Cardiovascular Therapeutics最新文献

Background

Effective rate control is important in the management of atrial fibrillation (AF). However, the relationship between resting heart rate (RHR) and adverse outcomes in hospitalized patients remains uncertain.

Objective

This study was to evaluate the association between RHR and in-hospital outcomes.

Methods

Data from the Improving Care for Cardiovascular Disease in China-AF project from 2014 to 2019 were retrospectively analyzed. The primary outcome was the composite of in-hospital all-cause mortality and in-hospital acute heart failure (AHF). Secondary outcomes included stroke/transient ischemic attack (TIA) and bleeding during hospitalization. Logistic regression analyses were used to assess the association between RHR and outcomes.

Results

Our study included 12,775 patients hospitalized for AF in 236 hospitals. Logistic regression analyses using different models showed a significant association between RHR exceeding 80 bpm and an increased risk of the primary outcome (adjusted OR: 1.79 [95% CI: 1.44–2.22]). A positive association between RHR and the primary outcome was identified with RHR ≥ 80 bpm. Marginal effect analyses showed that patients with advanced AF types were at higher risk across the range of RHR. Conversely, catheter ablation, but not antiarrhythmic drug use, was associated with a decreased risk.

Conclusion

A significant association was identified between RHR and adverse outcomes in patients hospitalized for AF, where RHR exceeding 80 bpm was associated with an increased risk.

Trial Registration: ClinicalTrials.gov identifier: NCT02309398

Aim

This network meta-analysis (NMA) evaluated four novel proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies for hypercholesterolemia management, comparing their lipid-lowering efficacy and safety.

Methods

We systematically identified randomized controlled trials employing the frequentist NMA method to assess reductions in low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and lipoprotein (a) (Lp[a]), alongside treatment-emergent adverse events (TEAEs) and serious TEAEs. P-scores ranked therapeutic hierarchies, with meta-regression and subgroup analyses exploring heterogeneity. Trial sequential analysis determined the adequacy of cumulative evidence. Confidence in the network meta-analysis approach was used to evaluate the confidence in the findings from NMA.

Results

A total of eight trials with 3,975 Chinese patients were included. Ongericimab 150 mg every 2 weeks (Q2W) ranked first in all efficacy outcomes, demonstrating pronounced effects in LDL-C, ApoB, and Lp(a) reduction versus placebo, with mean differences of −74.21% (95% confidence interval [CI]: −79.69% to −68.73%), −64.36% (95% CI: −68.58% to −60.13%), and −50.93% (95% CI: −56.24% to −45.61%), respectively. All interventions exhibited safety profiles comparable with placebo, with no significant differences in TEAEs or serious TEAEs incidence. The analyses suggested that a portion of the evidence base was robust and reliable.

Conclusion

These findings positioned ongericimab 150 mg Q2W as a clinically optimal PCSK9 inhibitor with robust lipid-lowering capacity. The results highlight the potential of next-generation PCSK9 monoclonal antibodies, particularly in East Asian populations, while underscoring the need for large-scale multinational trials to validate ethnic-specific responses.

Background

The association between the atherogenic index of plasma (AIP) and different cardiovascular disease (CVD) outcomes remains insufficiently studied.

Methods

Data from 16,302 US adults in NHANES 2005–2020 were analyzed. CVD outcomes included congestive heart failure, coronary heart disease, angina, heart attack, and stroke. Multivariable logistic regression models assessed the linear association between AIP and CVD. Restricted cubic splines were used to examine potential nonlinear relationships, whereas threshold effect analysis identified inflection points. Stratified analyses explored interactions between AIP and covariates.

Results

Compared with the lowest quartile, the highest AIP quartile was associated with increased odds of overall CVD (OR = 1.73, 95% CI = 1.20–2.52, p for trend = 0.001), coronary heart disease (OR = 2.20, 95% CI = 1.20–4.25, p for trend = 0.013), and heart attack (OR = 2.53, 95% CI = 1.42–4.74, p for trend = 0.008). A U-shaped relationship was observed between AIP and congestive heart failure (p overall = 0.0004, p nonlinear = 0.002), with a sharp odds increase when AIP exceeded 0.22 (OR = 3.40, 95% CI = 1.81–6.38, p < 0.01). Subgroup analysis revealed a significant age interaction: Among adults younger than 55 years, each AIP increment was associated with higher odds of CVD (OR = 2.53, 95% CI = 1.60–3.98, p = 0.001), heart attack (OR = 2.58, 95% CI = 1.21–5.54, p = 0.014), and stroke (OR = 2.98, 95% CI = 1.44–6.17, p = 0.003).

Conclusion

Elevated AIP is an independent predictor of CVD, coronary heart disease, and heart attack, particularly in younger adults (< 55 years). A U-shaped relationship was identified between AIP and congestive heart failure. These findings highlight AIP as a valuable biomarker for CVD risk assessment and emphasize the importance of age-specific intervention strategies targeting different CVD outcomes.

Background

This study is aimed at measuring the expression of serum cytokeratin 18 (CK18) in patients with nonalcoholic fatty liver disease (NAFLD) and at evaluating its ability to discriminate NAFLD patients with and without coronary heart disease (CHD), thereby elucidating its potential role in reflecting the link between NAFLD and increased cardiovascular involvement.

Methods

A total of 127 patients diagnosed with NAFLD and treated between September 2022 and July 2024 were enrolled in this cross-sectional study. Based on the presence or absence of CHD, they were divided into two subgroups: a CHD-present group (n = 79) and a CHD-absent group (n = 48). In addition, a control group consisting of 100 age-matched and sex-matched healthy individuals undergoing routine physical examinations during the same period was included for comparison.

Results

Compared with the control group, patients with NAFLD showed significantly higher levels of alanine aminotransferase (ALT), serum CK18-M65 and CK18-M30 levels, body mass index (BMI), homeostasis model assessment of insulin resistance index (HOMA-IR), triglyceride (TG), total cholesterol (TC), aspartate aminotransferase (AST), and waist-to-hip ratio (p < 0.05). Multivariate logistic regression analysis identified serum CK18-M65, CK18-M30, TC, ALT, AST, and HOMA-IR as independent factors in NAFLD patients (p < 0.05). The combination of CK18-M65 and CK18-M30 yielded an area under the curve of 0.843, with a sensitivity of 87.34% and a specificity of 75.00%. Functional enrichment analysis revealed that CK18-related genes were involved in inflammatory signaling and cardiovascular regulatory pathways, supporting a mechanistic role for CK18 in the liver–heart axis.

Conclusion

Serum CK18 may serve as a useful biomarker for identifying NAFLD patients with concurrent CHD, offering diagnostic value in clinical assessment.

Objectives

The objectives of this study is to investigate the correlation between genotype polymorphism of aldehyde dehydrogenase 2 (ALDH2) and coronary artery disease (CAD) in atrial fibrillation patients.

Methods

From November 2020 to December 2021, 80 patients with atrial fibrillation at a medical center in Chengdu were divided into two groups: CAD group (n = 25) and non-CAD group (n = 55). The genotype composition ratio of ALDH2 (mutant-type/wild-type), blood biochemical indexes, the proportion of the history of lipid-lowering drugs and time of taking lipid-lowering drug were compared between the two groups.

Results

The CAD group showed significantly lower levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C) compared with the non-CAD group (p < 0.05), and the proportion and time of taking lipid-lowering drugs in CAD group were significantly increased (p < 0.05). The frequency of the ALDH2 genotype (mutant-type/wild-type) in the CAD group was notably elevated compared with that in the non-CAD group (p < 0.05). In patients with atrial fibrillation, the risk of CAD in patients with ALDH2 mutant genotype (GA + AA) was 5.849 times that of ALDH2 wild-type genotype (GG) (95%CI = 1.437–23.795, p < 0.05). The area under ROC curve of ALDH2 mutant genotype (GA + AA) was 0.624 (SE = 0.069, 95%CI : 0.488–0.759). In patients with ALDH2 wild-type (GG), the levels of total cholesterol and LDL-C in CAD group were significantly lower than those in non-CAD group (p < 0.05). However, in patients with ALDH2 mutation genotype (GA + AA), the proportion of history of lipid-lowering drugs in CAD group was significantly higher than that in non-CAD group (p < 0.05).

Conclusions

The polymorphism of ALDH2 gene is a high risk factor for CAD in patients with atrial fibrillation. The ALDH2 mutation genotype (GA + AA) may reduce the lipid-lowering efficacy of statins.

Purpose

The purpose of this study is to investigate the role of aldehyde dehydrogenase-2 (ALDH2) in septic myocardial injury, focusing on noncanonical pyroptosis.

Methods

In vivo, C57BL/6J mice were divided into five groups: Sham, cecal ligation and puncture (CLP), CLP + Alda-1 (ALDH2 agonist), Sham + dimethyl sulfoxide (DMSO, solvent control), and CLP + DMSO. Cardiac function and histological/ultrastructural changes were assessed via echocardiography, hematoxylin–eosin (HE) staining, and transmission electron microscopy (TEM). Tumor necrosis factor-α (TNF-α) and noncanonical pyroptosis-related proteins (caspase-11, gasdermin-D [GSDMD], high mobility group box 1 [HMGB1], and receptor for advanced glycation end products [RAGE]) were measured by enzyme-linked immunosorbent assay (ELISA) and western blotting. Coimmunoprecipitation (CO-IP) explored molecular mechanisms. In vitro, H9C2 cells were divided into six groups: Control, lipopolysaccharide (LPS)-treated, ALDH2-green fluorescent protein (GFP), LPS + ALDH2-GFP, GFP, and GFP + LPS. Cell viability, lactate dehydrogenase (LDH) release, creatine kinase isoenzymes (CK-MB), and target protein levels were detected via spectrophotometry, western blotting, and immunofluorescence (IF).

Results

In vivo, Alda-1 significantly attenuated CLP-induced cardiac dysfunction and reduced myocardial histological damage and ultrastructural impairment. In vitro, ALDH2 overexpression lowered LPS-induced H9C2 cell viability, CK-MB, and LDH release. Upregulating ALDH2 significantly reduced caspase-11, HMGB1, and RAGE expression. CO-IP showed ALDH2 interacted with HMGB1, RAGE, and GSDMD.

Conclusion

ALDH2 protects the myocardium from septic injury by inhibiting caspase-11-mediated noncanonical pyroptosis, possibly via direct interactions with GSDMD, HMGB1, and RAGE.

Aims

Novel drugs that target apoC-III in lipoprotein metabolism to reduce plasma triglycerides are currently under development. Olezarsen, a drug similar to its predecessor, volanesorsen, is in Phase 3 trials. A meta-analysis of RCTs was done to study its effect on hypertriglyceridemia.

Material and Methods

Screening was done on PubMed, Embase, Scopus, and the Cochrane Library from inception to August 2024. We used Review Manager (Version 5.4) for statistical analysis. Subgroups of olezarsen at doses of 10, 50, and 80 mg were made. Continuous outcomes were reported as mean differences with 95% CIs. Adverse events were reported using risk ratios and 95% CIs. The risk of bias was analyzed using the Cochrane risk of bias tool.

Results

Four RCTs with 374 participants, 278 in intervention and 96 placebo controls, were included. At all doses of olezarsen, a significant reduction in fasting triglyceride levels (MD: 45.69; 95% CI: 35.84, 55.54; p < 0.00001) was seen. This was most pronounced at 80 mg dose (MD: 51.98 95% CI: 43.06, 60.90; p < 0.00001). A reduction in apoC-III (MD: 58.77; 95% CI: 35.94, 81.61; p < 0.00001) and an increase in HDL (MD: 0.21; 95% CI: 0.04, 0.37; p = 0.01) were also observed. No significant effect was observed on LDL levels (MD: −0.13; 95% CI: −0.40, 0.14; p = 0.34). Overall, no significant adverse effects were seen compared to placebo (RR: 1.42; 95% CI: 0.66, 3.05; p = 0.37).

Conclusion

Olezarsen showed remarkable efficacy in lowering triglycerides, with a dose-dependent effect, while significantly increasing HDL levels and reducing apoC-III. Its safety profile is commendable. Although it performed well compared to volanesorsen, inconsistencies in LDL reduction and heterogeneity in some groups warrant further large-scale RCTs to better assess its safety and efficacy. Clinical decisions should be tailored to individual patient profiles, as hypertriglyceridemia management may vary on a case-to-case basis.

Aims

To evaluate the real-world efficacy and safety of low-dose (2.5 mg) mavacamten initiation in Chinese patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM).

Methods and Results

This single-center observational study (Zhongshan Hospital, China; Oct 2024–Apr 2025) enrolled 72 symptomatic oHCM patients (NYHA II/III, LVEF ≥ 55%, resting/Valsalva-provoked LVOT gradient [LVOTG] ≥ 30 mmHg). All patients initiated mavacamten 2.5 mg once daily. Doses were adjusted at Weeks 4, 8, and 12 based on LVEF and LVOTG. Primary outcomes were changes in resting/provoked LVOTG, NT-proBNP, and NYHA class at Week 12. Safety outcomes included LVEF < 50%, cardiac hospitalization, and death.

Significant reductions from baseline to Week 12 were observed: Resting LVOTG (52.4 ± 28.7 to 32.1 ± 23.1 mmHg, p < 0.001), Valsalva-provoked LVOTG (74.1 ± 24.4 to 48.7 ± 25.4 mmHg, p < 0.001), NT-proBNP (1102.7 ± 1114.9 to 320.2 ± 406.2 pg/mL, p < 0.001). LVEF remained stable. NYHA class improved by ≥ 1 class in 83.3% (60/72) of patients.

Subgroup analyses revealed significantly greater LVOTG reductions in patients with classic HCM (vs. apical HCM, p < 0.001) and high baseline resting LVOTG (≥ 50 mmHg vs. < 50 mmHg, p < 0.001/p = 0.04). NYHA improvement was consistent across subgroups.

Twenty-two patients escalated to 5 mg at Week 12, achieving further significant LVOTG reductions (p < 0.001), particularly in apical HCM and high-baseline-gradient subgroups, with stable LVEF.

No safety events occurred (LVEF < 50%, arrhythmias, hospitalization, and death). Four patients reported transient minor adverse events (dizziness, nausea, and fatigue).

Conclusion

In this first Chinese real-world study, initiating mavacamten at 2.5 mg significantly improved haemodynamics (LVOTG), biomarkers (NT-proBNP), and functional status (NYHA) in oHCM patients over 12 weeks with an excellent safety profile. Greater haemodynamic efficacy was observed in classic HCM and high-baseline-gradient patients. Escalation to 5 mg provided additional benefit. Mavacamten is an effective and safe therapy for oHCM in this Asian population.

Background

The relationship between hypothyroidism and cardiovascular disease is well established. However, data on subclinical hypothyroidism (SH) and its impact on major adverse cardiovascular events (MACEs) and postoperative complications following coronary artery bypass grafting (CABG) remain limited. This study was aimed at evaluating whether SH is associated with an increased risk of these outcomes.

Methods

From 2010 to 2019, 863 patients who underwent CABG for cardiovascular diseases at a reference center were included. The primary outcomes included MACE (composite and individual events: all-cause death, cardiovascular death, stroke, acute myocardial infarction [AMI], and new revascularization) and postoperative complications, including atrial fibrillation (AF), pleural effusion (PLE), pericardial effusion (PCE), infections at any site (IASs), and mediastinitis.

Results

SH patients had higher rates of MACE (20.3% vs. 8.2%, p = 0.001), MACE 4p (22.0% vs. 12.9%, p = 0.002), and stroke (10.2% vs. 3.0%, p = 0.013) than those of euthyroid patients. No significant differences were observed in all-cause death, cardiovascular death, AMI, or new revascularization. Postoperative complications were also more frequent in the SH group: AF (18.6% vs. 9.7%, p = 0.043), PLE (52.6% vs. 19.2%, p < 0.0001), PCE (20.3% vs. 7.8%, p = 0.03), and IAS (28.8% vs. 16.9%, p = 0.032). However, no significant difference was noted in the incidence of mediastinitis.

Conclusions

SH patients who underwent CABG had a higher frequency of MACE and postoperative complications than those of euthyroid patients.