Journal of Cardiovascular Pharmacology and Therapeutics最新文献

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.

The prevalence of atrial fibrillation (AF) in acute coronary syndrome (ACS) patients is increasing. Data on outcomes of anticoagulation in ACS patients with AF are lacking.

The aim of our study was to investigate the prevalence of stroke, myocardial infarction, bleeding complications, and all-cause mortality in this population.

PL-ACS and AMI-PL registries gather an all-comer population of ACS patients in Poland, exceeding half a million records. We have selected ACS survivors with concomitant AF on admission, divided them into subgroups with regard to the administered anticoagulation, and followed up with them for a 12-month period (n = 13,973). Subsequently, groups were propensity score matched for age, sex, ejection fraction, diabetes, heart failure, renal impairment, and type of ACS.

The study population was divided with regard to the administration of anticoagulation. Anticoagulation was prescribed in 2,466 patients (17.6%). The (D)OAC+ patients were younger; however, comorbidities were more prevalent in this group. The 12-month follow-up showed that the (D)OAC+ patients had significantly lower rates of all-cause mortality, myocardial infarction, and ischemic stroke, with no significant increase in bleeding events. After matching, the study groups consisted of 2,194 patients each and showed no differences in baseline characteristics. The outcomes of the 12-month observation were similar to the findings before matching.

This all-comer national registry analysis shows that the use of guideline-recommended therapy and anticoagulation in ACS survivors with AF is associated with a lower rate of all-cause mortality, recurrent myocardial infarction, and ischemic stroke.

Background and aims: Esmolol is a common short-acting drug to control ventricular rate. This study aimed to evaluate the association between use of esmolol and mortality in critically ill patients.

Methods: This is a retrospective cohort study from MIMIC-IV database containing adult patients with a heart rate of over 100 beats/min during the intensive care unit (ICU) stay. Multivariable Cox proportional hazard models and logistic regression were used to explore the association between esmolol and mortality and adjust confounders. A 1:1 nearest neighbor propensity score matching (PSM) was performed to minimize potential cofounding bias. The comparison for secondary outcomes was performed at different points of time using an independent t-test.

Results: A total of 30,332 patients were reviewed and identified as critically ill. There was no significant difference in 28-day mortality between two groups before (HR = 0.90, 95% CI = 0.73-1.12, p = 0.343) and after PSM (HR = 0.84, 95% CI = 0.65-1.08, p = 0.167). Similar results were shown in 90-day mortality before (HR = 0.93, 95% CI = 0.75-1.14, p = 0.484) and after PSM (HR = 0.85, 95% CI = 0.67-1.09, p = 0.193). However, esmolol treatment was associated with higher requirement of vasopressor use before (HR = 2.89, 95% CI = 2.18-3.82, p < 0.001) and after PSM (HR = 2.66, 95% CI = 2.06-3.45, p < 0.001). Esmolol treatment statistically reduced diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (all p < 0.001) and increased fluid balance at 24 hours (p < 0.05) but did not significantly lower SBP (p = 0.721). Patients in esmolol group showed no significant difference in lactate levels and daily urine output when compared with those in non-esmolol group when adjusted for confounders (all p > 0.05).

Conclusion: Esmolol treatment was associated with reduced heart rate and lowered DBP and MAP, which may increase vasopressor use and fluid balance at the timepoint of 24 hours in critically ill patients during ICU stay. However, after adjusting for confounders, esmolol treatment was not associated with 28-day and 90-day mortality.

Introduction: Ticagrelor might reduce infarct size by exerting a more potent antiplatelet effect or by promoting a potential conditioning stimulus in ST-elevation myocardial infarction (STEMI) patients. Pre-infarction angina (PIA) is an effective preconditioning stimulus that reduces ischemia-reperfusion injury. Because little is known on the interaction of PIA in STEMI-patients loaded with ticagrelor, we sought to determine if patients loaded with ticagrelor had improved clinical outcomes as compared to clopidogrel and to study if it is modulated by the presence of PIA.

Methods: From 1272 STEMI patients submitted to primary percutaneous coronary intervention and treated with clopidogrel or ticagrelor from January 2008 to December 2018, 826 were analyzed after propensity score matching. Infarct size was estimated using peak creatine kinase (CK) and troponin T (TnT), and clinical impact was evaluated through cumulative major cardiac and cerebrovascular events (MACCE) at 1-year follow-up. Matched patients and their interaction with PIA were analyzed.

Results: Patients loaded with ticagrelor had lower peak CK [1405.50 U/L (730.25-2491.00), P < .001] and TnT [3.58 ng/mL (1.73-6.59), P < .001)], regardless of PIA. The presence of PIA was associated with lower CK (P = .030), but not TnT (P = .097). There was no interaction between ticagrelor loading and PIA (P = .788 for TnT and P = .555 for CK). There was no difference in MACCE incidence between clopidogrel or ticagrelor loading (P = .129). Cumulative survival was also similar between clopidogrel or ticagrelor, regardless of PIA (P = .103).

Conclusion: Ticagrelor reduced infarct sizes independently and without a synergic effect with PIA. Despite reducing infarct size, clinical outcomes were similar across both groups.

Cardiovascular disease (CVD) caused by atherosclerosis is the leading cause of death worldwide. The level of low-density lipoprotein cholesterol (LDL-C), considered as the initiator of atherosclerosis, is the most widely used predictor for CVD risk and LDL-C has been the primary target for lipid-lowering therapies. However, residual CVD risk remains high even with very low levels of LDL-C. This residual CVD risk may be due to remnant cholesterol, high triglyceride levels, and low high-density lipoprotein cholesterol (HDL-C). Non-high density lipoprotein cholesterol (non-HDL-C), which is calculated as total cholesterol minus HDL-C (and represents the cholesterol content of all atherogenic apolipoprotein B-containing lipoproteins), has emerged as a better risk predictor for CVD than LDL-C and an alternative target for CVD risk reduction. Major international guidelines recommend evaluating non-HDL-C as part of atherosclerotic CVD risk assessment, especially in people with high triglycerides, diabetes, obesity, or very low LDL-C. A non-HDL-C target of <130 mg/dL (3.4 mmol/L) has been recommended for patients at very high risk, which is 30 mg/dL (0.8 mmol/L) higher than the corresponding LDL-C target goal. Non-HDL-C lowering approaches include reducing LDL-C and triglyceride levels, increasing HDL-C, or targeting multiple risk factors simultaneously. However, despite the growing evidence for the role of non-HDL-C in residual CVD risk, and recommendations for its assessment in major guidelines, non-HDL-C testing is not routinely done in clinical practice. Thus, there is a need for increased awareness of the need for non-HDL-C testing for ascertaining CVD risk and concomitant prevention of CVD.