors associated with higher urinary albumin-to-creatinine ratio (uACR) categories in adults with T2DM receiving care at a regional hospital in western Mexico. Methods: This exploratory single-center cross-sectional study included 119 adults with T2DM (mean age, 53.3 ± 11.7 years), preserved eGFR (≥60 mL/min/1.73 m²), and no previous diagnosis of diabetic kidney disease. Albuminuria was classified from a single first-morning uACR measurement as A1 (<30 mg/g), A2 (30–300 mg/g), or A3 (>300 mg/g). Exploratory multivariable ordinal logistic regression evaluated factors associated with higher uACR categories. A secondary exploratory binary model evaluated screen-detected uACR ≥ 30 mg/g (A2/A3 versus A1). Results: A1 was observed in 67 patients (56.3%), A2 in 40 (33.6%), and A3 in 12 (10.1%); 52 patients (43.7%) had uACR ≥ 30 mg/g at screening. The median uACR was 25.6 mg/g, the median HbA1c was 11.2%, and the median fasting glucose was 280 mg/dL. In the exploratory ordinal model, longer T2DM duration (OR 1.51 per 5 years; 95% CI 1.09–2.10; p = 0.012), higher HbA1c (OR 1.18 per 1% increase; 95% CI 1.01–1.38; p = 0.036), and lower eGFR (OR 0.69 per 10 mL/min/1.73 m² increase; 95% CI 0.55–0.88; p = 0.003) were associated with higher uACR categories after adjustment for the measured covariates. In the secondary binary model, longer T2DM duration and lower eGFR were associated with screen-detected uACR ≥ 30 mg/g. Conclusions: A single screening assessment identified uACR ≥ 30 mg/g in 43.7% of this selected regional cohort. These findings represent screen-detected albuminuria and do not establish persistent albuminuria, diabetic kidney disease, temporality, or causality. Confirmation with repeated uACR measurements and validation in larger longitudinal multicenter studies with detailed medication data are required. Full article

Background/Objectives: Ambient fine particulate matter (PM_2.5) poses significant health risks to older adult populations, yet the specific contributions of its chemical constituents, particularly non-phthalate and non-organophosphate ester compounds, remain poorly understood. This study aimed to elucidate the mechanistic links between PM_2.5-bound ester exposures and metabolic pathway alterations in elderly individuals. Methods: A total of 258 elderly residents aged 60 years or older from Fuzhou, China, were recruited. Personal PM_2.5 exposure was monitored over 72 h using UPAS V2 samplers, with chemical components analyzed via gas chromatography–mass spectrometry (GC–MS). Plasma metabolomic profiling was conducted using liquid chromatography–mass spectrometry (LC–MS), and metabolic pathway enrichment was performed using MetaboAnalyst 5.0. Linear regression models adjusted for covariates (age, sex, BMI, lifestyle factors) assessed associations between ester exposures and metabolite abundance. Results: The mean PM_2.5 concentration was 38.06 μg/m³, with ester compounds dominating the chemical composition. Twenty high-concentration non-target esters were prioritized for analysis. PM_2.5 ester exposure was associated with alterations in key metabolic pathways, including steroid biosynthesis, glycolysis/gluconeogenesis, glycerophospholipid metabolism, and purine/pyrimidine metabolism. When interpreted alongside prior epidemiological evidence, these alterations represent putative links to increased risks of insulin resistance, cardiovascular dysfunction, and metabolic syndrome—relationships that require confirmation in prospective cohort studies and controlled toxicological experiments. Conclusions: Putatively annotated PM_2.5-bound ester compounds, particularly non-regulated subclasses, are associated with systemic metabolic alterations in older adults, coincident with perturbations in steroid and lipid metabolism. While these findings are exploratory and hypothesis-generating, they highlight the need to incorporate specific ester profiles into PM_2.5 risk assessments and develop targeted interventions for vulnerable aging populations. Full article