Coronary Ischemic Events Research Articles

Coronary vasodilation mediated by T cells expressing choline acetyltransferase

CD4+ T cells expressing choline acetyltransferase (ChAT) have recently been shown to cause a drop in systemic blood pressure when infused into mice. The aim of this study was to determine if ChAT-expressing T cells could regulate coronary vascular reactivity. Preconstricted segments of epicardial and intramyocardial porcine coronary arteries relaxed in response to Jurkat T cells (JT) that overexpressed ChAT (JTChAT cells). The efficacy of the JTChAT cells was similar in epicardial and intramyocardial vessels with a maximum dilator response to 3 × 105 cells/mL of 38.0 ± 6.7% and 38.7 ± 7.25%, respectively. In contrast, nontransfected JT cells elicited a weak dilator response, followed by a weak contraction. The response of JTChAT cells was dependent on the presence of the endothelial cells. In addition, the response could be significantly reduced by Nω-nitro-l-arginine methyl ester (l-NAME) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) in the presence of indomethacin. JTChAT cells, but not JT cells, increased the expression of phosphorylated endothelial nitric oxide synthase (eNOS). JTChAT cells contained significantly greater levels of acetylcholine compared with JT cells; however, the nonselective muscarinic antagonist atropine and the M1 receptor antagonist pirenzepine both failed to block the dilator effect of JTChAT cells. Exogenously added acetylcholine induced only a weak relaxation (∼10%) at low concentrations, which became a contractile response at higher concentrations. These data illustrate the capacity for cells that express ChAT to regulate coronary vascular reactivity, via mechanisms that are dependent on interaction with the endothelium and in part mediated by the release of nitric oxide.NEW & NOTEWORTHY This study shows ChAT-expressing T cells can induce vasodilation of the blood vessel in the coronary circulation and that this effect relies on a direct interaction between T cells and the coronary vascular endothelium. The study establishes a potential immunomodulatory role for T cells in the coronary circulation. The present findings offer an additional possibility that a deficiency of ChAT-expressing T cells could contribute to reduced coronary blood flow and ischemic events in the myocardium.

ПРОГРЕССИРУЮЩЕЕ АТЕРОСКЛЕРОТИЧЕСКОЕ ПОРАЖЕНИЕ КОРОНАРНЫХ АРТЕРИЙ У ПАЦИЕНТОВ С НЕСКОЛЬКИМИ ИШЕМИЧЕСКИМИ СОБЫТИЯМИ В АНАМНЕЗЕ

Вackground. Progressive atherosclerosis is accompanied by unfavorable clinical outcomes; study and understanding of this process is necessary to identify the appropriate risk groups. Purpose of the study to study the dynamics of atherosclerotic lesions of the coronary arteries in patients with several ischemic events in history. Patient Characterization and Research Methods. The present subanalysis included 51 patients with recurrent nonfatal myocardial infarction (MI) out of the initially included 100 patients with index MI. All 100 patients had a history of two or more ischemic coronary or cerebral events, which corresponds to the clinical signs of progressive atherosclerosis. The dynamics of the degree of coronary stenosis from the moment of index MI to repeated MI was assessed according to the data of selective coronary angiography. The statistical program Microsoft Office Excel 2019 was used. Results. All patients with recurrent myocardial infarction (51 people) had signs of progression of coronary artery stenosis: "mild" progression - 82.3%, "moderate" and "severe" - 15.6% and 2.1%, respectively. SYNTAX Score> 22.5 points was a predictor of one-year adverse outcomes: OR 6.349, CI (2.548-15.823). The results obtained make it possible to distinguish a group of patients with accelerated atherosclerosis syndrome in order to stratify the risk and optimally manage this complex category of patients.

Homocysteine and long-term recurrent infarction following an acute coronary syndrome.

There are no well-established predictors of recurrent ischemic coronary events after an acute coronary syndrome (ACS). Higher levels of homocysteine have been reported to be associated with an increased atherosclerotic burden. The primary endpoint was to assess the relationship between homocysteine at discharge and very long-term recurrent myocardial infarction (MI). 1306 consecutive patients with ACS were evaluated (862 with non-ST-segment elevation ACS [NSTEACS] and 444 with ST-segment elevation myocardial infarction [STEMI]) discharged from October 2000 to June 2003 in a single teaching-center. The relationship between homocysteine at discharge and recurrent MI was evaluated through bivariate negative binomial regression accounting for mortality as a competitive event. The mean age was 66.8 ± 12.4 years, 69.1% were men, and 32.2% showed prior diabetes mellitus. Most of the patients were admitted for an NSTEACS (66.0%). The median (interquartile range) GRACE risk score, Charlson comorbidity index, and homocysteine were 144 (122-175) points, 1 (1-2) points, and 11.9 (9.3-15.6) μmol/L, respectively. In-hospital revascularization was performed in 26.3% of patients. At a median follow-up of 9.7 (4.5-15.1) years, 709 (54.3%) deaths were registered and 779 recurrent MI in 478 (36.6%) patients. The rates of recurrent MI were higher in patients in the upper homocysteine quartiles (p < 0.001). After a multivariate adjustment, homocysteine along its continuum remained almost linearly associated with a higher risk of recurrent MI (p = 0.001) and all-cause mortality (p < 0.001). In patients with ACS, higher homocysteine levels identified those at a higher risk of recurrent MI at very long-term follow-up.

Re-evaluation of the Cardiovascular Safety Profile of Tegaserod: A Review of the Clinical Data

Tegaserod is a 5-HT4 receptor agonist approved for irritable bowel syndrome with constipation in women <65 years of age without a history of cardiovascular ischemic events. Safety data are presented from 2 external adjudications from the 2018 Gastrointestinal Drugs Advisory Committee meeting supporting tegaserod's reintroduction after its voluntary 2007 withdrawal. Withdrawal was based on an internal adjudication using pooled placebo-controlled tegaserod data to identify potential cardiovascular ischemic signals. An independent committee conducted an external adjudication to evaluate 24 possible cardiovascular ischemic events (tegaserod: n= 20; placebo: n= 4) identified internally. A second independent external adjudication further evaluated these events. A total of 18,645 patients were included (tegaserod: n= 11,614; placebo: n= 7031). The first adjudication identified 14 (0.075%) events (tegaserod: n= 13 [0.11%]; placebo: n= 1 [0.014%]). All patients had ≥1 cardiovascular risk factor, and 11 had ≥2. The second adjudication identified 390 events, 24 (0.13%) were classified as probable new or worsening events (tegaserod: 18 [0.16%]; placebo: 6 [0.09%]). For tegaserod, 7 (0.06%) were coronary or cerebrovascular ischemic events compared with 1 (0.01%) for placebo (odds ratio, 4.24; 95% confidence interval, 0.52-34.74; P= .273). All tegaserod patients reporting cardiovascular events had ≥1 risk, including cardiovascular disease, hyperlipidemia, ≥55 years of age, hypertension, diabetes, obesity, and smoking. Women <65 years of age without a history of cardiovascular ischemic events and ≤1 cardiovascular risk factor receiving tegaserod experienced no major adverse cardiovascular event(s). Two independent, external adjudications suggest that tegaserod is safe for women <65 years of age with irritable bowel syndrome with constipation, no history of cardiovascular ischemic events, and ≤1 cardiovascular risk factor.

Anticoagulation versus placebo for heart failure in sinus rhythm.

People with chronic heart failure (HF) are at risk of thromboembolic events, including stroke, pulmonary embolism, and peripheral arterial embolism; coronary ischaemic events also contribute to the progression of HF. The use of long-term oral anticoagulation is established in certain populations, including people with HF and atrial fibrillation (AF), but there is wide variation in the indications and use of oral anticoagulation in the broader HF population. To determine whether long-term oral anticoagulation reduces total deaths and stroke in people with heart failure in sinus rhythm. We updated the searches in CENTRAL, MEDLINE, and Embase in March 2020.We screened reference lists of papers and abstracts from national and international cardiovascular meetings to identify unpublished studies. We contacted relevant authors to obtain further data. We did not apply any language restrictions. Randomised controlled trials (RCT) comparing oral anticoagulants with placebo or no treatment in adults with HF, with treatment duration of at least one month.We made inclusion decisions in duplicate, and resolved any disagreements between review authors by discussion, or a third party. Two review authors independently assessed trials for inclusion, and assessed the risks and benefits of antithrombotic therapy by calculating odds ratio (OR), accompanied by the 95% confidence intervals (CI). We identified three RCTs (5498 participants). One RCT compared warfarin, aspirin, and no antithrombotic therapy, the second compared warfarin with placebo in participants with idiopathic dilated cardiomyopathy, and the third compared rivaroxaban with placebo in participants with HF and coronary artery disease. We pooled data from the studies that compared warfarin with a placebo or no treatment. We are uncertain if there is an effect onall-cause death (OR 0.66, 95% CI 0.36 to 1.18; 2 studies, 324 participants; low-certainty evidence); warfarin mayincreasethe risk of major bleeding events (OR 5.98, 95% CI 1.71 to 20.93, NNTH 17). 2 studies, 324 participants; low-certainty evidence). None of the studies reported stroke as an individual outcome. Rivaroxabanmakes little to no difference to all-cause death compared with placebo (OR 0.99, 95% CI 0.87 to 1.13; 1 study, 5022 participants; high-certainty evidence). Rivaroxaban probably reduces the risk of stroke compared to placebo (OR0.67, 95% CI0.47 to 0.95; NNTB 101; 1 study, 5022 participants; moderate-certainty evidence), and probably increases the risk of major bleeding events (OR1.65, 95% CI1.17 to 2.33; NNTH 79; 1 study, 5008 participants; moderate-certainty evidence). Based on the three RCTs, there is noevidence that oral anticoagulant therapy modifies mortalityin people with HF in sinus rhythm. The evidence is uncertain if warfarin has any effect on all-cause death compared to placebo or no treatment, but it may increase the risk of major bleeding events.There is no evidence of a differencein the effect ofrivaroxabanon all-cause death compared to placebo. It probably reducesthe risk of stroke, but probably increases the risk of major bleedings. The available evidence does not support the routine use of anticoagulation in people with HF who remain in sinus rhythm.

Pregnancy Outcomes in Women After Arterial Switch Operation for Transposition of the Great Arteries: Results From ROPAC (Registry of Pregnancy and Cardiac Disease) of the European Society of Cardiology EURObservational Research Programme.

BackgroundIn the past 3 decades, the arterial switch procedure has replaced the atrial switch procedure as treatment of choice for transposition of the great arteries. Although survival is superior after the arterial switch procedure, data on pregnancy outcomes are scarce and transposition of the great arteries after arterial switch is not yet included in the modified World Health Organization classification of maternal cardiovascular risk.Methods and ResultsThe ROPAC (Registry of Pregnancy and Cardiac disease) is an international prospective registry of pregnant women with cardiac disease, part of the European Society of Cardiology EURObservational Research Programme. Pregnancy outcomes in all women after an arterial switch procedure for transposition of the great arteries are described. The primary end point was a major adverse cardiovascular event, defined as combined end point of maternal death, supraventricular or ventricular arrhythmias requiring treatment, heart failure, aortic dissection, endocarditis, ischemic coronary events, and thromboembolic events. Altogether, 41 pregnant women (mean age, 26.7±3.9 years) were included, and there was no maternal mortality. A major adverse cardiovascular event occurred in 2 women (4.9%): heart failure in one (2.4%) and ventricular tachycardia in another (2.4%). One woman experienced fetal loss, whereas no neonatal mortality was observed.ConclusionsWomen after an arterial switch procedure for transposition of the great arteries tolerate pregnancy well, with a favorable maternal and fetal outcome. During counseling, most women should be reassured that the risk of pregnancy is low. Classification as modified World Health Organization risk class II seems appropriate.

Pregnancy outcomes in women with a systemic right ventricle and transposition of the great arteries. Results from the ESC-EORP Registry of Pregnancy and Cardiac disease (ROPAC)

Abstract Background Cardiac disease is one of the major causes of maternal mortality. We studied pregnancy outcomes in women with a systemic right ventricle (sRV) after the atrial switch procedure for transposition of the great arteries (TGA) or congenitally corrected TGA (CCTGA). Methods The ESC-EORP Registry of Pregnancy and Cardiac Disease is an international prospective registry of pregnant women with cardiac disease. Pregnancy outcomes (maternal and fetal) in women with a sRV are described. The primary endpoint was a major cardiovascular event (MACE) defined as maternal death, supraventricular or ventricular arrhythmias requiring treatment, heart failure, aortic dissection, endocarditis, ischemic coronary event and other thromboembolic events. Results Altogether, 163 women with a sRV (TGA n=121, CCTGA n=42, mean age 28.8±4.6 years) were included. Maternal mortality did not occur. At least one MACE occurred in 26 women (heart failure in 16 (9.8%), arrhythmias (atrial 5, ventricular 6) in 11 (6.7%), and others in 4 (2.5%)). Predictors of MACE were pre-pregnancy signs of heart failure [Odds ratio (OR) 6.05, 95% CI: 1.41–25.97, p=0.02] as well as a sRV ejection fraction below 40% [OR 2.81, 95% CI: 1.18–6.69, p=0.02]. One woman experienced fetal loss, while no neonatal mortality was observed. No significant differences were found between women with CCTGA and TGA. In the subset of women who had an echocardiogram before and after pregnancy, no clear deterioration in sRV was observed. Conclusion The majority of women with a sRV tolerated pregnancy well with a favorable maternal and fetal outcome. Heart failure and arrhythmias were the most common MACE. Funding Acknowledgement Type of funding source: None

A comparison of the safety and effectiveness of prasugrel and clopidogrel in younger population undergoing percutaneous coronary intervention: A retrospective study using a Japanese claims database

BackgroundPrasugrel inhibits platelet aggregation more potently than clopidogrel. In the global phase III trial, prasugrel [loading dose/maintenance dose (LD/MD), 60/10 mg] reduced the incidence of ischemic events but involved a higher risk of hemorrhage than clopidogrel in patients with acute coronary syndromes who were scheduled to undergo percutaneous coronary intervention (PCI). In the Japanese phase III trial for similar patients wherein the prasugrel dose regimen was adjusted (LD/MD, 20/3.75 mg), the efficacy of prasugrel and clopidogrel were comparable to that in the global trial; however, the safety could not be determined due to limited power. Given the strict enrollment criteria, the results of the Japanese phase III trial may not be applicable to routine clinical practice. We compared the safety and effectiveness of prasugrel and clopidogrel in the real-world setting in Japanese patients. MethodsWith an analysis of a large claims database prepared during the post-marketing stages in Japan, we identified patients undergoing PCI and compared the incidence of bleeding and ischemic coronary events between patients who received prasugrel and those receiving clopidogrel. ResultsBetween January 1, 2014 and December 31, 2018, we identified 1977 patients who were scheduled to undergo urgent PCI (urgent PCI cohort) and 1922 who were scheduled to undergo elective PCI (elective PCI cohort). After propensity-score matching, there were no significant differences in the baseline clinical characteristics of the prasugrel and clopidogrel groups in the urgent (n = 1080) and elective PCI (n = 1626) cohorts. In Cox proportional hazard analyses, there were no significant differences in the incidence of bleeding or ischemic coronary events during the median 8-month follow-up in both cohorts. ConclusionsThe safety and effectiveness of prasugrel was comparable to that of clopidogrel in real-world Japanese patients scheduled to undergo PCI.

Outcomes of Early Coronary Angiography or Revascularization After Cardiac Surgery

Early coronary ischemic events are uncommon after cardiac surgery, with little known about their management or associated outcomes. We evaluated clinical outcomes of patients undergoing coronary angiography ± percutaneous coronary intervention or redo coronary artery bypass grafting for suspected coronary ischemia within 3 weeks after index cardiac surgery. This is a retrospective observational study based on data from 53,287 patients who underwent cardiac surgery at our institution (1996-2017); 180 patients (0.34%) satisfied the inclusion criteria. The primary outcome was 1-year all-cause mortality. Statistical evaluation involved χ2, analysis of variance, Kaplan-Meier, and receiver operating characteristic curve analyses. Most coronary angiography ± percutaneous coronary intervention and redo coronary artery bypass grafting procedures occurred in the first 2 weeks after index cardiac surgery. Patients presenting with ST elevation myocardial infarction (STEMI)/non-STEMI had the lowest 1-year mortality (13.5%), followed by patients with ventricular tachycardia/fibrillation (28.1%), and patients with non-ventricular tachycardia/fibrillation arrest or hemodynamic instability alone the worst (38.6%) (χ2= 17.3, P= .001). Peak troponin T level after cardiac surgery was strongly predictive of 1-year mortality (area under the curve, 0.74; 95% confidence interval, 0.65-0.84; P < .001) but did not predict the presence of coronary compromise. For acute graft failure, 1-year mortality was better with percutaneous coronary intervention (18.2%) than redo coronary artery bypass grafting (23.5%) or no indicated/feasible intervention (29.2%). Although suspected myocardial ischemia requiring coronary angiography or intervention early after cardiac surgery was rare, mortality was high, particularly in presentations other than STEMI/non-STEMI. In patients with overt signs and symptoms of myocardial ischemia after index cardiac surgery, troponin T was not a reliable marker of underlying coronary or graft obstruction but was a robust predictor of 1-year mortality.

Updated mechanisms of calcification of cardiovascular system and its correction in chronic kidney disease

In chronic kidney disease (CKD), progressive decline in kidney function leads to disorders of mineral metabolism, which are usually called secondary hyperparathyroidism. An increase in the serum concentration of the parathyroid hormone is associ­ated with a decrease in the level of calcium and calcitriol and/or an increase in the level of fibroblast growth factor-23 and inorganic phosphate in serum. CKD-related disorders of mineral and bone metabolism are associated with other metabolic disorders, such as acidosis, protein-energy wasting, inflammation, and accumulation of uremic toxins. This contributes to vascular calcification, which is a consequence of an imbalance between numerous inhibitors and promoters of soft tissue min­eralization. Vascular calcification is a degenerative process characterized by the accumulation of calcium and phosphate salts in the artery wall. This is observed in almost all vascular areas and can develop in the media, intima, or both vascular layers of the arteries. Calcification of the intima usually occurs due to atherosclerosis and may be responsible for coronary ischemic events. Conversely, media calcification is non-exclusive and predominantly develops along elastic fibers. As a result, media calcification increases vascular stiffness, aortic pulse wave velocity, systolic and pulse blood pressure, contributing to the de­velopment of left ventricular hypertrophy and heart failure. This review examines the current understanding of the mechanisms that lead to the development of vascular calcification in CKD. The participation of factors such as inflammation, age glycation end products, indoxyl sulfate, and others in calcification processes is discussed. Promising therapeutic goals associated with a new understanding of the mechanisms of cardiovascular calcification in CKD are identified.

Periodontitis, coronary heart disease and myocardial infarction: treat one, benefit all.

: Periodontal disease is conventionally defined as an inflammatory condition affecting the tissues surrounding and supporting the teeth (i.e. gum and periodontium). Recent statistics show that the prevalence of this condition is continuously growing worldwide, thus raising severe healthcare concerns, not only for local problems emerging from poor oral health, but also for the potential risk of developing systemic complications. Therefore, this article aims to provide an update on the intriguing association between periodontitis, coronary heart disease (CHD) and/or myocardial infarction (MI). Taken together, the available published information seems to support the existence of a significant association between periodontitis and CHD, whilst the risk of acute ischemic cardiac events appears magnified in patients with preexisting coronary artery disease. This epidemiological link is supported by reliable biological evidence, showing that periodontal disease may unfavourably modulate the cardiovascular risk, whereby patients with periodontitis have increased frequency of overweight, hypertension, endothelial dysfunction, dyslipidaemia, platelet hyper-reactivity, and may also be characterized by a prothrombotic state. Apart from these critical atherogenic factors, translocation of periodontal microorganisms into the bloodstream, and their further accumulation within atherosclerotic plaques, would contribute to enhance plaque instability and the risk of developing acute ischemic coronary events. Interesting evidence is also emerging that local or systemic statins administration could be beneficial for safeguarding periodontal health, thus enlightening the intriguing relationship existing between CHD and periodontitis.

Healthcare knowledge of relationship between time series electrocardiogram and cigarette smoking using clinical records

BackgroundIn the few studies of clinical experience available, cigarette smoking may be associated with ischemic heart disease and acute coronary events, which can be reflected in the electrocardiogram (ECG). However, there is no formal proof of a significant relationship between cigarette smoking and electrocardiogram results. In this study, we therefore investigate and prove the relationship between electrocardiogram and smoking using unsupervised neural network techniques.MethodsIn this research, a combination of two techniques of pattern recognition; feature extraction and clustering neural networks, is specifically investigated during the diagnostic classification of cigarette smoking based on different electrocardiogram feature extraction methods, such as the reduced binary pattern (RBP) and Wavelet features. In this diagnostic system, several neural network models have been obtained from the different training subsets by clustering analysis. Unsupervised neural network of clustering cigarette smoking was then implemented based on the self-organizing map (SOM) with the best performance.ResultsTwo ECG datasets were investigated and analysed in this prospective study. One is the public PTB diagnostic ECG databset with 290 samples (age 17–87, mean 57.2; 209 men and 81 women; 73 smoking and 133 non-smoking). The other ECG database is from Taichung Veterans General Hospital (TVGH) and includes 480 samples (240 smoking, and 240 non-smoking). The diagnostic accuracy regarding smoking and non-smoking in the PTB dataset reaches 80.58% based on the RBP feature, and 75.63% in the second dataset based on Wavelet feature.ConclusionsThe electrocardiogram diagnostic system performs satisfactorily in the cigarette smoking habit analysis task, and demonstrates that cigarette smoking is significantly associated with the electrocardiogram.

Concomitant use of direct oral anticoagulants and aspirin versus direct oral anticoagulants alone in atrial fibrillation and flutter: a retrospective cohort

BackgroundThe benefit of combining aspirin and direct oral anticoagulants on the reduction of cardiovascular events in atrial fibrillation or flutter is not well studied. We aimed to assess whether concurrent aspirin and direct oral anticoagulant therapy for atrial fibrillation or flutter will result in less coronary, cerebrovascular and systemic ischemic events compared to direct oral anticoagulant therapy alone.MethodsRetrospective study of adult patients between 18 and 100 years old who have nonvalvular atrial fibrillation or flutter and were started on a direct oral anticoagulant (apixaban, rivaroxaban, or dabigatran), between January 1, 2010 and September 1, 2015 within the Beaumont Health System. Exclusions were history of venous thromboembolic disease and use of other antiplatelet therapies such as P2Y12 inhibitors. Patients were classified into two groups based on concurrent aspirin use and observed for a minimum of 2 years. Primary outcome was major adverse cardiac events, defined as acute coronary syndromes, ischemic strokes, and embolic events. Secondary outcomes were bleeding and death.ResultsSix thousand four patients were in the final analysis, 57% males and 80% Caucasians, median age 71, interquartile range (63–80). The group exposed to aspirin contained 2908 subjects, and the group unexposed to aspirin contained 3096 subjects. After using propensity scores to balance the baseline characteristics in both groups, the analysis revealed higher rate of major adverse cardiac events in the exposed group compared to the unexposed group, (HR 2.11, 95% CI (1.74–2.56)) with a number needed to harm of 11 (95% CI [9–11]). The rate of bleeding was also higher in the exposed group, (HR 1.30, 95% CI (1.11–1.52)). The rate of death was not statistically different between the groups, (HR 0.87, 95% CI (0.61–1.25)).ConclusionsIn this observational analysis of patients with atrial fibrillation and flutter, the concomitant use of direct oral anticoagulants and aspirin was associated with an increased risk of both major adverse cardiac and bleeding events when compared to the use of direct oral anticoagulants alone. These findings underscore the potential harm of this combination therapy when used without a clear indication.

The role of chemokine CCL5/RANTES and metalloproteinase-9 as inflammatory modulators in symptomatic internal carotid artery stenosis.

Up to 80% of all ischemic strokes (IS) attributed to internal carotid athero-occlusive artery stenosis (ICAS) are related to a thromboembolic mechanism. One athero-occlusive ischemic event increases the risk for ischemia in another vascular territory, resulting from inflammation within the atherosclerotic plaque induced by cytokines. Thus, ultrasonographic characteristics of vulnerable plaques in ICAS, including plaque echolucency and ulceration might correspond to cytokine activity. The present study aimed to investigate the associations between serum cytokines and atherosclerotic plaque characteristics and the 3-year risk of a major adverse coronary and carotid ischemic event (MACCE) in symptomatic patients treated for ICAS. Plaque characteristics on ultrasonography, serum levels of C-C motif chemokine ligand 5 (CCL5)/regulated on activation, normal T-cell expressed and secreted (RANTES), metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), transforming growth factor beta (TGF-β), C-X-C motif chemokine ligand 16 (CXCL16), FAS ligand (FASL) and high sensivity C-reactive protein (hs-CRP) were analyzed in 103 symptomatic patients with ICAS prior to carotid revascularization. The incidence of MACCE: cardiovascular death (CVD), myocardial infarction (MI) and recurrent ischemic stroke (IS) were recorded prospectively for up to 5 years (median 37; IQR 21 - 40 months). Echolucent plaques, in comparison to echogenic plaques, displayed lower median levels of RANTES (P = 0.042) but higher median levels of IL-6 (P = 0.039). There was no relationship between plaque characteristics and median levels of MMP-9, TGF β, CXCL16, FASL, or hs-CRP (P = NS). During follow-up, MACCE occurred in 15 (14.6%) patients. Univariate Cox proportional hazard analysis indicated median RANTES levels < 45.5ng/mL (hazard ratio (HR) = 3.95; 95%CI = 1.10 - 14.2; P = 0.035), MMP-9 > 0.6 μg/mL (HR 4.5; 95%CI = 1.4 - 13.9; P = 0.009), renal impairment (HR 3.48; 95%CI = 1.29 - 9.34; P = 0.013) as potential MACCE risk factors. On multivariate Cox proportional hazard analysis, MMP-9 > 0.6 μg/mL and RANTES < 45.5 ng/ml were associated with a 4.72-fold (95%CI = 1.3 - 17.0; P = 0.017) and a 3.8-fold risk increase (95%CI = 1.07 - 13.89; P = 0.038) of MACCE. Kaplan-Meier analysis showed significant differences in MACCE-free survival rates depending on RANTES and MMP-9 median levels. We conclude that serum RANTES, IL-6, and MMP-9 were associated with plaque vulnerability and predicted adverse MACCE in patients treated for ICAS.

Triple Antithrombotic Therapy vs. Double Antithrombotic Therapy: One Scenario, 8 Questions, Many Conclusions

In patients with atrial fibrillation undergoing percutaneous coronary intervention with the placement of stents, a triple antithrombotic therapy is empirically established, which consists of a combination of dual antithrombotic therapy (aspirin plus a P2Y12 inhibitor) and an oral anticoagulant agent. This choice is guided by the desirable result of reducing cerebrovascular and coronary ischemic events. However, there is an unwelcome outcome: an increased incidence of bleeding. On this matter, in 2018, a North American Perspective Update was published, about a year later it was followed by the publication of the European focus update on the dual antiplatelet therapy. After analysing the main differences between these two consensus documents, this review aims at examining the major studies on which they are based on, as a starting point to define the foundation of new trials that can help shed light on this prominent topic.

Rosuvastatin Alleviates Ischemia/Reperfusion Injury in Cardiomyocytes by Downregulating Hsa-miR-24-3p to Target Upregulated Uncoupling Protein 2.

Statins could reduce the risks of coronary heart disease death and ischemic cardiovascular events. In this study, we aim to explore the role of rosuvastatin in ischemia/reperfusion (I/R)-injured cardiomyocytes and the possible mechanism. An I/R model was established by oxygen-glucose deprivation/reperfusion (OGD/R). The protective effects of rosuvastatin pretreatment on OGD/R-injured cardiomyocytes were performed using MTT assay, lactate dehydrogenase (LDH) release assay, and quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatics software TargetScan and miRTarBase were used to predict the targeted miRNAs with uncoupling protein (UCP)2. Furthermore, verify the binding capacity of hsa-miR-24-3p and UCP2 with qRT-PCR and dual-luciferase reporter assay. The expression of UCP2, cell viability, LDH level, and apoptosis level affected by downregulated hsa-miR-24-3p were assessed using qRT-PCR, western blotting, MTT, the LDH kit, and flow cytometry. Pretreatment with rosuvastatin could significantly augment cell viability, reduce LDH level, increase the expression of UCP2, and downregulate hsa-miR-24-3p in OGD/R-injured H9c2 cells. miR-24-3p was closely connected with UCP2, and downregulated miR-24-3p could promote UCP2 expression, which presented cell viability increasing, LDH release and cell apoptosis inhibition in OGD/R condition. Moreover, it decreased the protein expression of Cleaved-Caspase-9 and Cyto C. This is the first time our study suggests that rosuvastatin pretreatment protects cardiomyocytes from OGD/R through upregulating UCP2 through downregulation of hsa-miR-24-3p.

Risk for vascular thromboembolic events (VaTEs) in patients (pts) with advanced urinary tract cancer (aUTC) treated with chemotherapy.

383 Background: Venous thromboembolism (VTE) is a frequent complication of cancer or its treatment. Khorana (KRS) and Compass scores are two Risk Assessment Models for VTE. However, aUTC was not adequately represented and arterial events were not included, in these models. Methods: Data from pts with aUTC treated with at least one line of chemotherapy in our institution were analyzed. VaTE definition included: DVT and PE defined as venous events and peripheral arterial thrombosis or embolus, ischemic stroke and coronary events, grouped as arterial events. The association of baseline and treatment-related factors with the development of VaTE was assessed using competing-risk regressions. According to the results of our multivariate analysis we stratified patients according to the number of the identified risk factors. Results: 354 aUTC pts treated between 4/1995 and 9/2015 entered our study. 53% of pts had received cisplatin and 42% carboplatin-based regimens. 44 pts (12.4%) suffered 45 VaTEs (13 arterial, 32 venous) within a median time of 3.3 months. The cumulative and 6-month incidence was 14.8% (95% CI: 10.9-19.4) and 9.7% (95% CI: 6.8-13.1), [venous 10.5% (95% CI: 7.3-14.3)/7.5% (95% CI: 5-10.7); arterial 5.3% (95% CI: 2.8-9)/2.7% (95% CI: 1.3-5), respectively]. No association of the KRS and the COMPASS score with the incidence of VaTEs was observed. In the univariate and multivariate analysis, cumulative VaTE incidence was significantly increased in pts with “peripheral arterial disease (PAD) or history of VΤE” (adjusted SHR: 3.29; 95% CI: 1.65-6.55; p=0.001) and pts with other solid tumor (SHR: 2.20; 95% CI: 1.05-4.62; p=0.038). There was a strong correlation between the number of risk factors and the risk for VaTE development (p&lt;0.001). Patients with 1 or 2, vs 0 factors had a 3-fold increased risk [cumulative incidence was 10.9% (95% CI: 7.4.-15.2) and 30.2% (95% CI: 18.4-42.8), respectively; SHR: 3.01 95% CI: 1.65-5.51]. Conclusions: Development of tumor-specific algorithms for the risk of vascular events is supported by our results. Pts with aUTC and a history of VTE, PAD and other solid tumor have a very high risk for VaTE. The role of prophylaxis should be prospectively studied.

Lifestyle after seven years of post ischemic coronary event: cross-sectional study

BACKGROUND: The population’s accelerated aging process and unhealthy lifestyle imply in the appearance of comorbidities, thus leading to the loss of functional capacity, limiting the individual in labor, recreational and social activities. The magnitude of the problem reflects on the importance of multidisciplinary programs, awakening the need to change lifestyle, especially in individuals who have suffered a long-term ischemic event. OBJECTIVE: To compare the lifestyle of individuals after seven years of ischemic coronary event. METHOD: This is a retrospective cohort composed of individuals with Ischemic Coronary Syndrome (ICS) Inclusion criteria: participants from a previous study, in the period from April 2006 to January 2007. After the consent, a brief interview was performed by telephone contact, with the following questions: sociodemographic data; comorbidities; Lifestyle; number of hospitalizations due to cardiac problems; presence of chest pain. The categorical variables presented in terms of absolute frequency, while the numerical data, in terms of mean and standard deviation (XD ± SD). The McNemar test for comparison of the categorical variables paired and chi-square test for comparison of the categorical variables, p ? 0.05. CAAE: 05874112.9.0000.5544. RESULTS: We highlight the most prevalent comorbidities, Hypertension 24 (80%), Dyslipidemia 21 (70%), Diabetes 14 (46.6%). After seven years event, there was an increase in hypertensive patients (p = 0.01) in contrast smokers reduction (p = 0.02). CONCLUSION: Although the individuals have modified two significant lifestyles such as the relevant, hypertension and smoking, the studied population maintains high rates of cardiovascular risk factors, necessitating an intervention by the multidisciplinary team.

Association between Smoking and Alcohol Consumption and the Severity of Coronary Artery Injuries in Patients with AMI

Background: Smoking is the most important risk factor for coronary heart disease (CHD) and ischemic events; alcohol consumption, on the other hand, appears to have a protective role. Objective: Assess the association between smoking and alcohol consumption with the severity of coronary artery injuries in patients with acute myocardial infarction (AMI). Methods: Cross-sectional study, performed in Santa Catarina. Variables were evaluated using the Chi-squared T/Fisher’s exact test, Kendall’s correlation coefficient, Student’s t test or Mann-Whitney U test. Values of p [...]

Platelet function, coagulation and fibrinolysis in patients with previous coronary and cerebrovascular ischemic events

OBJECTIVES:Ischemic stroke (IS) or transient ischemic attack (TIA) history is present in 4-17% of patients with coronary artery disease (CAD). This subgroup of patients is at high risk for both ischemic and bleeding events. The aim of this study was to determine the role of platelet aggregability, coagulation and endogenous fibrinolysis in patients with CAD and previous IS or TIA.METHODS:A prospective case-control study that included 140 stable CAD patients divided into two groups: the CASE group (those with a previous IS/TIA, n=70) and the CONTROL group (those without a previous IS/TIA, n=70). Platelet aggregability (VerifyNow Aspirin® and VerifyNow P2Y12®), coagulation (fibrinogen and thromboelastography by Reorox®) and endogenous fibrinolysis (D dimer and plasminogen activator inhibitor-1) were evaluated.RESULTS:Patients in the CASE group presented significantly higher systolic blood pressure levels (135.84±16.09 vs 123.68±16.11, p<0.01), significantly more previous CABG (25.71% vs 10%, p=0.015) and significantly higher calcium channel blocker usage (42.86% vs 24.29%, p=0.02) than those in the control group. In the adjusted models, low triglyceride values, low hemoglobin values and higher systolic blood pressure were significantly associated with previous IS/TIA (CASE group). Most importantly, platelet aggregability, coagulation and fibrinolysis tests were not independently associated with previous cerebrovascular ischemic events (CASE group).CONCLUSION:Platelet aggregability, coagulation and endogenous fibrinolysis showed similar results among CAD patients with and without previous IS/TIA. Therefore, it remains necessary to identify other targets to explain the higher bleeding risk presented by these patients.