Journal of Cardiovascular Pharmacology and Therapeutics最新文献

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.

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.

Objective: The triglyceride-glucose (TyG) index is a simple and reliable surrogate for insulin resistance. Recent studies have suggested that the TyG index is an independent predictor of cardiovascular disease. However, the prognostic value of the TyG index in patients with acute myocardial infarction (AMI) remains uncertain. Thus, this study aimed to evaluate the prognostic value of the TyG index in patients with AMI. Methods: AMI patients admitted to Zhongda Hospital from 2018 to 2020 were successively enrolled. After screening the inclusion criteria, 1144 patients were divided into three groups according to the tertiles of the TyG index distribution. Patients were followed up for 1 year as outpatients or contacted via telephone, and the occurrence and timing of all-cause deaths were recorded. Results: The TyG index was significantly correlated with heart failure (HF) in AMI patients. Patients with a high TyG index (group 3) (odds ratio: 9.070, 95% confidence interval [CI] 4.359-18.875, P＜.001) had a significantly higher incidence of HF compared with patients with median TyG index (group 2). Similarly, the incidence of all-cause death in group 3 was significantly higher than that in group 2 during the 1-year follow-up (hazard ratio: 2.996, 95% CI 1.058-8.487, P = .039). Conclusion: The TyG index is closely related to HF and may be a valuable indicator to predict the long-term prognosis of patients with AMI.

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.

Aims: In recent large trials, sacubitril/valsartan demonstrated favorable effects in patients with HF. However, many patients do not achieve the target dose of treatment. This study investigated the factors linked to up-titration of sacubitril/valsartan in patients with heart failure and preserved ejection fraction (HFpEF).

Methods: Using a multicenter retrospective database, 204 consecutive patients with HFpEF (left ventricular ejection fraction ≥ 40%) who were treated with sacubitril/valsartan between October 2020 and March 2022 were analyzed. Up-titration was defined as an increase in dosage above 24/26 mg BID beyond 12 weeks after the initiation of sacubitril/valsartan.

Results: Among the patients, 55% underwent up-titration, and 8% discontinued the drug. The baseline systolic blood pressure (SBP) was higher in patients with up-titration than in those with no up-titration; SBP values similar to that at baseline were observed between the 2 groups at 2 to 4 weeks and at 12 weeks after the commencement of sacubitril/valsartan treatment. The majority of those who discontinued sacubitril/valsartan did so because of hypotension. The multivariable logistic regression model showed that a history of hypertension, history of atrial fibrillation, baseline SBP, and baseline estimated glomerular filtration rate <60 mL/min/1.73 m² were associated with sacubitril/valsartan up-titration.

Conclusion: Approximately half of all patients did not undergo up-titration, and 8% of those with HFpEF discontinued the sacubitril/valsartan therapy. For aggressive up-titration and continuation of sacubitril/valsartan, patients with lower baseline SBP, renal dysfunction, absence of a history of hypertension, and presence of atrial fibrillation may require more careful monitoring.

Background: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are low-density lipoprotein cholesterol (LDL-C)-lowering drugs that play a critical role in lipoprotein clearance and metabolism. PCSK9i are used in patients with familial hypercholesterolemia and for the secondary prevention of acute cardiovascular events in patients with atherosclerotic cardiovascular disease (CVD). Methods: We focused on the literature from 2015, the year of approval of the PCSK9 monoclonal antibodies, to the present on the use of PCSK9i not only in the lipid field but also by evaluating their effects on metabolic factors. Results: PCSK9 inhibits cholesterol efflux from macrophages and contributes to the formation of macrophage foam cells. PCSK9 has the ability to bind to Toll-like receptors, thus mediating the inflammatory response and binding to scavenger receptor B/cluster of differentiation 36. PCSK9i lower the entire spectrum of apolipoprotein B-100 containing lipoproteins (LDL, very LDLs, intermediate-density lipoproteins, and lipoprotein[a]) in high CVD-risk patients. Moreover, PCSK9 inhibitors are neutral on risk for new-onset diabetes mellitus and might have a beneficial impact on the development of nonalcoholic fatty liver disease by improving lipid and inflammatory biomarker profiles, steatosis biomarkers such as the triglyceride-glucose index, and hepatic steatosis index, although there are no comprehensive studies with long-term follow-up studies. Conclusion: The discovery of PCSK9i has opened a new era in therapeutic management in patients with hypercholesterolemia and high cardiovascular risk. Increasingly, there has been mounting scientific and clinical evidence supporting the safety and tolerability of PCSK9i.

The indications of direct oral anticoagulants (DOACs) have expanded over the past 15 years. DOACs are effective and safe oral anticoagulants associated with lower bleeding risks and mortality than vitamin K antagonists. However, DOAC users are prone to a considerable bleeding risk, which can occur at critical sites or lead to severe life-threatening conditions. Recent statistics indicated that major bleeding occurs in up to 6.62 DOAC users per 100 treatment years. With the increased use of DOACs in clinical practice, DOAC-associated major bleeding is expected to be encountered more frequently in the emergency department. The current international guidelines recommend specific reversal agents for the management of DOAC users with severe bleeding to reverse the anticoagulant effect and restore normal hemostasis. An individualized assessment was incorporated in specific clinical situations to guide the decision pathway of major bleeding management. However, specific reversal agents are unavailable or have limited availability in many countries, which is expected to negatively impact the clinical outcomes of DOAC-associated major bleeding. Limited real-world evidence is available from these countries regarding the clinical outcomes of patients with DOAC-associated major bleeding. This narrative review provided an updated assessment of the evidence-based approaches for the management of major bleeding in DOAC users. We also explored the clinical outcomes of patients with major bleeding from clinical settings where specific reversal agents are unavailable.

Introduction: Metabolic syndrome (MS) is associated with abnormalities in atrial mechanics, atrial remodeling, and an increased risk of heart rhythm disorders. One of the most commonly used approaches to the prevention of cardiac remodeling in arterial hypertension is the administration of renin-angiotensin system (RAS) inhibitors. Therefore, this study aimed to investigate the effects of RAS inhibitors on atrial mechanics parameters in patients with MS.

Methods and materials: This longitudinal observational study included 55 patients with hypertension and MS, as defined by the ATP III criteria. The patients were evaluated at the start of antihypertensive treatment with an RAS inhibitor. The patients' clinical characteristics, chosen pharmacological treatment, and transthoracic echocardiography findings were recorded at baseline and 6 months thereafter. A student's dependent sample t-test was used for comparisons between groups. Pearson correlation was used to evaluate the relationships between variables.

Results: Patients with MS had higher peak atrial longitudinal strain (PALS) values at 6 months than at baseline. Meanwhile, systolic strain and peak late strain rates were lower at follow-up than at baseline. The different antihypertensive treatments had comparable effects on the PALS changes during the follow-up period. Higher high-density lipoprotein levels at baseline were correlated with changes in PALS.

Conclusion: The administration of RAS inhibitors improved atrial mechanics parameters in the early stages of antihypertensive management in MS.