Journal of Cardiovascular Pharmacology and Therapeutics最新文献

{"title":"Serial Platelet Function-Guided Antiplatelet Modulation After STEMI: A Randomized Pilot Study.","authors":"Hrvoje Jurin, Irzal Hadžibegović, Jure Samardžić, Joško Bulum, Boško Skorić, Maja Čikeš, Ivo Planinc, Zvonimir Ostojić, Igor Tagasovski, Davor Miličić","doi":"10.1177/10742484261483397","DOIUrl":"10.1177/10742484261483397","url":null,"abstract":"<p><p>BackgroundPlatelet reactivity varies after ST-segment-elevation myocardial infarction (STEMI). We evaluated serial platelet function-guided P2Y12 modulation after a 1-month ticagrelor run-in.MethodsAt month 1, 114 patients were randomized to continued ticagrelor (n=59) or an adenosine diphosphate (ADP)-guided strategy (n=55). Month-1 ADP was the preintervention baseline; months 2, 3, 6, 9, and 12 were analyzed using baseline-adjusted generalized estimating equations. Exploratory net adverse clinical events (NACE) were assessed from randomization through month 12 after STEMI.ResultsIn the guided group, month-1 ADP was 52 U (range, 4-466); 37 patients received clopidogrel 75 mg and 18 received 150 mg, with 17 dose-threshold discordances. Adjusted postrandomization ADP was higher with the guided strategy (geometric mean ratio, 1.26; 95% confidence interval [CI], 1.05-1.51). NACE occurred in 14/59 versus 4/55 patients (risk ratio [RR], 0.31; 95% CI, 0.11-0.87; absolute risk difference, -16.5 percentage points; exact P=.020). Any investigator-classified BARC bleeding occurred in 13/59 versus 3/55 (RR, 0.25; 95% CI, 0.07-0.82; exact P=.014), and the post hoc ischemic-or-BARC ≥2 composite in 9/59 versus 2/55 (RR, 0.24; 95% CI, 0.05-1.06; exact P=.055). One ischemic event occurred in each group.ConclusionsSerial ADP-guided modulation produced pharmacodynamic separation and was associated with fewer investigator-recorded, bleeding-driven events. Dose-threshold deviations, unverified extreme ADP values, incomplete BARC 2 documentation, and only 2 ischemic events restrict interpretation to hypothesis generation; efficacy and safety cannot be established.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"31 ","pages":"10742484261483397"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148828759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"β3-Adrenergic Receptor Agonism Reduces Right Ventricular Systolic Pressure in a Preclinical Model of Heart Failure With Preserved Ejection Fraction-Associated Pulmonary Hypertension.","authors":"Christelle Lteif, Brian E Gawronski, Rylie M Flohr, Ryanne J Mulligan, Grace C Hogan, Alyse S Gomez, Ravindra K Sharma, Julio D Duarte","doi":"10.1177/10742484261495417","DOIUrl":"https://doi.org/10.1177/10742484261495417","url":null,"abstract":"<p><p>PurposePulmonary hypertension (PH) commonly complicates heart failure with preserved ejection fraction (HFpEF), driving morbidity and mortality, yet no therapies exist for HFpEF-PH. β3-adrenergic receptor (ADRB3) agonists may provide cardiometabolic and anti-inflammatory benefits. We evaluated pharmacological ADRB3 modulation in a preclinical HFpEF-PH model.MethodsHFpEF-PH was induced in male and female AKR/J mice via high-fat diet feeding for 16-20 weeks. At 12-16 weeks of feeding, mice were randomized to low-dose mirabegron (LDM, 3.6 mg/kg/day), high-dose mirabegron (HDM, 14.4 mg/kg/day), nebivolol (1.0 mg/kg/day), or vehicle for 4 weeks. A separate cohort received the ADRB3 antagonist SR59230A (0.5 mg/kg/day) or vehicle. Right ventricular systolic pressure (RVSP), left ventricular end-diastolic pressure (LVEDP), body weight change, and gene expression of nitric oxide synthases (<i>Nos1</i>, <i>Nos2</i>, <i>Nos3</i>), thermogenic markers (<i>Ucp1</i>, <i>Ppargc1a</i>), and inflammatory cytokines (<i>Il1b</i>, <i>Il6</i>, <i>Tnf</i>) were assessed.ResultsHDM and nebivolol significantly reduced RVSP compared to controls (<i>P</i>=0.010 and <i>P</i>=1.0×10^-4), whereas SR59230A increased RVSP (<i>P</i>=0.006). LDM did not significantly affect RVSP, and LVEDP was unchanged across all treatment groups. HDM also reduced weight gain vs. control (<i>P</i>=0.023). HDM increased <i>Ucp1</i> and <i>Ppargc1a</i> expression in adipose tissue, and nebivolol increased <i>Ppargc1a</i> expression in adipose tissue. These molecular findings remained significant in sensitivity analyses.ConclusionHDM and nebivolol reduced RVSP in a preclinical model of HFpEF-PH, whereas ADRB3 antagonism increased RVSP. These findings provide pharmacological evidence consistent with involvement of ADRB3 signaling and support further investigation of ADRB3-targeted approaches; the molecular pathways underlying these hemodynamic effects remain to be established.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"31 ","pages":"10742484261495417"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors Associated With the Selection of Anti-Hypertensive Medications: A Retrospective Cross-Sectional Analysis.","authors":"Aymen Alqurain, Arif Aldihani, Hadeel Almousa, Gofran Alkhalaf, Fatimah Alqurayn, Luma Ameer, Sherihan Ghosn, Marwa Algoraini, Samaher Al-Shaibi, Ghadeer Alowaywi, Hassan Althabet, Reem Ashoor, Afnan Alshnbari, Salah Abohelaika, Shahad Alghamdi, Abdulkhaliq Alsalman, Bander Alanazi, Fadhel Alomar","doi":"10.1177/10742484261431512","DOIUrl":"10.1177/10742484261431512","url":null,"abstract":"<p><p>BackgroundHypertension remains a leading modifiable risk factor for cardiovascular disease, and effective anti-hypertensive prescribing is essential for optimal management. This study will evaluate the patterns of anti-hypertensive prescriptions, characteristics of specific drug class users, and significant factors influencing prescription choices within a Saudi Arabian cohort.MethodsThis retrospective, cross-sectional study at Al-Qatif Central Hospital included patients aged ≥40 years who attended outpatient cardiology and internal medicine clinics between January 2020 and December 2021. The characteristics of anti-hypertensive medication users and nonusers were compared using descriptive statistics. Logistic regression models were performed to identify factors associated with anti-hypertensive prescribing patterns adjusted for significant covariates, with results presented as adjusted odds ratios (OR) and corresponding 95% confidence interval (95% CI).ResultsAbout 62% of 5,852 patients were prescribed anti-hypertensive medication, with beta blockers (BBs) and calcium channel blockers (CCBs) being the most prescribed. BBs were primarily prescribed as monotherapy, constituting for 24% of prescriptions. Older patients (≥65 years) were more likely to receive combination therapy, with 17% receiving four anti-hypertensives medications. Diabetes mellitus was positively associated with the prescription of angiotensin receptor blockers (OR = 1.2, <i>P</i> < 0.05) and negatively associated with BBs prescribing (OR = 0.6, <i>P</i> < 0.05). Constipation exhibited a significant association with CCBs prescribing (OR = 1.4, <i>P</i> < 0.05).ConclusionThis study demonstrates significant deviations from existing clinical guidelines, notably the overprescription of BBs in the management of hypertension. The findings highlight where doctors need to look more closely at their prescribing habits and suggest to promote the alignment of prescribing practices with emerging evidence-based recommendations.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"31 ","pages":"10742484261431512"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147498824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eleutheroside E Attenuates Doxorubicin-Induced Cardiotoxicity by Suppressing Ferroptosis Through Activation of the Nrf2/SLC7A11/GPX4 Signaling Pathway.","authors":"Peng Sun, Liheng Chen, Xiangzhou Chen, Xuwei Zhang, Junjie Guan, Hongwei Mo, Yu Liang, Jingchao Li, Jing Yan, Deshu Chen, Chongbin Zhong, Pingzhen Yang","doi":"10.1177/10742484261428559","DOIUrl":"10.1177/10742484261428559","url":null,"abstract":"<p><p>Doxorubicin (DOX)-induced cardiotoxicity significantly impairs cancer patient survival rates. Eleutheroside E (EE), a polyphenolic compound with established cardioprotective properties against high-altitude myocardial injury and ischemia/reperfusion damage, has not previously been investigated in the context of DOX-induced cardiac toxicity. This study aimed to elucidate the therapeutic potential of EE against DOX-associated cardiotoxicity and its underlying mechanisms. Cardiomyocyte viability was quantified using the CCK-8 assay and Hoechst 33342/PI dual staining. Cardiac function was evaluated by echocardiography. Morphological alterations in cardiomyocytes were analyzed through phalloidin, hematoxylin-eosin (H&E), and wheat germ agglutinin staining. Ferroptosis-related biomarkers including malondialdehyde (MDA), Ptgs2 mRNA levels, Fe²⁺ concentration, and lipid peroxidation were assessed respectively. EE administration attenuated DOX-induced cardiomyocyte atrophy <i>in-vitro</i> and improved cardiac function <i>in-vivo</i>. Mechanistically, EE counteracted DOX-mediated suppression of Nrf2 expression and inhibited ferroptosis via activation of the Nrf2/SLC7A11/GPX4 signaling axis. siRNA-mediated Nrf2 knockdown partly abolished EE's cardioprotective effects. These findings conclusively demonstrate that EE mitigates DOX-induced cardiotoxicity through Nrf2-dependent ferroptosis regulation, highlighting its therapeutic potential for preventing chemotherapy-associated cardiac complications.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"31 ","pages":"10742484261428559"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimal Switching Antiplatelet Regimen in Patients with Ticagrelor to a Thienopyridine in Korean Patients (SWAPT-K Study).","authors":"Hyoun-Woo Noh, Sung-Hyo Seo, Yong-Lee Kim, Chang-Ok Seo, Moojun Kim, Jeong Rang Park, KyeHwan Kim, Hye Ree Kim, Jin-Yong Hwang, Seok-Jae Hwang, Min Gyu Kang, Hangyul Kim, Yongwhi Park, Jin-Sin Koh","doi":"10.1177/10742484261440340","DOIUrl":"10.1177/10742484261440340","url":null,"abstract":"<p><p>BackgroundDual antiplatelet therapy (DAPT) with aspirin and potent P2Y₁₂ inhibitors such as ticagrelor effectively reduces ischemic events but increases bleeding risk. In patients requiring long-term DAPT, switching from ticagrelor to a thienopyridine is often considered to reduce bleeding risk or address other clinical concerns. However, such switching may cause a transient reduction in platelet inhibition, raising concerns about thrombotic complications. In particular, evidence is limited regarding the optimal loading dose strategy for East Asian patients undergoing this transition.MethodsIn this randomized, open-label trial, 43 patients with acute coronary syndrome (ACS) who had received ticagrelor-based DAPT for > 6 months after stent implantation were randomized to clopidogrel 600 mg loading/75 mg maintenance, clopidogrel 300 mg loading/75 mg maintenance, or prasugrel 30 mg loading/5 mg maintenance. Platelet reactivity and inflammatory markers (MMP-2, MMP-9, TNF-α) were assessed at baseline, 48 h, and 5 days after switching. The primary endpoint was the proportion of patients achieving optimal platelet reactivity (OPR).ResultsThe proportion of patients achieving OPR was similar among groups at baseline (p = 0.483), 48 h (p = 0.699), and 5 days (p = 0.729). No significant intergroup differences were observed in inflammatory marker levels at any time point. No major adverse cardiovascular events occurred during follow-up.ConclusionsIn stable ACS patients on long-term DAPT, switching from ticagrelor to either clopidogrel or prasugrel maintained consistent platelet inhibition and inflammatory profiles, indicating that these switching strategies produce comparable pharmacodynamic profiles in East Asian populations during the early post-switch period.Trial RegistrationThis investigator-initiated pharmacodynamic study was not prospectively registered.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"31 ","pages":"10742484261440340"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147690302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors Associated With Loop Diuretic De-escalation in Patients With Acute Decompensated Heart Failure: The Influence of Guideline Directed Medical Therapy Initiation.","authors":"Satoshi Hanazawa, Noriko Kohyama, Erika Iwasaki, Kenta Muraoka, Mayumi Inamoto, Mio Ebato, Hiroshi Suzuki, Mari Kogo","doi":"10.1177/10742484261431652","DOIUrl":"10.1177/10742484261431652","url":null,"abstract":"<p><p>BackgroundIn patients with heart failure (HF), loop diuretics (LD) are recommended to relieve congestion and may be de-escalated if symptoms improve. However, long-term use of the same LD dose is sometimes required owing to potential congestion exacerbation. Therefore, we investigated the factors associated with LD de-escalation in patients with acute decompensated HF (ADHF) and the relationship between this de-escalation and initiating guideline directed medical therapy (GDMT) during hospitalization.MethodsIn this retrospective cohort study, patients with ADHF who were prescribed LD and GDMT at discharge were included. The primary endpoint was LD de-escalation at 6 months post-discharge. Factors associated with this de-escalation were extracted using multivariate analysis. The Cochran-Armitage trend test was used to analyze the relationship between the number of GDMT initiated during hospitalization and LD de-escalation.ResultsOf 193 eligible patients, 40.4% underwent LD de-escalation. Significant de-escalation-associated factors were age <75 years (odds ratio, 2.114; 95% confidence interval, 1.125-3.972), body mass index (BMI) ≥ 22.0 kg/m² (2.022; 1.073-3.811), and no atrial fibrillation (1.948; 1.047-3.625). The LD de-escalation rate tended to increase with the number of angiotensin receptor-neprilysin inhibitor, mineralocorticoid receptor antagonists, and sodium-glucose transporter 2 inhibitors initiated during hospitalization (<i>P</i> = .013).ConclusionYounger age, high BMI, and no atrial fibrillation were LD de-escalation-associated factors in patients with ADHF. LD de-escalation post-discharge may occur more frequently if the number of GDMT with diuretic effects was increased during hospitalization.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"31 ","pages":"10742484261431652"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147355162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Effect of Ticagrelor and Clopidogrel on Left Ventricular Remodeling in Acute Coronary Syndrome Patients: A Retrospective Cohort Study.","authors":"Fawaz H Tawhari, Mohammad F Zaitoun, Ehab Elmongui, Arwa Alhuwail, Ali Najmi, Wasayef M Alqahtani, Zeyad H Sabey, Atheer Almohammed, Abdulrahman Al Qahtani, Hani Sultan, Ahmed R N Ibrahim, Sultan Alshahrani, Reem Bahmaid","doi":"10.1177/10742484261433147","DOIUrl":"10.1177/10742484261433147","url":null,"abstract":"<p><p>BackgroundAcute coronary syndrome (ACS) remains a leading cause of mortality globally. Dual antiplatelet therapy (DAPT) is standard after percutaneous coronary intervention (PCI). While ticagrelor has demonstrated favorable myocardial effects in preclinical studies, limited clinical data compared its impact on left ventricular (LV) remodeling versus clopidogrel.ObjectiveTo evaluate and compare the effect of ticagrelor and clopidogrel on LV remodeling among ACS patients post-PCI.MethodsEligible participants were adults (≥18 years) with confirmed ACS who were prescribed ticagrelor or clopidogrel for at least 3 months after PCI and had complete echocardiographic data at baseline and within one-year follow-up. Patients with missing follow-up imaging, switching between antiplatelets, contraindications to DAPT, or noncompliance were excluded. Echocardiographic parameters-LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV ejection fraction (LVEF)-and B-type natriuretic peptide (BNP) were assessed, and multivariable regression models adjusted for confounders.ResultsA total of 137 patients met criteria (87 on ticagrelor, 50 on clopidogrel). Ticagrelor was associated with an adjusted LVEDV reduction of 8.17 mL compared with clopidogrel (95% CI -15.84 to -0.50; <i>P</i> = .039), an LVESV reduction of 8.09 mL (95% CI -13.88 to -2.29; <i>P</i> = .007), and a greater LVEF improvement of 4.05% (95% CI 2.41-5.70; <i>P</i> < .001). The reduction in BNP was also greater with ticagrelor by 73.56 pg/mL (95% CI -144.08 to -3.05; <i>P</i> = .043).ConclusionTicagrelor was associated with more favorable LV remodeling parameters compared with clopidogrel in this cohort. These findings warrant confirmation in randomized trials.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"31 ","pages":"10742484261433147"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147463475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shared Genetic Liability Between Heart Failure and Myocardial Infarction Revealed by Genome-Wide Cross-Trait Analysis.","authors":"Ruikang Liu, Chiyun Sun, Nan Jiang, Yang Liu, Jun Li, Fuyuan Zhang, Cong Chen, Yiying Liu, Xiaodi Qi, Bingting Guo, Kai Yang","doi":"10.1177/10742484261452728","DOIUrl":"10.1177/10742484261452728","url":null,"abstract":"<p><p>BackgroundThe extent and biological relevance of shared genetic architecture between myocardial infarction (MI) and heart failure (HF) remain incompletely understood.MethodsWe analyzed large-scale European-ancestry genome-wide association studies summary statistics for MI and HF. Genome-wide genetic correlation was estimated using linkage disequilibrium score regression, and polygenic overlap was quantified using MiXeR. Shared loci were identified via conditional and conjunctional false discovery rate (condFDR/conjFDR) approaches. Functional prioritization incorporated Functional Mapping and Annotation-based annotation, Bayesian fine-mapping, transcriptome-wide association studies (TWAS), FOCUS gene fine-mapping, and summary-level Mendelian randomization (SMR) integrating UKB-PPP proteomic data.ResultsLinkage disequilibrium score regression revealed a robust positive genetic correlation between MI and HF (rg = 0.494, <i>P</i> = 1.12 × 10^-15). MiXeR demonstrated substantial polygenic overlap, with approximately 90% of MI-associated variants shared with HF and strong concordance in effect direction. The cond/conjFDR analyses identified multiple pleiotropic loci, including novel HF-associated regions. Fine-mapping prioritized rs544366796 within the SLC22A2/SLC22A3 locus as a high-confidence candidate variant for MI based on posterior probability. The TWAS and FOCUS highlighted canonical MI genes (CDKN2B, CELSR2, BRAP, NBEAL1) and identified MYOZ1 as an HF-specific candidate gene. Proteome-wide SMR analysis provided statistical evidence consistent with apolipoprotein E being a shared protein influenced by variants associated with both MI and HF.ConclusionThe MI and HF share substantial genetic liability characterized by strong polygenic overlap and pleiotropic loci. Our integrative analyses suggest a potential 2-stage genetic framework linking ischemic susceptibility to myocardial remodeling and HF progression, which should be interpreted as a hypothesis-generating conceptual model rather than direct evidence of temporal progression.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"31 ","pages":"10742484261452728"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147959982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Underuse of Guideline-Directed Medical Therapy Across Heart Failure Phenotypes in Older Outpatients: A Multicenter Cross-Sectional Study in Vietnam.","authors":"Huan Thanh Nguyen, Huong Thi Mai Nguyen, Kieu Dang Phuong Nguyen, Duc Thien Tran","doi":"10.1177/10742484261438177","DOIUrl":"10.1177/10742484261438177","url":null,"abstract":"<p><p>BackgroundHeart failure (HF) is common among older adults; however, data on phenotype distribution and real-world pharmacologic management remain limited. This study assessed the prevalence of guideline-directed medical therapy (GDMT) underuse across HF phenotypes and identified factors associated with GDMT underuse among older outpatients in Vietnam.MethodsIn this multicenter cross-sectional study, 504 outpatients aged ≥60 years with HF were enrolled. Patients were classified into HF with reduced ejection fraction (HFrEF), mildly reduced ejection fraction (HFmrEF), and preserved ejection fraction (HFpEF). HFmrEF and HFpEF were combined as a non-HFrEF group for analysis. Multivariable logistic regression was performed to identify factors independently associated with GDMT underuse.ResultsHFrEF, HFmrEF, and HFpEF accounted for 54.6% (<i>n</i> = 275), 13.3% (<i>n</i> = 67), and 32.1% (<i>n</i> = 162) of patients, respectively. GDMT underuse was observed in 49.8% of patients with HFrEF and 38.0% of those with non-HFrEF phenotypes. In HFrEF, hypertension was associated with lower GDMT underuse (odds ratio [OR] 0.38; 95% confidence interval [CI] 0.15-0.98), whereas chronic obstructive pulmonary disease (COPD) was associated with higher underuse (OR 4.42; 95% CI [1.38-14.2]). In non-HFrEF, diabetes mellitus was independently associated with lower GDMT underuse (OR 0.52; 95% CI [0.30-0.91]).ConclusionIn this study, GDMT underuse was observed in nearly half of patients with HFrEF and over one-third of those with non-HFrEF phenotypes. In HFrEF, hypertension was associated with lower GDMT underuse and COPD with higher GDMT underuse, whereas in non-HFrEF, diabetes mellitus was independently associated with lower GDMT underuse.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"31 ","pages":"10742484261438177"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiomics Mendelian Randomization of GWAS, eQTL, and pQTL Combined With Drug Analysis to Predict Drug Targets in Myocardial Infarction.","authors":"Didi Yuan, Lian Hu, Yanqing Huang, Haotian Tang, Yuchen Ma, Sai Hu, Junwen Liu","doi":"10.1177/10742484261440344","DOIUrl":"10.1177/10742484261440344","url":null,"abstract":"<p><p>Despite significant advances in the management of myocardial infarction (MI), therapeutic options targeting upstream pathogenic mechanisms remain scarce. This study introduces a novel multiomics-to-drug discovery framework to identify and validate causal therapeutic targets for MI. We conducted a systematic two-sample Mendelian randomization (MR) analysis integrating expression quantitative trait loci (eQTL) and protein quantitative trait loci (pQTL) data from the IEU OpenGWAS database, with replication in the UK Biobank cohort. Causal inference was rigorously validated using HEIDI heterogeneity tests, Bayesian colocalization, bidirectional MR, and multivariate MR (MVMR) to account for potential confounders. Downstream applications were explored via protein-protein interaction (PPI) network analysis, phenome-wide association studies (PheWAS), and molecular docking simulations. Initial screening identified four candidate genes (BMP1, APOB, FABP2, and ALDH2) associated with MI risk in both discovery and replication cohorts. However, only BMP1 demonstrated consistent causal effects at both transcriptional and proteomic levels, passing all sensitivity analyses with no evidence of horizontal pleiotropy in PheWAS. Colocalization and bidirectional MR further confirmed BMP1 as a robust, independent causal driver of MI. Molecular docking revealed that UK-383367, a selective BMP1 inhibitor, exhibits high binding affinity to the BMP1 active site. While BMP1 is traditionally associated with extracellular matrix remodeling, this study provides the first genetic evidence establishing it as an independent causal risk factor for MI, distinct from conventional traits such as hypertension. By bridging causal genetic inference with structure-based drug prediction, we propose BMP1 inhibition, specifically via agents like UK-383367, as a promising therapeutic strategy to mitigate MI-related pathological remodeling.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"31 ","pages":"10742484261440344"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147690275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}