Cardiovascular Events In Patients Research Articles

Cut-off values of Geriatric Nutritional Risk Index for cardiovascular events in Japanese patients with acute myocardial infarction.

The Geriatric Nutritional Risk Index (GNRI) is a straightforward nutritional risk assessment tool with an established relationship with poor prognosis in patients with heart failure. However, the utility of the GNRI in patients with acute myocardial infarction (AMI) remains unclear given the time-dependent changes in the pathophysiology of AMI and the selected endpoints. Accordingly, we aimed to evaluate the optimal cut-off values of the GNRI for cardiovascular events in patients with AMI. We used time-dependent receiver operating characteristic analysis to identify the optimal cut-off values for two endpoints, all-cause death and major adverse cardiac events (MACE: all-cause death, non-fatal myocardial infarction, hospitalization for heart failure, and stroke), over 4years in 360 patients with AMI between 2012 and 2020. The cumulative incidence of MACE was 11.6%. The cut-off value of the GNRI for all-cause death was 82.7 (area under the curve [AUC], 0.834) at 3months and 90.3 (AUC 0.854) at 4years. The cut-off value of the GNRI for MACE was 83.0 (AUC 0.841) at 3months and 95.3 (AUC 0.821) at 4years. The GNRI demonstrated consistently high reliability relative to other indicators of AMI. Our findings indicated that the optimal cut-off value and reliability of the GNRI for cardiovascular events varied according to the endpoints and observation periods. GNRI emerges as a crucial predictor of prognosis for patients with AMI.

Long-term major events after hospital discharge for out-of-hospital cardiac arrest.

Cardiac arrest remains a global health issue with limited data on long-term outcomes, particularly regarding recurrent cardiovascular events in patients surviving out-of-hospital cardiac arrest. (OHCA). We aimed to describe the long-term occurrence of major cardiac event defined by hospital admission for cardiovascular events or death in OHCA hospital survivors, whichever came first. Our secondary objective were to assess separately occurrence of hospital admission and death, and to identify the factors associated with major event occurrence. We hypothesized that patients surviving an OHCA has a protracted increased risk of cardiovascular events, due to both presence of the baseline conditions that lead to OHCA, and to the cardiovascular consequences of OHCA induced acute ischemia-reperfusion. Consecutive OHCA patients from three hospitals of Sudden Death Expertise Center (SDEC) Registry, discharged alive from 2011 to 2015 were included. Long-term follow-up data were obtained using national inter-regime health insurance information system (SNIIRAM) database and the national French death registry. The primary endpoint was occurrence of a major event defined by hospital admission for cardiovascular events and death, whichever came first during the follow-up. The starting point of the time-to-event analysis was the date of hospital discharge. The follow-up was censored on the date of the first event. For patients without event, follow-up was censored on the date of December, 29th, 2016. A total of 306 patients (mean age 57; 77% male) were analyzed and followed over a median follow-up of 3 years for hospital admission for cardiovascular event and 6 years for survival. During this period, 38% patients presented a major event. Hospital admission for cardiovascular events mostly occurred during the first year after the OHCA whereas death occurred more linearly during the all period. A previous history of chronic heart failure and coronary artery disease were independently associated with the occurrence of major event (HR 1.75, 95%CI[1.06-2.88] and HR 1.70, 95%CI[1.11-2.61], respectively), whereas post-resuscitation myocardial dysfunction, cardiogenic shock and cardiologic cause of cardiac arrest did not. Survivors from OHCA must to be considered at high risk of cardiovascular event occurrence whatever the etiology, mainly during the first year following the cardiac arrest and should require closed monitoring.

Influenza Vaccination and Cardiovascular Events in Japanese Patients With Heart Failure - Findings From the PARALLEL-HF Trial.

Influenza is associated with an increased risk for cardiovascular events in patients with heart failure (HF). This study aimed to investigate the prevalence of influenza vaccination among Japanese patients with HF enrolled in the PARALLEL-HF (Prospective comparison of ARNI with ACEi to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients) trial and the association between receiving influenza vaccination and cardiovascular events including death or HF hospitalization. In PARALLEL-HF, in which 223 patients with HF and reduced ejection fraction (HFrEF) were randomized to the angiotensin-receptor neprilysin inhibitor (sacubitril/valsartan) or enalapril, 97 (43%) received influenza vaccination. Influenza vaccination tended to be associated, though statistically not significant, with a lower risk for all-cause death (adjusted hazard ratio [HR]: 0.67; 95% confidence interval [CI]: 0.32-1.39) and cardiopulmonary or influenza-related hospitalization or death (adjusted HR: 0.72; 95% CI: 0.46-1.11) in propensity score-adjusted models. The influenza vaccination rate in Japanese patients with HFrEF who were well managed on guideline-directed medical therapy was suboptimal despite recommendations from clinical practice guidelines. However, importantly, it could be associated with better clinical benefits.

Early statin use is associated with improved survival and cardiovascular outcomes in patients with atrial fibrillation and recent ischaemic stroke: A propensity-matched analysis of a global federated health database.

Statins reduce recurrent stroke and cardiovascular events in patients with non-cardioembolic stroke. The benefits of statins in patients with AF and recent IS remain unclear. We aimed to investigate the benefits of statins in patients with AF and recent IS. This retrospective, cohort study was conducted using deidentified electronic medical records within TriNetX platform. Patients with AF and recent IS, who received statins within 28 days of their index stroke were propensity score-matched with those who did not. Patients were followed up for up to 2 years. Primary outcomes were the 2-year risk of recurrent IS, all-cause mortality and the composite outcome of all-cause mortality, recurrent IS, transient ischaemic attack (TIA), and acute myocardial infarction (MI). Secondary outcomes were the 2-year risk of TIA, intracranial haemorrhage (ICH), acute MI, and hospital readmission. Cox regression analyses were used to calculate hazard ratios (HRs) with 95% confidence intervals (95%CI). Of 20,902 patients with AF and recent IS, 7500 (35.9%) received statins within 28 days of their stroke and 13,402 (64.1%) did not. 11,182 patients (mean age 73.7 ± 11.5; 5277 (47.2%) female) remained after propensity score matching. Patients who received early statins had significantly lower risk of recurrent IS (HR: 0.45, 95%CI: 0.41-0.48, p < 0.001), mortality (HR: 0.75, 95%CI: 0.66-0.84, p < 0.001), the composite outcome (HR: 0.48, 95%CI: 0.45-0.52, p < 0.001), TIA (HR: 0.37, 95%CI: 0.30-0.44, p < 0.001), ICH (HR: 0.59, 95%CI: 0.47-0.72, p < 0.001 ), acute MI (HR: 0.35, 95%CI: 0.30-0.42, p < 0.001) and hospital readmission (HR: 0.46, 95%CI: 0.42-0.50, <0.001). Beneficial effects of early statins were evident in the elderly, different ethnic groups, statin dose intensity, and AF subtypes, large vessel occlusion and embolic strokes and within the context of statin lipophilicity, optimal LDL-cholesterol levels, various cardiovascular comorbidities, treatment with intravenous thrombolysis or endovascular thrombectomy, and NIHSS 0-5 and NIHSS > 5 subgroups. Patients with AF and recent IS, who received early statins, had a lower risk of recurrent stroke, death, and other cardiovascular outcomes including ICH, compared to those who did not.

Associations between glucocorticoid use and major adverse cardiovascular events in patients with prostate cancer receiving antiandrogen: a retrospective cohort study.

Prednisolone/prednisone coadministration with abiraterone may explain abiraterone-related increase in cardiovascular risk. We explored this postulation and glucocorticoid's association with cardiovascular risk. Patients with prostate cancer on androgen deprivation therapy and enzalutamide, or abiraterone with 5 mg (ABI + P5) or 10 mg (ABI + P10) daily total prednisolone/prednisone were followed up for major adverse cardiovascular events (MACE). We analyzed 933 patients. ABI + P10, but not enzalutamide, had higher risk of MACE than ABI + P5. Cumulative glucocorticoid dose before enzalutamide/abiraterone initiation was associated with MACE. Prednisolone/prednisone coadministration with abiraterone likely contributed to abiraterone-related increased cardiovascular risk. Prevalent cumulative glucocorticoid dose was associated with cardiovascular risk.

Telomere length is associated with increased risk of cardiovascular events in patients with end-stage kidney disease on hemodialysis.

Patients with chronic kidney disease (CKD), especially those with end-stage kidney disease (ESKD) on hemodialysis (HD), are at increased risk for cardiovascular disease (CVD), including myocardial infarction and ischemic stroke. A shortening in telomere length, as a parameter for accelerated vascular aging, is an established biomarker for CVD in the general population. We aimed to elucidate the role of telomere length in ESKD patient on HD and its association with cardiovascular outcomes. Telomere length was measured in a prospective population-based cohort study of prevalent HD patients. DNA was isolated from whole blood, sampled at baseline, and analyzed for telomere length via a qPCR-based approach. The risk for the occurrence of the independently adjudicated 3P-MACE outcome (myocardial infarction, ischemic stroke, and cardiovascular death) was statistically analyzed considering the competing risk of non-cardiovascular death. In the cohort of 308 patients with ESKD (115 (37.3%) women, median (25th-75th percentile) age: 67.0 (56.8 - 76.0), the median telomere length was 1.51 kb (25th-75th percentile 0.6-3.2 kb). The 3P-MACE outcome occurred with an incidence rate of 9.4 per 100 patient-years. Patients with longer telomere length more frequently had vascular nephropathy compared to patients with shorter telomere length. Interestingly, patients in the highest quartile of telomere length had a 1.8-fold increased risk for 3P-MACE (95%CI 1.051-3.201, p=0.033), after multivariable adjustment for age, history of stroke, myocardial infarction, venous thromboembolism, presence of heart valve replacement, atrial fibrillation, smoking, anticoagulation, or immunosuppressive use. Surprisingly, in this high-risk cohort of patients with ESKD on HD, longer telomere lengths were associated with increased risk of cardiovascular events.

The Analysis Study of Effects of Glucagon-Like Peptide-1 Receptor to Reduce Adverse Cardiovascular Events in Patients with Type 2 Diabetes Mellitus: A Comprehensive Systematic Review

Background: The aim of this study to show about effects of glucagon-like peptide-1 receptor to reduce adverse cardiovascular events in patients with type 2 diabetes mellitus. Methods: By the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020, this study was able to show that it met all of the requirements. Result: Eight publications were found to be directly related to our ongoing systematic examination after a rigorous three-level screening approach. Subsequently, a comprehensive analysis of the complete text was conducted, and additional scrutiny was given to these articles. Conclusion: GLP‐1 receptor agonists represent a relatively new class of drugs used for the treatment of T2DM. They are not only able to improve hyperglycaemia of diabetic patients but also directly influence in addition other significant risk factors for CVD such as high blood pressure, dyslipidaemia or obesity. These properties explain at least in part the positive results of the CV outcome studies for liraglutide, semaglutide, dulaglutide and albiglutide, all of which showed not only CV safety but also an improvement in CV prognosis.

Serum calciprotein particle-to-phosphate ratio as a predictor of cardiovascular events in incident hemodialysis patients.

Recent studies have identified increased blood calciprotein particle (CPP) levels as risk factors for vascular calcification and cardiovascular events in patients undergoing maintenance hemodialysis. Although positively correlated with serum phosphate levels, serum CPP levels vary considerably among patients with similar serum phosphate levels. We investigated the capacity of the ratio of serum CPP levels to serum phosphate levels (CPP/Pi ratio) to predict cardiovascular events in incident hemodialysis patients compared to the serum calcification propensity test (T50). The association between the CPP/Pi ratio and major adverse cardiac and cerebrovascular events (MACCE) was investigated in 174 incident hemodialysis patients. Multivariate analysis revealed that the CPP/Pi ratio was independently associated with MACCE [hazard ratio 1.60, 95% confidence interval (1.15-2.23), p = 0.006] but serum T50 levels were not. The CPP/Pi ratio is a useful, novel biomarker for predicting the risk of cardiovascular events in patients undergoing incident hemodialysis.

Association of serum cystatin C level and major adverse cardiovascular events in patients with percutaneous coronary intervention.

Recurrent acute myocardial infarction requiring unplanned percutaneous coronary intervention (PCI) is one of the major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS) after PCI. There is a continuing controversy about the association between serum cystatin C, a biomarker for the evaluation of renal function, and the prognosis of ACS patients following PCI. The retrospective study evaluated the association between serum cystatin C level and MACE in ACS patients after PCI. Data were retrieved for 330 patients with ACS for primary PCI in a single center. Serum cystatin C levels were measured before PCI. All patients underwent regular follow-ups after PCI, and the studied endpoint was MACE, defined as the need for a repeat revascularization in the heart. The predictive value of serum cystatin C for MACE was analyzed using univariate and multivariate analysis. Restricted cubic spline (RCS) analysis was applied to evaluate the dose-response relationship between serum cystatin C level and MACE in ACS patients following PCI. After a median follow-up of 63 months (range, 1-148 months), 121 of the 330 patients experienced MACE. Compared to patients who did not have MACE, patients who had MACE showed a significant decrease in serum cystatin C levels (0.99±0.32 vs. 1.15±0.78 mg/L, P=0.03). In multivariate regression analysis, serum cystatin C level was an independent risk factor for MACE. According to the serum cystatin C level, patients were divided into 4 categories, Cox regression analysis illustrated that the second quartile of serum cystatin C level indicated an increased risk of MACE in patients with PCI for primary ACS compared to the highest quartile [Q2: adjusted hazard ratio (HR) =2.109; 95% confidence interval (CI): 1.193-3.727; P=0.01]. RCS analysis showed a significant U-shaped dose-response relationship between cystatin C level and MACE in patients with PCI for ACS (P for non-linearity =0.004). These results indicated an association between serum cystatin C level and post-PCI MACE in ACS patients.

Inhibition of the RXRA-PPARα-FABP4 signaling pathway alleviates vascular cellular aging by an SGLT2 inhibitor in an atherosclerotic mice model.

Atherosclerosis is the pathological cause of atherosclerotic cardiovascular disease (ASCVD), which rapidly progresses during the cellular senescence. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce major cardiovascular events in patients with ASCVD and have potential antisenescence effects. Here, we investigate the effects of the SGLT2 inhibitor dapagliflozin on cellular senescence in atherosclerotic mice. Compared with ApoE-/- control mice treated with normal saline, those in the ApoE-/- dapagliflozin group, receiving intragastric dapagliflozin (0.1 mg kg-1 d-1) for 14 weeks, exhibited the reduction in the total aortic plaque area (48.8%±6.6% vs. 74.6%±8.0%, P<0.05), the decrease in the lipid core area ((0.019±0.0037) mm2vs. (0.032±0.0062) mm2, P<0.05) and in the percentage of senescent cells within the plaques (16.4%±3.7% vs. 30.7%±2.0%, P<0.01), while the increase in the thickness of the fibrous cap ((21.6±2.1) µm vs. (14.6±1.5) µm, P<0.01). Transcriptome sequencing of the aortic arch in the mice revealed the involvement of the PPARα and the fatty acid metabolic signaling pathways in dapagliflozin's mechanism of ameliorating cellular aging and plaque progression. In vitro, dapagliflozin inhibited the expression of PPARα and its downstream signal FABP4, by which the accumulation of senescent cells in human aortic smooth muscle cells (HASMCs) was reduced under high-fat conditions. This effect was accompanied by a reduction in the intracellular lipid content and alleviation of oxidative stress. However, these beneficial effects of dapagliflozin could be reversed by the PPARα overexpression. Bioinformatics analysis and molecular docking simulations revealed that dapagliflozin might exert its effects by directly interacting with the RXRA protein, thereby influencing the expression of the PPARα signaling pathway. In conclusion, the cellular senescence of aortic smooth muscle cells is potentially altered by dapagliflozin through the suppression of the RXRA-PPARα-FABP4 signaling pathway, resulting in a deceleration of atherosclerotic progression.

Prediction of fatal cardiovascular events in patients with newly diagnosed non-small cell lung cancer

Aim. To study risk factors for fatal cardiovascular events in patients with non-small cell lung cancer over two years of standard treatment.Material and methods. This pilot retrospective non-randomized cohort study included 179 patients who were consecutively admitted to the chemotherapy department of City Clinical Hospital 1 from January to December 2020 with a confirmed diagnosis of non-small cell lung cancer based on the comprehensive examination and morphological verification according to the 2018 clinical guidelines on bronchial and lung cancer. Diagnosis and treatment of cardiovascular diseases were carried out according to national clinical guidelines. The follow-up period for non-small cell lung cancer and cardiovascular disease was 2 years. Logistic regression models were considered to assess the risk of cardiovascular death. The model accuracy was assessed by a cross-validation.Results. The best model in terms of the sensitivity and specificity sum according to a cross-validation was the model with the following explanatory variables: sex, cancer stage, platinum-based chemotherapy, etoposide, immunotherapy, surgical treatment. This model showed a sensitivity of 70,1% and a specificity of 82,1%.Conclusion. This approach is easy to implement and may optimize treatment for patients with non-small cell lung cancer.

Copeptin associates with major adverse cardiovascular events in patients on maintenance hemodialysis

BackgroundEnd-stage renal disease (ESRD) necessitating hemodialysis pose substantial cardiovascular risks, with cardiovascular disease (CVD) as a leading cause of mortality. Biomarkers like copeptin have emerged as potential indicators of cardiovascular stress and prognosis in CKD populations. ObjectiveThis study aimed to assess the prognostic value of copeptin in predicting major adverse cardiovascular events (MACEs) among hemodialysis patients, alongside traditional cardiac biomarkers. MethodsESRD patients undergoing maintenance hemodialysis were enrolled. Copeptin levels were measured, and patients were followed for MACEs, defined as cardiovascular deaths, myocardial infarction, stroke, or heart failure-related hospitalizations. Cox proportional-hazards models were used to evaluate the association between copeptin and outcomes, adjusting for relevant covariates. ResultsAmong 351 patients followed for a median of 22.7 months, elevated copeptin levels were significantly associated with an increased risk of MACEs (HR 1.519, 95 % CI 1.140 to 2.023; p = 0.00425). Copeptin demonstrated predictive capability across multiple statistical tests (Log-rank p = 0.024; Gehan p < 0.001; Tarone-Ware p < 0.001; Peto-Peto p = 0.027), although significance was attenuated in pairwise comparisons post-adjustment for multiple testing. Combining copeptin with NT-proBNP or hs-cTnT further enhanced risk stratification for MACEs. ConclusionElevated copeptin levels independently predict adverse cardiovascular outcomes in hemodialysis patients. Integrating copeptin with traditional cardiac biomarkers may refine risk stratification and guide personalized therapeutic strategies in this high-risk population.

Elevated plasma hepcidin concentrations are associated with an increased risk of mortality and nonfatal cardiovascular events in patients with type 2 diabetes: a prospective study

BackgroundThe effect of plasma hepcidin concentrations on the long-term risk of developing adverse cardiovascular outcomes in people with type 2 diabetes mellitus (T2DM) is unclear.MethodsWe followed for a median of 55.6 months 213 outpatients with established T2DM (45.5% women, mean age 69 ± 10 years; BMI 28.7 ± 4.7 kg/m2; median diabetes duration 11 years). Baseline plasma ferritin and hepcidin concentrations were measured with an electrochemiluminescence immunoassay and mass spectrometry-based assay, respectively. The primary study outcome was a composite of all-cause mortality or incident nonfatal cardiovascular events (inclusive of myocardial infarction, permanent atrial fibrillation, ischemic stroke, or new hospitalization for heart failure).Results42 patients developed the primary composite outcome over a median follow-up of 55.6 months. After stratifying patients by baseline hepcidin tertiles [1st tertile: median hepcidin 1.04 (IQR 0.50–1.95) nmol/L, 2nd tertile: 3.81 (IQR 3.01-4-42) nmol/L and 3rd tertile: 7.72 (IQR 6.37–10.4) nmol/L], the risk of developing the primary composite outcome in patients in the 3rd tertile was double that of patients in the 1st and 2nd tertile combined (unadjusted hazard ratio [HR] 2.32, 95%CI 1.27–4.26; p = 0.007). This risk was not attenuated after adjustment for age, sex, adiposity measures, smoking, hypertension, statin use, antiplatelet medication use, plasma hs-C-reactive protein and ferritin concentrations (adjusted HR 2.53, 95%CI 1.27–5.03; p = 0.008).ConclusionsIn outpatients with T2DM, higher baseline hepcidin concentrations were strongly associated with an increased long-term risk of overall mortality or nonfatal cardiovascular events, even after adjustment for established cardiovascular risk factors, plasma ferritin concentrations, medication use, and other potential confounders.

Smoking and 10-year risk of cardiovascular and non-cardiovascular events after contemporary coronary stenting

The impact of smoking cessation on long-term clinical outcomes after contemporary percutaneous coronary intervention (PCI) is not well known. We estimated the association of smoking and smoking cessation on the 10-year risk of cardiovascular and non-cardiovascular events in patients after contemporary PCI in a multicenter retrospective cohort of all patients having PCI with second generation drug-eluting stents in the VA Healthcare System between 2008 and 2016. Smoking status, comorbidities and clinical outcomes were extracted from the medical record and the National Death Index. Hazard ratios and 95 % confidence intervals (HR, 95 %CI) were derived from Cox Proportional Hazards Models. Estimates of events prevented from smoking cessation were derived from the differences in absolute risks between subjects who smoked and had stopped smoking. Among 29,001 patients, 10,598 (36.5 %) were current smoking patients, 13,093 (45.1 %) were former smoking patients, and 5,310 (18.3 %) never smoked. Over 10 years, 7,806 (26.9 %) subjects died with non-cardiovascular deaths exceeding cardiovascular deaths. In multivariable models, current smoking was significantly associated with increased long-term risks of all-cause death (HR = 1.27, 95 %CI = 1.19, 1.36), myocardial infarction (HR = 1.32, 95 %CI = 1.21–1.43), cancer death (HR = 2.55, 95 % CI = 2.10, 3.08), and pulmonary death (HR = 4.07, 95 % CI = 2.85, 5.83). Smoking cessation may prevent 18.5 % (95 %CI = 16.0 %, 20.9 %) all-cause deaths, 14.8 % (95 %CI = 9.8 %, 19.6 %) cardiovascular deaths, 42.6 % (95 %CI = 37.7 %, 47.2 %) cancer deaths, and 48.3 % (95 %CI = 41.8 %, 54.2 %) pulmonary deaths among smokers. Stopping smoking will likely have major impacts on non-cardiovascular events as well as cardiovascular events in patients after PCI with second generation drug-eluting stents.

Reduction in glomerular filtration rate and phosphate predicts the risk of mortality and cardiovascular events in patients with calcific aortic valve stenosis

Reduction in glomerular filtration rate and phosphate predicts the risk of mortality and cardiovascular events in patients with calcific aortic valve stenosis

The Effect of Low-Dose Colchicine on the Phenotype and Function of Neutrophils and Monocytes in Patients with Chronic Coronary Artery Disease: A Double-Blind Randomized Placebo-Controlled Cross-Over Study.

Recent landmark trials showed that colchicine provides a substantial benefit in reducing major cardiovascular events in patients with coronary artery disease. Yet, its exact mechanism of action is still poorly understood. This study aimed to unravel the effect of colchicine on monocyte and neutrophil phenotype and function. A randomized double-blind placebo-controlled cross-over intervention study was executed in patients with a history of myocardial infarction. In neutrophils, colchicine treatment decreased CD62L expression and NGAL release upon ex vivo stimulation and increased PMA-induced ROS production. The effects of colchicine on monocytes were limited to a decrease in HLA-DR expression in the intermediate and nonclassical monocytes. Also, on the level of RNA expression, colchicine did not affect monocyte phenotype, while affecting various immunomodulating genes in neutrophils. Overall, our study suggests that treatment with colchicine affects neutrophil function, particularly by reducing neutrophil recruitment, lowering concentrations of NGAL, and changing the expression of various genes with immunomodulatory potential, whereas the effect on monocytes is limited.

Empagliflozin mitigates ponatinib-induced cardiotoxicity by restoring the connexin 43-autophagy pathway

BackgroundEmpagliflozin (EMPA), a selective sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has been shown to reduce major adverse cardiovascular events in patients with heart failure of different etiologies, although the underlying mechanism still remains unclear. Ponatinib (PON) is a multi-tyrosine kinase inhibitor successfully used against myeloid leukemia and other human malignancies, but its cardiotoxicity remains worrisome. Cardiac connexins (Cxs) are both substrates and regulators of autophagy and responsible for proper heart function. Alteration in connexin expression and localization have been described in patients with heart failure. AimsTo assess whether EMPA can mitigate PON-induced cardiac dysfunction by restoring the connexin 43-autophagy pathway. Methods and ResultsMale C57BL/6 mice, randomized into four treatment groups (CNTRL, PON, EMPA, PON+EMPA) for 28 days, showed increased autophagy, decreased Cx43 expression as well as Cx43 lateralization, and attenuated systo-diastolic cardiac dysfunction after treatment with EMPA and PON compared with PON alone. Compared with CNTRL (DMSO), cardiomyocyte-differentiated H9c2 (dH9c2) cells treated with PON showed significantly reduced cell viability to approximately 20 %, decreased autophagy, increased cell senescence and reduced DNA binding activity of serum response factor (SRF) to serum response elements (SRE), which were paralleled by reduction in cardiac actin expression. Moreover, PON induced a significant increase of Cx43 protein and its S368-phosphorylated form (pS368-Cx43), as well as their displacement from the plasma membrane to the perinuclear and nuclear cellular region. All these effects were reverted by EMPA. ConclusionEMPA attenuates PON-induced cardiotoxicity by reducing senescence, enhancing the SRE-SRF binding and restoring the connexin 43-autophagy pathway. This effect may pave the way to use of SGLT2 inhibitors in attenuating tyrosine-kinase inhibitor cardiotoxicity.

Aspirin-Free Strategy for Percutaneous Coronary Intervention in Patients With Oral Anticoagulation: Prespecified Subgroup Analysis From the STOPDAPT-3 Trial.

The effects of aspirin-free strategy on bleeding and cardiovascular events in patients undergoing percutaneous coronary intervention with oral anticoagulation (OAC) have not been fully elucidated. We conducted the prespecified subgroup analysis based on the use of OAC, including vitamin K antagonist and direct oral anticoagulants, within 7 days before percutaneous coronary intervention in the STOPDAPT-3 (Short and Optimal Duration of Dual Antiplatelet Therapy-3) trial, which randomly compared prasugrel monotherapy (2984 patients) to dual antiplatelet therapy (DAPT) with prasugrel and aspirin (2982 patients) in patients with acute coronary syndrome or high bleeding risk. The coprimary end points were major bleeding events (Bleeding Academic Research Consortium types 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) at 1 month. Among 5966 study patients, there were 530 patients (8.9%) with OAC (no aspirin: N=248, and DAPT: N=282) and 5436 patients (91.1%) without OAC (no aspirin: N=2736, and DAPT: N=2700). Regardless of the use of OAC, the effects of no aspirin compared with DAPT were not significant for the bleeding end point (OAC: 4.45% and 4.27%, hazard ratio [HR], 1.04 [95% CI, 0.46-2.35]; no-OAC: 4.47% and 4.75%, HR, 0.94 [95% CI, 0.73-1.20]; P for interaction=0.82), and for the cardiovascular end point (OAC: 4.84% and 3.20%, HR, 1.53 [95% CI, 0.64-3.62]; no-OAC: 4.06% and 3.74%, HR, 1.09 [95% CI 0.83-1.42]; P for interaction =0.46). The no-aspirin strategy compared with the DAPT strategy failed to reduce major bleeding events irrespective of the use of OAC. There was a numerical excess risk of the no-aspirin strategy relative to the DAPT strategy for cardiovascular events in patients with OAC.

Major bleeding increases the risk of subsequent cardiovascular events in patients with atrial fibrillation: insights from the SAKURA AF registry and RAFFINE registry.

Bleeding events are one of the major concerns in patients using oral anticoagulants (OACs). We aimed to evaluate the association between major bleeding and long-term clinical outcomes in atrial fibrillation (AF) patients taking OACs. We analyzed a database comprising two large-scale prospective registries of patients with documented AF: the RAFFINE and SAKURA registries. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), defined as the composite of all-cause death, ischemic stroke, and myocardial infarction. Major bleeding was defined in accordance with the criteria of the International Society on Thrombosis and Hemostasis. Cox multivariate analysis was used to determine the impact of major bleeding on the incidence of MACCE. The median follow-up period was 39.7 (interquartile range, 33.1-48.1) months. Among 6,633 patients with AF who were taking OAC, 298 (4.5%) had major bleeding and 737 (11.1%) had MACCE. The incidence of MACCE was higher in patients with bleeding than in those without (18.33 and 3.22, respectively, per 100 patient-years; log-rank p < 0.0001). Multivariate logistic regression analysis revealed older age, vitamin K antagonist use, and antiplatelet drug use as independent predictors of major bleeding. Median duration of MACCE occurrence after major bleeding was 41 (interquartile range, 3-300) days. Multivariate Cox hazard regression analysis showed that the risk of MACCE was significantly higher in patients with major bleeding compared to those without (hazard risk, 4.64; 95% confidence interval, 3.62-5.94; p < 0.0001). Major bleeding was associated with long-term adverse cardiovascular events among AF patients taking OAC. Therefore, reducing the risk of bleeding is important for improving clinical outcomes in patients with AF.

New perspectives on the high-density lipoprotein system and its role in the prevention and treatment of atherosclerotic cardiovascular disease.

The causal role of high-density lipoprotein (HDL) in atherosclerotic cardiovascular disease (CVD) remains debated. Considering recent evidence, the purpose of this review is to a provide a focused update and new perspectives on HDL and CVD. A Mendelian randomization study demonstrated an increased risk of CVD when HDL-cholesterol was predominantly transported in larger HDL particles and a decreased risk of CVD when HDL-cholesterol was predominantly transported in smaller HDL particles. Moreover, another Mendelian randomization study demonstrated that concentration and content of medium HDL particles is associated with CVD. A Mendelian randomization study that utilized stratified analyses demonstrated that individuals with HDL-cholesterol 50 mg/dl or less were at increased risk of CVD. Lastly, the AEGIS-II trial demonstrated that CSL112, a human apolipoprotein A-I that increases cholesterol efflux, did not significantly reduce cardiovascular events in patients at very high risk. Exploratory analyses showed that patients treated with CSL112 had numerically lower rates of cardiovascular events. Qualitative markers of HDL may be causally related to CVD. There is a need for ongoing research into HDL therapeutics that promote the biological properties of HDL. The optimal cohort or disease state that will benefit from these therapies needs to be identified.