Eicosanoids are a diverse family of oxygenated derivatives of 20-carbon polyunsaturated fatty acids that play crucial roles in maintaining cardiovascular homeostasis. The metabolic profiles of eicosanoids preceding the onset of severe preeclampsia remain incompletely understood. This study aimed to use a targeted metabolomic approach to identify eicosanoid metabolites in first-trimester blood samples and assess their potential to predict severe preeclampsia. Within a prospective cohort of 5,809 pregnant women, a nested case-control study analyzed 45 participants who later developed severe preeclampsia and 41 controls with uncomplicated pregnancies. Targeted metabolomic analysis was performed using Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS). Metabolomic data were examined, and predictive performance of these metabolites was evaluated using receiver operating characteristic curves. Among 40 eicosanoids metabolites quantified, 10 metabolites differed statistically between the severe preeclampsia and control groups. Specifically, metabolites in the cyclooxygenase (COX) pathway, such as thromboxane B2 (TXB2), and the 12/15-lipoxygenase (LOX) pathway, such as 14-hydroxy-docosahexaenoic acid (14-HDoHE), were significantly upregulated in the severe preeclampsia group. Conversely, metabolites in the cytochrome P450 (CYP450) pathway, notably 19,20-epoxy-docosapentaenoic acid (19,20-EDP), were significantly downregulated. The 14-HDoHE/19,20-EDP ratio was identified as the most significant predictive marker. Integrating this ratio into the Fetal Medicine Foundation (FMF) screening algorithms significantly improved the area under the curve (AUC) from 0.77 to 0.87 (ΔAUC = 0.10, 95

Lipid nanoparticles (LNPs) are widely used for nucleic acid delivery but often rely on synthetic ionizable cationic lipids that pose concerns regarding immunogenicity, metabolic compatibility, and tolerability. Here, we report an endogenous-metabolite-inspired lipid design strategy in which biogenic polyamines, including agmatine, putrescine, cadaverine, spermidine and spermine, were conjugated with oleic acid to generate polyamine-oleic acid lipids for mRNA delivery. Among these candidates, agmatine-oleic acid (Agm-oa) showed the best overall performance, forming LNPs with high mRNA encapsulation efficiency, uniform particle size distribution and robust in vitro transfection activity. Agm-oa displayed behavior distinct from that of classical ionizable lipids, with strong mRNA association likely mediated by its guanidinium-containing headgroup through electrostatic interactions and hydrogen bonding. Beyond its delivery function, Agm-oa retained bioactivity associated with its agmatine-derived headgroup. Notably, agmatine and other bioactive metabolites released during Agm-oa degradation may suppress nitric oxide (NO) generation in macrophages while enhancing NO production in endothelial cells, suggesting that Agm-oa LNPs may confer anti-inflammatory and vascular protective effects following LNP decomposition. Moreover, Agm-oa LNPs-mediated adenine base editor delivery achieved efficient on-target editing at the PCSK9 locus. In hypercholesterolemic mice, Agm-oa LNPs enabled effective in vivo mRNA delivery and significant reduction of circulating LDL-C. Importantly, Agm-oa LNPs demonstrated a highly favorable safety profile compared to the benchmark formulations, with significantly lower serum LDH and IL-6 levels and minimal immunogenicity, alongside no detectable hepatotoxicity after repeated administration. Therefore, Agm-oa LNPs represent a safe, well-tolerated platform for nucleic acid delivery, with intrinsic bioactivity that may synergistically enhance therapeutic performance.

Background Malnutrition is a prevalent comorbidity in nonvalvular atrial fibrillation (NVAF), yet comparative evidence on oral anticoagulants in this vulnerable population is scarce. Objectives We aimed to compare the safety and effectiveness of dabigatran with those of rivaroxaban in NVAF patients at nutritional risk. Methods This new-user, active-comparator cohort study utilized data from the Tianjin Health and Medical Data Platform (2015-2020). We identified 10,658 NVAF patients (dabigatran n = 1819; rivaroxaban n = 8839) at nutritional risk, defined as a Prognostic Nutritional Index score ≤50. Multivariable Cox proportional hazards models were used to compare the risks of intracranial hemorrhage (ICH), gastrointestinal bleeding, ischemic stroke, and all-cause mortality over a maximum 3-year follow-up. Extensive sensitivity analyses were performed to ensure the robustness of the findings. Results The incidence of ICH was significantly lower in the dabigatran group compared with the rivaroxaban group (0.55% vs 1.27%; hazard ratio [HR], 0.42; 95% CI, 0.22-0.80). This lower risk was particularly evident in patients receiving low-dose regimens (HR, 0.33; 95% CI, 0.16-0.69) and was consistent in short-term analyses. There were no significant differences between the 2 groups in the risks of gastrointestinal bleeding (HR, 0.99; 95% CI, 0.72-1.35), ischemic stroke (HR, 1.06; 95% CI, 0.86-1.31), or all-cause mortality (HR, 0.93; 95% CI, 0.80-1.09). Conclusion In NVAF patients at nutritional risk, dabigatran was associated with a lower risk of ICH compared with rivaroxaban, without compromising effectiveness.

Background: Current diagnostic criteria for metabolic syndrome (MetS) may inadequately capture underlying metabolic heterogeneity and associated risks. Identifying cardiometabolic phenogroups with prognostic relevance could improve risk stratification. Methods: Latent class analysis (LCA) was used to identify cardiometabolic phenogroups in a discovery cohort (RESET; n=1,034), using the 6 conventional MetS measures, and 8 additional indicators, BMI defined obesity, visceral adiposity, hepatic steatosis, elevated LDL cholesterol, HbA1c, hsCRP, hyperuricemia, and insulin resistance (IR). A decision tree model was constructed using the most important indicators to enable practical phenogroup classification and facilitate external validation. External validation was conducted in three independent cohorts – PICMAN (n = 120), UK Biobank (n = 344,817), and CHARLS (n = 12,145) – analysing for molecular signatures and prognostic associations across the identified phenogroups. Findings: Five latent phenogroups were identified in the discovery cohort: Metabolically Preserved with and without isolated hypertension (each n=244; 23.6%), Lean-Insulin Resistant (IR) (n=140; 13.5%), Obese-Insulin Sensitive (IS) (n=211; 20.4%), and Obese-IR (n=195; 18.9%). Lean-IR and Obese-IS showed discordant adiposity and insulin/glycemic status, and a low prevalence of MetS (21.4% and 31.3%, respectively), whereas MetS was high (75.9%) only in the Obese-IR group. A decision tree model using four binary indicators (visceral adiposity, IR, elevated SBP, and HbA1c) accurately classified individuals into the five latent phenogroups and was subsequently used for external validation. Validation in PICMAN highlighted higher liver fat (Mean 9.0% [SD 6.3%]) in Lean-IR versus Metabolically Preserved (Mean 2.8% [SD 1.8%], P=0.002). Plasma proteomic analyses further reflected unique metabolic–inflammation signatures across the 5 groups. Validation in the UK Biobank showed significant associations between the latent phenogroups with the composite outcome of myocardial infarction and stroke. HRs after adjusting for age and sex were 1.52 (95% CI, 1.43-1.61) for isolated hypertension, 1.86 (1.75-1.98) for Lean-IR, 1.85 (1.75-1.97) for Obese-IS, and 2.75 (2.56-2.95) for Obese-IR, compared with the Metabolically Preserved group. Interpretation: Expanded cardiometabolic risk factors suggest metabolic heterogeneity beyond the current MetS criteria. Incorporating visceral adiposity and IR into a novel classification system may improve precision risk stratification and management of cardiometabolic disease.

Objectives To identify multifactorial contributors to treatment-seeking delays among Chinese young and middle-aged stroke patients using socioecological model.Design Descriptive phenomenological interview study.Setting A tertiary hospital in China.Participants Twenty acute stroke patients with treatment-seeking delays and 16 family members were recruited for dyadic semistructured interviews.Primary and secondary outcome measures Barriers influencing treatment-seeking delays across individual, interpersonal and systemic levels. And how do interlevel interactions shape decision-making trajectories?Results Data analysis revealed 5 overarching themes encompassing 12 subthemes: (1) limited stroke-specific health literacy; (2) psychological barriers at symptom onset; (3) inadequate interpersonal support systems; (4) structural impediments to timely care; (5) decision-making dynamics across levels. Delay was characterised as a sequential cascade mediated by cognitive misattribution, emotional paralysis, relational dependency, institutional constraints and cross-level feedback loops. Two dominant pathways, silent progression and diverted seeking, were identified.Conclusion Treatment-seeking delay among young and middle-aged stroke patients arises through dynamic interactions across socioecological strata rather than isolated factors. Integrated interventions targeting public awareness, familial preparedness, workplace policies and healthcare accessibility are required to disrupt this cascade.

BACKGROUND To examine how mid-trimester systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels, considered both independently and jointly, are associated with individual and co-occurring adverse pregnancy outcomes (APOs).METHODS We analyzed two cohorts from northern and southern China, consisting of 78,891 singleton pregnancies. Mid-trimester (20-28 weeks' gestation) SBP and DBP were evaluated as qualitative classifications (isolated systolic, isolated diastolic, and systolic-diastolic hypertension) and quantitative measurements (levels of SBP/DBP and pulse pressure). Using two-dimensional SBP-DBP heat maps, we assessed their associations with major APOs (gestational diabetes mellitus [GDM], preterm birth, small for gestational age [SGA], postpartum hemorrhage [PPH], placental abruption [PA], and severe preeclampsia) by latent class analysis (LCA).RESULTS LCA identified four latent APO classes: (1) preterm placental dysfunction, with 100% preterm birth, 26.6% SGA, 21.4% GDM and 13.2% severe preeclampsia, associated with concurrent SBP-DBP association (SBP+/DBP+); (2) term placental dysfunction, with 44.0% PPH, 34.0% PA, 25.2% severe preeclampsia and no preterm birth, associated with DBP elevation (DBP+); (3) term GDM, with 100% probability for GDM, no preterm birth and minimal other APOs, associated with SBP elevation (SBP+) and wider pulse pressure; (4) term SGA, with 100% SGA, 16.2% GDM and no preterm birth, associated with a divergent changes in SBP and DBP (SBP-/DBP+) and narrower pulse pressure.CONCLUSIONS Mid-trimester SBP and DBP interact in distinct patterns to influence co-occurring APO risks. This study demonstrates the independent and joint influence of BP components on risk, emphasizing the role of BP stratification in guiding pregnancy management strategies.

INTRODUCTION:Patients with chronic kidney disease (CKD) are at a high risk of adverse outcomes after acute myocardial infarction (AMI); however, evidence on long-term outcomes after percutaneous coronary intervention (PCI) in this population remains limited. METHODS:This prospective cohort study, nested within the Kailuan Study, included patients with CKD who experienced AMI between 2006 and 2020. Participants were classified into PCI and non-PCI groups based on documented PCI receipt and were matched 1:2 on age and sex (452 PCI; 745 non-PCI). Follow-up began at the time of AMI diagnosis or PCI and continued until December 31, 2023. The primary outcome was all-cause mortality, with secondary outcomes being new-onset heart failure and CKD progression. Time-segmented Cox models were used for all-cause mortality, and standard Cox models were used for secondary outcomes. RESULTS:During follow-up, PCI receipt was associated with a lower risk of all-cause mortality compared with no PCI. The association was stronger during the first 5 years of follow-up (hazard ratio [HR], 0.34; 95% confidence interval [CI], 0.24-0.47) and was attenuated thereafter (HR, 0.73; 95% CI, 0.51-1.04). No significant associations were observed between PCI receipt and either new-onset heart failure (HR, 1.06; 95% CI, 0.72-1.57) or CKD progression (HR, 1.11; 95% CI, 0.72-1.71). CONCLUSION:In patients with CKD and AMI, PCI was associated with lower all-cause mortality during the first 5 years of follow-up, with no significant differences in new-onset heart failure or CKD progression.

Abstracts Background Cardiometabolic disease is heterogeneous and incompletely resolved by conventional classification. We aimed to use expanded variables to identify data-driven phenogroups and characterise their echocardiographic and proteomic features. Methods Latent class analysis was applied to a discovery cohort (RESET; n=1,034) using fourteen cardiometabolic variables. A decision tree model was constructed using the most important variables to enable practical phenogroup classification and facilitate external validation. External validation used three cohorts: PICMAN (n = 120, proteomics), the UK Biobank (n = 344,817, proteomics and outcomes) and CHARLS (n = 12,145, outcomes). Results Five latent phenogroups were identified: Metabolically Preserved (lowest burden of adiposity, insulin resistance and hyperglycemia), with and without hypertension (each n=244; 23.6%); Lean-Insulin Resistant (IR) (n=140; 13.5%); Obese-Insulin Sensitive (IS) (n=211; 20.4%); and Obese-IR (n=195; 18.9%). Although Lean-IR and Obese-IS showed discordant adiposity and insulin/glycemic status, both exhibited greater subclinical diastolic dysfunction (36.7% and 38.8%, respectively) than the Metabolically Preserved group (16.5%; P<0.001), with impaired global longitudinal strain more prominent in Obese-IS (22.5% vs 13.6%; P<0.001). A decision tree model nominated four variables as most discriminative for the phenogroups (visceral adiposity, IR, elevated SBP, and HbA1c), classifying individuals with an AUC of 0.84 (0.81-0.86), and was used for external validation. Validation in the PICMAN cohort using plasma proteomes showed signatures for the two discordant phenotypes: an inflammatory emphasis in Lean-IR (IL-6, PLCB2) and a stronger hepatic metabolic/injury signature in Obese-IS (ADH4, KRT8/KRT18), upon a shared insulin–endocrine core in both (LEP, IGFBP1, FGF21). In the UK Biobank, phenogroups assigned using surrogates for visceral adiposity and IR (waist circumference and TG:HDL-C ratio) replicated the proteomic signature, and were associated with incident myocardial infarction and stroke. Hazard ratios for the composite outcome after adjusting for age and sex were 1.86 (1.75-1.98) for Lean-IR, 1.85 (1.75-1.97) for Obese-IS, and 2.75 (2.56-2.95) for Obese-IR, compared with the Metabolically Preserved group. Conclusion Data-driven classification with expanded variables reveals underlying heterogeneity. Phenogroups with discordant adiposity and insulin/glycemic status are associated with subclinical cardiac dysfunction, but differ in their proteomic pathways. The inferred divergent biology implies that individuals of different phenogroups may benefit from differing targeted prevention. Condensed Abstract Cardiometabolic disease is heterogeneous and incompletely resolved by conventional classification. Using latent class analysis, we identified five phenogroups, including two discordant phenotypes: lean insulin-resistant (Lean-IR) and obese insulin-sensitive (Obese-IS). Despite opposite adiposity, both had a higher prevalence of subclinical cardiac dysfunction than metabolically preserved individuals. Plasma proteomics, validated in the PICMAN cohort, showed an inflammatory signature in Lean-IR and a stronger hepatic metabolic/injury signature in Obese-IS, on a shared insulin–endocrine core. In the UK Biobank, both phenotypes carried a similarly elevated CVD risk, showing that this convergent risk can arise from divergent biology, with implications for precision prevention. Graphic Abstract BMI, body mass index; WC, Waist circumference; TG, Triglyceride; LDL-C, Low density lipoprotein cholesterol; HDL-C, High density lipoprotein cholesterol; FPG, Fasting plasma glucose; HbA1c, Glycated Hemoglobin A1c; HOMA-IR, Homeostatic Model Assessment of Insulin Resistance; SBP, systolic blood pressure; DBP, diastolic blood pressure; DD, Diastolic dysfunction; GLS, Global longitudinal strain; MI, myocardial infarction

The association between maternal morning blood pressure (BP) levels and adverse pregnancy outcomes (APOs), including severe preeclampsia, target organ damage, preterm birth, placental abruption, postpartum hemorrhage, small-for-gestational-age infants, and pregnancy loss, is not well understood. In a retrospective cohort study of 1833 high-risk singleton pregnancies with outpatient ambulatory BP monitoring, 26.7% had morning hypertension. Morning BP strongly correlated with non-morning daytime BP (Pearson r = 0.89) and nighttime BP (r = 0.78), but only moderately with office BP (r = 0.54). Compared to office BP, adding morning BP improved diagnostic accuracy for nighttime, masked, and non-morning daytime hypertension (Δ area under the curve 0.062 to 0.127, all P < 0.001). A J-shaped, non-linear association was observed between morning BP and the risk of composite APOs, with identified thresholds at systolic/diastolic BP ≥ 132/79 mmHg. Isolated morning hypertension, compared to isolated nighttime or non-morning daytime hypertension, did not independently increase composite APO risk. However, co-occurrence of morning hypertension with nighttime (odds ratio [OR] 3.16, 95% confidence interval [CI]: 2.34 to 4.27) or non-morning daytime (OR 3.41, 95% CI: 2.54 to 4.60) hypertension amplified the risks for APOs. The strongest association between co-occurring morning and nighttime hypertension and APO risk was observed between 28+6 and 34+6 weeks of gestation (OR 5.50, 95% CI: 2.13 to 7.43). Sensitivity analyses with alternative morning time windows and adjustments for non-morning mean arterial pressure consistently confirmed these findings. Our findings support morning BP measurement as a valuable and practical marker for screening and identifying high-risk BP patterns during pregnancy.

BACKGROUND:Emerging evidence suggests that sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce cardiovascular events in patients with diabetes mellitus (DM) after acute myocardial infarction (AMI), but evidence in Asian populations remains limited. OBJECTIVE:We assessed the impact of SGLT2 inhibitors on in-hospital, 30-day, and 30-day to 1-year mortality in a Northern Chinese real-world cohort. METHODS:An electronic health record-based cohort was constructed from the Tianjin Health and Medical Data Platform from January 2013 to December 2022. Statistical analyses, including Kaplan-Meier survival analysis, multivariable regression analysis, and propensity score matching, were undertaken to evaluate the impact of SGLT2 inhibitors on in-hospital, 30-day, and 1-year mortality rates. RESULTS:A total of 23,486 patients with both AMI and DM were included. Patients treated with SGLT2 inhibitors (n = 5053) were younger (64.2 vs 67.2 years) and had a higher frequency of dyslipidemia (26.4% vs 18.5%) and history of percutaneous coronary intervention (17.1% vs 15.3%) than those who did not receive them. After multivariable adjustment, the use of SGLT2 inhibitors showed a lower mortality rate during hospitalization (odds ratio 0.44; 95% confidence interval [CI] 0.33-0.58), at 30 days (hazard ratio 0.44; 95% CI 0.36-0.53), and at 30 days to 1 year (hazard ratio 0.86; 95% CI 0.73-1.00). These findings were further supported by propensity score matching and subgroup analyses, which consistently confirmed the reduction in mortality across all three time points. CONCLUSION:In a real-world electronic health record-based cohort in China, this study confirmed a mortality benefit with the use of SGLT2 inhibitors in patients with combined DM and AMI. Further studies are needed to validate these benefits across broader populations.

Background and purpose: Direct-acting oral anticoagulants (DOACs) therapy reduces ischemic stroke (IS) risk but increases the risk of intracranial hemorrhage (ICH). Evidence regarding the safety of low low-density lipoprotein cholesterol (LDL-C) levels in patients undergoing DOACs therapy is limited. This study aimed to assess the dose-response relationship between LDL-C levels and ICH risk in patients on DOACs therapy. Methods: Using a new-user design, 24,794 DOACs-treated patients were identified from the medical and health data platform of Tianjin, China. During a 3-year follow-up, 188 ICH events, 718 IS events, and 2,472 deaths were recorded. The hazard ratios (HRs) between LDL-C levels and study outcomes were estimated using restricted cubic splines in Cox regression models. Results: A negative, non-linear relationship between baseline LDL-C levels and ICH risk was identified, with higher risk at low LDL-C levels (threshold value: LDL-C <70 mg/dL). After multivariable adjustment, low LDL-C levels were associated with increased ICH risk, reduced IS risk, and no significant impact on all-cause mortality, with the HRs of 1.58, 0.73, and 0.91; 95% confidence interval (95% CI) of 1.11-2.25, 0.59-0.92, and 0.81-1.01; and P values of 0.012, 0.007, and 0.083, respectively. Multiple sensitivity analyses confirmed these findings. Conclusions: LDL-C <70 mg/dL is an independent risk factor for ICH in patients receiving DOACs therapy in this province-wide cohort from China. Additional validation is required to optimize LDL-C targets and DOACs use to balance IS benefits against ICH risks.

OBJECTIVES:The purpose of this study was to verify whether guideline-directed medical therapy (GDMT, ie, the combined use of β-blocker, ACE inhibitor/angiotensin receptor blocker, dual antiplatelet drugs and statin) could improve in-hospital mortality in acute coronary syndrome (ACS) patients with advanced renal dysfunction (estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2). DESIGN:Retrospective cohort study. SETTING:This study used data from two large, multicentre, observational cohorts: the Chinese National Electronic Disease Surveillance System Platform (CNEDSSP) and the Improving Care for Cardiovascular Disease in China-ACS (CCC-ACS) project. These cohorts consist of ACS patients admitted to 47 and 241 hospitals, respectively, across China from 2014 to 2019. PARTICIPANTS:A total of 6260 patients diagnosed with advanced renal dysfunction (eGFR <30 mL/min/1.73 m²) on admission were included in the analysis. Among these, 3013 patients were from the CNEDSSP cohort and 3247 from the CCC-ACS cohort. Patients were categorised based on receipt of GDMT within 24 hours of admission. MAIN EXPOSURE MEASURE:The main exposure measure was the early use of GDMT, defined as the administration of all four components of GDMT within 24 hours of hospital admission. MAIN OUTCOME MEASURE:The primary outcome was in-hospital mortality, assessed within the study cohort. RESULTS:In a pooled analysis of the CNEDSSP and CCC-ACS cohorts, early GDMT was associated with a significant reduction in in-hospital mortality (relative risk (RR): 0.62, 95% CI: 0.47 to 0.81). More pronounced reductions were observed in myocardial infarction (MI) patients, with HRs of 0.31 (95% CI: 0.17 to 0.55) in the CNEDSSP cohort and 0.47 (95% CI: 0.28 to 0.77) in the CCC-ACS cohort. A random-effects pooled analysis of MI patients with advanced renal dysfunction at admission showed a 61% reduction in in-hospital mortality among GDMT users (RR: 0.39, 95% CI: 0.27 to 0.58). CONCLUSIONS:This nationwide study highlights that early GDMT is associated with a reduced risk of in-hospital mortality in ACS patients (particularly in MI patients) with advanced renal dysfunction.

BACKGROUND:The relationship between dyslipidemia, a significant contributor to atherosclerotic cardiovascular disease, and atrial fibrillation remains unclear. This study aims to investigate the impact of remnant cholesterol (RC) on the prognosis of patients with atrial fibrillation on oral anticoagulants. METHODS:A total of 23 267 patients with atrial fibrillation on oral anticoagulants from the Tianjin Health Medical Data Platform in China were identified for the analysis. We categorized participants into RC tertiles and used a multivariate Cox model to evaluate outcomes. Subgroup and sensitivity analyses were used to evaluate the association between RC tertiles and all-cause death. The study analyzed the combined effect of RC and low-density lipoprotein cholesterol on outcomes on the basis of the median levels of both lipids. RESULTS:The top RC tertile (tertile 3) was associated with a 24% increased risk of all-cause death (hazard ratio [HR], 1.24 [95% CI, 1.11-1.38]), 18% increased risk of ischemic stroke (HR, 1.18 [95% CI, 1.00-1.38]), and 35% increased risk of acute myocardial infarction (HR, 1.35 [95% CI, 1.07-1.71]) compared with the bottom RC tertile (tertile 1). A sex-specific interaction was noted for RC and death, with the association appearing more evidently in men. The results remained consistent throughout various sensitivity analyses. This association with RC appeared to persist even when low-density lipoprotein cholesterol levels were relatively low (below the median of 102 mg/dL), showing a 17% increased risk of composite ischemic outcomes (HR, 1.17 [95% CI, 1.01-1.37]). CONCLUSIONS:Higher RC levels in patients with atrial fibrillation receiving oral anticoagulation therapy were associated with an increased risk of death, acute myocardial infarction, and ischemic stroke.

BACKGROUND:Acute myocardial injury is defined by elevated cardiac troponin levels with a rising and/or falling pattern, and is associated with increased mortality risk compared to patients without myocardial injury. The role of β-blockers in patients with acute myocardial injury remains unclear. METHODS:This multicenter, retrospective cohort study used data from the Tianjin Health and Medical Data Platform to assess the impact of early β-blocker use on 1-year all-cause mortality and major adverse cardiovascular events (MACE) in acute myocardial injury patients, employing a new user and target trial emulation design. Propensity score matching was applied, and Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS:After propensity score matching, a total of 25,966 participants were included: 8667 to the β-blocker group and 17,299 to the non-β-blocker group. A total of 4113 deaths (15.8%) and 5795 MACE (22.3%) occurred. Compared with nonusers, β-blocker was associated with the reduced risk of all-cause mortality (HR: 0.89, 95% CI: 0.83-0.95) and MACE (HR: 0.90, 95% CI: 0.85-0.95). In the subgroup analysis, β-blockers were associated with a significantly reduced risk of mortality in patients without stroke (HR 0.85, 95% CI: 0.78-0.93), while no significant association was observed in patients with stroke (HR 1.04, 95% CI: 0.93-1.16). CONCLUSIONS:Early use of β-blockers is associated with the reduced risk of 1-year mortality in patients with acute myocardial injury. To more accurately assess the therapeutic effects, prospective trials are necessary, and these data provide key research directions for future trials.

Background:Hypertension is a critical modifiable risk factor for mortality in the elderly, yet optimal systolic blood pressure (SBP) targets for older adults remain unclear. This study examined the association between SBP trajectories and all-cause mortality in Chinese elderly individuals, aiming to identify age-adjusted SBP ranges for survival benefits. Methods:A population-based prospective cohort study was conducted in Luzhou, China (2017-2023). A total of 390,100 participants aged ≥65 years were followed for 1,994,050 person-years, with 48,013 deaths analyzed. Cox proportional hazards and restricted cubic spline (RCS) Cox regression models were used to evaluate baseline SBP categories, 7-year mean SBP, and longitudinal trajectories (Class 1: ideal to elevated; Class 2: normal-high to elevated; Class 3: mild hypertension to elevated). Results:Baseline SBP: Lowest mortality risk at 100-139 mmHg (HR < 1). 7-year mean SBP: Optimal range at 120-159 mmHg. Trajectories: Class 2 (normal-high to elevated) had the lowest all-cause mortality (HR: 0.90, 95% CI: 0.88-0.92). Class 1 showed the lowest cardiovascular mortality. Class 3 exhibited the lowest non-cardiovascular/cancer mortality. Conclusions:Gradual SBP increases from normal (≤160 mmHg) with age are associated with reduced mortality in the elderly. These findings challenge strict hypertension control guidelines, advocating for age-adjusted SBP targets to optimize survival outcomes. Further validation across different ethnic groups and regions will be needed in the future.