Journal of Cardiovascular Pharmacology最新文献

Abstract: In this study, we compared the effects of various doses of dexmedetomidine on the incidence of atrial fibrillation (AF) after cardiac surgery in adults. A total of 224 adult patients who underwent elective cardiac surgery were randomly assigned to two groups. The DEX0.5 group received a continuous infusion of dexmedetomidine at a rate of 0.5 μg·kg⁻ 1 ·h⁻ 1 , while the DEX1 group received it at a rate of 1 μg·kg⁻ 1 ·h⁻ 1 during the induction of anesthesia, which was maintained for 24 hours. The primary outcome was the incidence of AF, while the secondary outcomes included other tachyarrhythmias, bradycardia, hypotension, duration of mechanical ventilation, time spent in the cardiac care unit, and length of hospitalization. A total of 101 patients were included in the DEX0.5 group, while 104 patients were included in the DEX1 group. The incidence of AF was significantly lower in the DEX1 group compared with the DEX0.5 group (10.6% vs. 21.8%, P = 0.029). In addition, the duration of mechanical ventilation was shorter in the DEX1 group than in the DEX0.5 group (8.9 vs. 15.2 hours, P = 0.018). Logistic regression analyses were conducted to investigate the factors influencing AF. The results indicated that the dose of dexmedetomidine was the only independent predictor (odds ratio = 0.394, 95% confidence interval 0.172 to 0.903, P = 0.028). Compared with a continuous infusion of 0.5 μg·kg⁻ 1 ·h⁻ 1 , this study suggested that administering dexmedetomidine at a dose of 1 μg·kg⁻ 1 ·h⁻ 1 for 24 hours is effective in reducing the incidence of AF after cardiac surgery.

Abstract: Acute coronary syndromes (ACS) continue to pose significant challenges for clinical practitioners, particularly regarding the prediction of mid- to long-term outcomes. This study aims to investigate the impact of in-hospital bleeding (IHB) at 1-year follow-up in patients admitted for ACS. Data from 23,270 patients enrolled in the international PRAISE registry and discharged after ACS were analyzed. A total of 1060 patients experienced IHB, whereas 18,765 did not; 3445 were excluded because of missing data. The primary endpoint was all-cause mortality at 1 year. Secondary endpoints included major bleeding, reinfarction, and composite endpoints at 1 year. Patients with IHB were older, more frequently female, and had a higher prevalence of cardiovascular risk factors (all P < 0.05). At discharge, IHB patients were less likely to receive optimal medical therapy. At the 1-year follow-up, all-cause mortality, major bleeding, and reinfarction were significantly higher in the IHB group (all P s < 0.001). Bivariate analysis showed a strong association between IHB and all the outcomes of interest (all odds ratios >1; all P s < 0.001). These associations remained significant even after adjusting for several covariates, except for reinfarction (odds ratio 1.3; 95% confidence interval 0.9-2.11; P = 0.149). Age, female sex, hypertension, and peripheral artery disease were found to be independent predictors of IHB, whereas drug-eluting stent implantation, radial access, and left ventricular ejection fraction were identified as protective factors. IHB is a hallmark of frailty in patients with ACS; therefore, greater attention should be given during follow-up to patients experiencing this condition.

Abstract: Immuno-cardiology is an emerging field that explores the interplay between the immune system, inflammation, and cardiovascular health/disease, aiming to develop innovative therapies for preventing and treating cardiac diseases. Indeed, chronic inflammation and immune dysregulation play pivotal roles in most cardiovascular conditions, including arrhythmias, atherothrombosis, ischemic heart disease, heart failure, and valve disease. Recent advances in immune-based therapies, including chimeric antigen receptor-T and chimeric antigen receptor-macrophage technologies, have demonstrated potential in impacting on cardiac fibrosis and thus improving surrogate end points in preclinical studies. Immune checkpoint inhibitors, while already established as an effective intervention in oncology, present challenges in their cardiovascular applications because of cardiotoxic side effects, highlighting the need for dedicated cardioprotective strategies or further molecular refinements. Nanoparticle-based delivery systems and cytokine-targeted therapies may offer precise modulation of immune responses, while gut microbiota interventions could exploit the systemic impact of inflammation on cardiovascular health. Despite these quite promising advances, barriers such as safety, scalability, and patient-specific responses must be addressed, and thus precision and personalized approaches will be crucial to overcoming these challenges and ensuring safe and also equitable access. By leveraging interdisciplinary collaboration and technological innovations, immuno-cardiology holds the promise of transforming the prevention and treatment landscape for cardiac diseases, paving the way for improved outcomes and quality of life for patients worldwide.

Abstract: The NC1 domains of collagens have been shown to possess antiangiogenic potential and, therefore, are of therapeutic interest for cancer. However, endostatin and other NC1 domains have not been successful in clinical tests. Therefore, we used evolutionary conservation to perform molecular deconstruction of the domains to further understand their structure-activity relationship, thereby deciphering their antiangiogenic potential. Homology exploration revealed that collagen type X contains a highly interesting NC1 domain (decastatin), with several sequences showing significant homology with vastatin, which is a known collagen type VIII-derived NC1 domain. For comparison, endostatin and vastatin were split into fragments, some of which contained highly conserved regions. The testing of these peptides revealed that the peptides containing conserved regions induced signaling, and fragment 4 of decastatin showed the highest potency of all fragments, with a calculated inhibitory concentration value of 2.7 μM in the human umbilical vein endothelial cell-based tube formation assay, which is like that of an intact NC1 domain. Notably, the corresponding fragment from vastatin (V4) also inhibited tube formation, suggesting that this region is of therapeutic interest. In summary, we used evolutionary conservation to identify a novel NC1 domain of collagen type X, a collagen playing a role in angiogenesis of the growth plate. Furthermore, we provided data indicating that the antiangiogenic activity of NC1 domain-derived peptides reside within their conserved domains. As a result, we identified a fragment called Decastatin fragment 4 (D4) derived from the NC1 domain of collagen type X, and which has potent antiangiogenic activity.

Abstract: Hypertension is a major risk factor for cardiovascular disease, and a major contributor to global morbidity and mortality. In particular, resistant hypertension (rHTN), defined as blood pressure that remains elevated despite treatment with at least three antihypertensive agents including a diuretic, continues to be a major pharmacotherapeutic challenge. Traditional antihypertensive drugs often fail in patients with rHTN, underscoring the need for novel therapies. This is a brief mini-review of aprocitentan, a new drug that promises a glimmer of hope for patients with rHTN. This drug is a dual endothelin (ET) receptor antagonist that blocks both ET A and ET B receptors. Given that these two receptors are critical players in vasotone regulation, antagonizing them, such as by aprocitentan, would be expected to significantly reduce blood pressure in patients with rHTN. Indeed, the PRECISION clinical trial demonstrated aprocitentan's superior effectiveness in reducing blood pressure in resistant patients, and the effects were sustained. Aprocitentan has been recently FDA-approved, marking a major milestone in hypertension management, offering hope for patients with difficult-to-treat hypertension.

Abstract: Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme that facilitates the biologic metabolism of nitroglycerin. However, no study investigated the association between ALDH2 gene polymorphism and the vasodilation of coronary arteries after intracoronary administration of nitroglycerin. In this study, we enrolled 427 patients with suspected angina pectoris. ALDH2 genotyping was performed and all patients were given 200 µg nitroglycerin in the right coronary artery during the coronary angiography. The invasive hemodynamic parameters including systolic blood pressure (SBP), diastolic blood pressure, and heart rate were monitored. The reference diameter and stenosis diameter of the right coronary artery were measured with the Stenosis Analysis 1.6 software. Both wild-type and mutant-type groups exhibited significant decreases in SBP, diastolic blood pressure values, and increases in heart rate value after administration of nitroglycerin ( P < 0.05). The wild-type group showed significantly higher absolute difference values in SBP than the mutant-type group ( P < 0.05). The mutant-type group exhibited significantly lower difference values and rates of change in reference diameter than the wild-type group [0.3 ± 0.3 vs. 0.5 ± 0.2, P < 0.001 for the difference value of diameter; 9.6 ± 9.5 vs. 15.8 ± 8.5, P < 0.001 for the rate of change (%)]. Conversely, no differences were observed between the wild-type and mutant-type groups in terms of the difference value and rate of change of the stenosis diameter ( P > 0.05). In conclusion, ALDH2 gene polymorphism (Glu504Lys) is associated with changes in invasive hemodynamic parameters and coronary artery diameter after intracoronary injection of nitroglycerin.

Abstract: Large scale randomized trials have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors can reduce cardiovascular events in patients with cardiovascular disease or with increased risks of cardiovascular disease. However, the evidence from older patients is limited. To compare the efficacy of SGLT2 inhibitors among nonolder and older patients, we have searched PubMed, Cochrane Central, and Embase until February 2023 for randomized controlled trials investigating SGLT2 inhibitors in older (age ≥65 years) patients with diabetes mellitus, chronic kidney disease, and chronic heart failure. The primary outcome was a composite outcome of cardiovascular death, acute myocardial infarction, and stroke. The secondary outcomes were exacerbation of heart failure, kidney disease progression, and a composite of cardiovascular death and heart failure. Our search identified 11 randomized controlled trials with a total of 79,370 patients. SGLT2 inhibitors were associated with a reduced risk of the primary outcome in the total cohort [hazard ratio (HR): 0.91; confidence intervals (CI), 0.84-0.99] with concordant results in both nonolder and older populations (HR: 0.96; CI, 0.88-1.05, HR: 0.87; CI, 0.75-1.01, respectively) without subgroup differences ( P = 0.23), and a reduced risk of developing the composite of cardiovascular death and heart failure exacerbation in both nonolder and older populations (HR: 0.77; CI, 0.67-0.87, HR: 0.76; CI, 0.71-0.82, respectively) without subgroup differences ( P = 0.96). A meta-analysis could not be performed for the other outcomes. These results suggested that SGLT2 inhibitors were similarly associated with reduced risks of cardiovascular events across the spectrum of nonolder and older patients with risk factors for developing cardiovascular disease.