Journal of Cardiovascular Pharmacology and Therapeutics最新文献

Background: The effect of combined nicorandil and beta-adrenergic receptor blockers (BBs) compared with that of BBs alone on long-term clinical outcomes in patients with coronary artery disease (CAD) remains undetermined.

Methods: A multicenter retrospective cohort study was performed. Adult patients who had been hospitalized for CAD and treated for angina with a combination of nicorandil and BBs or BBs alone were included. The effect of different treatments on the cumulative incidence of major adverse cardiovascular event (MACE) and their components within a follow-up duration of 2.5 years were analyzed using Kaplan-Meier survival curves. An inverse probability of treatment weighting (IPTW) method was used to adjust for the possible effect of confounding factors.

Results: A total of 137,714 patients were screened, of whom 16,912 individuals (mean age: 61.5 years, men: 67.1%) were successfully enrolled. Among the enrolled participants, 4669 received the combined treatment of nicorandil and BBs, while 12,243 received BBs alone. After IPTW, the results demonstrated that the combined treatment was associated with a significantly reduced incidence of MACE (hazard ratio [HR] 0.79, 95% conidence interval [CI] 0.72-0.87) and stroke (HR 0.48, 95% CI 0.42-0.54) but not of MI (HR 1.03, 95% CI 0.92-1.15) or all-cause mortality (HR 0.93, 95% CI 0.64-1.37). Sensitivity analyses revealed similar results.

Conclusions: A combined antiangina treatment of nicorandil and BBs may be more effective than treatment of BBs alone in reducing the long-term incidence of MACE in patients with CAD.

Objective: To investigate the protective effect of nicorandil on contrast-induced acute kidney injury (CIAKI) in patients with acute ST-segment elevation myocardial infarction (STEMI) after emergency percutaneous coronary intervention (PCI). Methods: This is a single-center, retrospective control study. A total of 156 patients with STEMI were divided into the nicorandil group (n  =  55) and the control group (n  =  101). The incidence of CIAKI, defined as an increase of >25% or absolute values > 44.2 μmol/L in serum creatinine (Scr) from baseline within 72 h of exposure to a contrast agent after exclusion of other causes, was the primary endpoint. The secondary endpoints were: (1) changes of Scr, estimated glomerular filtration rate (eGFR), uric acid, and β2-microglobulin at 24/48/72 h and 5 to 7 days after PCI; (2) the peak value difference of creatine kinase isoenzymes (CK-MB) after PCI; (3) adverse events within 6 months after PCI. Results: The overall incidence of CIAKI was 21.8%; the incidence of CIAKI in the nicorandil group was significantly lower (12.7% [7/55]) than in the control group (26.7% [27/101]) (P  =  .043). Compared with the control group, Scr, uric acid, and β2-microglobulin levels were lower, and the level of eGFR was higher in nicorandil group (P all < .05). The peak value of CK-MB in the nicorandil group was lower than that in the control group (105.30 [56.61, 232.04] vs 178.00 [77.08, 271.91]U/L, P  =  .042). There was no significant difference in adverse events between the 2 groups within 6 months after PCI. Moreover, multivariate logistic regression analysis showed that hypertension and diabetes were independent risk factors for CIAKI, while nicorandil treatment was a protective factor. Conclusion: Our data suggest that intravenous nicorandil after emergency PCI has a protective effect on the occurrence of CIAKI in STEMI patients.

Introduction: This study evaluated the efficacy and safety of a single-pill triple-combination of olmesartan/amlodipine/rosuvastatin (Olme/Amlo/Rosu) in comparison with a single-pill dual-combination of olmesartan/amlodipine (Olme/Amlo) in hypertensive patients with low-to-moderate cardiovascular risk.

Methods: This multicenter, active-control, randomized study included 106 hypertensive patients at low-to-moderate cardiovascular risk who were randomly assigned to receive either Olme/Amlo/Rosu 20/5/5 mg (Treatment 1), Olme/Amlo/Rosu 20/5/10 mg (Treatment 2), or Amlo/Olme 20/5 mg (Control) once daily for 8 weeks. The primary endpoint was the difference of the percent change in low-density lipoprotein cholesterol (LDL-C) level at 8 weeks from baseline in the 3 groups.

Results: The difference in the least square mean percent change (standard deviation) of LDL-C in the Treatment 1 and 2 groups compared with the Control group at 8 weeks was -32.6 (3.7) % and -45.9 (3.3) %, respectively (P < .001). The achievement rates of LDL-C level <100 mg/dL at 8 weeks were significantly different between the 3 groups (65.8%, 86.7%, and 6.3% for Treatment 1, 2, and Control groups, respectively, P < .001). The results of total cholesterol, triglycerides, high-density lipoprotein cholesterol, apolipoprotein B, and apolipoprotein B/apolipoprotein A1 were superior in the Treatment 1 and 2 groups compared with the Control group. Serious adverse drug reaction did not occur in the 3 groups. Medication adherence rates were excellent in the 3 groups (98.0% for Treatment 1 group, 99.7% for Treatment 2 group, and 96.3% for the Control group, P > .05).

Conclusion: Single-pill triple-combination of olmesartan/amlodipine/rosuvastatin was superior to the single-pill dual-combination of amlodipine/olmesartan in LDLC-lowering effects, with excellent safety profiles and adherence rates, in hypertensive patients at low-to-moderate cardiovascular risk.Trial Registration: CLinicalTrials.gov identifier NCT04120753.

Introduction: Both exercise and pre-meal metformin could lower postprandial glucose and lipid profiles.

Aims: To explore whether pre-meal metformin administration is superior to metformin administration with the meal in reducing postprandial lipid and glucose metabolism, and whether its combination with exercise confer superior benefits in metabolic syndrome patients.

Materials and methods: In a randomized crossover design, 15 metabolic syndrome patients were assigned to 6 sequences including 3 experimental conditions: metformin administration with a test meal (met-meal), metformin administration 30 min prior to a test meal (pre-meal-met) with or without an exercise bout designed to expend 700 Kcal at 60% VO₂ peak performed the evening just before pre-meal-met condition. Only 13 participants (3 males, 10 females; age: 46 ± 9.86, HbA1c: 6.23 ± 0.36) were included in the final analysis.

Results: Postprandial triglyceridemia was unaffected by any condition (all P > .05). However, both pre-meal-met (-7.1%, P = .009) and pre-meal-metx (-8.2%, P = .013) significantly reduced total cholesterol AUC with no significant differences between the two latter condition (P = .616). Similarly, LDL-cholesterol levels were significantly lower during both pre-meal-met (-10.1%, P = .013) and pre-meal-metx (-10.7%, P = .021) compared to met-meal with no difference between latter conditions (P = .822). Plasma glucose AUC was significantly reduced by pre-meal-metx compared to both pre-meal-met (-7.5%, P = .045) and met-meal (-8%, P = .03). Insulin AUC was significantly lower during pre-meal-metx compared to met-meal (-36.4%, P = .044).

Conclusions: Metformin administration 30 minutes prior to meal seems to exert favorable effects on postprandial TC and LDL-Cholesterol levels compared to its administration with meal. Addition of one exercise bout only improved postprandial glycemia and insulinemia.

Trial registry: Pan African clinical trial registry, Identifier PACTR202203690920424.

Objective: To investigate the safety and effectiveness of catheter-based therapy (CBT) compared to conventional catheter-directed thrombosis (CDT) for non-oncological patients with inferior vena cava thrombosis (IVCT), as well to evaluate the differences between CBTs using AngioJet rheolytic thrombectomy (ART) and large lumen catheter aspiration (LLCA).

Methods: This retrospective single-center study included eligible patients with IVCT treated with CBTs coupled with/without CDT or CDT alone as the first-line treatment between January 3, 2015 and January 28, 2022. The baseline demographics, comorbidities, clinical characteristics, treatment details, course data were all reviewed.

Results: A total of 106 patients (128 limbs) were included, with 42 cases were treated with ART, 30 with LLCA, and 34 with CDT alone. Technical success rates were 100% (128/128), and 95.5% (84/88) limbs treated with CBT subsequently underwent CDT. The mean duration of CDT time and total infusion agent dosage in patients with CBTs were lower than those who underwent CDT alone (P < .05). Similarities were observed in ART compared to LLCA (P < .05). At the end of CDT, clinical success was achieved in 85.2% (75/88) of limbs treated with CBTs and 77.5% (31/40) of limbs with CDT alone, and 88.5% (46/52) in ART and 80.6% (29/36) in LLCA. The 12-month follow-up showed slightly lower incidences of recurrent thrombosis (7.7% vs 15.2%) and post-thrombotic syndrome (14.1% vs 21.2%), which persisted in patients who underwent ART compared to LLCA (4.3% vs 12.9% and 8.5% vs 22.6%). Patients who underwent CBTs tended to have lower minor complications (5.6% vs 17.6%) but were at higher risk of transient macroscopic hemoglobinuria (58.3% vs 0%) and recoverable acute kidney injury (11.1% vs 2.9%) compared to CDT alone. These findings were similar in ART compared to LLCA (2.4% vs 10.0%, 100% vs 0%, and 16.7% vs 3.3%, respectively). LLCA seemed to have more hemoglobin losses (10.50 ± 9.20 vs 5.57 ± 10. 42 g/L, P < .05).

Conclusion: CBTs coupled with/without CDT are safe and effective in patients with IVCT, reducing the clot burden in a moderate time, restoring blood flow rapidly, minimizing thrombolytic drug requirement and lowering minor bleeding complication compared to CDT alone. ART and LLCA have comparable outcomes but with different adverse event profiles.

Background: Heart failure (HF) is an important adverse outcome of diabetes mellitus (DM) with high rates of mortality and HF-related hospitalizations. The risk of HF is 2 times higher in patients with DM compared to those without DM. Due to under-recognition and underdiagnoses, HF is often a neglected outcome in the diabetic population. There is a dearth of data regarding the true prevalence of HF and the management protocols for diabetic patients at risk of HF in the UAE and the Middle East. This lacuna in the information has led to the inception of this "call to action" paper, which identifies the gaps in the true prevalence of HF and describes the importance of early diagnosis and appropriate management of HF in the Middle East.

Methodology: An advisory board meeting was convened and a group of key opinion leaders and experts in cardiology and endocrinology assembled to describe the prevalence, diagnosis, and management of HF in diabetes patients and to present a "call to action" in the UAE and Middle East scenario. After the group discussion, key expert opinions were formulated and "call to action" recommendations were proposed.

Conclusion: This "call to action" is mainly based on the available evidence from the literature and the experts' clinical experience. Based on the new evidence from various cardiovascular outcome trials, the "call to action" highlights a series of collaborative learning regarding the role of newer antidiabetic therapies like sodium-glucose cotransporter-2 inhibitors in the prevention and management of HF. This "call to action" intends to serve as a guide for physicians, including primary healthcare providers, in their management of diabetic patients with HF.

Backgrounds: Our study aimed to identify and predict patients with heart failure (HF) taking novel-dose Sacubitril/Valsartan (S/V) at risk for all-cause readmission, as well as investigate the possible role of left ventricular reverse remodeling (LVRR). Methods and results: There were 464 patients recruited from December 2017 to September 2021 in our hospital with a median follow-up of 660 days (range, 17-1494). Competing risk analysis with Gray's Test showed statistically significant differences in all-cause readmission (p-value< .001) across the three different dose groups. Models 1 and 2 were developed based on the results of univariable competing risk analysis, least absolute shrinkage and selection operator approach, backward stepwise regression, and multivariable competing risk analysis. The internal verification (data-splitting method) indicated that Model 1 had better discrimination, calibration, and clinical utility. The corresponding nomogram showed that patients aged 75 years and above, or taking the lowest-dose S/V (≤50 mg twice a day), or diagnosed with ventricular tachycardia, or valvular heart disease, or chronic obstructive pulmonary disease, or diabetes mellitus were at the highest risk of all-cause readmission. In the causal mediation analysis, LVRR was considered as a critical mediator that negatively affected the difference of novel-dose S/V in readmission. Conclusions: A significant association was detected between novel-dose S/V and all-cause readmission in HF patients, in part negatively mediated by LVRR. The web-based nomogram could provide individual prediction of all-cause readmission in HF patients receiving novel-dose S/V. The effects of different novel-dose S/V are still needed to be explored further in the future.

Diabetes is a long-term chronic disease, and cardiovascular disease is the leading cause of death. Diabetic cardiomyopathy (DCM), one of the cardiovascular complications of diabetes, has many uncertain factors. Epicardial fat, as the heart fat bank, functions as fatty tissue and is the heart's endocrine organ. The existence of diabetes affects the distribution of heart fat and promotes the secretion of adipokine. In different pathological conditions, it can promote the secretion of pro-inflammatory adipokine, reactive oxygen species, oxidative stress, and even autophagy, thus affecting cardiac function. In this paper, we will elaborate on the mechanism of epicardial fat in the pathogenesis of diabetic cardiomyopathy.

Purpose: We investigated the effects of exposure to electronic cigarettes (E-cig) vapor on the sizes of the no-reflow and myocardial infarction regions, and cardiovascular function compared to exposure to purified air and standard cigarette smoke.

Methods and results: Sprague Dawley rats (both male and female, 6 weeks old) were successfully exposed to filtered air (n = 32), E-cig with nicotine (E-cig Nic⁺, n = 26), E-cig without nicotine (E-cig Nic^-, n = 26), or standard cigarette smoke (1R6F reference, n = 31). All rats were exposed to inhalation exposure for 8 weeks, prior to being subjected to 30 minutes of left coronary artery occlusion followed by 3 hours of reperfusion. Exposure to E-cig vapor with or without nicotine or exposure to standard cigarettes did not increase myocardial infarct size or worsen the no-reflow phenomenon. Exposure to E-cig Nic⁺ reduced the body weight gain, and increased the LV weight normalized to body weight and LV wall thickness and enhanced the collagen deposition within the LV wall. E-cig exposure led to cardiovascular dysfunction, such as reductions in cardiac output, LV positive and negative dp/dt, suggesting a reduction in contractility and relaxation, and increased systemic arterial resistance after coronary artery occlusion and reperfusion in rats compared to air or cigarette exposure.

Conclusions: E-cig exposure did not increase myocardial infarct size or worsen the no-reflow phenomenon, but induced deleterious changes in LV structure leading to cardiovascular dysfunction and increased systemic arterial resistance after coronary artery occlusion followed by reperfusion.

Background: Hyperlipidemia is one of the independent risk factors for the onset of coronary heart disease (CHD), and our aim is to construct a coronary risk prediction model for patients with hyperlipidemia based on carotid ultrasound in combination with other risk factors.

Methods: The nomogram risk prediction model is based on a retrospective study on 820 patients with hyperlipidemia. The predictive accuracy and discriminative ability of the nomogram were determined by receiver operating characteristic (ROC) curves and calibration curves. The results were validated using bootstrap resampling and a prospective study on 39 patients with hyperlipidemia accepted at consenting institutions from 2021 to 2022.

Result: In the modeling cohort, 820 patients were included. A total of 33 variables were included in univariate logistic regression. On multivariate analysis of the modeling cohort, independent factors for survival were sex, age, hypertension, plaque score, LVEF, PLT, and HbAlc, which were all selected into the nomogram. The calibration curve for probability of survival showed good agreement between prediction by nomogram and actual observation. The area under the curve (AUC) of the nomogram model was 0.881 (95% CI 0.858∼0.905), with a sensitivity of 79% and a specificity of 81.7%. In the validation cohort, the AUC was 0.75, 95% CI (0.602∼0.906). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of this model were 54.16%, 80%, 81.25%, 52.17% and 64.1%. This model showed a good fitting and calibration and positive net benefits in decision curve analysis.

Conclusion: A nomogram model for CHD risk in patients with hyperlipidemia was developed and validated using 7 predictors, which may have potential application value in clinical risk assessment, decision-making, and individualized treatment associated with CHD.