Showing papers in "Cardiovascular Therapeutics in 2019"
TL;DR: CAD and PAD represent a substantial humanistic and economic burden worldwide, highlighting a need for new interventions to reduce the incidence of atherothrombotic disease.
Abstract: Background. Atherothrombotic disease, including coronary artery disease (CAD) and peripheral artery disease (PAD), can lead to cardiovascular (CV) events, such as myocardial infarction, stroke, limb ischemia, heart failure, and CV death. Aim. Evaluate the humanistic and economic burden of CAD and PAD and identify unmet needs through a comprehensive literature review. Methods. Relevant search terms were applied across online publication databases. Studies published between January 2010 and August 2017 meeting the inclusion/exclusion criteria were selected; guidelines were also included. Two rounds of screening were applied to select studies of relevance. Results. Worldwide data showed approximately 5–8% prevalence of CAD and 10–20% prevalence of PAD, dependent on the study design, average age, gender, and geographical location. Data from the REACH registry indicated that 18–35% of patients with CAD and 46–68% of patients with PAD had disease in one or more vascular beds. Use of medication to control modifiable CV risk factors was variable by country (lower in France than in Canada); statins and aspirin were the most widely used therapies in patients with chronic disease. Survival rates have improved with medical advancements, but there is an additional need to improve the humanistic burden of disease (i.e., associated disability and quality of life). The economic burden of atherothrombotic disease is high and expected to increase with increased survival and the aging population. Conclusion. CAD and PAD represent a substantial humanistic and economic burden worldwide, highlighting a need for new interventions to reduce the incidence of atherothrombotic disease.
156 citations
TL;DR: It is clarified that intestinal barrier damage and bacterial translocation induced inflammation and immune response aggravated heart failure, and altered intestinal microflora affected various metabolic pathways including trimethylamine/TMAO, SCFA, and Bile acid pathway leads to heart failure.
Abstract: Although the mechanism of the occurrence and development of heart failure has been continuously explored in the past ten years, the mortality and readmission rate of heart failure is still very high. Modern studies have shown that gut microbiota is associated with a variety of cardiovascular diseases, among which the study of gut microbiota and heart failure attracts particular attention. Therefore, understanding the role of gut microbiota in the occurrence and development of heart failure will help us further understand the pathogenesis of heart failure and provide new ideas for its treatment. This paper introduced intestinal flora and its metabolites, summarized the changes of intestinal flora in patients with heart failure, clarified that intestinal barrier damage and bacterial translocation induced inflammation and immune response aggravated heart failure, and altered intestinal microflora affected various metabolic pathways including trimethylamine/TMAO, SCFA, and Bile acid pathway leads to heart failure. At the same time, regulating intestinal microflora through diet, probiotics, antibiotics, fecal transplantation and microbial enzyme inhibitors has grown up to be a potential treatment for many metabolic disorders.
54 citations
TL;DR: Current evidence on sex-specific cut-off values of hs-cTn and their application and usefulness in clinical practice is summarized and an extensive overview of thresholds reported in literature and of the mechanisms underlying such differences among sexes are offered.
Abstract: Management of patients presenting to the Emergency Department with chest pain is continuously evolving. In the setting of acute coronary syndrome, the availability of high-sensitivity cardiac troponin assays (hs-cTn) has allowed for the development of algorithms aimed at rapidly assessing the risk of an ongoing myocardial infarction. However, concerns were raised about the massive application of such a simplified approach to heterogeneous real-world populations. As a result, there is a potential risk of underdiagnosis in several clusters of patients, including women, for whom a lower threshold for hs-cTn was suggested to be more appropriate. Implementation in clinical practice of sex-tailored cut-off values for hs-cTn represents a hot topic due to the need to reduce inequality and improve diagnostic performance in females. The aim of this review is to summarize current evidence on sex-specific cut-off values of hs-cTn and their application and usefulness in clinical practice. We also offer an extensive overview of thresholds reported in literature and of the mechanisms underlying such differences among sexes, suggesting possible explanations about debated issues.
36 citations
TL;DR: This study may provide credible molecular biomarkers in terms of screening, diagnosis, and prognosis for AMI and also serves as a basis for exploring new therapeutic target for AMi.
Abstract: Background. Acute myocardial infarction (AMI) is a common disease with high morbidity and mortality around the world. The aim of this research was to determine the differentially expressed genes (DEGs), which may serve as potential therapeutic targets or new biomarkers in AMI. Methods. From the Gene Expression Omnibus (GEO) database, three gene expression profiles (GSE775, GSE19322, and GSE97494) were downloaded. To identify the DEGs, integrated bioinformatics analysis and robust rank aggregation (RRA) method were applied. These DEGs were performed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses by using Clusterprofiler package. In order to explore the correlation between these DEGs, the interaction network of protein-protein internet (PPI) was constructed using the STRING database. Utilizing the MCODE plug-in of Cytoscape, the module analysis was performed. Utilizing the cytoHubba plug-in, the hub genes were screened out. Results. 57 DEGs in total were identified, including 2 down- and 55 upregulated genes. These DEGs were mainly enriched in cytokine-cytokine receptor interaction, chemokine signaling pathway, TNF signaling pathway, and so on. The module analysis filtered out 18 key genes, including Cxcl5, Arg1, Cxcl1, Spp1, Selp, Ptx3, Tnfaip6, Mmp8, Serpine1, Ptgs2, Il6, Il1r2, Il1b, Ccl3, Ccr1, Hmox1, Cxcl2, and Ccl2. Ccr1 was the most fundamental gene in PPI network. 4 hub genes in total were identified, including Cxcl1, Cxcl2, Cxcl5, and Mmp8. Conclusion. This study may provide credible molecular biomarkers in terms of screening, diagnosis, and prognosis for AMI. Meanwhile, it also serves as a basis for exploring new therapeutic target for AMI.
36 citations
TL;DR: Clinical benefit for single antiplatelet therapy with clopidogrel over aspirin for secondary prevention in patients with recent ischemic stroke is supported, showing lower risks of major adverse cardiovascular or cerebrovascular events, recurrent stroke, and bleeding events for clopidoogrel monotherapy compared to aspirin.
Abstract: Aim. Though combination of clopidogrel added to aspirin has been compared to aspirin alone in patients with stroke or transient ischemic attack, limited data exists on the relative efficacy and safety between clopidogrel and aspirin monotherapy in patients with a recent ischemic stroke. We aimed to compare clopidogrel versus aspirin monotherapy in this population. Methods. PubMed, Embase, and CENTRAL databases were searched from inception to May 2018 to identify clinical trials and observational studies comparing clopidogrel versus aspirin for secondary prevention in patients with recent ischemic stroke within 12 months. Pooled effect estimates were calculated using a random effects model and were reported as risk ratios with 95% confidence intervals. Results. Five studies meeting eligibility criteria were included in the analysis. A total of 29,357 adult patients who had recent ischemic stroke received either clopidogrel ( ) or aspirin ( ) for secondary prevention. Pairwise meta-analysis showed a statistically significant risk reduction in the occurrence of major adverse cardiovascular and cerebrovascular events (risk ratio 0.72 [95% CI, 0.53–0.97]), any ischemic or hemorrhagic stroke (0.76 [0.58, 0.99), and recurrent ischemic stroke (0.72 [0.55, 0.94]) in patients who received clopidogrel versus aspirin. The risk of bleeding was also lower for clopidogrel versus aspirin (0.57 [0.45, 0.74]). There was no difference in the rate of all-cause mortality between the two groups. Conclusions. The analysis showed lower risks of major adverse cardiovascular or cerebrovascular events, recurrent stroke, and bleeding events for clopidogrel monotherapy compared to aspirin. These findings support clinical benefit for single antiplatelet therapy with clopidogrel over aspirin for secondary prevention in patients with recent ischemic stroke.
29 citations
TL;DR: As compared with enalapril therapy, LCZ696 therapy led to improvement of LVEF, reduced VA inducibility, and upregulated expression of K+ channel proteins.
Abstract: Background. LCZ696 (valsartan/sacubitril) therapy significantly reduced mortality in patients with heart failure (HF). Although a clinical trial (PARADISE-MI Trial) has been ongoing to examine the effects of LCZ696 in myocardial infarction (MI) patients, the effects of LCZ696 on remodeling of cardiac electrophysiology in animal models remain largely unclear. Methods. We performed coronary artery ligation to create MI in Sprague-Dawley rats. Echocardiography was performed one week after MI to confirm the development of HF with left ventricular ejection fraction ≤ 40%. MI rats were randomly assigned to receive medical therapy for 4 weeks: LCZ696, enalapril, or vehicle. The sham-operation rats received sham operation without MI creation. In vivo electrophysiological exams were performed under general anesthesia. Western blot analyses were conducted to quantify ion channel proteins. Results. The HF-vehicle group did not show significant changes in LVEF. Both enalapril and LCZ696 therapy significantly improved LVEF. The HF-vehicle group had higher ventricular arrhythmia (VA) inducibility than the sham group. As compared with the HF-vehicle group, LCZ696 therapy significantly reduced VA inducibility, but enalapril therapy did not. Western blot analyses showed significant downregulation of 1.5, ERG, KCNE1, and KCNE2 channel proteins in the HF vehicle group compared with the sham group. LCZ696 therapy upregulated protein expression of ERG, KCNE1, and KCNE2. Conclusion. As compared with enalapril therapy, LCZ696 therapy led to improvement of LVEF, reduced VA inducibility, and upregulated expression of K+ channel proteins.
26 citations
TL;DR: YP2C19 and PON1 Q192R variants influence ADP-induced platelet inhibition by thrombelastography (TEG) in ACS patients with clopidogrel and are independent risk factors of HPR, which is measured by the relative platelets inhibition.
Abstract: Objective. The objective of this study is to explore the relationships of the effects of CYP2C19 and PON1 Q192R polymorphism on the activity of clopidogrel and the risk of high platelet responsiveness (HPR) by thrombelastography in patients with acute coronary syndrome (ACS). Methods. 459 ACS patients with aspirin and clopidogrel were enrolled in this observational case control study from July 13, 2015, to November 11, 2017. The patients with <30% platelet inhibition were defined as HPR group, while the others were defined as normal platelet responsiveness (NPR) group. The genotypes distribution between the groups was assessed, and the clinical impact of genetic variants was investigated by comparing the relationship between the risk of HPR and genotypes including CYP2C19⁎2, CYP2C19⁎3, CYP2C19⁎17, ABCB1, and PON1. Results. Compared with CYP2C19⁎1/⁎1 wild type carriers, CYP2C19⁎2 and ⁎3 carriers showed a significant association with the lower platelet inhibition (P=0.048). The platelet inhibition in carriers of at least one CYP2C19 loss-of-function (LOF) alleles was obviously higher than noncarriers (P=0.031). The platelet inhibition of PON1 192R carriers was lower than PON1 192Q carriers (P=0.044). Patients with the CYP2C19⁎2 and ⁎3 alleles had a greater risk of HPR than CYP2C19 wild type carriers (adjusted P=0.018 and adjusted P=0.005). At least one PON1 192R carrier predicted a significantly higher risk of HPR than PON1 192Q carriers (adjusted P=0.021). Individual CYP2C19⁎17 and ABCB1 variants did not differ significantly between the two groups. Conclusions. CYP2C19 and PON1 Q192R variants influence ADP-induced platelet inhibition by thrombelastography (TEG) in ACS patients with clopidogrel. In addition, both LOF CYP2C19 and PON1 192R variants are independent risk factors of HPR, which is measured by the relative platelet inhibition.
25 citations
TL;DR: OCS is able to prolong the ischemic time of donors' hearts by perfusing the organ at 34°C in a beating state, potentially reducing the detrimental effect of cold storage and providing additional assessment options.
Abstract: Introduction. Cardiovascular diseases are the number one cause of death globally contributing to 37% of all global deaths. A common complication of cardiovascular disease is heart failure, where, in such cases, the only solution would be to conduct a heart transplant. Every 10 minutes a new patient is added to the transplant waiting list. However, a shortage of human donors and the short window of time available to find a correct match and transplant the donors’ heart to the recipient means that numerous challenges are faced by the patient even before the operation could be done, reducing their chances of living even further. Methods. This review aims to evaluate the application of the Organ Care System (OCSTM) in improving the efficiency of heart storage based on journal articles obtained from PubMed, Elsevier Clinical Key, and Science Direct. Results. Studies have shown that OCS is capable of extending the ischemic time 120 minutes longer than conventional methods without any detrimental effect on the recipient nor donor’s safety. Based on the PROTECT I and PROCEED II study, 93% of transplantation recipients using the OCS system passed through the 30-day mortality period. Discussion. OCS is able to prolong the ischemic time of donors’ hearts by perfusing the organ at 34°C in a beating state, potentially reducing the detrimental effect of cold storage and providing additional assessment options. Another clear advantage is the implanting surgeon can assess the quality of the donor heart before surgery as well as providing a time safety buffer in unanticipated circumstances that will reduce the mortality risk of transplant recipients.
19 citations
TL;DR: Higher preprocedural Gal-3 levels may be associated with increased risk of AF recurrence in patients undergoing catheter ablation and there was a significant publication bias for predicting efficacy.
Abstract: Background. Galectin-3 (Gal-3) is involved in fibrosis and heart failure. However, epidemiological studies evaluating the association between Gal-3 and atrial fibrillation (AF) recurrence after catheter ablation showed inconsistent results. We conducted a meta-analysis to comprehensively evaluate the relationship between baseline circulating Gal-3 levels and AF recurrence in patients undergoing catheter ablation. Methods. Relevant studies were identified by systematically searching the PubMed and Embase databases. A random-effect model was used to synthesize the results. Sensitivity analyses, performed by omitting one study at a time, were used to evaluate the robustness of the results. Results. Seven prospective cohort studies including 645 AF patients were included. Within a follow-up duration of up to 18 months, 244 patients developed AF recurrence. Pooled results showed that baseline circulating Gal-3 levels were significantly higher in patients with AF recurrence compared to those without (standardized mean difference: 0.74; 95% confidence interval (CI): 0.21 - 1.27; p = 0.007; I2 = 89%). Moreover, higher baseline Gal-3 levels were independently associated with a significantly higher risk of AF recurrence after catheter ablation (risk ratio: 1.17 per unit of Gal-3; 95% CI: 1.01 - 1.35; p = 0.03; I2 = 40%), which was independent of age, gender, and left atrial dimension. Sensitivity analyses did not significantly affect the results. However, there was a significant publication bias for predicting efficacy of associating preprocedural Gal-3 levels with AF recurrence. Conclusions. Higher preprocedural Gal-3 levels may be associated with increased risk of AF recurrence in patients undergoing catheter ablation.
18 citations
TL;DR: Short-term treatment with CCM may improve MLFHQ without significant difference in 6MWD, arrhythmic events, HF hospitalizations, all-cause hospitalizations; there is a trend towards increased pacemaker/ICD device malfunction.
Abstract: Background. Cardiac contractility modulation (CCM) is a device therapy for systolic heart failure (HF) in patients with narrow QRS. We aimed to perform an updated meta-analysis of the randomized clinical trials (RCTs) to assess the efficacy and safety of CCM therapy. Methods. We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) between January 2001 and June 2018. Outcomes of interest were peak oxygen consumption (peak VO2), 6-Minute Walk Distance (6MWD), Minnesota Living with Heart Failure Questionnaire (MLHFQ), HF hospitalizations, cardiac arrhythmias, pacemaker/ICD malfunctioning, all-cause hospitalizations, and mortality. Data were expressed as standardized mean difference (SMD) or odds ratio (OR). Results. Four RCTs including 801 patients (CCM n = 394) were available for analysis. The mean age was 59.63 ± 0.84 years, mean ejection fraction was 29.14 ± 1.22%, and mean QRS duration was 106.23 ± 1.65 msec. Mean follow-up duration was six months. CCM was associated with improved MLWHFQ (SMD -0.69, p = 0.0008). There were no differences in HF hospitalizations (OR 0.76, p = 0.12), 6MWD (SMD 0.67, p = 0.10), arrhythmias (OR 1.40, p = 0.14), pacemaker/ICD malfunction/sensing defect (OR 2.23, p = 0.06), all-cause hospitalizations (OR 0.73, p = 0.33), or all-cause mortality (OR 1.04, p = 0.92) between the CCM and non-CCM groups. Conclusions. Short-term treatment with CCM may improve MLFHQ without significant difference in 6MWD, arrhythmic events, HF hospitalizations, all-cause hospitalizations, and all-cause mortality. There is a trend towards increased pacemaker/ICD device malfunction. Larger RCTs might be needed to determine if the CCM therapy will be beneficial with longer follow-up.
15 citations
TL;DR: Inulin supplementation could be an innovative nutraceutical approach to prevent hypertension present in women with this type of cancer at an early stage and may improve the quality of life of the patients and their prognostic development through chemotherapy.
Abstract: Introduction. Breast cancer is the most frequently diagnosed malignancy in women, and comorbidities like hypertension and obesity diminish their quality of life and negatively affect their response to chemotherapy. Furthermore, inulin supplementation is associated with the reduction of cardiovascular diseases (CVD) risk. Objective. To determine whether inulin supplementation prevents the elevation of blood pressure in women with breast cancer undergoing neoadjuvant therapy with cyclophosphamide and doxorubicin. Methods. This was a randomized, double-blind placebo controlled trial which included women with early-stage breast cancer undergoing neoadjuvant therapy (n=38). Patients were randomly assigned to participate in two different groups to receive either 15 g of inulin or 15 g of placebo (maltodextrin) for 21 days. Body composition and blood pressure were evaluated before and after the supplementation period. Results. Women in the inulin group showed a lower systolic blood pressure (SBP) after the supplementation (-4.21 mmHg, p ACTRN12616001532493 .
TL;DR: This review highlights the pharmacokinetic clinically relevant interactions between major conventional cardiovascular medicines and plant products with an emphasis on their putative mechanisms, drawbacks of herbal products use, and the perspectives for further well-designed studies.
Abstract: The growing use of plant products among patients with cardiovascular pharmacotherapy raises the concerns about their potential interactions with conventional cardiovascular medicines. Plant products can influence pharmacokinetics or/and pharmacological activity of coadministered drugs and some of these interactions may lead to unexpected clinical outcomes. Numerous studies and case reports showed various pharmacokinetic interactions that are characterized by a high degree of unpredictability. This review highlights the pharmacokinetic clinically relevant interactions between major conventional cardiovascular medicines and plant products with an emphasis on their putative mechanisms, drawbacks of herbal products use, and the perspectives for further well-designed studies.
TL;DR: In conclusion, atrial fibrillation ablation in patients with systolic heart failure is associated with significant improvement in LVEF, quality of life, 6MWT, and overall mortality.
Abstract: Atrial fibrillation (AF) and heart failure (HF) are two common conditions that often coexist and predispose each to one another. AF increases hospitalization rates and overall mortality in patients with HF. The current available therapeutic options for AF in patients with HF are diverse and guidelines do not provide a clear consensus regarding the best management approach. To determine if catheter ablation for AF is superior to medical therapy alone in patients with coexisting HF, we conducted this systematic review and meta-analysis. The primary outcomes evaluated are left ventricular ejection fraction (LVEF), Minnesota Living with Heart Failure Questionnaire (MLWHFQ) scores, 6-minute walk test (6MWT) distance, heart failure hospitalizations, and mortality. The results are presented as a mean difference for continuous outcome measures and odds ratios for dichotomous outcomes (using Mantel-Haenszel random effects model). 7 full texts met inclusion criteria, including 856 patients. AF catheter ablation was associated with a significant increase in LVEF (mean difference 6.8%; 95% CI: 3.5 – 10.1; P<0.001) and 6MWT (mean difference 29.3; 95% CI: 11.8 – 46.8; P = 0.001), and improvement in MLWHFQ (mean difference -12.1; 95% CI: -20.9 – -3.3; P = 0.007). The risk of all-cause mortality was significantly lower in the AF ablation arm (OR 0.49; 95% CI: 0.31 – 0.77; P = 0.002). In conclusion, atrial fibrillation ablation in patients with systolic heart failure is associated with significant improvement in LVEF, quality of life, 6MWT, and overall mortality.
TL;DR: The presence of a virus did not worsen the long-term prognosis of patients with suspected myocarditis or dilated cardiomyopathy, however, virus-positive patients who did not undergo specific treatment or who underwent right ventricular biopsy did have a worse prognosis.
Abstract: Aim. Myocarditis and cardiomyopathy impose a substantial economic burden on society. Many studies have examined the effects of various predictors on the prognosis of these diseases, such as the left ventricular systolic function, the New York Heart Association glomerular filtration rate, the QT interval, and the presence of viruses. In the present study, we conducted a meta-analysis of cohort studies to investigate the significance of the presence of viruses in the myocardial tissue on the prognosis of these diseases. Methods. The Embase, PubMed, and Cochrane library databases were searched for relevant literature that had been published between January 1, 1964 and August 14, 2018. The inclusion criteria were patients over 18 years of age, suspected myocarditis or dilated cardiomyopathy, accepted myocardial biopsy, and the detection of virus in the myocardial tissue. Results. In total, 10 studies met the inclusion criteria. These studies included 1006 patients with suspected myocarditis or idiopathic heart disease for whom the primary endpoint was all-cause death, heart transplant, or re-hospitalization due to fatal arrhythmia and heart failure. There was no significant difference in the prognosis of virus-positive and virus-negative patients with myocarditis or dilated cardiomyopathy confirmed by endomyocardial biopsy (EMB) [hazard ratio (HR) = 1.40, 95% confidence interval (CI) = 0.93–2.12, ]. However, virus-negative patients had a better prognosis following nonspecific treatment (HR = 1.40, 95% CI = 1.06–1.86, ) and right ventricular biopsy (HR = 2.08, 95% CI = 1.07–4.04, ). Conclusions. The presence of a virus did not worsen the long-term prognosis of patients with suspected myocarditis or dilated cardiomyopathy. However, virus-positive patients who did not undergo specific treatment or who underwent right ventricular biopsy did have a worse prognosis. Thus, the early diagnosis of the presence of viral infection in the myocardium will improve the prognosis of patients.
TL;DR: Diabetes, higher BMI, and ACS are independently associated with coronary vulnerability as detected by optical coherence tomography (OCT) in patients with coronary heart disease, while serum fibrinogen was not related to coronary vulnerability in this cohort.
Abstract: Background. Fibrinogen levels have been associated with coronary plaque vulnerability in experimental studies. However, it has yet to be determined if serum fibrinogen levels are independently associated with coronary plaque vulnerability as detected by optical coherence tomography (OCT) in patients with coronary heart disease. Methods. Patients with coronary heart disease (CHD) who underwent coronary angiography and OCT in our department from January 2015 to August 2018 were included in this study. Coronary lesions were categorized as ruptured plaque, nonruptured with thin-cap fibroatheroma (TCFA), and nonruptured and non-TCFA. Presence of ruptured plaque and nonruptured with TCFA was considered to be vulnerable lesions. Determinants of coronary vulnerability were evaluated by multivariable logistic regression analyses. Results. A total of 154 patients were included in this study; 17 patients had ruptured plaques, 15 had nonruptured plaques with TCFA, and 122 had nonruptured plaques with non-TCFA. Results of univariate analyses showed that being male, diabetes, current smoking, high body mass index (BMI), and clinical diagnosis of acute coronary syndrome (ACS) were associated with coronary vulnerability. No significant differences were detected in patient characteristics, coronary angiographic findings, and OCT results between patients with higher and normal fibrinogen. Results of multivariate logistic analyses showed that diabetes and ACS were associated with TCFA, while diabetes, higher BMI, and ACS were associated with plaque rupture. Conclusions. Diabetes, higher BMI, and ACS are independently associated with coronary vulnerability as detected by OCT. Serum fibrinogen was not associated with coronary vulnerability in our cohort.
TL;DR: Investigation of the correlation between complement C1q tumor necrosis factor-related protein 1 (CTRP1) and subclinical target organ damage (STOD) in essential hypertension found CTRP1 levels were higher in patients with EH than those in healthy subjects, which can be regarded as a novel biomarker in the prediction of prognosis for patients with essential hypertension.
Abstract: This study aimed to investigate the correlation between complement C1q tumor necrosis factor-related protein 1 (CTRP1) and subclinical target organ damage (STOD) in essential hypertension (EH). 720 patients were enrolled in this study, including 360 healthy subjects and 360 patients with EH. The EH group included 183 patients complicated with STOD and 177 patients without STOD. In the STOD group, there were 87 patients with left ventricular hypertrophy (LVH), 32 patients with microalbuminuria (MAU), and 58 patients with complication of LVH and MAU. Enzyme-linked immunosorbent assay (ELISA) was used to detect the CTRP1, adiponectin (APN), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). We found that CTRP1 levels were higher in patients with EH than those in healthy subjects; moreover, the level of CTRP1 of patients in the group complicated with EH and STOD was increased compared with EH patients without STOD. CTRP1 levels in the group complicated with LVH and MAU were significantly higher than those in the LVH group and the MAU group. Furthermore, APN, CTRP1, and IL-6 were three factors that influenced the STOD of EH patients, among which CTRP1 and IL6 were positively related with the complication of hypertension and STOD. In conclusion, CTRP1 levels are increased and associated with the STOD (heart and kidney) in essential hypertension, which can be regarded as a novel biomarker in the prediction of prognosis for patients with essential hypertension.
TL;DR: It is suggested that antiplatelet treatment is overused and anticoagulant treatment is underused both in Chinese patients with VAF and NVAF, even though usage of anticoaggulants is associated with better QoL.
Abstract: Objective. To investigate the contemporary status of stroke risk profile, antithrombotic treatment, and quality-of-life (QoL) of patients with all types of atrial fibrillation (AF) in China. Design. This is a multicenter, cross-sectional study. Setting. Tertiary (80%) and Tier 2 hospitals (20%) were identified in different economic regions (Northeast, East, West, and Middle) by using a simple random sampling. Participants. A total of 3562 (85.6%) patients with nonvalvular atrial fibrillation (NVAF) and 599 (14.4%) with rheumatic valvular atrial fibrillation (VAF) were consecutively enrolled from 111 hospitals from July 2012 to December 2012. Data Collection. Patient information was collected and QoL was assessed using Short-Form 36 Health Survey (SF-36) questionnaire. Primary and Secondary Outcome Measures. The risk of stroke was assessed using the CHADS2 and CHA2DS2-VASc. QoL was assessed using Medical Outcomes Study SF-36 questionnaire. Results. Overall, 31.7% of the patients received anticoagulant treatment and 61.2% received antiplatelet treatment. The rate of anticoagulant treatment was higher in patients with VAF than in those with NVAF. The anticoagulant use was the lowest in Northeast and the highest in Middle regions. Independent risk factors associated with underuse of anticoagulants for NVAF were age, systolic blood pressure (SBP), non-Middle regions, nontertiary hospitals, and new-onset or paroxysmal AF. For VAF patients, the independent factors were age, paroxysmal AF, treatment in Tier 2 hospitals, SBP, diastolic blood pressure, history of coronary artery disease, and nonreceipt of antiarrhythmic therapy. Patients receiving anticoagulants fared significantly better in some QoL domains than those who received no antithrombotic therapy. Conclusions. These findings suggest that antiplatelet treatment is overused and anticoagulant treatment is underused both in Chinese patients with VAF and NVAF, even though usage of anticoagulants is associated with better QoL. Risk factors with underuse of anticoagulants were not identical in patients with NVAF and VAF.
TL;DR: PCO and SCWA both enhance the beneficial functions of HDL to maximize its antioxidant, antiglycation, and antiatherosclerotic activities and the inhibition of CETP.
Abstract: Background. Cuban sugarcane wax acids (SCWA) and policosanol (PCO) are mixtures of higher aliphatic acids and alcohols, respectively, purified from sugarcane wax with different chief components. Although it has been known that they have antioxidant and anti-inflammatory activities, physiological properties on molecular mechanism of SCWA have been less studied than PCO. Methods. In this study, we compared antiatherogenic activities of SCWA and PCO via encapsulation with reconstituted high-density lipoproteins (rHDL). Results. After reconstitution, SCWA-rHDL showed smaller particle size than PCO-rHDL with increase of content. PCO-rHDL or SCWA-rHDL showed distinct inhibition of glycation with similar extent in the presence of fructose. PCO-rHDL or SCWA-rHDL showed strong antioxidant activity against cupric ion-mediated oxidation of low-density lipoproteins (LDL), and inhibition of oxLDL uptake into macrophages. Although PCO-rHDL showed 1.2-fold stronger inhibition against cholesteryl ester transfer protein (CETP) activity than SCWA-rHDL, SCWA-rHDL enhanced 15% more brain cell (BV-2) growth and 23% more regeneration of tail fin in zebrafish. Conclusion. PCO and SCWA both enhance the beneficial functions of HDL to maximize its antioxidant, antiglycation, and antiatherosclerotic activities and the inhibition of CETP. These enhancements of HDL functionality by PCO and SCWA could exert antiaging and rejuvenation activity.
TL;DR: Elevated serum levels of GDF-15 are independently associated with the risk of MI, and G DF-15 may serve as a protective factor for MI in the cardiovascular system.
Abstract: Aims. GDF-15 is considered to be an important biomarker for cardiovascular events, but the differences in serum GDF-15 levels between acute myocardial infarction (AMI) patients and non-AMI patients warrant further investigation. Methods. A cohort of 409 subjects was enrolled in the current study. The Syntax score was calculated from the baseline coronary angiography results by using online methods. Blood samples were obtained at the start of the study for an assessment of GDF-15 by using ELISA methods. Results. Patients with AMI had significantly higher levels of serum GDF-15 (Wilcox test, P < 0.001), Syntax scores (Wilcox test, P = 0.006), and left ventricular ejection fractions (LEVF, Wilcox test, P< 0.001). However, no significant differences were present among the other clinical characteristics. The logistical regression analysis indicated that serum GDF-15 levels (P=0.01534) were independent predictors of non-AMI and AMI after adjusting for age, sex, smoking status, and LVEF. Conclusions. Elevated serum levels of GDF-15 are independently associated with the risk of MI, and GDF-15 may serve as a protective factor for MI in the cardiovascular system.
TL;DR: Test the hypothesis that RIPC in PAD patients suffering from IC would increase muscle resistance to ischemia and thus improve walking-capacity by observing a significant increase in ICD and TWD and a significant decrease in TRC was observed in last/treadmill test in RIPC-group.
Abstract: Background/Objective. Intermittent claudication (IC) is the symptom of peripheral artery disease (PAD) and causes functional disability. Remote ischemic preconditioning (RIPC), is a phenomenon in which a short period of sub-critical ischemia, protects tissues against ischemia/reperfusion/injury. We considered to test the hypothesis that RIPC in PAD patients suffering from IC would increase muscle resistance to ischemia and thus improve walking-capacity. Materials/Methods. A total of 63 patients with proven-IC underwent two treadmill tests (graded treadmill protocol) with a 28-day interval in between. Patients were consecutively assigned for the non/RIPC-group and RIPC-group procedure one by one. Patients received 5-cycles of alternating 5-minute inflation and 5-minute deflation of blood-pressure cuffs on nondominant upper-limb every day for four weeks. Initial claudication distance (ICD), total walking distance (TWD) and time to relief of claudication (TRC) were recorded during procedure. Results. Patients receiving-RIPC exhibited a marked increase in ICD and TWD between basal and last tests: 209.1 ± 15.4 m vs. 226 ± 15.0 m and 368.8 ± 21.0 m vs. 394 ± 19.9 m, respectively ( ). In addition, patients receiving-RIPC represented a significant decrease in TRC between basal and last tests: 7.8 ± 1.3 min vs. 6.4 ± 1.1 min, respectively ( ). Patients not receiving-RIPC did not exhibit improvement in ICD, TWD, and TRC between basal and last tests: 205.2 ± 12.1 min vs. 207.4 ± 9.9 min, 366.5 ± 24.2 min vs. 369.4 ± 23.2 min and 7.9 ± 1.4 min vs. 7.7 ± 1.3 min, respectively ( ). Conclusion. A significant increase in ICD and TWD were observed in last/treadmill test in RIPC-group. In addition, a significant decrease in TRC was observed in last/treadmill test in RIPC-group. In non/RIPC-group, no improvement was observed in ICD, TWD and TRC.
TL;DR: Investigating the safety and tolerability of switching patients on target dose ACE inhibitors or ARBs directly to maximum-dose sacubitril-valsartan found it safe and generally well tolerated.
Abstract: Aim. Sacubitril-valsartan has proven beneficial in heart failure with reduced ejection fraction. Guidelines recommend initiating half-dose sacubitril-valsartan before up-titration even to patients already on target dose angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB). To reduce the number of titration steps needed in order to simplify for the patient as well as the clinic, we aimed to investigate the safety and tolerability of switching patients on target dose ACE inhibitors or ARBs directly to maximum-dose sacubitril-valsartan. Methods. This prospective cohort study was conducted between April 2016 and November 2017. A total of 66 patients with heart failure and reduced ejection fraction already on guideline-recommended target dose ACE inhibitors or ARBs (equivalent to enalapril 10 mg twice daily) were switched to maximum-dose sacubitril-valsartan (200 mg twice daily). The patients were followed for twelve months. Results. Patients had a mean age of 72 ± 10 years, mean systolic blood pressure of 121 ± 17 mmHg, and 92% were male. At 12-month follow-up, nine patients (14%) had discontinued sacubitril-valsartan, four patients (6%) had a dose reduction, and 17 patients (26%) had developed symptomatic hypotension. No angioedema occurred within the 12-month follow-up and there were no hospitalizations or emergency room visits within the first 14 days. Conclusions. Switching directly from target dose ACE inhibitors or ARBs to maximum-dose sacubitril-valsartan was safe and generally well tolerated.
TL;DR: It is suggested that followed-up hsCRP can be more useful for predicting future cardiovascular outcome than achieved LDL-C in PCI-naïve patients with statin therapy.
Abstract: In statin therapy, the prognostic role of achieved low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hsCRP) in cardiovascular outcomes has not been fully elucidated. A total of 4,803 percutaneous coronary intervention (PCI)-naive patients who prescribed moderate intensity of statin therapy were followed up. Total and each component of major adverse cardiovascular events (MACE) according to LDL-C and hsCRP quartiles were compared. The incidence of 5-year total MACEs in the highest quartile group according to the followed-up hsCRP was higher than that in the lowest quartile (hazard ratio (HR) = 2.16, ). However, there was no difference between the highest and lowest quartiles of the achieved LDL-C (HR = 0.95, ). After adjustment of potential confounders, the incidence of total death, de novo PCI, atrial fibrillation, and heart failure in the highest quartile of followed-up hsCRP, was higher than that in the lowest quartile (all ). However, other components except for de novo PCI in the highest quartile by achieved LDL-C was not different to that in the lowest quartile. These results suggest that followed-up hsCRP can be more useful for predicting future cardiovascular outcome than achieved LDL-C in PCI-naive patients with statin therapy.
TL;DR: Pitavastatin increases ICAM-1 mRNA expression in saphenous vein endothelial cells and appears independent of NF-κB, suggesting its pleotropic properties are independent of nuclear factor-kappa B.
Abstract: Objective. To study pitavastatin’s effects on nuclear factor-kappa B (NF-κB ) and adhesion molecules in human saphenous vein graft endothelial culture indicating its pleotropic properties. Materials and Method. Low-dose (0.1 μM/L) and high-dose (1μM/L) pitavastatin calcium were administered as a frontline therapy in human saphenous endothelial cell culture, followed by induction of inflammation by TNF-α and determination of mRNA level alterations of ICAM-1 and NF-κB genes of endothelial cells using the qRT-PCR method. Additionally, immunofluorescence method was used to show the expression of NF-κB and ICAM-1. Finally, LDH levels were determined by the ELISA method to quantify cytotoxicity. Results. ICAM-1 mRNA expression in the low-dose pitavastatin+TNF-α group was significantly higher than that in the TNF-α group and significantly lower than that in the high-dose pitavastatin+TNF-α group (for all comparisons, P = 0.001). The low-dose pitavastatin+TNF-α group had a similar NF-κB mRNA expression with TNF-α and high-dose pitavastatin+TNF-α groups. Conclusion. Pitavastatin increases ICAM-1 mRNA expression in saphenous vein endothelial cells. Furthermore, the effect of pitavastatin on adhesion molecules appears independent of NF-κB. Novel studies are needed in this field.
TL;DR: Bleeding complications during warfarin therapy were associated with 8q24 polymorphisms and atrial fibrillation in patients with mechanical heart valves.
Abstract: Objectives. This study aimed to identify the possible effects of Myc and 8q24 polymorphisms on bleeding complications in patients who maintained international normalized ratio (INR) of 2.0-3.0 with warfarin therapy after cardiac valve replacement. Methods. Twenty-five single nucleotide polymorphisms were analyzed, including VKORC1, CYP2C9, Myc, and 8q24. Univariate and multivariate analyses were conducted to evaluate the associations between genetic polymorphisms and bleeding complications. Attributable risk and the number needed to genotype (NNG) were also calculated to evaluate the potential clinical value of genotyping. Results. We included 142 patients, among whom 21 experienced bleeding complications. Multivariate models showed that patients carrying the CC genotype of rs6983561 and the A allele of rs13281615 at 8q24 had 27.6- and 10.0-fold higher bleeding complications, compared with patients with the A allele and the GG genotype, respectively. For rs6983561, the attributable risk and NNG were 96.4% and 36.8, respectively, whereas, for rs13281615, the attributable risk and NNG were 90.0% and 8.3, respectively. Atrial fibrillation was associated with a 5.5-fold increased risk of bleeding complications. The AUROC value was 0.761 (95% CI 0.659-0.863, p<0.001), and the Hosmer–Lemeshow test showed that the fitness of the multivariate analysis model was satisfactory (χ2=0.846; 3 degrees of freedom; p=0.838). Conclusions. Bleeding complications during warfarin therapy were associated with 8q24 polymorphisms and atrial fibrillation in patients with mechanical heart valves.
TL;DR: It was showed that fimasartan had greater effect on reducing BPV after acute ischemic stroke than valsartan.
Abstract: Higher blood pressure variability (BPV) is associated with poor functional outcome and mortality in acute stroke. This randomized controlled trial was conducted to compare the effect on BPV between fimasartan and valsartan (Boryung Pharmaceutical Co., Ltd., Seoul, Republic of Korea) in patients with acute ischemic stroke. Eighty patients were randomly assigned to receive either valsartan or fimasartan after 7 days of acute ischemic stroke onset, for duration of 8 weeks. Of them, 62 patients completed the study [valsartan (n=31), fimasartan (n=31)]. We measured BP for 24 hours using ambulatory BP monitoring device before and after 8 weeks of starting BP medication. We calculated several indexes such as standard deviation (SD), weighted 24-hour BP with SD (wSD), coefficient of variation (CV), and average real variability (ARV) to assess BPV and to compare indexes of BPV between 2 drugs. SD values of systolic BP in daytime, nighttime, and 24 h period (15.55±4.02 versus 20.55±8.77, P=0.006; 11.98±5.52 versus 16.47±6.94, P=0.007; 17.22±5.30 versus 21.45±8.51, P=0.024), wSD of systolic BP (8.27±3.01 versus 10.77±4.18, P=0.010), and ARV of systolic BP (15.85±6.17 versus 19.68±7.83, P=0.040) of patients receiving fimasartan after 8 weeks were significantly lower than patients receiving valsartan. In paired t-test, SD values of daytime, nighttime, and 24 h period of systolic BP of patients receiving fimasartan were significantly decreased after 8 weeks (15.55±4.02 versus 18.70±7.04, P=0.038; 11.98±5.52 versus 17.19±7.35, P=0.006; 17.22±5.30 versus 20.59±5.91, P=0.015). Our study showed that fimasartan had greater effect on reducing BPV after acute ischemic stroke than valsartan. Trials registry number is KCT0003254 .
TL;DR: Perioperative continuation of statin therapy did not improve early graft patency in OPCAB patients and a lower risk of graft occlusion was observed among smoking patients.
Abstract: Background. Decreased graft patency after off-pump coronary artery bypass grafting (OPCAB) leads to substantial increases in cardiac events. However, there is paucity of data on efficacy and safety of perioperative statin therapy for OPCAB populations. Methods. 582 patients undergoing OPCAB in a single-institution database (October 1, 2009–September 30, 2012) were stratified by perioperative continuation of statin therapy (CS group, n=398) or not (DS group, n=184). Inverse probability weighted propensity adjustment was used to account for treatment assignment bias, resulting in a well-matched cohort. Primary outcomes were graft patency at an average of five days after operation and in-hospital mortality. Secondary outcomes included intraoperative blood loss, liver, and renal functions. Results. No in-hospital death occurred in this study. Early graft patency rates after OPCAB were 98.4% (1255 of 1275 grafts) in the CS group and 98.0% (583 of 595 grafts, P=0.486) in the DS group. Secondary outcomes showed a reduction in blood loss during operation (438.53 mL versus 480.47 mL, P=0.01). Continuation of statin therapy is associated with alanine transaminase (ALT) elevation (49.67 U/L versus 34.52 U/L, P NCT 01268917 ).