Search Results (1,674)

Background: The elderly are vulnerable to chronic diseases and altered lipid metabolism, leading to poor outcomes, including mortality. We investigated the association between Korean Medicine (KM) utilization, blood lipid levels, and health outcomes using the National Health Insurance Service Sample Cohort (NHIS-NSC) database. Methods: This retrospective cohort study included elderly participants who underwent health examinations (2009–2010). Participants were divided into KM and non-KM groups and matched 1:1 using propensity score matching (PSM) for age, sex, income, and comorbidities. Primary outcomes were mortality and disease diagnosis; secondary outcomes included medical spending and utilization. Results: After PSM, 13,044 subjects were analyzed. KM utilization was associated with a significantly lower risk of all-cause mortality (HR 0.93; 95% CI 0.87–1.00; p = 0.048). However, the hypolipidemia subgroup showed no significant differences in all-cause mortality and medical expenses compared to other lipid status subgroups. While the KM group showed a higher incidence of disease diagnosis (HR 1.09; 95% CI 1.04–1.14; p < 0.001), this may reflect increased healthcare engagement and proactive health-seeking behavior. Subgroup analysis revealed that statin users in the KM group had a significantly reduced mortality risk (HR 0.91; 95% CI 0.84–0.99; p = 0.022). Medical expenses and utilization were higher in the KM group. Being underweight or aged over 85 was associated with higher mortality. Conclusions: KM utilization is associated with reduced all-cause mortality after propensity score matching, particularly among statin users. Although KM users had a higher cumulative incidence of disease diagnosis, this potentially reflects increased diagnostic opportunities from prolonged survival. Hypolipidemia, underweight, and late-elderly status remain significant risk factors associated with frailty. KM may support improved survival in the elderly, warranting further prospective studies. Full article

Background/Objectives: The appropriateness of statin treatment in frail older adults is controversial because of insufficient evidence on its efficacy. The aim of this study was to assess the appropriateness of statin prescription at admission and discharge from hospital and the association of deprescription with one-year mortality in a cohort of older patients. Methods: Monocentric retrospective observational study of older (≥65 year) adults admitted to a Geriatric Unit. Patients underwent comprehensive geriatric assessment and prevalence of statin prescription at admission and discharge was recorded. Appropriateness of prescription was determined using the Medication Appropriateness Index (MAI), multidimensional frailty using the Multidimensional Prognostic Index (MPI). Mortality at 12 months was recorded. Results: Among 528 consecutively admitted patients, 112 (mean age 83.6 ± 6.2 years) were treated with statins and were included in the study. In addition, 87.5% of patients showed at least one inappropriate criterion for statin prescription at admission and 91.7% at discharge. Deprescription occurred in 46.4% of patients at discharge, particularly in those who were older and in MPI high mortality risk class. Mean MAI did not differ between admission and discharge in the whole study cohort, but it decreased in patients at highest mortality risk (from 3.2 ± 4.0 to 2.0 ± 1.2). In multivariate analysis, compared with patients who continued statins after discharge, those who were deprescribed did not show increased one-year mortality risk. Conclusions: Inappropriate statin prescription is common at hospital admission in frail older patients and deprescription does not affect one-year residual survival. Therefore, rigorous assessment of mortality risk and medication appropriateness should be encouraged. Full article

Background: Disseminated coccidioidomycosis (DCM) often requires prolonged antifungal therapy (AFT). Real-world data on AFT duration in DCM are limited. We evaluated time to AFT discontinuation among patients with DCM in the United States clinical practice. Methods: This retrospective, longitudinal study used STATinMED data (2016–2024). Patients had ≥1 International Classification of Diseases, Tenth Revision (ICD-10) code for DCM (B38.3, B38.4, B38.7, B38.81) during January 2017–December 2023, ≥1 claim for a triazole or amphotericin B within 21 days of the DCM diagnosis (index date), and continuous medical/pharmacy coverage during the 6-month baseline period. Discontinuation was defined as a ≥21-day gap without AFT. Antifungal agent/formulation switches were not considered discontinuations unless accompanied by a qualifying gap. The Kaplan–Meier methods were used to estimate time to discontinuation. Results: We identified 991 patients with DCM. Median age was 52 years (IQR 36, 65); 60.0% were men. Most resided in California (42.8%) or Arizona (33.6%). Initial AFT consisted predominantly of triazoles (96.8%), primarily fluconazole (83.2%). Discontinuation occurred in 27.6%, 40.0%, 54.2%, and 68.0% of patients by 3, 6, 12, and 36 months. Median AFT duration was 9.9 months. Conclusions: In a large US claims cohort, there was substantial variability in AFT duration in routine practice. Many patients had AFT durations under the lower limit of guideline recommendations for DCM, suggesting potential under-treatment, though appropriate clinical justifications may have existed. Full article

Atherosclerotic cardiovascular disease (ASCVD) is increasingly recognized not merely as a lipid-storage disorder but as a chronic, lipid-driven inflammatory condition of the arterial wall. Despite the widespread use of statins and other lipid-lowering therapies, a substantial “residual inflammatory risk” persists, propelling the search for targeted immunopharmacological interventions. At the forefront of this inflammatory cascade is the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, which serves as a central orchestrator of vascular inflammation by linking metabolic dysregulation to the innate immune response. Atherogenic danger signals—such as oxidized low-density lipoprotein (ox-LDL) and cholesterol crystals—trigger NLRP3 activation through reactive oxygen species (ROS) generation, lysosomal rupture, and potassium efflux. This, in turn, drives the maturation of pro-inflammatory cytokines (IL-1β and IL-18) and initiates macrophage pyroptosis. In this review, we systematically evaluate the immunomodulatory potential of natural products—both complex extracts and single bioactive compounds—in inhibiting the NLRP3 inflammasome axis. We detail the pharmacological mechanisms by which these natural agents intercept inflammatory signaling at multiple stages: suppressing TLR4/NF-κB-mediated priming, scavenging mitochondrial ROS, and restoring autophagic flux via AMPK/mTOR pathways to prevent inflammasome assembly. By critically analyzing these pathways, we highlight natural product-derived inhibitors as a promising class of immunomodulators capable of attenuating atherosclerotic progression and addressing the persistent challenge of residual inflammatory risk. Full article

Background/Objective: Immunoglobulin G (IgG) N-glycosylation is an important regulator of immune function and systemic inflammation and has been associated with cardiometabolic diseases. However, little is known about how IgG glycosylation changes during the course of acute coronary syndrome (ACS) and whether these alterations relate to lipid-lowering response after the initiation of statin therapy. The primary aim of this study was to investigate IgG N-glycosylation following ACS and evaluate its association with response to atorvastatin therapy defined as baseline LDL cholesterol reduction of ≥50%. Methods: In this prospective cohort study, 79 statin-naïve patients hospitalized for the first episode of ACS and treated with atorvastatin 80 mg daily after percutaneous coronary intervention were followed longitudinally. Plasma samples were collected at admission (acute phase), discharge (subacute phase), and follow-up (chronic phase). A control group of 21 individuals received atorvastatin for primary prevention. IgG was isolated from plasma, and N-glycans were released, fluorescently labeled with 2-aminobenzamide, and analyzed using hydrophilic interaction-based ultra-high-performance liquid chromatography with fluorescence detection. Derived glycan traits were calculated, including agalactosylated (G0), monogalactosylated (G1), digalactosylated (G2), core fucosylated (F), bisected (B), and sialylated (S) glycans. Results: No significant differences in derived IgG glycan traits were observed between ACS patients and controls at baseline or follow-up. Within the ACS group, a longitudinal analysis revealed significant increases in G0 and F and a decrease in G2 between the acute and chronic phases. A total of 65% of patients achieved ≥50% reduction in LDL cholesterol (LDL-C), whereas only 22% reached the guideline-recommended LDL-C target of <1.4 mmol/L. Patients achieving ≥50% LDL-C reduction exhibited consistently higher G0 and lower G2 and S across disease phases. In a subgroup of patients with baseline LDL-C >3.9 mmol/L, those who failed to achieve ≥50% LDL-C reduction had significantly lower G0 and higher S across all time points. Conclusions: Specific glycan traits are associated with the degree of LDL-C reduction achieved during statin therapy, particularly in patients with high baseline LDL-C. These findings suggest that IgG glycosylation patterns may reflect biological phenotypes associated with differential lipid-lowering responsiveness after ACS. Full article

The ATP-binding cassette subfamily G member 2 (ABCG2), also known as breast cancer resistance protein (BCRP), is an efflux transporter expressed in key pharmacokinetic tissues and biological barriers. It regulates exposure to many endogenous compounds, drugs, and environmental toxins. Genetic variability in ABCG2 has been recognised as an important contributor to interindividual variability in drug response, especially in terms of efficacy and toxicity. This narrative review summarises current knowledge on the clinical relevance of ABCG2 genetic variants, with a focus on their effects on pharmacokinetics, adverse drug reactions and drug–drug–gene interactions, as well as their potential implementation in personalised therapy. A literature search was performed in PubMed, Scopus and the Clinical Pharmacogenomics Database (ClinPGx), with an emphasis on clinically relevant studies and available pharmacogenomic guidelines. The most investigated ABCG2 variant, c.421C>A (rs2231142; p.Gln141Lys), is consistently associated with reduced transporter activity and increased systemic exposure to several substrate drugs, including statins, allopurinol and anticancer agents, which may influence both treatment response and the risk of toxicity. Although growing evidence supports the clinical relevance of ABCG2 genotyping, its routine implementation remains limited. Integration of ABCG2 variability into polygenic models and clinical decision-support tools may further improve individualised treatment, particularly in patients with multimorbidity and polypharmacy. Full article

Age-related macular degeneration (AMD) remains the leading cause of irreversible central vision loss in the elderly. Increasing attention has been directed toward lipid metabolism as a potential contributor to disease onset and progression. The overlap between AMD and atherosclerosis—particularly regarding lipid accumulation, endothelial dysfunction, and chronic inflammation—has prompted interest in lipid-lowering therapies. This narrative review synthesizes the clinical evidence published between 2020 and 2025 on the potential role of statins and fenofibrate in AMD risk modification and disease progression. A structured literature search was conducted in PubMed, Scopus, and Web of Science using combined MeSH and free-text terms related to lipid-lowering agents and AMD. Human studies evaluating clinical incidence or progression outcomes were considered alongside contextual evidence from prior evidence syntheses. Overall, findings remain heterogeneous. Most studies did not demonstrate a consistent association between statin therapy and AMD incidence or progression in unselected populations. However, selected reports suggested a potential delay in dry AMD onset or slower disease progression among patients receiving prolonged or higher-intensity statin treatment. Evidence regarding fenofibrate was more limited and heterogeneous, with only a tentative protective signal observed in adherent users, particularly for non-exudative AMD. The current literature does not support lipid-lowering therapy as a universal preventive strategy for AMD. Nonetheless, subgroup-specific benefits cannot be excluded, especially in early disease stages or metabolically high-risk populations. Further well-designed prospective and randomized studies are needed to clarify therapeutic relevance and identify the patients who are most likely to benefit. Full article

Background/Objectives: Cardiovasc{Citation}ular disease accounts for 50% of chronic kidney disease (CKD) mortality, yet fewer than 40% of patients achieve guideline LDL-cholesterol (LDL-C) targets on statins. Injectable lipid-lowering therapies (ILLTs)—PCSK9 inhibitors and inclisiran—offer 50–70% LDL-C reductions but lack comprehensive CKD-specific evidence synthesis. This systematic review evaluated ILLT efficacy, safety, and implementation across kidney function stages including dialysis. Methods: Following PROSPERO registration (CRD42024612594), we searched MEDLINE, Embase, Cochrane Library, CINAHL, and Google Scholar (1995–August 2025). Two reviewers independently screened studies using PICOS criteria: adults with CKD stages G3-G5, dialysis, or transplant recipients receiving injectable lipid therapies. Primary outcomes were LDL-C percentage change and major adverse cardiovascular events. Quality was assessed using NIH tools. Given heterogeneity, we performed narrative synthesis following SWiM guidance. Results: Eight studies (n = 28,013) met the criteria. The FOURIER trial demonstrated that evolocumab achieved 58–59% LDL-C reductions across kidney function strata (interaction p = 0.77) with preserved cardiovascular benefit (HR 0.82–0.89). Absolute risk reduction was greater in advanced CKD (2.5% vs. 1.7%), reflecting higher baseline rates. Pharmacokinetic studies showed no eGFR-exposure correlation requiring dose adjustment; evolocumab was not removed by haemodialysis. Inclisiran achieved a 67–80% PCSK9 reduction and a 35–58% LDL-C reduction across renal groups, with twice-yearly maintenance dosing. Both classes reduced non-HDL-C (45–50%), apoB (40–45%), and lipoprotein(a) (20–25%). Safety was favourable, with mild injection-site reactions (< 5%); no renal decline signals emerged. Conclusions: Evidence for injectable lipid-lowering therapies in CKD are driven largely by a single large post hoc subgroup analysis (FOURIER) and small phase 1–2 PK/PD studies, with minimal dialysis representation and no transplant data. These agents appear to provide substantial LDL-C reductions across CKD stages G3–G5 without dose adjustment, but cardiovascular and renal outcome data in advanced CKD and dialysis remain limited and should be interpreted cautiously. Full article

Background/Objectives: Metabolic alterations, including dyslipidemia, may influence tumor biology and treatment outcomes in neuroendocrine tumors. However, the clinical relevance of dyslipidemia and lipid-lowering therapy in bronchopulmonary neuroendocrine tumors (BP-NETs) treated with somatostatin analogues (SSAs) remains poorly defined. This translational proof-of-concept study evaluated progression-free survival (PFS) in patients with advanced BP-NETs receiving SSAs according to dyslipidemia and statin therapy and explored the effects of statin-SSA combination treatment in vitro. Methods: We retrospectively analyzed 24 patients with advanced well-differentiated BP-NETs treated with SSAs as first-line therapy. Fourteen patients (58.3%) had dyslipidemia, and 11 of them were receiving statins. In parallel, NCI-H727 cells were treated with atorvastatin (10 µM), lanreotide (5 or 10 µM), or their combination for 48–72 h. Cell viability, proliferation, cell death, apoptosis, DNA damage, and ATP production were assessed. Results: Median PFS was 22.5 months overall. A trend toward longer PFS was observed in non-dyslipidemic vs. dyslipidemic patients (70 vs. 36 months, p = 0.08). Among dyslipidemic patients, statin therapy was associated with a non-significant trend toward longer PFS compared with no statin therapy (36 vs. 18 months, p = 0.30). In vitro, combined atorvastatin–lanreotide treatment reduced cell viability and proliferation, increased cell death, enhanced cleaved caspase-3 and p-γH2AX expression, and reduced ATP production. Conclusions: These findings support the potential relevance of lipid metabolism modulation as an adjunct strategy in advanced BP-NETs while highlighting the need for larger prospective studies and dedicated biochemical investigation of the underlying lipid-related pathways. Full article

Background: Cardiovascular disease (CVD) represents the second leading cause of death among kidney transplant recipients (KTRs). CVD risks post-transplantation increase with aging, obesity, dyslipidemia, diabetes, hypertension, inactivity, sleep disturbances, immunosuppressant medications use, and graft dysfunction. This study assessed CVD prevalence and risk factors among KTRs. Methods: A cross-sectional study was conducted at National Guard Hospital, Jeddah between 2012–2022. Information was collected from the patients’ medical records. Physical activity, sleep, and adherence to immunosuppressant therapy were evaluated via interviews with adult KTRs using the International Physical Activity Scale, Jenkins Sleep Scale, and Immunosuppressant Therapy Barrier Adherence Scale, respectively. Results: Sixty-four KTRs were included: 67% were males, and the median age was 44.7 years. Eighteen patients (28.1%) had CVD, and 61.1% of them developed ischemic heart disease. KTRs with CVD were older, had lower estimated glomerular filtration rate (eGFR), and higher Hemoglobin A1c (HbA1c), but these differences were not statistically significant (p > 0.05). Patients with CVD had significantly lower LDL (p = 0.02) and more aspirin and statin use (p < 0.05). Forty-five patients (70.3%) completed the interview; most of them had few sleep disturbances and good adherence to immunosuppressant therapy. Low physical activity was reported by KTRs with CVD. Conclusions: CVD was present in over one-quarter of KTRs. Patients with CVD were older, less active, had lower GFR, higher HbA1c, and significantly lower LDL. More use of aspirin and statin improved the glycemic control, physical activity, and medication adherence, and may help in reducing CVD burden among KTRs. Full article

Background: Statins have been associated with a reduced risk of primary liver cancer (PLC), primarily hepatocellular carcinoma (HCC). However, the optimal use for effective protection and whether benefits vary by patient characteristics remain unclear. We evaluated the association between statin use and PLC risk in metabolic-dysfunction-associated steatotic liver disease (MASLD), considering cumulative exposure and potential effect modifiers. Methods: We conducted a retrospective cohort study using the Veteran Affairs electronic health records. Patients with chronically elevated liver enzymes and metabolic dysfunction, without other chronic liver diseases, were identified between 2007 and 2009 and followed through 2019 for incident PLC. Statin exposure was assessed at baseline and during the follow-up, with dose standardization by LDL-lowering potency (simvastatin-equivalent units). Time to PLC was analyzed using Cox models adjusted for covariates, considering potential interactions. Results: Among 329,577 patients (92% male; median age 62 years), 0.82% developed PLC (median follow-up of 9.7 years). Baseline statin use showed a significantly lower PLC risk (adjusted hazard ratio 0.64; 95% CI, 0.57–0.71; p < 0.0001). No significant interaction was observed with age, sex, metabolic syndrome, or cirrhosis. Higher cumulative statin exposure demonstrated a dose-dependent risk reduction, remaining significant at simvastatin-equivalent doses > 15,561 mg annually after accounting for incident cirrhosis. Atorvastatin/rosuvastatin use provided comparable protection, despite different lipophilicity, and demonstrated stronger effects than others. Conclusions: In MASLD, statin therapy was associated with a dose-dependent PLC risk reduction. High-intensity therapy (simvastatin-equivalent > 40 mg daily) conferred substantial protection regardless of age, sex, insulin resistance, or cirrhosis, supporting a potential statin-based PLC chemoprevention in MASLD. Full article

Despite the availability of numerous lipid-lowering agents, the treatment of lipid disorders remains a public health challenge. A substantial portion of patients, especially those with severe dyslipidemia or familial hypercholesterolemia (FH), fail to achieve the LDL-C goal. The leading causes of suboptimal LDL-C control include underprescription and poor adherence; however, in rare cases, it may result from an unusual biological response to treatment. In the presented case, a 78-year-old female with a history of transient ischemic attack and myocardial infarction was diagnosed with a heterozygous variant of FH and true statin intolerance following trials of simvastatin, rosuvastatin and pitavastatin. Initially, inclisiran was added to ezetimibe, leading to an unexpected increase in LDL-C. Due to the patient’s refusal of another statin re-challenge and the unavailability of bempedoic acid, nutraceuticals were introduced. After 6 months, inclisiran was discontinued because only a 22% reduction in LDL-C was achieved, likely attributable to the nutraceutical’s effect. Another PCSK9 inhibitor, evolocumab, was subsequently initiated. Shortly after the treatment onset, the patient complained of paraesthesia in the upper extremities and discontinued therapy. LDL-C levels increased by 7% after one month of treatment with evolocumab. The patient refused treatment with lipid apheresis. Possible causes of poor response to PCSK9 inhibitors include elevated lipoprotein(a) and FH. Full article

When using traditional approaches, such as pharmacokinetics and pharmacodynamics, the entire cellular or molecular response to drugs in the body cannot be fully ascertained or established. The oral medication process involves pharmacokinetics, followed by oral microbiomics and then gut microbiomics and pharmacodynamics. Recently, there has been increasing interest in the role of genetics (pharmacogenetics and pharmacogenomics) in both humans and microbiomes, as well as omics alterations (e.g., epigenetic, transcriptomic, proteomic, and metabolomic alterations as a consequence of drug exposure), which can help to ascertain the cellular responses to medications. Both the efficacy and toxicity of a drug are influenced by these factors. To assess these at an individual level, an integrative Personalized Medicine Model may be needed to help with medication management. Two example application cases for SSRIs and statins demonstrate the clinical usefulness of such a model, which can guide clinicians during drug selection and dosing to reduce reliance on trial-and-error, thus potentially improving patient outcomes and safety. Integrating this framework into practical clinical workflows requires the capture, analysis, and translation of multi-omics data in order to realize decision support protocols and actionable drug recommendations. This review also discusses IT requirements and different stakeholder roles. Although the proposed model can guide the treatment of diseases at the individual patient level, further research is still needed before it can be implemented as part of drug development research, clinical care, and healthcare delivery systems. Full article

Background/Objectives: The study’s goal is to assess the association between long-term statin therapy and influenza incidence, influenza severity, and all-cause mortality. Methods: Two population-based dynamic cohorts (exposed and unexposed to statins) were followed from 2010 to 2019. Participants were 60 years or older; frail patients were excluded. The primary outcomes were influenza incidence, influenza-related intensive care unit (ICU) admission as a proxy for severity, and all-cause mortality. The exposed cohort comprised new statin users with a minimum of two pharmacy invoices within 90 days of enrollment. Adjusted risk ratios (aRRs) for influenza incidence, ICU admission, and mortality rate were calculated using Poisson regression. Results: The initial study population of 639,564 individuals was evenly split into exposed (319,782) and unexposed (319,782) cohorts; mean age was 71 years (standard deviation: 8 years), and 57% were women. Compared to non-users, new statin users showed a higher influenza incidence [9.39 (95% confidence interval: 9.36–9.42) vs. 7.64 (7.61–7.66) per 1000 person-years], ICU admission [1.65 (1.65–1.66) vs. 1.36 (1.35–1.36) per 1000 person-years], and overall mortality rate [97.09 (96.75–97.43) vs. 94.15 (93.82–94.47) per 1000 person-years]. Adjusted analysis revealed no significant association between statin use and influenza incidence [aRR: 1.04 (0.98–1.10)] or influenza-related ICU admission [aRR: 1.03 (0.89–1.19)] and shifted the effect on mortality from harmful to beneficial [aRR: 0.88 (0.87–0.89)]. Conclusions: Despite new users’ greater vulnerability at the start of treatment, our findings indicate that statins do not influence influenza incidence or severity but reduce all-cause mortality, warranting further exploration of their anti-inflammatory properties. Full article

Pancreatic ductal adenocarcinoma (PDAC) has limited effective therapeutic strategies. Statins inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and may affect tumor cell fitness via the mevalonate pathway, mitochondrial function, and redox homeostasis. We systematically compared seven statins in patient-derived PDAC cell lines and related viability effects to mitochondrial, redox, cell-cycle, apoptotic, and metabolic responses. Statins were tested in three PDAC cell lines (PDAC-1/2/3) using MTT assays (5–20 µM; 24–120 h). Based on MTT responses, mechanistic profiling was performed after 72 h at 20 µM concentration using lipophilic statins, including apoptosis (Annexin V/7-AAD), cell-cycle distribution, mitochondrial membrane potential (Δψm), intracellular ROS, and ¹H-NMR quantification of intracellular and extracellular metabolites. Statins reduced viability in a concentration- and time-dependent manner, with lipophilic statins more active than hydrophilic. PDAC-1 was highly sensitive, PDAC-3 intermediate, and PDAC-2 comparatively resistant. PDAC-1 and PDAC-3 showed G0/G1 accumulation, Δψm depolarization, reactive oxygen species (ROS) elevation, and Annexin V–positive apoptosis, whereas PDAC-2 (high basal ROS) showed ROS reduction and limited apoptosis despite Δψm loss. Metabolomics indicated reduced glucose and amino-acid utilization and lactate secretion while preserving line-specific metabolic fingerprints. PDAC cell lines display marked inter-tumoral heterogeneity in statin responses, supporting evaluation of statins as chemosensitizing adjuvants in functionally guided PDAC treatment strategies. Full article