RESUMO
The global escalation of obesity has made it a worldwide health concern, notably as a leading risk factor for cardiovascular disease (CVD). Extensive evidence corroborates its association with a range of cardiac complications, including coronary artery disease, heart failure, and heightened vulnerability to sudden cardiac events. Additionally, obesity contributes to the emergence of other cardiovascular risk factors including dyslipidaemia, type 2 diabetes, hypertension, and sleep disorders, further amplifying the predisposition to CVD. To adequately address CVD in patients with obesity, it is crucial to first understand the pathophysiology underlying this link. We herein explore these intricate mechanisms, including adipose tissue dysfunction, chronic inflammation, immune system dysregulation, and alterations in the gut microbiome.Recent guidelines from the European Society of Cardiology underscore the pivotal role of diagnosing and treating obesity to prevent CVD. However, the intricate relationship between obesity and CVD poses significant challenges in clinical practice: the presence of obesity can impede accurate CVD diagnosis while optimizing the effectiveness of pharmacological treatments or cardiac procedures requires meticulous adjustment, and it is crucial that cardiologists acknowledge the implications of excessive weight while striving to enhance outcomes for the vulnerable population affected by obesity. We, therefore, sought to overcome controversial aspects in the clinical management of heart disease in patients with overweight/obesity and present evidence on cardiometabolic outcomes associated with currently available weight management interventions, with the objective of equipping clinicians with an evidence-based approach to recognize and address CVD risks associated with obesity.
Assuntos
Doenças Cardiovasculares , Obesidade , Redução de Peso , Humanos , Obesidade/complicações , Obesidade/terapia , Obesidade/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/terapia , Fatores de Risco de Doenças Cardíacas , Fatores de Risco , Cirurgia Bariátrica , Medição de RiscoRESUMO
To evaluate if integrating platelet reactivity (PR) evaluation in the original age, creatinine and ejection fraction (ACEF) score could improve the diagnostic accuracy of the model in patients with stable coronary artery disease (CAD). We enrolled patients treated with percutaneous coronary intervention between 2010 and 2011. High PR was included in the model (PR-ACEF). Co-primary end points were a composite of death/myocardial infarction (MI) and major adverse cardiovascular events (MACE). Overall, 471 patients were enrolled. Compared to the ACEF score, the PR-ACEF showed an improved diagnostic accuracy for death/MI (AUC 0.610 vs 0.670, p < 0.001) and MACE (AUC 0.572 vs 0.634, p < 0.001). These findings were confirmed using internal validation with bootstrap resampling. At 5 years, the PR-ACEF value > 1.75 was independently associated with death/MI [HR 3.51, 95% CI (1.97-6.23)] and MACE [HR 2.77, 95% CI (1.69-4.53)]. The PR-ACEF score was effective in improving the diagnostic performance of the ACEF score at the long-term follow-up.
RESUMO
Despite continuous advances in both diagnosis and management, heart failure (HF) still represents a major worldwide health issue. Recently, sodium-glucose co-transporter 2 inhibitors (SGLT2i) have demonstrated to reduce cardiovascular death and hospitalization for HF across the entire spectrum of left ventricular ejection fraction. Therefore, dapagliflozin, empagliflozin and sotagliflozin are now recommended as part of the foundational therapy of HF. These agents are characterized by limited contraindications, low cost, non-relevant adverse effects and no need for titration. Although they have a prominent role in the latest recommendations for HF, drug prescriptions are definitely lower than the number of potentially eligible patients. In fact, awareness gaps, therapeutic inertia, concerns about safety and simultaneous initiation of comprehensive medical therapy may represent barriers to their use. This article aims to offer an overview of current knowledge on SGLT2i in HF and provide a comprehensive and updated practical guide on their use in de novo and chronic HF, including potential scenarios that a clinician, cardiologist or others, may face in everyday clinical practice.
Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Volume Sistólico , Função Ventricular Esquerda , Insuficiência Cardíaca/tratamento farmacológico , Prescrições de Medicamentos , Diabetes Mellitus Tipo 2/tratamento farmacológicoRESUMO
Atherosclerosis is the leading cause of death worldwide, especially in patients with type 2 diabetes mellitus (T2D). GLP-1 receptor agonists and DPP-4 inhibitors were demonstrated to play a markedly protective role for the cardiovascular system beyond their glycemic control. Several cardiovascular outcome trials (CVOT) reported the association between using these agents and a significant reduction in cardiovascular events in patients with T2D and a high cardiovascular risk profile. Moreover, recent evidence highlights a favorable benefit/risk profile in myocardial infarction and percutaneous coronary revascularization settings. These clinical effects result from their actions on multiple molecular mechanisms involving the immune system, platelets, and endothelial and vascular smooth muscle cells. This comprehensive review specifically concentrates on these cellular and molecular processes mediating the cardiovascular effects of incretins-like molecules, aiming to improve clinicians' knowledge and stimulate a more extensive use of these drugs in clinical practice as helpful cardiovascular preventive strategies.
RESUMO
New therapies are needed for patients with T-cell lymphoblastic leukemia (T-ALL) who do not respond to standard chemotherapy. Our previous studies showed that the mTORC1 inhibitor everolimus increases reactive oxygen species (ROS) levels, decreases the levels of NADPH and glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway (PPP), and induces apoptosis in T-ALL cells. Studies in T-ALL-xenografted NOD/SCID mice demonstrated that everolimus improved their response to the glucocorticoid (GC) dexamethasone. Here we show that verapamil, a calcium antagonist used in the treatment of supraventricular tachyarrhythmias, enhanced the effects of everolimus on ROS and cell death in T-ALL cell lines. The death-enhancing effect was synergistic and was confirmed in assays on a panel of therapy-resistant patient-derived xenografts (PDX) and primary samples from T-ALL patients. The verapamil-everolimus combination produced a dramatic reduction in the levels of G6PD and induction of p38 MAPK phosphorylation. Studies of NOD/SCID mice inoculated with refractory T-ALL PDX cells demonstrated that the addition of verapamil to everolimus plus dexamethasone significantly reduced tumor growth in vivo. Taken together, our results provide a rationale for repurposing verapamil in association with mTORC inhibitors and GC to treat refractory T-ALL.
RESUMO
Single antiplatelet therapy represents the cornerstone of thrombosis prevention in atherosclerotic cardiovascular disease. Dual antiplatelet therapy (DAPT), consisting of aspirin plus a P2Y 12 inhibitor, is the standard of care for patients with acute coronary syndrome or undergoing both coronary and peripheral percutaneous interventions. Recent data suggest the efficacy of DAPT also after minor stroke. In this setting, a large body of evidence has documented that genetic and acquired patients' characteristics may affect the magnitude of platelet inhibition induced by antiplatelet agents. The implementation of tools allowing the identification and prediction of platelet inhibition has recently been shown to improve outcomes, leading to an optimal balance between antithrombotic efficacy and bleeding risk. We are therefore clearly moving towards tailored antiplatelet therapy. The aim of this paper is to summarize the available evidence on the evaluation of platelet inhibition in patients with coronary, peripheral, or cerebrovascular atherosclerosis. We will here focus on antiplatelet therapy based on both aspirin and P2Y 12 inhibitors. In addition, we provide practical insights into the clinical settings in which it appears reasonable to implement antiplatelet therapy monitoring.
Assuntos
Aterosclerose , Intervenção Coronária Percutânea , Acidente Vascular Cerebral , Humanos , Inibidores da Agregação Plaquetária/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Aspirina/efeitos adversos , Anticoagulantes/efeitos adversos , Acidente Vascular Cerebral/prevenção & controle , Quimioterapia Combinada , Resultado do TratamentoRESUMO
AIM: To determine whether the magnitude of the cardiorenal benefits of sodium-glucose co-transporter-2 inhibitors (SGLT2is) varies with baseline kidney function. METHODS: We searched randomized, placebo-controlled trials testing the effects of SGLT2is on renal and cardiovascular outcomes. Efficacy outcomes, stratified by baseline estimated glomerular filtration rate (eGFR) categories, included renal disease progression, a composite heart failure (HF) outcome and mortality. RESULTS: Thirteen trials testing SGLT2is in 90 402 participants with available eGFR data were included. The risk of bias was judged as low for all trials. SGLT2is reduced the relative risks of renal disease progression by 27% to 57% and of HF outcomes by 13% to 32% across different eGFR categories, with an overall low heterogeneity. Meta-regression analyses showed a significant direct relationship between baseline eGFR and the magnitude of SGLT2is' renal protection (P = .003). The greatest risk reduction was in participants with an eGFR of 90 ml/min/1.73m2 or higher (HR 0.43, 95% CI: 0.32-0.58) and the smallest was in those with an eGFR of less than 30 ml/min/1.73m2 (HR 0.73, 95% CI: 0.62-0.86, P < .001). Conversely, for HF, the greatest risk reduction was in those with an eGFR of less than 30 ml/min/1.73m2 (HR 0.68, 95% CI: 0.48-0.96) and the smallest was in those with an eGFR of 90 ml/min/1.73m2 or higher (HR 0.87, 95% CI: 0.56-1.34). CONCLUSIONS: SGLT2is reduce the risk of renal and HF outcomes for all eGFR categories. The greatest benefits in terms of kidney protection may be achieved by early initiation of SGLT2is in people with preserved eGFR. The greatest risk reduction for HF outcomes is observed in people with lower eGFR values.
Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Nefropatias , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Progressão da Doença , Taxa de Filtração Glomerular , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/prevenção & controle , Rim , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologiaRESUMO
The clinical benefit of LDL cholesterol (LDL-C) lowering for cardiovascular disease prevention is well documented. This paper from the Italian Study Group on Atherosclerosis, Thrombosis and Vascular Biology summarizes current recommendations for treatment of hypercholesterolemia, barriers to lipid-lowering therapy implementation and tips to overcome them, as well as available evidence on the efficacy and safety of bempedoic acid. We also report an updated therapeutic algorithm for pharmacological LDL-C lowering in view of the introduction of bempedoic acid in clinical practice.
Assuntos
Aterosclerose , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Trombose , Humanos , LDL-Colesterol , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Consenso , Fatores de Risco , Ácidos Graxos , Aterosclerose/diagnóstico , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Trombose/tratamento farmacológico , Trombose/prevenção & controle , Biologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêuticoRESUMO
Patients with diabetes have a prothrombotic state and a 2 to 4 times higher risk of cardiovascular events than those without diabetes. Aspirin is the cornerstone of treatment in patients withcardiovascular disease, irrespective of diabetes status, being able to confer a 19% relative risk reduction per year in serious vascular events compared with placebo at long-term follow-up (6.7% vs 8.2% per year, p < 0.0001). Data regarding the benefit-risk ratio of aspirin prescribed to patients with diabetes without established cardiovascular disease are less convincing, especially when compared to other preventive strategies. Of note, in primary prevention trials, aspirin allocation yielded a significant 12% proportional reduction in serious vascular events, irrespective of diabetes status, corresponding to a small annual absolute risk reduction (0.06% per year). However, in everyday clinical practice aspirin is still largely prescribed by both diabetologists and cardiologists. In this article, we provide eight questions and answers corroborated by available evidence on the use of aspirin for primary prevention of cardiovascular disease in diabetes.
Assuntos
Aspirina , Doenças Cardiovasculares , Diabetes Mellitus , Aspirina/efeitos adversos , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus/tratamento farmacológico , Humanos , Prevenção Primária/métodos , Medição de RiscoRESUMO
Available evidence on left atrial (LA) thrombus dissolution in patients with atrial fibrillation (AF) largely refers to the use of vitamin K antagonist oral anticoagulants (VKAs), showing >50% thrombus resolution over a 4-week to 12-month treatment period. Available data on non-vitamin K antagonist anticoagulants (NOACs) in this setting are limited and derive from isolated case reports or observational small-sized investigations with dabigatran, rivaroxaban or apixaban. The aim of this study was to investigate the extent of thrombus resolution with edoxaban therapy in patients with AF and LA thrombosis. We conducted a prospective, observational, open-label pilot study in seven Italian institutions. We included a total of 25 patients with non-valvular AF and LA (or left atrial appendage (LAA)) thrombosis, documented by transesophageal echocardiography (TEE). All patients received edoxaban OD treatment (n = 23 on 60 mg daily; n = 2 on 30 mg daily) and underwent TEE examination after 4 weeks. The primary endpoint was the percentage of patients with complete thrombus resolution by TEE imaging at 4 weeks. The mean age of the study population was 68.3 ± 10.8 years with a female population of 16%. AF was permanent in all cases, with a mean arrhythmia duration of 4.3 ± 1.7 years. CHA2DS2-VASc and HAS-BLED scores were 3.2 ± 1.5 and 1.9 ± 1.1, respectively. We were able to demonstrate a complete thrombus resolution in 14 patients (56%) at 4 weeks. In patients with residual atrial thrombosis (n = 11), we observed a 15.4 ± 14.9% reduction in the thrombus area from baseline. As compared with patients without thrombus dissolution, those with thrombus resolution had a numerically lower-indexed LA diameter (27.9 ± 9.3 vs 34.8 ± 16.1 mm/m2), a smaller maximum thrombus area at baseline (45.5 ± 44.6 vs 63.9 ± 43.5 mm2), a higher left ventricular ejection fraction (47.4 ± 21.0% vs 38.4 ± 20.6%) and higher maximum LAA flow velocities (26.3 ± 15.2 vs 19.3 ± 10.0 cm/s). Figures on the percentage of thrombus resolution in this study are comparable to those reported in the literature for the other OACs. We conclude that, in patients with AF, the use of edoxaban is associated with a >50% resolution of atrial thrombus at 4 weeks, similar to studies using VKAs and the other NOACs (ClinicalTrials.gov identifier number: NCT034899395).
RESUMO
The relation between diabetes mellitus (DM) and bleeding complications after percutaneous coronary intervention (PCI) is controversial. This study investigates the role of low platelet reactivity (LPR) in the bleeding risk stratification of patients who underwent PCI according to DM status. A total of 472 patients who underwent PCI on aspirin and clopidogrel were included retrospectively. Platelet reactivity was assessed using the VerifyNow P2Y(12) assay. LPR was defined as platelet reactivity unit ≤178. The primary end point was the occurrence of any bleeding at 5 years stratified by DM status and LPR. DM was present in 30.5% of patients. LPR was less frequent in patients with DM (p = 0.077). Overall, 11.9% of patients experienced a bleeding complication at 5 years. The incidence of bleeding did not differ in subjects with and without DM (p = 0.24). LPR had a similar value for stratifying the increased bleeding risk in patients with and without DM (interaction p between DM and LPR 0.69). A stepwise increase in the crude rates of bleeding complications was observed across patients with and without LPR and DM (log-rank p = 0.004), with those affected by both conditions having the highest crude incidence rate. In conclusion, on top of aspirin, approximately 1/3 of patients who underwent PCI on clopidogrel have LPR. Assessment of LPR provides a significant incremental value for predicting bleeding irrespective of DM status. Although the presence of DM per se does not increase the incidence of hemorrhagic complications, the coexistence of DM and LPR identifies the subgroup with the highest bleeding risk.
Assuntos
Diabetes Mellitus , Intervenção Coronária Percutânea , Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Diabetes Mellitus/induzido quimicamente , Hemorragia/induzido quimicamente , Hemorragia/etiologia , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Estudos RetrospectivosRESUMO
mTOR activation is a hallmark of T-cell acute lymphoblastic leukemia (T-ALL) and is associated with resistance to glucocorticoid (GC)-based chemotherapy. We previously showed that altering redox homeostasis primes T-ALL cells to GC-induced apoptosis. Here we investigated the connection between the mTOR pathway and redox homeostasis using pharmacological inhibitors and gene silencing. In vitro studies performed on T-ALL cell lines and CG-resistant patient-derived T-ALL xenograft (PDX) cells showed that the mTOR inhibitor everolimus increased reactive oxygen species (ROS) levels, augmented lipid peroxidation, and activated the ROS-controlled transcription factor NRF2. These effects were accompanied by a decrease in the levels of NADPH and of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway (PPP), which is a major source of cytosolic NADPH needed for maintaining the cellular ROS-scavenging capacity. The mTOR inhibitor everolimus induced mitochondrial inner membrane depolarization and dose-dependent apoptosis of T-ALL cells, but did not kill normal T-cells. Importantly, the combination of everolimus and the GC dexamethasone had a synergistic effect on killing T-ALL cells. The effects of mTOR inhibition were blunted by ROS scavengers and phenocopied by siRNA-mediated G6PD silencing. In vivo studies of NOD/SCID mice inoculated with refractory T-ALL PDX demonstrated that everolimus overcame dexamethasone resistance in conditions of high tumor burden that mimicked the clinical setting of acute leukemia. These findings provide insight into the crosstalk between mTOR and ROS homeostasis in T-ALL cells and furnish mechanistic evidence to support the combination of glucocorticoids with mTOR inhibitors as a therapeutic avenue for treating refractory T-ALL.
Assuntos
Leucemia-Linfoma Linfoblástico de Células T Precursoras , Animais , Apoptose , Linhagem Celular Tumoral , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Everolimo/farmacologia , Everolimo/uso terapêutico , Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/metabolismo , Humanos , Inibidores de MTOR , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , NADP , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Linfócitos T/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
Heart failure (HF) represents a major global health and economic burden with still unacceptably high morbidity and mortality rates. In recent decades, novel therapeutic opportunities with a significant impact on HF outcomes have been introduced in addition to angiotensin-converting enzyme (ACE) inhibitors, ß-blockers, and mineralocorticoid receptor antagonists. These include drugs such as ivabradine, sacubitril-valsartan, and sodium-glucose cotransporter-2 (SGLT-2) inhibitors. The availability of an extremely large pharmacological armamentarium to face this chronic global disease highlights the importance of assessing cost effectiveness to promote sustainable healthcare. In light of the recent approval of SGLT-2 inhibitors for the treatment of HF with reduced ejection fraction, including in individuals without type 2 diabetes mellitus, the aim of this review was to provide an updated comparative evaluation of the efficacy and cost effectiveness of different pharmacological treatments for the prevention (stage A) and treatment of asymptomatic (stage B) and symptomatic (stages C-D) left ventricular dysfunction.
Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Disfunção Ventricular Esquerda , Aminobutiratos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Análise Custo-Benefício , Diabetes Mellitus Tipo 2/tratamento farmacológico , Combinação de Medicamentos , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Volume Sistólico/fisiologia , Tetrazóis/uso terapêutico , Resultado do Tratamento , Disfunção Ventricular Esquerda/tratamento farmacológicoRESUMO
AIMS: To investigate the levels of platelet reactivity and the impact of high platelet reactivity (HPR) on long-term clinical outcomes of complex higher-risk and indicated patients (CHIP) with stable coronary artery disease (CAD) treated with elective percutaneous coronary intervention (PCI). METHODS: We enrolled 500 patients undergoing elective PCI for stable CAD and treated with aspirin and clopidogrel. Patients were divided into four groups based on the presence of CHIP features and HPR. Primary endpoint was the occurrence of major adverse clinical events (MACE) at 5âyears. RESULTS: The prevalence of HPR was significantly greater in the CHIP population rather than non-CHIP patients (39.9% vs 29.8%, Pâ=â0.021). Patients with both CHIP features and HPR showed the highest estimates of MACE (22.1%, log-rank Pâ=â0.047). At Cox proportional hazard analysis, the combination of CHIP features and HPR was an independent predictor of MACE (hazard ratio 2.57, 95% confidence interval 1.30-5.05, Pâ=â0.006). CONCLUSION: Among patients with stable CAD undergoing elective PCI and treated with aspirin and clopidogrel, the combination of CHIP features and HPR identifies a cohort of patients with the highest risk of MACE at 5âyears, who might benefit from more potent antiplatelet strategies.
Assuntos
Doença da Artéria Coronariana/terapia , Intervenção Coronária Percutânea , Agregação Plaquetária/efeitos dos fármacos , Idoso , Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Doença da Artéria Coronariana/mortalidade , Feminino , Humanos , Masculino , Infarto do Miocárdio/epidemiologia , Inibidores da Agregação Plaquetária/uso terapêutico , Estudos Prospectivos , Antagonistas do Receptor Purinérgico P2Y , Medição de Risco , Trombose/epidemiologiaRESUMO
The miR-200 family of microRNAs (miRNAs) includes miR-200a, miR-200b, miR-200c, miR-141 and miR-429, five evolutionarily conserved miRNAs that are encoded in two clusters of hairpin precursors located on human chromosome 1 (miR-200b, miR-200a and miR-429) and chromosome 12 (miR-200c and miR-141). The mature -3p products of the precursors are abundantly expressed in epithelial cells, where they contribute to maintaining the epithelial phenotype by repressing expression of factors that favor the process of epithelial-to-mesenchymal transition (EMT), a key hallmark of oncogenic transformation. Extensive studies of the expression and interactions of these miRNAs with cell signaling pathways indicate that they can exert both tumor suppressor- and pro-metastatic functions, and may serve as biomarkers of epithelial cancers. This review provides a summary of the role of miR-200 family members in EMT, factors that regulate their expression, and important targets for miR-200-mediated repression that are involved in EMT. The second part of the review discusses the potential utility of circulating miR-200 family members as diagnostic/prognostic biomarkers for breast, colorectal, lung, ovarian, prostate and bladder cancers.
RESUMO
AIM: To analyze the prevalence and clinical implications of the eligibility criteria for prolonged dual antithrombotic therapy with ticagrelor 60 mg twice daily and/or rivaroxaban 2.5 mg twice daily in a contemporary real-world ACS registry. METHODS: Patients from the START-ANTIPLATELET registry (NCT02219984) were stratified according to the eligibility criteria of the PEGASUS and COMPASS studies to investigate the proportion of patients eligible for prolonged dual antithrombotic therapy at discharge and after 1-year of DAPT. Net adverse clinical events (NACE), defined as all-cause death, myocardial infarction, stroke, and major bleeding, at 1 year were also evaluated and compared among groups. RESULTS: 1844 were considered for the analysis at baseline. Out of 849 event-free patients continually receiving dual antiplatelet therapy for at least 1 year, 577 (68%) and 583 (68.7%) met at least one eligibility criterion for ticagrelor and rivaroxaban, respectively. In the PEGASUS-like patients, age was the most common criterion (71% of cases). The presence ≥2 cardiovascular risk factors was the most common eligibility criterion in the COMPASS-like patients (80.8%). At 1-year follow-up, 211 (11.4%) and 119 (6.5%) patients experienced NACE and MACE, respectively. The incidence of NACEs was higher in the PEGASUS-only group (15.4% vs. 8.4%; p = 0.008) and numerically higher in the COMPASS-only group (10.9% vs. 8.4%; p = 0.299). CONCLUSIONS: In a contemporary real-world ACS cohort, approximately two-thirds of patients that complete 1-year DAPT met the eligibility criteria for ticagrelor 60 mg twice daily or rivaroxaban 2.5 mg twice daily, showing a higher risk of NACEs.
Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/epidemiologia , Aspirina , Fibrinolíticos , Humanos , Fenótipo , Inibidores da Agregação Plaquetária , Prevalência , Sistema de Registros , Resultado do TratamentoRESUMO
Contrasting data have been published about the impact of cardiovascular disease on Covid-19. A comprehensive synthesis and pooled analysis of the available evidence is needed to guide prioritization of prevention strategies. To clarify the association of cardiovascular disease with Covid-19 outcomes, we searched PubMed up to 26 October 2020, for studies reporting the prevalence of cardiovascular disease among inpatients with Covid-19 in relation to their outcomes. Pooled odds-ratios (OR) for death, for mechanical ventilation or admission in an intensive care unit (ICU) and for composite outcomes were calculated using random effect models overall and in the subgroup of people with comorbid diabetes. Thirty-three studies enrolling 52,857 inpatients were included. Cardiovascular disease was associated with a higher risk of death both overall (OR 2.58, 95% confidence intervals, CI 2.12-3.14, p < 0.001, number of studies 24) and in the subgroup of people with diabetes (OR 2.91, 95% CI 2.13-3.97, p < 0.001, number of studies 4), but not with higher risk of ICU admission or mechanical ventilation (OR 1.35, 95% CI 0.73-2.50, p = 0.34, number of studies 4). Four out of five studies reporting OR adjusted for confounders failed to show independent association of cardiovascular disease with Covid-19 deaths. Accordingly, the adjusted-OR for Covid-19 death in people with cardiovascular disease dropped to 1.31 (95% CI 1.01-1.70, p = 0.041). Among patients hospitalized for Covid-19, cardiovascular disease confers higher risk of death, which was highly mitigated when adjusting the association for confounders.
Assuntos
COVID-19/mortalidade , Doenças Cardiovasculares/mortalidade , Cuidados Críticos/estatística & dados numéricos , COVID-19/complicações , Doenças Cardiovasculares/complicações , Comorbidade , Humanos , Unidades de Terapia Intensiva , Respiração Artificial/mortalidadeRESUMO
BACKGROUND: A growing body of evidence suggests a potential link between bone metabolism and cardiovascular disease. Aim of this study was to investigate the relationship between levels of circulating bone turnover biomarkers and advanced atherosclerosis. METHODS: Klotho (KL), sclerostin (SOST), osteopontin (OPN) and osteoprotegerin (OPG) were measured in patients undergoing elective coronary angiography and carotid Doppler ultrasound. The primary outcome was the difference in bone biomarkers levels between participants with and without advanced atherosclerosis, defined as the presence of a critical coronary (≥70%) and/or carotid (≥50%) stenosis. RESULTS: A total of 80 subjects (32.5% females) with a mean age of 68 ± 10 years were included. Advanced atherosclerosis was detected in 55 (68.8%) patients. Subjects with advanced atherosclerosis showed higher serum levels of OPG (p = 0.0015) and SOST (p = 0.017) and similar levels of KL (p = 0.62) and OPN (p = 0.06) compared to patients without. After adjustment for age and sex, only elevated levels of OPG remained significantly associated with advanced atherosclerosis (p = 0.011). CONCLUSIONS: Higher serum levels of OPG are independently associated with advanced atherosclerosis confirming a common bond between bone metabolism and vascular disease. Further investigations on the role of selected bone biomarkers in the pathogenesis of cardiovascular disease are needed.
Assuntos
Aterosclerose , Osteoprotegerina , Proteínas Adaptadoras de Transdução de Sinal/sangue , Idoso , Aterosclerose/diagnóstico por imagem , Biomarcadores , Feminino , Glucuronidase/sangue , Humanos , Proteínas Klotho , Masculino , Pessoa de Meia-Idade , Obesidade , Osteopontina/sangue , Osteoprotegerina/sangue , SobrepesoRESUMO
In type 2 diabetes, anti-thrombotic management is challenging, and current anti-platelet agents have demonstrated reduced efficacy. Old and new anti-diabetic drugs exhibited-besides lowering blood glucose levels-direct and indirect effects on platelet function and on thrombotic milieu, eventually conditioning cardiovascular outcomes. The present review summarizes existing evidence on the effects of glucose-lowering agents on platelet properties, addressing pre-clinical and clinical research, as well as drug-drug interactions with anti-platelet agents. We aimed at expanding clinicians' understanding by highlighting new opportunities for an optimal management of patients with diabetes and cardiovascular disease. We suggest how an improvement of the thrombotic risk in this large population of patients may be achieved by a careful and tailored combination of anti-diabetic and anti-platelet therapies.