BACKGROUND:Chronic kidney disease (CKD) represents one of the most significant risk factors for adverse cardiovascular events and mortality. Data on real-world clinical practice of Chinese patients with CKD in the cardiology department is limited. OBJECTIVES:This study aims to investigate the proportion of underdiagnosis, guideline-directed therapy and awareness of CKD among Chinese patients. METHODS:It was a multicentre observational study conducted in 25 tertiary hospitals across China. Patients with two consecutive measurements (separated by 90-730 days) of either: (1) estimated glomerular filtration rate 20-60 mL/min/1.73 m², or (2) urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g, with documented cardiology hospitalisation from 2022 to 2024 were eligible. Participants completed a lifestyle and awareness questionnaire after inclusion. The proportion of underdiagnosis, guideline-directed therapy and awareness of CKD was calculated. RESULTS:Among 2099 participants (median age 74.0 years; 64.6% male), 76.7% were underdiagnosed with CKD (lacked a CKD diagnostic code at discharge). Only 16.7% of participants underwent UACR testing and all individuals with isolated albuminuria (UACR >30 mg/g) remained underdiagnosed. Underdiagnosis was more common in patients aged 60-75, those with early-stage CKD, hospital stays <6 days or without comorbidities. The proportion of guideline-directed treatment was suboptimal: sodium-glucose cotransporter-2 inhibitors (36.5%), renin-angiotensin system inhibitors (56.5%) and only 32.2% of patients received guideline-directed treatment. CKD awareness lagged behind hypertension and diabetes, with <25% achieving guideline-recommended blood pressure and glycaemic targets. CONCLUSIONS:Alarmingly high proportion of underdiagnosed CKD, suboptimal guideline-directed treatment, and poor disease awareness of CKD in cardiology practice require urgent action. Closing these gaps is needed to reduce preventable cardiovascular morbidity and mortality.

To evaluate the efficacy and safety of sitokiren (SPH3127) tablet in patients with mild-to-moderate essential hypertension in comparison to valsartan capsule. This multicentre, randomised, double-blind, parallel Phase III trial was designed in 2 stages. In the 1st stage, eligible patients were randomised to receive 50 mg, 100 mg or 200 mg of SPH3127 tablet or 80 mg of valsartan capsule once daily (QD) for 12 consecutive weeks. In the 2nd stage, eligible patients were randomised to receive assigned dose of SPH3127 tablet based on the results from the 1st stage or valsartan 80 mg QD for 12 consecutive weeks. Primary outcome was the change from baseline in mean sitting diastolic blood pressure (msDBP) at Week 12. Safety outcome measures included any adverse events. Exploratory outcomes included plasma concentration of SPH3127, as well as the assessment of the correlation between SPH3127 exposure with the level of renin inhibition, clinical efficacy and occurrence of adverse events. The 1st stage enrolled 189 patients, of which 129 eligible patients were randomised. High plasma renin activity (PRA) inhibitory effect (83

Inflammation is associated with the prognosis of patients with coronary artery disease (CAD). However, the joint association of systemic inflammation and the local inflammation index of the coronary artery in adverse prognosis remains unclear. This study included patients who underwent coronary computed tomographic angiography (CCTA) and were diagnosed with CAD. The pericoronary fat attenuation index (pFAI) represents local inflammation in the coronary arteries and is measured from CCTA images. The primary outcome was major adverse cardiovascular and cerebrovascular event (MACCE). Cox proportional hazards models were used to evaluate the association between systemic inflammation response index (SIRI), pFAI and MACCE, with interaction effects estimated. 560 participants with CAD (mean age: 67.7 ± 10.7 years; 29.1

AIMS:Lipoprotein(a) [Lp(a)] and diabetes mellitus (DM) are independent risk factors for worse outcomes in coronary artery disease (CAD) patients. Evidence of their joint association is limited. We aimed to investigate the combined effect of elevated Lp(a) and DM on survival outcomes in CAD patients. METHODS AND MATERIALS:This study included 65 547 CAD patients (62.6 ± 10.7 years, 27.7% female) from CIN-II and RED-CARPET cohorts. Patients were stratified into four groups by Lp(a) levels (< or ≥ 30 mg/dL) and DM status. Multivariable Cox regression models estimated associations with cardiovascular and all-cause mortality, examining additive and multiplicative interactions. RESULTS:During a median follow-up of 5.5 years, 10 686 (16.3%) patients died from all causes and 5106 (7.8%) died from cardiovascular causes. Patients with Lp(a) ≥ 30 mg/dL and DM were independently associated with cardiovascular mortality (adjusted hazard ratio [aHR]: 1.28, 95% CI: 1.20-1.35; aHR: 1.53, 95% CI: 1.44-1.62, all p < 0.001, respectively). Compared to patients with Lp(a) < 30 mg/dL without DM, the aHRs were 1.26 (95% CI: 1.16-1.36, p < 0.001), 1.51 (95% CI: 1.40-1.62, p < 0.001) and 2.00 (95% CI: 1.83-2.18, p < 0.001) for those with Lp(a) ≥ 30 mg/dL without DM, Lp(a) < 30 mg/dL with DM and Lp(a) ≥ 30 mg/dL with DM, respectively. Significant additive interaction between elevated Lp(a) and DM on cardiovascular mortality was observed, with 12% of the excess risk attributed. Similar associations were observed in all-cause mortality. CONCLUSIONS:In patients with CAD, elevated Lp(a) and DM act synergistically to increase the risk of cardiovascular and all-cause mortality, suggesting that both risks should be considered to integrate management.

BACKGROUND:The novel thin-strut sirolimus-eluting iron bioresorbable scaffold (IBS) demonstrated safety and efficacy in a nonrandomized first-in-human study. OBJECTIVES:The objective of this study was to compare the IBS with contemporary metallic cobalt chromium everolimus-eluting stents (CoCr-EES) in patients with coronary artery disease. METHODS:IRONMAN-II was a prospective, multicenter, single-blinded, noninferiority randomized trial across 36 centers in China. Eligible patients had myocardial ischemia and 1 or 2 de novo target lesions. Patients were randomly assigned (1:1) to IBS or CoCr-EES, with allocation masked. Optical coherence tomography (OCT) was performed in the first 25 participant pairs. Clinical follow-up was scheduled at 1, 6, and 12 months, and annually to 5 years, with angiographic and OCT follow-up at 2 years. The primary endpoint was 2-year angiographic in-segment late lumen loss (LLL). Powered secondary endpoints included target vessel quantitative flow ratio (QFR) and OCT-derived cross-sectional mean flow area. Other secondary endpoints included target lesion failure (cardiac death, target vessel myocardial infarction [MI], or ischemia-driven target vessel revascularization), the patient-oriented composite endpoint (all-cause death, MI, or any revascularization), their individual components, and device thrombosis. RESULTS:Between March 10 and December 13, 2022, 518 patients were randomized to IBS (n = 259) or CoCr-EES (n = 259). At 2 years, lesion-level in-segment LLL was 0.28 (0.52) mm with IBS and 0.23 (0.43) mm with CoCr-EES (difference: 0.08 mm; 95% CI: -0.02 to 0.18; Pnoninferiority = 0.03). Mean QFR was 0.90 (0.13) with IBS and 0.92 (0.09) with CoCr-EES (difference: -0.02; 95% CI: -0.04 to 0; Pnoninferiority = 0.05). Mean OCT flow area was 6.92 (3.48) mm2 with IBS and 6.64 (2.44) mm2 with CoCr-EES (difference: 0.27; 95% CI: -0.09 to 0.63; Pnoninferiority < 0.0001). Two-year target lesion failure occurred in 7.4% of IBS patients and 5.4% of CoCr-EES patients (HR: 1.37; 95% CI: 0.69-2.73; P = 0.37). No significant between-group differences in the rates of patient-oriented composite endpoint, death, or MI were present between the 2 groups. No scaffold thromboses occurred in the IBS group, whereas 1 stent thrombosis occurred with CoCr-EES. Binary restenosis and revascularization rates were higher with IBS, however, most such events were non-ischemia-driven. CONCLUSIONS:In IRONMAN-II, the sirolimus-eluting IBS was noninferior to CoCr-EES for 2-year in-segment LLL, QFR, and OCT-derived flow area. Clinical event rates were also comparable between groups although non-ischemia-driven revascularization rates were higher after IBS. Longer-term follow-up is necessary to demonstrate whether late benefits are realized after complete IBS resorption. (A Clinical Investigation to Evaluate the Safety and Efficacy of IBS in Patients With Coronary Artery Disease; NCT05206084).

Residual cardiovascular risk persists in statin-treated patients with coronary artery disease (CAD), even when low-density lipoprotein cholesterol (LDL-C) targets are met. Excess apolipoprotein B (apoB), defined as measured apoB minus LDL-C-predicted apoB, may capture atherogenic particle burden beyond LDL-C, but its prognostic value for long-term mortality in secondary prevention remains uncertain. We conducted a pooled analysis of two nationwide Chinese cohorts (CIN-II and RED-CARPET) comprising 68,616 statin-treated CAD patients. Excess apoB was calculated using an internal reference population (triglycerides ≤ 1.0 mmol/L). Associations with all-cause and cardiovascular mortality were assessed using multivariable Cox models, with adjustment for clinical covariates including nutritional status. External validation was performed in 13,702 participants from the UK Biobank. Over a median follow-up of 5.2 years, 10,835 deaths occurred (5,090 cardiovascular). Each 1-standard deviation (15.4 mg/dL) increase in excess apoB was associated with a 12

BACKGROUND:Patients with atherosclerotic cardiovascular disease (ASCVD) have a high risk of recurrent major adverse cardiovascular events (MACE) and chronic kidney disease (CKD). Although Life's Essential 8 (LE8) has been studied for cardiovascular outcomes in secondary prevention, systematic evaluations of its association with cardiorenal events remain lacking. OBJECTIVES:To evaluate whether optimal cardiovascular health (CVH) was associated with lower risks of MACE and CKD in ASCVD patients. METHODS:This study included 10,253 UK Biobank participants with ASCVD, categorized into low (<50), moderate (50‒79), and high (≥80) CVH groups by LE8 score. Associations with MACE and CKD were assessed using Fine-Gray regression models, population-attributable fractions (PAF), and 1:2 propensity-matched analyses versus 16,545 non-ASCVD participants. RESULTS:During a median 13.3 years follow-up, 2,069 MACE and 1,290 CKD events occurred. Compared with high CVH, low CVH was associated with higher risks of MACE (subdistribution HR [sHR] 2.68, 95% CI 2.02-3.56, p <0.001) and CKD (sHR 2.34, 95% CI 1.57-3.48, p <0.001). Glucose control contributed the largest PAF to both MACE (10.5%) and CKD (15.1%), followed by smoking cessation (6.9% for MACE and 11.1% for CKD). Compared with matched non-ASCVD participants, ASCVD patients with high LE8 attenuated MACE (sHR 0.83, 95% CI 0.58-1.20; p = 0.33) and CKD (sHR 0.69, 95% CI 0.42-1.13; p = 0.14) risks. CONCLUSIONS:Higher LE8 scores were associated with lower risks of MACE and CKD in ASCVD patients. Glucose control and smoking were key modifiable contributors. High LE8 achievement may attenuate risks toward non-ASCVD levels.

BACKGROUND:Protection against vascular inflammation in endothelial cells represents a pivotal atheroprotective attribute of high-density lipoproteins (HDL). OBJECTIVE:The present study sought to assess the predictive value of the HDL anti-inflammatory property for major adverse cardiovascular events (MACE). METHODS:The anti-inflammatory property of HDL was evaluated by its ability to suppress vascular cell adhesion molecule-1 mRNA expression stimulated by tumor necrosis factor α in endothelial cells in a prospective study of patients with coronary artery disease from South China (n = 466, median follow-up of 2.3 years). The primary endpoint was MACE, encompassing nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death. RESULTS:Within the study population (mean age 64.0 years, 77.9% male), 12.7% experienced recurrent MACE. After multivariable adjustment, higher HDL anti-inflammatory property was independently linked to lower residual cardiovascular risk (adjusted hazard ratio [aHR]: 0.96, 95% CI: 0.92-0.99; P = .022), with a linear inverse relationship (P for nonlinearity = .128). When divided into tertiles, patients with the highest HDL anti-inflammatory property showed significantly reduced MACE risk compared with the reference group in the multivariable-adjusted model (aHR: 0.48, 95% CI: 0.24-0.97; P = .040). Mediation analysis revealed that estimated glomerular filtration rate mediated 36.6% (P < .001) of the observed association. Moreover, subgroup analysis revealed a stronger protective effect in female patients (aHR: 0.73, 95% CI: 0.55-0.97). CONCLUSION:Our findings indicate that better HDL anti-inflammatory function was linked to reduced recurrent MACE risk, independent of HDL cholesterol levels and statin treatment. Kidney function partially mediated this association. These findings underscore the prognostic relevance of HDL functional assessment in secondary cardiovascular prevention.

BACKGROUND:Early reperfusion therapy is critical in patients with ST-segment elevation myocardial infarction (STEMI). However, limitations in resources and patient-level and system-level barriers delay the administration of reperfusion therapy. This study evaluated the impact of an integrated care strategy for STEMI management in China. METHODS:This prospective, multicentre, non-randomised controlled study consecutively enrolled patients with acute STEMI, who were admitted to eight tertiary hospitals in different regions of China (August 2015-February 2019). An integrated care model was used in four hospitals (intervention). This model mainly included regular community public education, skills training for the diagnosis and treatment of STEMI in percutaneous coronary intervention-incapable centres, referral system improvement and optimal green channel for primary percutaneous coronary intervention-capable centres. In the other four hospitals (control), usual care of acute myocardial infarction public management and medical health service was provided. The primary outcome was the proportion of patients receiving symptom-to-reperfusion within 12 hours. RESULTS:A total of 6817 patients with acute STEMI were analysed (age (mean±SD): 61±13 years; female: n=1242 (18.2%)). Of those, 2452 and 4365 patients were included in the intervention and control groups, respectively. Between 2015 and 2019, the rates of symptom-to-reperfusion within 12 hours and symptom-to-admission within 12 hours increased in the intervention group (from 65.3% to 91.4%; and from 74.2% to 96.4%, respectively; Ptrend=0.015 for both). In addition, there was no significant difference in door-to-balloon time within 90 min observed among the two groups (adjusted relative risk=0.96, 95% CI: 0.89 to 1.02; p=0.18). Moreover, the rates of in-hospital mortality and major adverse cardiac events exhibited a nearly onefold decrease in the intervention group versus the control group (p<0.001). CONCLUSIONS:Use of an integrated care model focusing on prehospital delay may increase the rate of timely treatment in areas with limited medical resources in China. TRIAL REGISTRATION NUMBER:NCT03928119.

Combining ezetimibe (EZ) and statins is recommended for the treatment of elevated low-density lipoprotein-cholesterol (LDL-C). This subgroup analysis evaluated the efficacy of fixed-dose combination (FDC) therapy with EZ and atorvastatin (AS) versus AS monotherapy on attaining LDL-C goals in Chinese patients with very high risk of atherosclerotic cardiovascular disease (ASCVD) grouped by ASCVD risk, age, and sex. Data from the phase III, randomized, double-blind study (NCT03768427) compared EZ10/AS10 mg FDC versus AS20 mg (cohort A), and EZ10/AS20 mg FDC versus AS40 mg monotherapy (cohort B) in Chinese patients with uncontrolled hypercholesterolemia. Proportions of patients attaining 2016 Chinese guideline-recommended LDL-C goals (low/medium risk [< 130 mg/dL], high risk [< 100 mg/dL], very high risk [< 70 mg/dL]) were assessed at weeks 6 and 12. Subgroup analyses by ASCVD risk, age (< 65 and ≥ 65 years), and sex were conducted. LDL-C goal attainment was significantly higher with FDCs versus AS monotherapy at week 12 (cohort A: 62.7

Background and purpose: Matching the anti-proliferative drug effect with endothelial healing after drug-eluting stent (DES) implantation may help reduce cardiac events, especially stent thrombosis. A previous PIONEER II optical coherence tomography (OCT) sub-study demonstrated significantly better 1-month strut coverage with the novel healing-targeted BuMA Supreme DES, which was designed with a drug elution period of 4 to 6 weeks after implantation, compared with the XIENCE everolimus eluting stent (EES). This clinical trial aimed to evaluate whether the early endothelial healing observed in previous OCT sub-study would translate into improved intermediate-term angiographic and short-term clinical outcomes. Methods: PIONEER II was a multicenter, prospective, tandem clinical trial conducted in China. It was part of a series of clinical investigations of the BuMA Supreme DES, together with PIONEER I in Europe and PIONEER III in the United States, Canada, Europe, and Japan. The efficacy and safety of the BuMA Supreme DES were evaluated in patients with de novo coronary artery lesions. Results: From December 2015 to March 2018, 459 patients were randomly assigned to the randomized controlled trial (RCT) arm and received either the BuMA Supreme DES (n = 226) or the BuMA biodegradable polymer sirolimus-eluting stent (BP-SES; n = 233). In addition, 819 patients were enrolled in the objective performance criteria (OPC) arm. In the RCT arm, the BuMA Supreme DES was non-inferior to the BuMA BP-SES with respect to 9-month in-stent late lumen loss (LLL), with values of 0.23 ± 0.37 mm and 0.27 ± 0.36 mm, respectively (difference: −0.046 mm, 95% confidence interval: −0.107 to 0.015; P < 0.001 for non-inferiority). Furthermore, the BuMA Supreme DES demonstrated significantly lower values for secondary angiographic endpoints, including in-segment LLL and in-stent/in-segment diameter stenosis, compared with the BuMA BP-SES. In the OPC arm analysis, which combined patients from the BuMA Supreme group of the RCT arm with patients enrolled in the single-arm cohort, the 1-year target lesion failure rate was 4.17%. Both primary endpoints met the pre-specified non-inferiority criteria. Conclusion: The BuMA Supreme DES was non-inferior to the BuMA BP-SES with respect to 9-month in-stent LLL and was associated with the expected target lesion failure rate and a low incidence of stent thrombosis at 1-year follow-up.

Importance:Homozygous familial hypercholesterolemia (HoFH) is a rare, life-threatening genetic disorder. Patients with HoFH have markedly elevated low-density lipoprotein cholesterol (LDL-C) levels from birth, and their activity of LDL receptor (LDLR) is typically absent or severely impaired. However, efficacy of traditional lipid-regulating agents relies on residual LDLR function. Angiopoietinlike 3 (ANGPTL3)-directed therapies could reduce lipid levels through an LDLR-independent pathway. Objective:To evaluate SHR-1918, a fully human monoclonal antibody targeting ANGPTL3, in adults with HoFH taking stable lipid-lowering therapy. Design, Setting, and Participants:This was a multicenter, single-arm, phase 2 nonrandomized clinical trial conducted at 8 sites in China between December 19, 2023, and April 2, 2024. Included were participants with HoFH taking stable lipid-lowering therapy. Interventions:Patients were given subcutaneous SHR-1918 at 600 mg every 4 weeks for 12 weeks, followed by an 8-week follow-up. Main Outcomes and Measures:The primary end point was the percent change in serum LDL-C level from baseline to week 12. Results:A total of 26 patients (mean [SD] age, 36.1 [12.2] years; 16 female [61.5%]) were included in this analysis. The mean (SD) baseline LDL-C level was 433.59 (173.74) mg/dL. At week 12, the mean percent change in LDL-C level was -59.09% (SD, 11.71%; 95% CI, -63.81% to -54.36%). The reduction was observed throughout the entire 8-week follow-up period. SHR-1918 suggested similar LDL-C reduction across HoFH genotypes, with a percent change from baseline to week 12 of -61.32% for homozygous, -56.40% for compound heterozygous, and -72.21% for double heterozygous. Overall, 16 patients (61.5%) had at least 1 treatment-emergent adverse event, with the most common being proteinuria (4 [15.4%]). Injection site reaction occurred in only 1 patient (3.8%) and included pain and rash or erythema (both grade 1). Conclusions and Relevance:Results show that SHR-1918 was associated with a substantial reduction in LDL-C level and favorable safety profile among patients with HoFH taking stable lipid-lowering therapy. Trial Registration:ClinicalTrials.gov Identifier: NCT06009393.

BACKGROUND:The constant resistance ratio (cRR) is a novel nonhyperemic pressure ratio based on piezoresistive pressure microcatheter (PMC) measurements. With repeated measurements in randomized order of PMC and pressure wire techniques, this study aimed primarily to validate the diagnostic performance of cRR compared with fractional flow reserve (FFR) in coronary lesions of 30% to 90% diameter stenosis. METHODS:SUPREME II (Sensor-Equipped Ultrathin Pressure Microcatheter Versus Pressure Wire for Physiological Measurements) was a multicenter, prospective study that included 466 patients (483 vessels) from 11 centers. All target vessels were assessed using both pressure wire and PMC separately in randomized order under resting and hyperemic conditions. The primary end point was the diagnostic accuracy of the cRR using a PMC-based FFR of ≤0.80 as the reference standard. Secondary end points included the cRR "gray zone" of the cRR-FFR hybrid strategy and the proportion of patients in whom diagnosed was achieved without vasodilator use. RESULTS:The optimal cRR cutoff was 0.89, which correctly classified 82.8% of the patients, with a sensitivity and specificity of 87.0% and 80.1%, respectively, and achieved an area under the curve of 0.92 with FFRPMC as reference (area under the curve 0.90 with FFRpressure wire as reference). If FFR was added for decision-making in cases of cRR values between 0.85 and 0.91, a cRR--FFR hybrid strategy achieved a 95.3% agreement with the FFR-only strategy and allowed 68.5% of the patients to not require using vasodilator. CONCLUSIONS:In coronary stenosis of 30% to 90% diameter stenosis, cRR measurements were highly feasible. The diagnostic accuracy of cRR with FFRPMC as reference was excellent. Further, a cRR-FFR hybrid strategy may reduce vasodilator use without compromising diagnostic accuracy. REGISTRATION:URL: https://clinicaltrials.gov/study/NCT05417763; Unique Identifier: NCT05417763.

Background:Transcatheter edge-to-edge repair (TEER) has become an effective alternative for treating degenerative mitral regurgitation (DMR) in patients at high surgical risk. The SQ-Kyrin-M TEER system (SQ-Kyrin-M system) is a novel TEER device developed in China. This study aimed to evaluate the feasibility, safety, and 12-month clinical efficacy of the SQ-Kyrin-M system in patients with high-risk degenerative mitral regurgitation. Methods:In this prospective, multicenter, single-arm study (ClinicalTrials.gov: NCT06467110), 120 patients with symptomatic DMR (grade ≥3+) had the device implanted. The primary endpoint was the clinical success rate at 12 months. Secondary endpoints included technical, device, and procedural success rate; New York Heart Association (NYHA) class improvement; Kansas City Cardiomyopathy Questionnaire (KCCQ) score change; and mitral regurgitation (MR) reduction. Safety endpoints encompassed all-cause mortality, cardiovascular mortality, and major adverse event rate. Results:A total of 120 patients received the TEER procedure across 25 participating sites in China; the mean age was 71.9 years, and the mean Society of Thoracic Surgeons (STS) risk score was 9.3. At 12 months, the Kaplan-Meier estimates were 82.5% for clinical success, 7.6% for all-cause mortality, and 10.8% for major adverse events; MR ≤2+ and MR ≤1+ were achieved in 91.7 and 70.4% of the patients, respectively; 88.9% of patients were in NYHA class I or II; and KCCQ score had improved by 18.9 points. Favorable left ventricular remodeling was observed with sustained reductions in left ventricular end-diastolic and end-systolic volumes. Conclusions:This study demonstrates that the SQ-Kyrin-M system is a safe and effective therapeutic option for DMR patients.

This nonrandomized clinical trial investigates if HR-1918, a fully human monoclonal antibody targeting angiopoietinlike 3 (ANGPTL3), is associated with a reduction in low-density lipoprotein cholesterol level in adults with homozygous familial hypercholesterolemia taking stable lipid-lowering therapy. QuestionDoes SHR-1918, a fully human monoclonal antibody targeting angiopoietinlike 3 (ANGPTL3), lower the low-density lipoprotein cholesterol (LDL-C) level in adults with homozygous familial hypercholesterolemia (HoFH) taking stable lipid-lowering therapy?FindingsIn this phase 2 nonrandomized clinical trial of 26 patients, SHR-1918 at 600 mg every 4 weeks was associated with a substantial reduction in LDL-C level exceeding half in adults with HoFH taking stable lipid-lowering therapy and was also associated with lower levels of other lipids, with evidence of a manageable safety profile.MeaningThe promising findings observed in this trial support the launch of a double-blind, placebo-controlled, phase 3 randomized clinical trial to verify the effect and safety of SHR-1918 for HoFH management. ImportanceHomozygous familial hypercholesterolemia (HoFH) is a rare, life-threatening genetic disorder. Patients with HoFH have markedly elevated low-density lipoprotein cholesterol (LDL-C) levels from birth, and their activity of LDL receptor (LDLR) is typically absent or severely impaired. However, efficacy of traditional lipid-regulating agents relies on residual LDLR function. Angiopoietinlike 3 (ANGPTL3)-directed therapies could reduce lipid levels through an LDLR-independent pathway.ObjectiveTo evaluate SHR-1918, a fully human monoclonal antibody targeting ANGPTL3, in adults with HoFH taking stable lipid-lowering therapy.Design, Setting, and ParticipantsThis was a multicenter, single-arm, phase 2 nonrandomized clinical trial conducted at 8 sites in China between December 19, 2023, and April 2, 2024. Included were participants with HoFH taking stable lipid-lowering therapy.InterventionsPatients were given subcutaneous SHR-1918 at 600 mg every 4 weeks for 12 weeks, followed by an 8-week follow-up.Main Outcomes and MeasuresThe primary end point was the percent change in serum LDL-C level from baseline to week 12.ResultsA total of 26 patients (mean [SD] age, 36.1 [12.2] years; 16 female [61.5%]) were included in this analysis. The mean (SD) baseline LDL-C level was 433.59 (173.74) mg/dL. At week 12, the mean percent change in LDL-C level was -59.09% (SD, 11.71%; 95% CI, -63.81% to -54.36%). The reduction was observed throughout the entire 8-week follow-up period. SHR-1918 suggested similar LDL-C reduction across HoFH genotypes, with a percent change from baseline to week 12 of -61.32% for homozygous, -56.40% for compound heterozygous, and -72.21% for double heterozygous. Overall, 16 patients (61.5%) had at least 1 treatment-emergent adverse event, with the most common being proteinuria (4 [15.4%]). Injection site reaction occurred in only 1 patient (3.8%) and included pain and rash or erythema (both grade 1).Conclusions and RelevanceResults show that SHR-1918 was associated with a substantial reduction in LDL-C level and favorable safety profile among patients with HoFH taking stable lipid-lowering therapy.Trial RegistrationClinicalTrials.gov Identifier: NCT06009393

Patients with chronic kidney disease (CKD) without atherosclerotic cardiovascular disease (ASCVD) have high mortality rates. Guidelines indicate that statin therapy can reduce mortality in CKD patients with ASCVD; however, its benefits for CKD patients without ASCVD remain unclear. This study examined the survival benefits of statin therapy in CKD patients without ASCVD in American and Chinese cohorts. A total of 4369 patients diagnosed with CKD without concurrent ASCVD were included from the American Medical Information Mart for Intensive Care (MIMIC)-IV database (n = 1786) and the Chinese Multicenter Registry Cohort for Cardiorenal Improvement II (CIN-II, n = 2583). Participants were grouped by statin use (treated and untreated). The two groups were compared for key indicators, including: (1) statin use rate; (2) 4-year all-cause mortality; (3) 4-year cardiovascular mortality (assessed in the CIN-II cohort). Statistical analyses included Kaplan–Meier survival curves (with log-rank test for group differences) and Cox proportional hazard models (adjusted for confounders) to estimate the association between statin use and mortality. In the MIMIC-IV cohort, 37.6

Aims To investigate the relationship between glucose-lowering medications and cardio-renal-liver-metabolic (CRLM) health. Methods Two-sample Mendelian randomization (MR) was applied to assess the causal relationships between seven classes of glucose-lowering drugs and CRLM health outcomes. Genetic proxies for drug exposure were identified as cis-acting single nucleotide polymorphisms in the drug target genes, linked to both gene expression levels and glycosylated hemoglobin (HbA1c) or body mass index (BMI). Validation included colocalization and linkage disequilibrium analyses. A two-step MR strategy was employed to explore potential metabolite mediators. Results Sulfonylureas were associated with a reduced heart failure (HF) risk (odds ratio [OR] = 0.38 per standard deviation change in glucose-lowering drug target perturbation equivalent to 1 unit of HbA1c lowering, P = 2.46E-04) but increased aspartate aminotransferase levels (OR = 1.39, P = 9.50E-07). Sodium-glucose cotransporter-2 inhibitors reduced the risk of acute myocardial infarction (AMI) (OR = 0.37, P = 1.36E-05), venous thromboembolism (VTE) (OR = 0.48, P = 1.89E-04), microalbuminuria (MA) (OR = 0.49, P = 1.65E-06), and increased estimated glomerular filtration rate (eGFR) (OR = 1.04, P = 2.98E-05). They also showed a potential protective effect against general liver disorders (OR = 0.41, P = 4.79E-04), metabolic dysfunction-associated steatotic liver disease (MASLD) (OR = 0.25, P = 0.008), and metabolic syndrome (MetS) (OR = 0.63, P = 5.40E-04). Thiazolidinediones (TZDs) reduced the risk of AMI (OR = 0.44, P = 4.31E-38), hypertension (HT) (OR = 0.60, P = 1.40E-43), MASLD (OR = 0.53, P = 5.61E-05), and MetS (OR = 0.66, P = 1.00E-20) but increased the risk of VTE (OR = 1.40, P = 2.53E-07), atrial fibrillation (OR = 1.61, P = 1.43E-09), and alcoholic liver disease (OR = 3.00, P = 6.56E-11). TZDs also negatively affected eGFR (OR = 0.97, P = 4.68E-05) and increased blood urea nitrogen levels (OR = 1.03, P = 2.52E-09). Glucagon-like peptide-1 receptor agonists demonstrated significant benefits for chronic kidney disease, driven by reductions in both glucose levels (OR = 0.11, P = 0.016) and BMI (OR = 0.20, P = 0.012), with potential cardiometabolic benefits from BMI reduction. Some mediating roles of metabolites have been identified (e.g., SGLT2 inhibitors mediate effects on MA via isoleucine and TZDs mediate effects on MASLD through lipid metabolites). Conclusions Glucose-lowering medications exert significant and heterogeneous effects on CRLM health, highlighting the need for personalized treatments and further investigations into their mechanisms and long-term impacts on CRLM outcomes.

Whether percutaneous coronary intervention (PCI) can improve the long-term prognosis of patients with stable coronary artery disease (SCAD) in comparison to conservative treatment remains controversial. The present study sought to evaluate the impacts of initial invasive versus conservative strategy on long-term clinical outcomes for patients with SCAD stratified by risk scores. This was a sub-analysis of the multicenter, observational Optimal antiPlatelet Therapy for Chinese patients with Coronary Artery Disease (OPT-CAD) study. Clinical outcomes were compared in SCAD patients who initially received PCI (invasive strategy) or conservative treatment according to risk stratification by OPT-CAD score. The primary outcome was ischemic events at 5 years, composed of cardiac death, myocardial infarction, and ischemic stroke. Secondary outcomes included all-cause death, Bleeding Academic Research Consortium (BARC) types 2, 3, or 5, and 3 or 5 bleeding. The conservative group comprised 1767 (58.0

BACKGROUND:Transcatheter edge-to-edge repair (TEER) improves outcomes in patients with heart failure and moderate-to-severe functional mitral regurgitation (FMR) who remain symptomatic despite the use of maximal doses of guideline-directed medical therapy (GDMT). The SQ-Kyrin-M system is a novel TEER device designed for FMR treatment. AIMS:This multicenter, prospective, single-arm study (ClinicalTrials.gov number: NCT05988450) evaluates the safety and efficacy of the SQ-Kyrin-M system in severe symptomatic FMR. METHODS:A total of 125 eligible patients (mean age 65.5 ± 8.1 years) with heart failure and moderate-to-severe or severe FMR who remained symptomatic despite the use of maximal doses of GDMT were involved in the analysis. The primary endpoint was the composite rate of all-cause mortality and heart failure hospitalization at 1 year post-intervention. Independent assessments were conducted by an echocardiography core laboratory (ECL) and a clinical events committee (CEC). RESULTS:At 1 year, the primary endpoint rate was 16.0% (20/125), and the composite major adverse event rate was 10.4%. Mitral regurgitation was reduced to ≤ 2+ in 94.2% of patients, with significant left ventricular reverse remodeling (LVEDV reduction: 33.8 ± 55.4 mL, p < 0.001). Patient-reported outcomes improved significantly, with Kansas City Cardiomyopathy Questionnaire (KCCQ) scores increasing by 15.9 ± 18.8 points (p < 0.001) and 6-minute walk distance (6MWD) improving by 46.7 ± 90.7 m (p < 0.001). The proportion of patients in New York Heart Association (NYHA) class I/II increased from 30.4% to 84.4% (p < 0.001). CONCLUSIONS:The SQ-Kyrin-M transcatheter mitral valve repair system bolsters the evidence supporting the safety and efficacy of TEER interventions for FMR patients.