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OBJECTIVE: Circulating microvesicles (MV) are surrogate biomarkers of atherosclerosis. However, their role in acute coronary syndromes (ACS) has not been fully elucidated yet. We sought to examine the association of circulating apoptotic MVs with ACS pathophysiology. APPROACH AND RESULTS: One hundred and fifty-three patients (n = 153) were included in the study; 49 patients with ST-elevation myocardial infarction (STEMI), 35 with non-STEMI (NSTEMI), 38 with unstable angina, 15 with stable coronary artery disease and 16 control individuals. Flow cytometry analysis was used to quantify circulating apoptotic/non-apoptotic (phospatidyloserine+/phospatidyloserine-) endothelial cell (EMV), red blood cell (RMV) and platelet (PMV) derived MV. Flow-mediated dilatation (FMD) of the brachial artery was assessed by ultrasound to estimate endothelial function. The inflammatory profile was assessed by serum C-reactive protein (hsCRP) levels. Apoptotic only (but not non-apoptotic) MV were increased in patients with ACS (EMV, P = 2.32 × 10-9; RMV, P = .0019; PMV, P = .01). Hierarchical clustering of the total population of ACS patients (n = 122) by circulating levels of phospatidyloserine+ EMV, RMV and PMV identified two discreet clusters of patients without any differences in traditional risk factors, but significant differences in brachial FMD (5.2% (2.5) vs. 4.1% (2.3), P < .05) that remained significant after adjustment for co-variates. The prevalence of STEMI, a surrogate for plaque rupture and vessel thrombotic occlusion, was significantly higher in the patient cluster with impaired endothelial function (60% vs 32%, P = .016, adjusted odds ratio for STEMI, 3.041, 95%CI, 1.160 to 7.968, p = .024). CONCLUSION: Our findings indicate that the circulating levels of apoptotic MV are increased in ACS patients and their plasma profiles associate with endothelial dysfunction and thrombotic complications in ACS patients.
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Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/fisiopatologia , Apoptose , Micropartículas Derivadas de Células/metabolismo , Endotélio Vascular/fisiopatologia , Placa Aterosclerótica/sangue , Placa Aterosclerótica/fisiopatologia , Endotélio Vascular/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RupturaRESUMO
Although ventricular dysfunction is associated with the occurrence of ventricular arrhythmia (VA), most patients with cardiomyopathy do not experience VA. We therefore investigated other predictors of VA in a large contemporary cohort of patients with cardiomyopathy. All patients at a large academic medical system with left ventricular ejection fraction (LVEF) ≤50% were enrolled at the time of first documented low LVEF. Predictors of hospital admission for VA were examined using multivariable Cox models. The incidence of implantable defibrillator (ICD) placement was also examined. A total of 18,003 patients were enrolled. Over a median follow-up of 3.35 years, 389 patients (2.2%) were admitted for VA (304 of 12,037 [2.5%] among patients with LVEF ≤35% vs 85 of 5,966 [1.4%] among those with LVEF 36% to 50%). Predictors of VA hospitalization included lower LVEF (hazard ratio (HR) = 1.43 per 10% decrease, p <0.001), the presence of an ICD at baseline (HR = 1.63, p = 0.010), higher blood glucose (HR = 1.02 per 10 mg/100 ml increase, p = 0.050), the presence of end-stage renal disease (HR = 3.59, p <0.001), and the presence of liver cirrhosis (HR = 1.93, p = 0.013). During follow-up, 626 patients were implanted with a new ICD. In addition to being admitted with VA, a lower LVEF and a history of coronary artery disease or heart failure were the main predictors of ICD therapy in this population. In conclusion, in addition to more severe cardiomyopathy and the presence of an implanted ICD, metabolic derangements on initial contact are independent predictors of hospital admissions for VA in patients with cardiomyopathy. Noncardiac co-morbidities play an important role in stratifying patients with cardiomyopathy for their risk of VA or cardiac arrest.
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Cardiomiopatias , Desfibriladores Implantáveis , Parada Cardíaca , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/terapia , Cardiomiopatias/complicações , Cardiomiopatias/epidemiologia , Cardiomiopatias/terapia , Morte Súbita Cardíaca , Hospitalização , Hospitais , Humanos , Fatores de Risco , Volume Sistólico , Função Ventricular EsquerdaRESUMO
BACKGROUND: Despite the recent advances in the treatment of Acute Coronary Syndromes (ACS), patients with ACS are still exposed to an increased risk for adverse cardiovascular events, while their prognosis is difficult to determine. Experimental and clinical studies have shown that cell-derived Microparticles (MPs) are associated with the underlying pathophysiological processes that are responsible for atherogenesis and may be causally implicated in the induction of atherothrombosis. OBJECTIVE: In the present article, we aimed to review the available evidence regarding the predictive role of MPs in patients with ACS. RESULTS: Evidence suggests that endothelial MPs are associated with future adverse cardiovascular events in patients with ACS. Platelet-derived MPs have been excessively studied, since they have been found to trigger the coagulation cascade; however, their role as predictors of future cardiovascular events remains debatable. The role of red blood cell-derived MPs is more intriguing; they have been proposed as markers of ongoing thrombosis in patients with ACS, while previous studies have shown that they have anti-coagulant properties in healthy individuals. Leukocyte-derived MPs may also have a predictive role, although the studies regarding these are still limited. Last but not least, it was an interesting discovery that circulating MPs can provide information regarding the angiographic lesions in patients with ACS. CONCLUSION: The concept of MPs as potential circulating biomarkers in patients with ACS holds much promise. However, large-scale clinical studies are required to evaluate whether the measurement of plasma MPs could be of clinical significance and, thus, dictate a more aggressive treatment strategy in patients with high levels of circulating MPs.
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Síndrome Coronariana Aguda , Micropartículas Derivadas de Células , Coagulação Sanguínea , Humanos , Leucócitos , TromboseRESUMO
PRéCIS:: Pseudoexfoliative glaucoma (PExG) patients present with not only endothelial dysfunction and arterial stiffness but also with a specific profile of circulating apoptotic endothelial microparticles which may be owing to the accumulation of pseudoexfoliative material in vessels walls. PURPOSE: PExG is characterized by the deposition of pseudoexfoliative material in several tissues and organs including in the cardiovascular system. This study aimed to evaluate the vascular endothelial function, arterial stiffness, inflammatory status, and circulating microparticle (MP) levels in PExG patients compared with those in primary open-angle glaucoma (POAG) patients and control subjects. METHODS: Vascular endothelial function was evaluated by flow-mediated dilation. Pulse wave velocity and augmentation index were measured as indices of aortic stiffness and arterial wave reflections, respectively. Growth-differentiation factor-15 and intercellular adhesion molecule1 levels were measured to evaluate the systemic inflammatory status. Circulating MPs that constitute an emerging marker of vascular endothelial dysfunction and platelet activation were isolated and analyzed by flow cytometry. RESULTS: There was a stepwise impairment from the control to the POAG patients and PExG subjects in the flow-mediated dilation (8.21%±2.94% vs. 7.56%±3.12% vs. 5.79±3.13, P=0.005), pulse wave velocity (8.14±1.79 vs. 9.21±2.27 vs. 9.95±3.28 m/s, P=0.007), augmentation index (24.71%±7.84% vs. 26.78%±7.21% vs. 29.96%±7.58%, P=0.02), and growth-differentiation factor-15 (P=0.001) and intercellular adhesion molecule1 levels (P=0.08). PExG patients expressed greater levels of total circulating MPs (Annexin V+) (P=0.004) and endothelial-derived MPs (CD144+) (P<0.001) compared with POAG and control subjects. CONCLUSIONS: PExG patients with an accumulation of pseudoexfoliative microfibrillar material presented with vascular endothelial dysfunction and arterial wall impairment associated with the levels of circulating proinflammatory molecules and circulating apoptotic endothelial MPs. These findings highlight the underlying systemic pathophysiological mechanisms associated with the progress of the pseudoexfoliative syndrome.
Assuntos
Apoptose/fisiologia , Micropartículas Derivadas de Células/fisiologia , Endotélio Vascular/fisiopatologia , Síndrome de Exfoliação/fisiopatologia , Glaucoma de Ângulo Aberto/fisiopatologia , Rigidez Vascular/fisiologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Micropartículas Derivadas de Células/patologia , Células Endoteliais/patologia , Células Endoteliais/fisiologia , Endotélio Vascular/patologia , Síndrome de Exfoliação/complicações , Síndrome de Exfoliação/diagnóstico , Feminino , Glaucoma de Ângulo Aberto/complicações , Glaucoma de Ângulo Aberto/diagnóstico , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Doenças Vasculares/complicações , Doenças Vasculares/diagnóstico , Doenças Vasculares/fisiopatologiaRESUMO
BACKGROUND: Atrial fibrillation (AF) is associated with an increased risk of cardioembolic stroke. The risk of cardioembolism is not adequately reduced with the administration of oral anticoagulants, since a number of patients continue to experience thromboembolic events despite receiving treatment. Therefore, identification of a circulating biomarker to identify these high-risk patients would be clinically beneficial. OBJECTIVE: In the present article, we aim to review the available data regarding use of biomarkers to predict cardioembolic stroke in patients with AF. METHODS: We performed a thorough search of the literature in order to analyze the biomarkers identified thus far and critically evaluate their clinical significance. RESULTS: A number of biomarkers have been proposed to predict cardioembolic stroke in patients with AF. Some of them are already used in the clinical practice, such as d-dimers, troponins and brain natriuretic peptide. Novel biomarkers, such as the inflammatory growth differentiation factor-15, appear to be promising, while the role of micro-RNAs and genetics appear to be useful as well. Even though these biomarkers are associated with an increased risk for thromboembolism, they cannot accurately predict future events. In light of this, the use of a scoring system, that would incorporate both circulating biomarkers and clinical factors, might be more useful. CONCLUSIONS: Recent research has disclosed several biomarkers as potential predictors of cardioembolic stroke in patients with AF. However, further research is required to establish a multifactorial scoring system that will identify patients at high-risk of thromboembolism, who would benefit from more intensive treatment and monitoring.
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Fibrilação Atrial/complicações , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Animais , Biomarcadores/análise , Humanos , Prognóstico , Fatores de RiscoRESUMO
During the last few years, a significant number of studies have attempted to clarify the underlying mechanisms that lead to the presentation of atrial fibrillation (AF). Inflammation is a key component of the pathophysiological processes that lead to the development of AF; the amplification of inflammatory pathways triggers AF, and, in tandem, AF increases the inflammatory state. Indeed, the plasma levels of several inflammatory biomarkers are elevated in patients with AF. In addition, the levels of specific inflammatory biomarkers may provide information regarding to the AF duration. Several small studies have assessed the role of anti-inflammatory treatment in atrial fibrillation but the results have been contradictory. Large-scale studies are needed to evaluate the role of inflammation in AF and whether anti-inflammatory medications should be routinely administered to patients with AF.
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Fibrilação Atrial/diagnóstico , Fibrilação Atrial/etiologia , Inflamação/complicações , Inflamação/diagnóstico , Animais , Anti-Inflamatórios/uso terapêutico , Fibrilação Atrial/sangue , Fibrilação Atrial/tratamento farmacológico , Biomarcadores/análise , Biomarcadores/sangue , Proteína C-Reativa/análise , Humanos , Inflamação/sangue , Inflamação/tratamento farmacológico , Interleucinas/análise , Interleucinas/sangueRESUMO
Cardiac metabolism affects systemic energetic balance. Previously, we showed that Krüppel-like factor (KLF)-5 regulates cardiomyocyte PPARα and fatty acid oxidation-related gene expression in diabetes. We surprisingly found that cardiomyocyte-specific KLF5 knockout mice (αMHC-KLF5-/-) have accelerated diet-induced obesity, associated with increased white adipose tissue (WAT). Alterations in cardiac expression of the mediator complex subunit 13 (Med13) modulates obesity. αMHC-KLF5-/- mice had reduced cardiac Med13 expression likely because KLF5 upregulates Med13 expression in cardiomyocytes. We then investigated potential mechanisms that mediate cross-talk between cardiomyocytes and WAT. High fat diet-fed αMHC-KLF5-/- mice had increased levels of cardiac and plasma FGF21, while food intake, activity, plasma leptin, and natriuretic peptides expression were unchanged. Consistent with studies reporting that FGF21 signaling in WAT decreases sumoylation-driven PPARγ inactivation, αMHC-KLF5-/- mice had less SUMO-PPARγ in WAT. Increased diet-induced obesity found in αMHC-KLF5-/- mice was absent in αMHC-[KLF5-/-;FGF21-/-] double knockout mice, as well as in αMHC-FGF21-/- mice that we generated. Thus, cardiomyocyte-derived FGF21 is a component of pro-adipogenic crosstalk between heart and WAT.
Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/patologia , Animais , Peso Corporal , Dieta Hiperlipídica , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Fatores de Crescimento de Fibroblastos/genética , Humanos , Fatores de Transcrição Kruppel-Like/genética , Leptina/sangue , Masculino , Complexo Mediador/genética , Complexo Mediador/metabolismo , Camundongos , Camundongos Knockout , MicroRNAs/metabolismo , Miocárdio/metabolismo , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Obesidade/etiologia , Transdução de SinaisRESUMO
The authors investigated the relationship of white-coat hypertension (WCH) with subclinical organ damage and potential relevant mechanisms. A total of 386 untreated patients were enrolled and divided into 204 patients with WCH and 183 with normotension. Flow-mediated dilation (FMD), pulse wave velocity (PWV), intima-media thickness, left ventricular mass index (LVMI), and cystatin C levels were measured. All tests were two-sided, and a P value <.05 was considered statistically significant. The WCH group exhibited higher LVMI and PWV values, decreased E/A ratio and FMD values, and increased prevalence for left ventricular hypertrophy compared with controls (P<.001 for all). Cystatin C was significantly higher in the WCH group compared with controls (P=.035) and was positively associated with LVMI (P<.05 for both). The presence of WCH is associated with more pronounced subclinical organ damage compared with normotension. Cystatin C may play a significant role and therefore warrants further investigation.
Assuntos
Cistatina C/metabolismo , Hipertrofia Ventricular Esquerda/epidemiologia , Hipertensão do Jaleco Branco/complicações , Espessura Intima-Media Carotídea , Feminino , Humanos , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Hipertensão do Jaleco Branco/metabolismo , Hipertensão do Jaleco Branco/fisiopatologiaRESUMO
BACKGROUND: Low-density lipoprotein cholesterol (LDL), and especially its oxidized form, renders the atherosclerotic plaque vulnerable to rupture in acute coronary syndromes (ACS). On the other hand, high-density lipoprotein (HDL) is considered an anti-atherogenic molecule. The more recent HDL-targeted drugs may prove to be superior to those used before. Indeed, delipidated HDL and HDL mimetics are efficient in increasing HDL levels, while the apoA-I upregulation with RVX-208 appears to offer a clinical benefit which is beyond the HDL related effects. HDL treatment however has not shown a significant improvement in the outcomes of patients with ACS so far, studies have therefore focused again on LDL. In addition to statins and ezetimibe, novel drugs such as PSCK9 inhibitors and apolipoprotein B inhibitors appear to be both effective and safe for patients with hyperlipidemia. CONCLUSION: Data suggest these could potentially improve the cardiovascular outcomes of patient with ACS. Yet, there is still research to be done, in order to confirm whether ACS patients would benefit from LDL- or HDL-targeted therapies or a combination of both.
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Síndrome Coronariana Aguda/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Síndrome Coronariana Aguda/sangue , Biomarcadores/sangue , HumanosRESUMO
INTRODUCTION AND OBJECTIVES: We examined whether the rs180070 and rs2070011 polymorphisms of the fibrinogen gene could affect the risk of coronary artery disease in hypertensive patients by modifying the inflammatory process and coagulation. METHODS: A total of 744 participants underwent coronary angiography due to symptoms of stable angina, while hypertension was present in 332 patients. RESULTS: The presence of the A allele (rs180070) was associated with significantly high levels of fibrinogen in hypertensive patients (P=.05). On multivariate analysis, A homozygosity (rs180070) (ß = 0.257 ± 18.6; P<.001), but not hypertension status (ß = 0.05 ± 11.9; P=.29) was an independent predictor of fibrinogen levels. In hypertensive patients, higher fibrinogen levels>443mg/dL (odds ratio = 3.50; 95% confidence interval, 1.14-10.90; P=.029), but not A homozygosity (odds ratio = 3.00; 95% confidence interval, 0.78-11.90; P = .110) were independent predictors of the presence of coronary artery disease. Moreover, interleukin-6 levels were higher in A homozygotes for the rs180070 polymorphism compared with all other genotypes (P=.046). Indeed, this genotype was the only adjusted independent predictor of interleukin-6 levels (ß = 0.151 ± 0.642; P=.032). It was also associated with higher D-dimer levels in hypertension compared with G allele carriers (P=.048). CONCLUSIONS: The presence of A homozygosity (rs180070) is associated with increased levels of inflammatory mediators and a higher incidence of angiographic coronary artery disease. Importantly, fibrinogen is an independent predictor of the angiographic presence of coronary artery disease in hypertensive patients.
Assuntos
Aterosclerose/genética , Doença da Artéria Coronariana/genética , Vasos Coronários/diagnóstico por imagem , DNA/genética , Fibrinogênio/genética , Hipertensão/complicações , Polimorfismo Genético , Alelos , Aterosclerose/sangue , Aterosclerose/complicações , Angiografia Coronária , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/complicações , Feminino , Fibrinogênio/metabolismo , Variação Genética , Genótipo , Humanos , Hipertensão/sangue , Hipertensão/genética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Fatores de RiscoRESUMO
We read with interest the article entitled "Circulating microRNAs characterizing patients with insufficient coronary collateral artery function" which was recently published in the PLOS ONE journal. It was demonstrated for the first time that specific circulating microRNAs (miRNAs) can distinguish patients with sufficient from those with insufficient coronary collateral circulation. Circulating miRNAs in the plasma of patients with stable CAD and chronic CTO could provide information with regard to the coronary collateral artery capacity. However, several aspects need to be taken into consideration before the use of miRNAs in the clinical practice. A risk model that would incorporate risk factors for cardiovascular disease and miRNAs could prove to be very useful. Although an association between the levels of miRNAs and the collateral artery capacity appears promising, it still does not confirm any causal role for miRNAs. Therefore, large clinical studies in populations with CTO are warranted to evaluate this finding.
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INTRODUCTION: It is widely accepted that inflammation plays a pivotal role in the progression of atherosclerosis. Anti-inflammatory drugs and especially selective cyclooxygenase-2 (COX-2) inhibitors have attracted a keen interest. AREAS COVERED: In the present drug evaluation article, the authors elucidate the role of celecoxib, a selective COX-2 inhibitor, in the treatment of atherosclerosis. They discuss the atherogenic properties of the COX-2 enzyme. In addition, they address the studies that support an atheroprotective role of celecoxib. Moreover, they provide a review of the literature on the role of COX-2 inhibitors in increasing the rate of major adverse cardiovascular events. Finally, they discuss the emerging evidence that supports celecoxib as an adjuvant or neo-adjuvant therapy to percutaneous coronary intervention (PCI). EXPERT OPINION: Several studies have demonstrated a beneficial effect of celecoxib on the progression of atherosclerosis. Nevertheless, this evidence is mainly derived from preliminary data, while a substantial number of clinical studies have raised concerns regarding the cardiovascular safety of COX-2 inhibitors. Interestingly, recent clinical studies have supported the advantages of short-term celecoxib administration in patients undergoing PCI. However, many more large scale clinical trials are required to assess the long-term safety and efficacy of celecoxib administration in patients with cardiovascular disease.
Assuntos
Aterosclerose/tratamento farmacológico , Celecoxib/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Animais , Celecoxib/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , HumanosRESUMO
Patients with ST-elevation myocardial infarction (STEMI) constitute a vulnerable group that demands the careful assessment and application of all the up-to-date clinical and experimental knowledge, with final aim, the improvement of their prognosis. Statins are an indispensable part of the primary and secondary prevention of coronary artery disease (CAD), not only due to their strong hypolipidemic effect, but also due to their numerous pleiotropic properties that play an important role in the treatment of CAD, especially when the more vulnerable group of STEMI patients is addressed. Nevertheless, there are still issues that require further discussion and clarification, such as the type of statin, the dose of the regimen, the administration time, and the treatment duration.
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Síndrome Coronariana Aguda/prevenção & controle , Doença da Artéria Coronariana/prevenção & controle , Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Prevenção Primária/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/prevenção & controle , Prevenção Secundária/métodos , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/etiologia , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/etiologia , Esquema de Medicação , Cálculos da Dosagem de Medicamento , Dislipidemias/complicações , Dislipidemias/diagnóstico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Medição de Risco , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
INTRODUCTION: Emerging evidence suggests that the role of high density lipoprotein (HDL) in the atherosclerotic process is not as clear as previously thought, since atheroprotective HDL becomes atherogenic in states of increased inflammatory processes. AREAS COVERED: In this review we aim to elucidate the role of HDL as a prognostic biomarker and we discuss therapeutic approaches that aim to increase HDL and their possible clinical benefit. EXPERT OPINION: Given the structural variability and biological complexity of the HDL particle, its role in the atherosclerotic process is far from clear. According to current evidence, the atheroprotective role of HDL turns atherogenic in states of increased inflammatory processes, while even minor alterations in systemic inflammation are likely to hinder the endothelial protective effects of HDL. In accordance, significant data have revealed that HDL-related drugs may be effective in reducing cardiovascular mortality; however they are not as encouraging or unanimous as expected. Possible future goals could be to quantify either HDL subclasses or functions in an attempt to reach safer conclusions as to the prognostic importance of HDL in coronary atherosclerosis. Having achieved that, a more targeted therapy that would aim to raise either HDL functionality or to remodel HDL structure would be more easily designed.
Assuntos
Doença da Artéria Coronariana/patologia , Inflamação/patologia , Lipoproteínas HDL/metabolismo , Animais , Biomarcadores/metabolismo , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/mortalidade , Desenho de Fármacos , Endotélio Vascular/metabolismo , Humanos , PrognósticoRESUMO
BACKGROUND: Apart from the acute thrombotic complications that lead to acute coronary syndromes (ACS), platelet activation also plays an important role in the initiation and progression of atherosclerosis. In addition, it is speculated that anti-platelet therapy can be beneficial for patients with stable coronary artery disease (CAD). Of note, patients on optimal anti-platelet treatment still experience thrombotic events, whereas complications, such as bleeding, cannot be ignored. In this light, novel antiplatelet regimens have been used to minimize the residual platelet activation without compromising normal haemostasis. METHODS: We performed a thorough search of the literature in order to review the beneficial role of novel antiplatelets in patients with stable CAD. We have also focused on studies that examine the effect of these drugs on platelet reactivity as well as on cardiovascular outcomes. CONCLUSION: Specific agents, such as vorapaxar and cilostazol, have been found to reduce platelet reactivity as well as to improve patients' prognosis. Of note, the use of novel antiplatelets is of clinical importance in patients with increased thrombotic status and in those with resistance to classic antiplatelets. However, the available data on most of the novel antiplatelets are mainly derived from studies including ACS patients undergoing angioplasty Therefore, large randomized controlled studies are required to evaluate the clinical benefit of novel antiplatelets in patients with stable CAD.
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Doença da Artéria Coronariana/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Humanos , Inibidores da Agregação Plaquetária/administração & dosagem , Receptores Purinérgicos P2Y12/metabolismoRESUMO
Environmental factors constitute an important but underappreciated risk factor towards the development and progression of cardiovascular disease (CVD). Environmental exposure to variable pollutants is implicated in the derangement or propagation of adverse pathophysiological processes linked with atherosclerosis, including genetic, hemodynamic, metabolic, oxidative and inflammation parameters. However, no data exist on environmental pollution in rural or semi-rural areas. Therefore, the purpose of the "Corinthia" study is to examine the impact of environmental pollution in indices of cardiovascular morbidity and mortality in a cross-sectional and longitudinal design. The Corinthia study began in October 2015 and is planned to recruit 1,500 individuals from different regions of Corinthia country with different environmental exposures to pollutants and different patterns of soil/ground and/or air pollution until December 2016. Baseline measurements will include lifestyle measurements, anthropometric characteristics and a comprehensive cardiovascular examination. The follow-up is planned to extend prospectively up to 10 years and this study is anticipated to provide valuable data on the distinct impact of soil and air pollution on early markers of atherosclerosis and cardiovascular disease and on the overall impact of environment pollution to cardiovascular morbidity and mortality.
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Poluição do Ar/efeitos adversos , Doenças Cardiovasculares/mortalidade , Estudos Transversais , Grécia/epidemiologia , Humanos , Estudos Longitudinais , Fatores de RiscoRESUMO
Introducción y objetivos: Se examina si los polimorfismos rs180070 y rs2070011 del gen del fibrinógeno podrían afectar al riesgo de enfermedad coronaria de los pacientes hipertensos al modificar el proceso inflamatorio y la coagulación. Métodos: Se practicó una angiografía coronaria a causa de síntomas de angina estable a 744 participantes, de los que 332 tenían hipertensión. Resultados: La presencia del alelo A (rs180070) se asoció a cifras de fibrinógeno significativamente elevadas en los pacientes hipertensos (p = 0,05). En el análisis multivariable, la homocigosis para A (rs180070) (β = 0,257 ± 18,6; p < 0,001), pero no la presencia de hipertensión (β = 0,05 ± 11,9; p = 0,29), fue un factor independiente predictivo de la concentración de fibrinógeno. En los pacientes hipertensos, la concentración de fibrinógeno > 443 mg/dl (odds ratio = 3,50; intervalo de confianza del 95%, 1,14-10,90; p = 0,029), pero no la homocigosis para A (odds ratio = 3,00; intervalo de confianza del 95%, 0,78-11,90; p = 0,110), fueron un factor independiente predictivo de enfermedad coronaria. Además, los valores de interleucina 6 fueron más altos en los individuos homocigotos para el polimorfismo rs180070 que en todos los demás genotipos (p = 0,046). De hecho, este genotipo fue el único factor independiente predictivo de la concentración de interleucina 6 en el análisis ajustado (β = 0,151 ± 0,642; p = 0,032). También se asoció a cifras de dímero D superiores en la hipertensión en comparación con los portadores del alelo G (p = 0,048). Conclusiones: La presencia de homocigosis para A (rs180070) se asocia a un aumento de las concentraciones de mediadores inflamatorios y mayor incidencia de enfermedad coronaria angiográfica. Tiene importancia que el fibrinógeno es un factor independiente predictivo de la presencia angiográfica de enfermedad coronaria en los pacientes hipertensos (AU)
Introduction and objectives: We examined whether the rs180070 and rs2070011 polymorphisms of the fibrinogen gene could affect the risk of coronary artery disease in hypertensive patients by modifying the inflammatory process and coagulation. Methods: A total of 744 participants underwent coronary angiography due to symptoms of stable angina, while hypertension was present in 332 patients. Results: The presence of the A allele (rs180070) was associated with significantly high levels of fibrinogen in hypertensive patients (P = .05). On multivariate analysis, A homozygosity (rs180070) (β = 0.257 ± 18.6; P < .001), but not hypertension status (β = 0.05 ± 11.9; P = .29) was an independent predictor of fibrinogen levels. In hypertensive patients, higher fibrinogen levels > 443 mg/dL (odds ratio = 3.50; 95% confidence interval, 1.14-10.90; P = .029), but not A homozygosity (odds ratio = 3.00; 95% confidence interval, 0.78-11.90; P = .110) were independent predictors of the presence of coronary artery disease. Moreover, interleukin-6 levels were higher in A homozygotes for the rs180070 polymorphism compared with all other genotypes (P = .046). Indeed, this genotype was the only adjusted independent predictor of interleukin-6 levels (β = 0.151 ± 0.642; P = .032). It was also associated with higher D-dimer levels in hypertension compared with G allele carriers (P = .048). Conclusions: The presence of A homozygosity (rs180070) is associated with increased levels of inflammatory mediators and a higher incidence of angiographic coronary artery disease. Importantly, fibrinogen is an independent predictor of the angiographic presence of coronary artery disease in hypertensive patients (AU)