Insulin resistance (IR) is mechanistically linked to hypertension, yet no study has directly compared fasting-insulin-based and non-insulin-based IR surrogates for predicting mortality across the glycemic spectrum in hypertensive adults. We evaluated ten IR indices, three insulin-based [homeostasis model assessment of insulin resistance (HOMA-IR), McAuley index, and quantitative insulin sensitivity check index (QUICKI)] and seven non-insulin-based [triglyceride-glucose index (TyG), stress hyperglycemia ratio (SHR), cardiometabolic index (CMI), atherogenic index of plasma (AIP), estimated glucose disposal rate (eGDR), metabolic score for insulin resistance (METS-IR), and lipid accumulation product (LAP)], for all-cause mortality (ACM) and cardiovascular mortality (CVM) by glycemic status. This prospective cohort study included 7,548 hypertensive adults from NHANES 1999–2018, classified as normoglycemia (n = 1,869), prediabetes (n = 3,389), and diabetes (n = 2,290). Mortality data were collected through December 31, 2019. Associations were analyzed using Cox models with three levels of adjustment. Dose-response relationships were modeled with restricted cubic splines. Over a mean follow-up of 8.7 ± 5.3 years, 1,752 ACM events (23.2

BACKGROUND:The functional implications of renal artery variations-including accessory renal artery (ARA) and early branching-in hypertensive chronic kidney disease remain poorly understood. METHODS:This prospective cohort study enrolled 38 patients with hypertensive chronic kidney disease with unilateral solitary renal artery variation (24 ARA, 14 early branching) undergoing pressure wire-based hemodynamic evaluation and selective segmental renal vein renin sampling; 35 patients completed 2-year follow-up. RESULTS:Mean pressure gradient was higher in variant artery than in ipsilateral main (1.10±3.39 versus -0.15±2.21 mm Hg, P=0.04) and contralateral renal artery (versus -0.10±1.56 mm Hg, P=0.04) in the overall cohort, a difference limited to the ARA subgroup. Plasma renin activity was elevated in ARA-supplied segments compared with the ipsilateral main trunk (1.77±1.86 versus 1.24±1.40 ng/(mL·h), P=0.004) and contralateral artery-supplied segments (versus 1.24±1.37, P=0.002), whereas no significant difference was observed in the early branching subgroup. After multivariable adjustment, variant artery systolic pressure gradient was positively associated with variant-supplied segmental (β=0.41, P=0.02) and peripheral (β=0.37, P=0.04) plasma renin activity, angiotensin II, and nighttime mean arterial pressure. Peripheral aldosterone was associated with lower estimated glomerular filtration rate and higher urinary protein. All adjusted associations represent exploratory signals given limited sample size. Over 2 years, an intragroup estimated glomerular filtration rate decline was observed within the ARA subgroup (-5.2 mL/[min·1.73 m2]; P=0.02) while the early branching subgroup remained stable (P=0.47); however, the group-by-time interaction was not significant (P=0.06), indicating these preliminary trends require larger validation cohorts. CONCLUSIONS:Renal artery variations may alter intrarenal hemodynamics, with functional impairment and segmental renin hypersecretion observed primarily in ARA. This suggests a potential role for functional evaluation.

AIMS:We aimed to investigate the association between liver fibrosis scores (LFS) and major adverse cardiovascular events (MACE) in patients with myocardial infarction and non-obstructive coronary arteries (MINOCA), particularly in those with and without diabetes (DM) or prediabetes (pre-DM). METHODS:Consecutive MINOCA patients were enrolled, and LFS were assessed using the fibrosis-4 index (FIB-4) and nonalcoholic fatty liver disease fibrosis score (NFS). High LFS were defined as FIB-4 ≥ 2.67 or NFS ≥ 0.676. Kaplan-Meier, restricted cubic spline (RCS) analysis, and Cox regression were used to assess MACE risk. RESULTS:Among 406 MINOCA patients (mean age 63.7 years; 211 men), 271 had DM/pre-DM. Of these, 38.9% had high FIB-4, and 28.3% had high NFS. Over 32 months, high LFS predicted higher MACE rates (log-rank p < 0.05), particularly in patients with DM or pre-DM. RCS analysis showed a linear association between FIB-4 and MACE and a nonlinear association for NFS. Fully adjusted Cox models revealed that FIB-4 ≥ 2.67 or NFS ≥ 0.676 were independently associated with an increased risk of MACE in DM/pre-DM patients, but not in non-DM/pre-DM. CONCLUSION:Elevated LFS predicts a higher risk of MACE in MINOCA, especially in patients with DM/pre-DM, and may aid in risk stratification.

The EAT-Lancet diet (ELD) and plant-based diets (PBDs) are recommended for their potential health and environmental benefits, but comparative analyses of these dietary patterns in relation to mortality risk remain limited. This study aimed to evaluate the associations of ELD and PBDs with mortality and life expectancy in two nationwide cohorts. Participants from the UK Biobank and the US National Health and Nutrition Examination Survey (NHANES) (2003–2018) were included. Dietary intake was assessed using 24-h dietary recalls. The ELD index (ELD-I), overall PBD index (PDI), healthful PBD index (hPDI), and unhealthful PBD index (uPDI) were calculated and categorized into tertiles. Primary outcomes were all-cause mortality, cause-specific mortality, and life expectancy. After full adjustment, the hazard ratio (HR) for all-cause mortality when comparing the highest versus lowest tertiles was 0.87 (95

BackgroundMetabolic disturbances in lipid and glucose metabolism underlie coronary microvascular dysfunction (CMD) in chronic coronary syndromes (CCS), yet a practical biomarker integrating this metabolic risk is lacking.MethodsIn this single-center retrospective cohort, 421 CCS patients undergoing coronary angiography were included. CMD was defined by caIMR ≥ 25 U. C-reactive protein-triglyceride-glucose index (CTI), triglyceride-glucose index (TyG), and C-reactive protein (CRP) were measured. Associations with CTI and major adverse cardiovascular events (MACE) in CMD patients were analyzed using Cox regression, mediation, and ROC analyses.ResultsCTI was independently associated with CMD after full adjustment (Q4 vs. Q1: OR: 2.28, 95% CI: 1.16–4.49, p = 0.017), outperforming TyG and CRP. Over a median 35-month follow-up, higher CTI predicted increased MACE risk (fully adjusted HR for Q4: 2.62, 95% CI: 1.25–5.51, p = 0.011), especially in CMD patients (fully adjusted HR: 2.84, 95% CI: 1.06–7.62, p = 0.039). CTI demonstrated a superior predictive accuracy for CMD-related MACE compared with TyG (DeLong test p = 0.020).ConclusionCTI is a robust and independent predictor of both CMD and MACE in patients with CCS, supporting its use for early risk stratification and personalized management in patients with suspected or confirmed microvascular dysfunction.

Tubular epithelial cell (TEC)-macrophage crosstalk contributes to aldosterone (Aldo)-dependent renal fibrosis in hypertension. Extracellular ATP (eATP) can act as a mediator of TEC-macrophage crosstalk. However, whether and how eATP functions in Aldo-induced renal injury remain unknown. A deoxycorticosterone acetate (DOCA)-salt-induced hypertensive mouse model and a primary mouse renal tubular epithelial cell (mTEC)-bone marrow-derived macrophage (BMDM) coculture model were developed. To investigate the relationship between Aldo/MR and eATP signaling in TEC-macrophage crosstalk, specific inhibitors, adeno-associated virus (AAV)-shRNA and small interfering RNA (siRNA) were used. scRNA-seq analysis of kidneys from DOCA-salt mice was performed for verification. Urinary ATP levels and renal pannexin1 (PANX1, an ATP efflux channel) expression increased significantly in DOCA-salt mice, whereas the selective mineralocorticoid receptor (MR) antagonist finerenone treatment reduced urinary ATP levels, PANX1 expression, tubular injury, and macrophage-related inflammation. Inhibiting PANX1-eATP-P2X7 signaling with the PANX1 inhibitor probenecid, specifically knocking down tubular PANX1, or using the eATP ectonucleotidase apyrase or the P2X7 blocker AZ10606120 mitigated renal tubular damage and NLRP3-mediated pyroptosis in the renal cortex of DOCA-salt mice. Similarly, in mTECs, finerenone suppressed Aldo-induced ATP release and PANX1 upregulation. A luciferase assay confirmed the binding site of MR to the PANX1 transcription promoter. Coculture of BMDMs with mTECs under Aldo stimulation significantly increased NLRP3-mediated BMDM pyroptosis and migration. However, these effects were reversed by treating the mTECs with MR or PANX1 siRNA. Similar results were observed after treatment with apyrase or AZ10606120 in the coculture system. scRNA-seq analysis further identified the activation of P2X7/NLRP3-related pyroptosis pathway in macrophages from DOCA-salt mice. In conclusion, TECs play a critical role in macrophage pyroptosis in Aldo-induced renal injury. eATP is a key messenger involved in TEC-macrophage crosstalk. PANX1-eATP-P2X7 signaling mediates TEC‒macrophage interactions to exacerbate Aldo-driven renal inflammation in hypertension. Mechanism through which Aldo/MR-induced PANX1-eATP-P2X7 signaling activation promotes macrophage pyroptosis in hypertensive renal injury.

AimsCoronary microvascular dysfunction (CMD) is a crucial prognostic indicator in chronic coronary syndrome (CCS) patients. The stress hyperglycemia ratio (SHR), a novel biomarker of acute hyperglycemia, has demonstrated predictive value for adverse outcomes in various diseases. However, its association with CMD remains unclear. This study aims to evaluate the prognostic role of SHR in predicting CMD outcomes in CCS patients.MethodsCCS patients who underwent coronary angiography (CAG) were included. Microvascular function was assessed using coronary angiography-derived index of microcirculatory resistance (caIMR), with CMD defined as caIMR > 25U. Patients were divided into three groups based on SHR values: T1 (SHR < 0.73), T2 (SHR 0.73–0.80), and T3 (SHR≥0.80). The primary endpoint was major adverse cardiac events (MACE).Results379 CCS patients were included, among which 196 were identified with CMD. The CMD group exhibited higher SHR levels. During a mean follow-up of 32.9 months, 53 MACE events occurred in CMD patients, with a higher incidence in the T3 group compared to the T1/T2 groups (37.681% vs. 16.667% vs. 26.230%, P = 0.023). SHR was identified as an independent predictor of CMD (OR 7.379, 95% CI: 1.305–41.725, P = 0.024). The T3 group demonstrated a 2.325-fold increased risk of MACE (HR 2.325, 95% CI: 1.228–5.033, P = 0.011), with a non-linear relationship observed between SHR and MACE (P for non-linear < 0.001).ConclusionsElevated SHR is associated with adverse outcomes and predicts MACE in CMD patients with CCS. These results highlight the potential of SHR as a valuable tool for early risk stratification and prevention in CMD management.Trial RegistrationClinicalTrials.gov, NCT06698432 (Registration Date: November 19, 2024)

Heart failure (HF) due to left ventricular (LV) dysfunction remains a major global health challenge, with inflammation driving its progression under chronic pressure overload, such as hypertension. This study explored the role of interleukin-22 (IL-22), a cytokine associated with tissue protection, in HF induced by transverse aortic constriction (TAC). IL-22 knockout (KO) mice exhibited exacerbated HF, marked by worsened LV hypertrophy, heightened inflammation, and impaired cardiac function compared to wild-type controls. Conversely, treatment with recombinant IL-22Fc improved LV function, reduced inflammatory cell infiltration, and alleviated cardiac remodeling and inflammation. These findings demonstrate that IL-22 plays a critical role in regulating inflammation and cardiac remodeling in pressure overload-induced HF. Targeting IL-22 may represent a promising therapeutic strategy to alleviate HF progression and associated pulmonary complications.

Background Strain assessed by cardiac magnetic resonance (CMR) is a key prognostic indicator in myocardial infarction. However, the strain characteristics and prognostic value in myocardial infarction with nonobstructive coronary arteries (MINOCA) with different causes are unclear. This study aims to describe left atrial (LA) and left ventricular strain in patients with MINOCA and evaluate their predictive value for major adverse cardiovascular events (MACEs) in “true MINOCA” cases. Methods and Results This single‐center retrospective study included patients suspected of myocardial infarction who completed CMR during hospitalization. CMR images were used to obtain LA and left ventricular strain via CMR feature tracking. True MINOCA was defined by evidence of ischemia or infarction on CMR. MACEs included all‐cause death, recurrent myocardial infarction, stroke, heart failure, atrial fibrillation, and angina pectoris. This study included 386 patients, with a median time from admission to CMR of 4 days. LA and left ventricular strains varied by pathogenesis, with the lowest strain in patients with cardiomyopathy. For patients with true MINOCA, Cox regression showed that global longitudinal strain (hazard ratio [HR], 0.90 [95% CI, 0.82–0.99]; P=0.022) and LA reservoir strain (HR, 0.95 [95% CI, 0.91–0.99]; P=0.014) were independently associated with MACEs. Kaplan–Meier analysis indicated that patients with LA reservoir strain ≤21.25% or global longitudinal strain ≤16.4% had a significantly higher MACE risk (P<0.001). Integrating global longitudinal strain and LA reservoir strain improved MACE prediction. Conclusions LA and left ventricular strains vary among MINOCA pathogeneses. In true MINOCA patients, global longitudinal strain and LA reservoir strains independently predict MACE risk. Integrating these strains enhances MACE prediction. Registration URL: https://www.clinicaltrials.gov; Unique Identifier: NCT06502899.

Heart failure (HF) continues to pose a significant global health burden, necessitating accurate prognostic tools to guide patient management. This mini-review presents grading systems, frailty scales, and scoring models, followed by challenges and future directions. We traces the evolution of stratification and prognostic assessments in HF, beginning with the foundational NYHA functional classification and progressing to the advanced prognostic scores currently in use. We examine the historical significance and clinical relevance of NYHA grades, which have long been pivotal in evaluating HF severity. The review then shifts focus to contemporary prognostic scores, including the Seattle Heart Failure Model (SHFM), the Heart Failure Survival Score (HFSS), and emerging tools leveraging machine learning (ML) and big data. We explore specific challenges encountered in current clinical practice and outline future directions. By highlighting the strengths and limitations of these tools, this mini-review aims to provides a critical appraisal of stratification and scoring models for HF to inform their optimal application in clinical practice, ultimately enhancing patient care and outcomes in HF.

Contrast-induced acute kidney injury (CI-AKI) is a common complication of percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) patients. Our aim was to assess the lymphocyte to C-reactive protein ratio (LCR) to predict CI-AKI in patients with acute STEMI. A total of 777 patients with STEMI undergoing primary PCI were continuously included in this study. The occurrence of CI-AKI was monitored during the follow-up period for all patients. Logistic regression analysis was employed to assess the relationship between LCR and CI-AKI. Furthermore, ROC analysis was conducted to establish the optimal LCR cut-off value for the prediction of CI-AKI. The incidence of CI-AKI after PCI was 12.2

Background Infarct size (IS) and microvascular obstruction (MVO), measured by cardiovascular magnetic resonance, are key prognostic markers after myocardial infarction (MI). The index of microcirculatory resistance (IMR) predicts MVO and IS; however, its role in MI with nonobstructive coronary arteries (MINOCA) is unclear. This study explored the relationship between coronary angiography‐derived IMR, MVO, and IS in true MINOCA and assessed the prognostic value of coronary microvascular dysfunction (CMD), IS, and MVO. Methods Patients with suspected MINOCA who completed cardiovascular magnetic resonance and coronary angiography‐derived IMR were included. CMD was defined as coronary angiography‐derived IMR >25, and IS as a percentage of left ventricular mass (IS%LV) measured by late gadolinium enhancement. True MINOCA was identified by cardiovascular magnetic resonance evidence of ischemia or infarction. Individuals with true MINOCA were divided into 3 groups: non‐CMD and IS%LV <16.78%, CMD or IS%LV ≥16.78%, and CMD with IS%LV ≥16.78%. Follow‐up for major adverse cardiovascular events was conducted. Results Of 317 patients, 102 had true MINOCA (91.2% non–ST‐segment–elevation MI). CMD was similarly distributed across all suspected MINOCA. Coronary angiography‐derived IMR did not predict MVO or IS among true MINOCA. Over a median 27 months, 33.3% of patients with true MINOCA experienced major adverse cardiovascular events, with a higher risk in patients with CMD or IS%LV ≥16.78%. Multivariate Cox analysis revealed that CMD combined with IS%LV ≥16.78% had a hazard ratio (HR) of 7.40 (95% CI, 1.94–28.23), and either CMD or IS%LV ≥16.78% had an HR of 8.77 (95% CI, 2.57–29.94), but MVO did not. Sensitivity analyses excluding ST‐segment–elevation MI supported these findings. Conclusions CMD with larger IS strongly predicts major adverse cardiovascular events in MINOCA, underscoring their utility in risk stratification, especially for non–ST‐segment–elevation MI. REGISTRATION URL: https://clinicaltrials.gov. Unique identifier: NCT06502899.

Light chain deposition disease (LCDD) is a clonal plasma cell disorder characterized by the deposition of nonamyloid monoclonal light chains in multiple organs. It can affect various systems throughout the body, mainly the kidneys. Symptoms may include renal insufficiency, proteinuria, hematuria, and others. Due to the lack of effective treatment, LCDD patients with kidney involvement often progress to chronic kidney failure, ultimately requiring renal replacement therapy. Daratumumab, an anti-CD38 monoclonal antibody, is primarily used for the treatment of relapsed and refractory multiple myeloma. Recent studies have shown that daratumumab also has an encouraging effect on light-chain amyloidosis. Here, we report the case of an LCDD (κ chain) patient with proteinuria, renal insufficiency, and anemia who was followed up for 3 years, during which he received daratumumab treatment. After the daratumumab treatment, the hematologic response continued progressing to a complete response without any adverse effects and continuous renal function improvement at a low serum free light chain (sFLC) level. This case shows that daratumumab is effective at treating LCDD. For LCDD patients with kidney involvement, frequent monitoring and active control of free light chain levels are necessary, as reaching the lowest sFLC of < 20 mg/L may help to improve kidney function.

BACKGROUND AND AIMS:Stress hyperglycemia ratio (SHR) and pan-immune-inflammation value (PIV) are novel prognostic markers associated with metabolic changes and chronic inflammation, but their association with mortality risk in individuals with overweight and obesity remains unknown. We aimed to investigate impact of SHR and PIV on mortality risk in individuals with overweight and obesity. METHODS AND RESULTS:This cohort study included 16,703 U S adults with overweight and obesity. SHR and PIV were estimated, and Cox regression, ROC, and Kaplan-Meier curves analyzed their associations with all-cause and cause-specific mortality. Subgroup and interaction analyses tested SHR and PIV consistency. Over a median follow-up of 110 months, there were 2432 all-cause deaths (14.6 %), including 677 cardiovascular, 577 cancer, and 130 cerebrovascular deaths. Participants were categorized by optimal SHR (≥1.038 or <1.038) and PIV (≥301 or <301) cutoffs. High SHR was associated with higher overall and cause-specific mortality (log-rank p < 0.001). High PIV was linked to increased risks of overall, cardiovascular, and cancer mortality (log-rank p < 0.001). Multivariate Cox models showed elevated SHR was associated with increased all-cause, cardiovascular, and cancer mortality (HR:1.59; 95%CI: 1.34-1.89; HR:1.45; 95%CI: 1.03-2.04; HR:1.66; 95%CI: 1.15-2.38, respectively). Elevated PIV was linked to higher all-cause and cardiovascular mortality (HR: 1.18; 95%CI: 1.02-1.37; HR:1.35; 95%CI: 1.02-1.79, respectively). Poorer survival was noted in obesity + high SHR and overweight + high PIV subgroups (log-rank p < 0.001). CONCLUSIONS:Elevated SHR and PIV are significant predictors of increased all-cause and cause-specific mortality in individuals with overweight and obesity.

Macrophages are key players in the pathology of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Existing studies and our previous studies have documented the role of CD206-positive M2 macrophages in the inflammatory process of AAV. Inflammasome activation is a critical pathway through which macrophages release inflammatory factors. In this study, we investigate the role of the inflammasome in macrophages in AAV and explore the role of CD206 in this process. We recruit newly diagnosed AAV patients and disease controls from our department. The expression and localization of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) and CD206 in the kidney are determined via immunofluorescence experiments. Myeloperoxidase (MPO)-ANCA immunoglobulin G (MPO-ANCA IgG) is purified from new-onset AAV patients with MPO-ANCA and used to treat lipopolysaccharide (LPS)-primed macrophages in vitro. Our findings reveal that NLRP3 expression is significantly elevated in the kidneys of active AAV patients, accompanied by increased cleaved caspase-1 and N-terminal gasdermin-D (GSDMD) levels in peripheral blood mononuclear cells (PBMCs). In vitro, MPO-ANCA IgG induces NLRP3 inflammasome activation and interleukin (IL)-1β production in macrophages, which is associated with increased MPO expression and JNK signaling pathway activation. Immunofluorescence analysis demonstrates partial colocalization of CD206 and NLRP3 in AAV kidneys. Furthermore, silencing of MRC1 gene, which encodes CD206, reduces inflammasome activation induced by MPO-ANCA IgG. In conclusion, our study provides evidence that MPO-ANCA IgG contributes to NLRP3 inflammasome activation and macrophage pyroptosis, with CD206 playing a critical role in this process. These findings elucidate the mechanisms underlying inflammation in AAV and suggest potential therapeutic targets.

Porcine deltacoronavirus (PDCoV), a newly discovered intestinal coronavirus, has rapidly spread among pigs worldwide and has shown the potential for cross-species infection. However, the interaction mechanism between PDCoV and the host’s antiviral response is still poorly understood. In this study, an E3 ubiquitin ligase FBXW8 was explored on PDCoV proliferation. Our findings demonstrate that PDCoV infection increases the expression of FBXW8 through p65-mediated activation of its promoter. We also discovered that FBXW8 suppresses PDCoV replication by directly targeting and inducing the degradation of the PDCoV-encoded nucleocapsid (N) protein. Interestingly, FBXW8 catalyzes the K48-linked polyubiquitination of the PDCoV N protein at a unique lysine-rich region (KR). Furthermore, we observed that the FBXW8-ubiquitinated PDCoV N protein interacts with NDP52, a cargo receptor, leading to autophagic degradation instead of proteasomal degradation. In summary, these findings reveal FBXW8 as a novel host antiviral factor involved in PDCoV infection. It mediates the NDP52-dependent autophagic degradation of the PDCoV N protein. These results provide new insights and a potential target for host defenses against PDCoV.

Background The atherogenic index of plasma (AIP) is linked to lipid metabolism and has shown considerable prognostic value in cardiovascular disorders. However, its role in myocardial infarction with non-obstructive coronary arteries (MINOCA) has not been investigated. We assessed the relationship between AIP, the severity of coronary stenosis, and prognosis in MINOCA. Methods We included consecutive patients who were diagnosed with MINOCA. AIP was calculated using the base 10 logarithm of the ratio between the levels of TG and HDL-C. The patients were divided into four groups based on their AIP quartiles: Q1 (AIP<-0.145), Q2 (AIP≥-0.145and≤0.049), Q3 (AIP>0.049and≤0.253), and Q4 (AIP>0.253). All patients underwent follow-up for MACE. Results The final analysis included 421 patients, with 188 having normal coronaries (0 stenosis) and 233 exhibiting non-obstructive coronary artery disease (CAD) (<50 % stenosis). In the multivariate logistic analysis, highest AIP (Q4) group was significantly associated with increased risk of non-obstructive CAD in MINOCA (OR,1.994;95 % CI:1.075–3.698; P = 0.029). During the follow-up period, MACE occurred in 22.8 % of MINOCA patients. Q4 group exhibited a significantly higher rate of MACE (P = 0.021). Furthermore, when both AIP and coronary stenosis status were considered, the results revealed individuals in the Q4 group with non-obstructive CAD had the highest risk of MACE (log-rank P = 0.027). The adjusted Cox analysis indicated that the Q4 group was associated with a 2.052-fold increase in the HR of MACE. Conclusion AIP exhibits a notable association with the incidence of MACE in MINOCA patients and serves as a substantial marker for non-obstructive CAD in this patient group.

Objectives: Early-famine exposure was reported to be associated with metabolic associated fatty liver disease (MAFLD); however, it has not been fully elucidated whether the gene-famine interaction exist in this association. We aimed to investigate the association between early-life famine exposure in different genetic risk stratifications and the risk of MAFLD in adulthood. Design, setting, participants, and measurements: The study included 8213 participants from the SPECT-China study. Famine exposure subgroups was defined according to the birth year. A genetic risk score (GRS) was constructed with single nucleotide polymorphisms associated with MAFLD in East Asians. Logistic models were used to examine the association of famine exposure and GRS with MAFLD. Results: Early-life famine exposure was positively associated with MAFLD after adjusting for multiple confounders (OR (95% CI): fetal-exposure 1.3(1.11−1.53), childhood exposure 1.12(1−1.25)). Meanwhile, with per SD increment of GRS (2.49 points), the OR(95%CI) of MAFLD was 1.1(1.04−1.16). In high GRS group, fetal-exposure was positively associated with 45% higher risk of MAFLD (1.45(1.15–1.83)). In men, neither in low or high GRS subgroups observed an association between early-life famine exposure and MAFLD. But in women with high GRS of MAFLD, fetal-exposure was positively associated with even higher risk of MAFLD (1.64(1.22–2.22)). Conclusion: The positive association between early-life famine exposure and MAFLD is intensified by high genetic susceptibility of MAFLD in women and in general population in China; while this association does not exist in men or in those with low genetic risk scores.

Background Recent studies highlighted that stress hyperglycemia ratio (SHR) is a potential predictor for future risk in heart failure (HF) patients. However, its implications specifically in HF with preserved ejection fraction (HFpEF) are not yet fully elucidated. We aimed to investigate the association between SHR and long-term clinical outcomes in HFpEF patients. Methods HFpEF patients enrolled between 2015 and 2023, were followed (mean 41 months) for a composite outcome of all-cause, cardiovascular mortality, and HF rehospitalization. SHR was established as the ratio of acute-chronic glycemia from admission blood glucose and glycated hemoglobin. The optimal cut-off for SHR to predict outcomes based on event prediction was determined through ROC analysis, and the cutoff was identified at 0.99. The effect of SHR on adverse risk was examined through the Cox hazards and Kaplan-Meier survival methods. A Pearson correlation analysis was conducted to assess the relationship between SHR and the severity of HF, as indicated by N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Furthermore, the incremental prognostic value of SHR was further assessed by the integrated discrimination improvement (IDI) and the net reclassification improvement (NRI). Results Among the 400 enrolled patients, 190 individuals (47.5%) encountered composite events over the 41-month follow-up period. SHR was significantly elevated in patients with events compared with those without ( p < 0.001). All patients were stratified into high SHR ( n = 124) and low SHR ( n = 276) groups based on the SHR cutoff. The high SHR group had a significantly higher incidence of adverse events than the low SHR group (log-rank; p < 0.001). Additional analysis indicated a poorer prognosis in patients with low left ventricular EF (LVEF) levels (50 < LVEF < 60) and high SHR (SHR > 0.99) in comparison to the other groups (log-rank p < 0.001). In adjusted analysis, after accounting for age, sex, diabetes, and NT-proBNP, elevated SHR remained independently predictive of adverse outcomes (adjusted HR: 2.34, 95% CI 1.49–3.67; p < 0.001). Furthermore, adding SHR to a model with MAGGIC score provided an incremental improvement in predicting adverse events. Additionally, SHR displayed a slight correlation with NT-proBNP. Conclusion Elevated SHR was independently associated with an increased risk for composite events of all-cause, cardiovascular mortality, and HF readmission than those with lower SHR. SHR is a valuable tool for predicting and stratifying long-term adverse risks among HFpEF patients.

ABSTRACT Background This study investigates the link between genetic variants associated with kidney function and immunoglobulin A (IgA) nephropathy (IgAN) progression. Methods We recruited 961 biopsy-proven IgAN patients and 651 non-IgAN end-stage renal disease (ESRD) patients from Ruijin Hospital. Clinical and renal pathological data were collected. The primary outcome was the time to ESRD. A healthy population was defined as estimated glomerular filtration rate >60 mL/min/1.73 m2 without albuminuria or hematuria. Fifteen single-nucleotide polymorphisms (SNPs) were selected from a genome-wide association study of kidney function and genotyped by the SNaPshot. Immunohistochemistry in renal tissue and ELISA in urine samples were performed to explore the potential functions of genetic variations. Results The rs77924615-G was independently associated with an increased risk for ESRD in IgAN patients after adjustments for clinical and pathologic indices, and treatment (adjusted hazard ratio 2.10; 95% confidence interval 1.14–3.88). No significant differences in ESRD-free survival time were found among different genotypes in non-IgAN ESRD patients (log-rank, P = .480). Moreover, rs77924615 exhibited allele-specific enhancer activity by dual-luciferase reporter assay. Accordingly, the urinary uromodulin–creatinine ratio (uUCR) was significantly higher in healthy individuals with rs77924615 AG or GG than in individuals with AA. Furthermore, uromodulin expression in tubular epithelial cells was higher in patients with rs77924615 AG or GG. Finally, we confirmed that an increased uUCR (P = .009) was associated with faster IgAN progression. Conclusion The SNP rs77924615, which modulates the enhancer activity of the UMOD gene, is associated with renal function deterioration in IgAN patients by increasing uromodulin levels in both the renal tubular epithelium and urine.