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1.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(5): 588-593, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31198145

RESUMO

OBJECTIVE: To explore the relationship between serum levels of osteoprotein (OPG), soluble nuclear factor-κB receptor activator ligand (sRANKL), inflammatory factors and coronary heart disease (CHD) and its severity. METHODS: The patients who underwent coronary angiography (CAG) due to chest pain admitted to department of cardiology of Tianjin Chest Hospital from April 2017 to December 2018 were enrolled, and they were divided into CHD group and non-CHD group according to the CAG results. The gender, age, history of hypertension, smoking history, diabetes, the levels of cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein AI (apoAI), apolipoprotein B (apoB), lipoprotein (a) [Lp (a)], MB isoenzyme of creatine kinase (CK-MB) and other clinical data of patients were collected. The serum levels of OPG, sRANKL, matrix metalloproteinase-9 (MMP-9), monocyte chemotactic protein-1 (MCP-1), insulin-like growth factor-1 (IGF-1) and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA). According to the results of CAG, the patients with CHD were divided into single-, double-, triple-branch coronary artery lesion groups, and the relationship between the levels of serum OPG, sRANKL, inflammatory factors and the degree of coronary artery lesions was observed. Multivariate Logistic regression was used to analyze the risk factors of CHD, and receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of main risk factors for CHD. RESULTS: A total of 472 patients were enrolled in the final analysis during the study period, including 264 patients in the CHD group, 208 patients in the non-CHD group, 79 patients in the CHD group with single-branch disease, 75 patients with double-branch disease, and 110 patients with three-branch disease. (1) Compared with the non-CHD group, the CHD group had more older male patients, as well as higher proportion of hypertension and diabetes, the levels of serum Lp (a) and CK-MB were significantly increased, and the levels of serum HDL-C and apoAI were significantly lowered. There was no statistically significant difference in serum TC, LDL-C, or apoB between the two groups. The levels of serum OPG, MMP-9, MCP-1, IGF-1 and IL-6 in the CHD group were significantly higher than those in the non-CHD group [OPG (µg/L): 1.79±0.50 vs. 1.50±0.30, MMP-9 (µg/L): 57.91 (33.50, 130.46) vs. 38.33 (29.43, 109.78), MCP-1 (µg/L): 298.30 (207.96, 537.16) vs. 252.73 (165.22, 476.01), IGF-1 (µg/L): 734.03±486.11 vs. 217.75±126.45, IL-6 (ng/L): 64.76±40.25 vs. 48.60±15.80, all P < 0.05], and the levels of serum sRANKL was significantly lower than that in the non-CHD group (ng/L: 344.31±122.14 vs. 378.74±109.27, P < 0.05). (2) The serum OPG level showed a slight upward tendency with the increase in the number of coronary artery lesions, and the sRANKL level showed a slight downward tendency [OPG (µg/L) in the single-, double-, triple-branch coronary artery lesion groups was 1.74±0.49, 1.76±0.50, 1.85±0.52, and sRANKL (ng/L) was 354.96±116.64, 340.05±124.24, 339.57±125.03, respectively) without statistically significant differences (all P > 0.05). The levels of IGF-1 and IL-6 were increased with the number of coronary artery lesions [IGF-1 (µg/L) in the single-, double- and triple-branch coronary artery lesions groups was 372.13±258.42, 676.06±350.29, 1 033.47±468.06, and IL-6 (ng/L) was 48.87±16.72, 65.36±18.84, 75.76±22.72, respectively], and the differences among different lesion groups were statistically significant (all P < 0.01). Correlation analysis showed that IGF-1 level was significantly positively correlated with the number of coronary artery lesions (r = 0.612, P < 0.01), while IL-6 was not correlated with the number of coronary artery lesions (r = 0.185, P > 0.05). (3) Multivariate Logistic regression analysis showed that elevated serum OPG and IGF-1 levels were risk factors for CHD [OPG: odds ratio (OR) = 1.995, 95% confidence interval (95%CI) = 1.936-2.067, P = 0.012; IGF-1: OR = 1.009, 95%CI = 1.004-1.015, P = 0.001]. (4) ROC curve analysis showed that the area under ROC curve (AUC) of OPG and IGF-1 was 0.716 and 0.867, respectively. When the cut-off value of OPG was 1.13 µg/L, the sensitivity was 81.7%, the specificity was 58.1%; when the cut-off value of sRANKL was 401.20 µg/L, the sensitivity was 69.7%, the specificity was 95.7%. CONCLUSIONS: CHD was associated with increased in OPG, related inflammatory cytokines including MMP-9, MCP-1, IGF-1 and IL-6, and decreased in sRANKL. The level of IGF-1 was positively correlated with the severity of CHD. The serum levels of OPG and IGF-1 were risk factors for CHD, which had good predictive value for CHD.


Assuntos
Proteínas Morfogenéticas Ósseas/sangue , Doença das Coronárias/sangue , Citocinas/sangue , Idoso , Feminino , Humanos , Masculino , Fatores de Risco , Índice de Gravidade de Doença
2.
Chin J Integr Med ; 25(5): 327-333, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31065970

RESUMO

OBJECTIVE: To examine the prognostic value of serum levels of asymmetric dimethylarginine (ADMA) in patients with stable coronary heart disease (CHD) thus explore a potential biomarker of "toxin syndrome" in CHD. METHODS: In this prospective nested case-control study, 36 of 1,503 Chinese patients with stable CHD experienced at least 1 recurrent cardiovascular event (RCE) during 1-year follow-up. Serum levels of ADMA at the start of follow-up were compared between these 36 cases and 36 controls which matched to cases in terms of gender, age, history of hypertension, and myocardial infarction. RESULTS: Based on the crude model, subjects in the 2 highest ADMA quartiles showed significantly higher risk of developing RCE than those in the lowest ADMA quartile [odds ratio (OR) 4.09, 95% confidence interval (CI) 1.01 to 16.58; OR 6.76, 95% CI 1.57 to 29.07]. This association was also observed in the case-mix model (OR 5.51, 95% CI 1.23 to 24.61; OR 7.83, 95% CI 1.68 to 36.41) and multivariable model (OR 6.64, 95% CI 1.40 to 31.49: OR 13.14, 95% CI 2.28 to 75.71) after adjusting for confounders. The multivariable model which combined ADMA and high-sensitivity C-reactive protein (hsCRP) showed better predictive power with areas under the receiver operator characteristic curves (0.779) than the model of either ADMA (0.694) or hsCRP (0.636). CONCLUSION: Serum ADMA level may be a potential biomarker of "toxin syndrome" in CHD which shows favorable prognostic value in predicting 1-year RCE in patients with stable CHD. [The registration number is ChiCTR-PRNRC-07000012].


Assuntos
Arginina/análogos & derivados , Doença das Coronárias/sangue , Arginina/sangue , Biomarcadores/sangue , Humanos , Razão de Chances , Curva ROC , Recidiva , Fatores de Risco , Síndrome
3.
PLoS Genet ; 15(4): e1008009, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30951530

RESUMO

Recent and classical work has revealed biologically and medically significant subtypes in complex diseases and traits. However, relevant subtypes are often unknown, unmeasured, or actively debated, making automated statistical approaches to subtype definition valuable. We propose reverse GWAS (RGWAS) to identify and validate subtypes using genetics and multiple traits: while GWAS seeks the genetic basis of a given trait, RGWAS seeks to define trait subtypes with distinct genetic bases. Unlike existing approaches relying on off-the-shelf clustering methods, RGWAS uses a novel decomposition, MFMR, to model covariates, binary traits, and population structure. We use extensive simulations to show that modelling these features can be crucial for power and calibration. We validate RGWAS in practice by recovering a recently discovered stress subtype in major depression. We then show the utility of RGWAS by identifying three novel subtypes of metabolic traits. We biologically validate these metabolic subtypes with SNP-level tests and a novel polygenic test: the former recover known metabolic GxE SNPs; the latter suggests subtypes may explain substantial missing heritability. Crucially, statins, which are widely prescribed and theorized to increase diabetes risk, have opposing effects on blood glucose across metabolic subtypes, suggesting the subtypes have potential translational value.


Assuntos
Estudo de Associação Genômica Ampla/métodos , Modelos Genéticos , Herança Multifatorial , Fenótipo , Algoritmos , Glicemia/efeitos dos fármacos , Glicemia/genética , Análise por Conglomerados , Simulação por Computador , Doença das Coronárias/sangue , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/genética , Transtorno Depressivo Maior/classificação , Transtorno Depressivo Maior/genética , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Lipídeos/sangue , Polimorfismo de Nucleotídeo Único , Estado Pré-Diabético/genética , Locos de Características Quantitativas
4.
Biomolecules ; 9(4)2019 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-30934954

RESUMO

We sought to investigate whether levels of matrix metalloproteinases (MMPs) and their inhibitors predict coronary atherosclerotic plaque instability, as assessed by intravascular ultrasound (IVUS) virtual histology during coronary angiography. Blood samples were collected before angiography in 32 subjects (mean age 56 ± 8 years) with stable coronary heart disease (CHD) and elevated lipoprotein(a) (Lp(a), 94 ± 35 mg/dL). Levels of high-sensitivity C-reactive protein (hsCRP), apolipoprotein B100 (apoB100), MMP-7, MMP-9, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2 were determined using commercially available enzyme-linked immunosorbent assay kits. Results. The morphology of a total of sixty coronary lesions was assessed by virtual histology IVUS imaging. Eleven (18%) plaques in nine (28%) patients were classified as plaques with an unstable phenotype or a thin-cap fibroatheroma. Age, low-density lipoprotein cholesterol, apoB100, MMP-7, and MMP-9 levels were positively associated with necrotic core volume. Conversely, there was a negative relationship between MMP-7 and -9 levels and fibrous and fibro-fatty tissue volume. Multivariate regression analysis revealed that MMP-9 is a strong independent predictor of atherosclerotic plaque instability in stable CHD patients. In stable CHD patients with elevated Lp(a), MMP-9 levels are positively associated with the size of the necrotic core of coronary atherosclerotic plaques.


Assuntos
Angiografia Coronária , Doença das Coronárias/enzimologia , Lipoproteína(a)/sangue , Metaloproteinase 9 da Matriz/sangue , Placa Aterosclerótica/enzimologia , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/metabolismo , Doença das Coronárias/sangue , Doença das Coronárias/metabolismo , Feminino , Humanos , Lipoproteína(a)/metabolismo , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Placa Aterosclerótica/sangue , Placa Aterosclerótica/metabolismo , Software
5.
Med Sci Monit ; 25: 2633-2639, 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30968846

RESUMO

BACKGROUND This study investigated the expression of the BCL2 and BAX mRNA, inflammatory cytokines, interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-alpha (TNF-alpha), and cardiac function in patients with chronic heart failure (CHF). The New York Heart Association (NYHA) Functional Classification and measurement of the left ventricular ejection fraction (LVEF) evaluated cardiac function. MATERIAL AND METHODS Patients with CHF (n=60) due to coronary heart disease, hypertensive heart disease, and cardiomyopathy, and healthy controls (n=30) were studied. Enzyme-linked immunosorbent assay (ELISA) measured serum levels of IL-1ß, IL-6, and TNF-alpha. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) detected mRNA expression of BCL2 and BAX in peripheral blood mononuclear cells (PBMCs). Color Doppler ultrasound measured the LVEF, and the NYHA classification of CHF was used. RESULTS In patients with CHF, levels of IL-1ß, IL-6 and TNF-alpha, and mRNA expression of BAX were significantly increased compared with the control group (p<0.01); BCL2 mRNA level was significantly lower (p<0.01). There were no significant differences in the expression levels of inflammatory cytokines, or BCL2 or BAX mRNA in patients with CHF due to coronary heart disease, hypertensive heart disease, or cardiomyopathy. Expression levels of IL-1ß, IL-6, TNF-alpha, and BAX mRNA were significantly associated with the degree of CHF. Cardiac function was negatively correlated with LVEF (p<0.05). Expression levels of BCL2 mRNA level were negatively correlated with cardiac function (p<0.05), and positively correlated with LVEF (p<0.05). CONCLUSIONS Levels of IL-1ß, IL-6, TNF-alpha, and BAX mRNA were negatively correlated with cardiac function, and BCL2 mRNA expression was positively associated with CHF.


Assuntos
Citocinas/sangue , Regulação da Expressão Gênica , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/genética , Mediadores da Inflamação/sangue , Leucócitos Mononucleares/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteína X Associada a bcl-2/genética , Idoso , Cardiomiopatias/sangue , Cardiomiopatias/genética , Cardiomiopatias/fisiopatologia , Doença Crônica , Doença das Coronárias/sangue , Doença das Coronárias/genética , Doença das Coronárias/fisiopatologia , Feminino , Insuficiência Cardíaca/fisiopatologia , Testes de Função Cardíaca , Humanos , Hipertensão/sangue , Hipertensão/genética , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-2/sangue , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Volume Sistólico , Proteína X Associada a bcl-2/sangue
6.
Nat Commun ; 10(1): 1060, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30837465

RESUMO

Circulating levels of glycine have previously been associated with lower incidence of coronary heart disease (CHD) and type 2 diabetes (T2D) but it remains uncertain if glycine plays an aetiological role. We present a meta-analysis of genome-wide association studies for glycine in 80,003 participants and investigate the causality and potential mechanisms of the association between glycine and cardio-metabolic diseases using genetic approaches. We identify 27 genetic loci, of which 22 have not previously been reported for glycine. We show that glycine is genetically associated with lower CHD risk and find that this may be partly driven by blood pressure. Evidence for a genetic association of glycine with T2D is weaker, but we find a strong inverse genetic effect of hyperinsulinaemia on glycine. Our findings strengthen evidence for a protective effect of glycine on CHD and show that the glycine-T2D association may be driven by a glycine-lowering effect of insulin resistance.


Assuntos
Doença das Coronárias/genética , Diabetes Mellitus Tipo 2/genética , Glicina/sangue , Hiperinsulinismo/genética , Redes e Vias Metabólicas/genética , Doença das Coronárias/sangue , Doença das Coronárias/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Loci Gênicos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Glicina/metabolismo , Humanos , Hiperinsulinismo/sangue , Hiperinsulinismo/epidemiologia , Incidência , Polimorfismo de Nucleotídeo Único
7.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(3): 319-324, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-30914093

RESUMO

OBJECTIVE: To explore the polymorphisms of T149C and T950C gene in osteoprotectin (OPG) promoter sites and the levels of serum OPG and soluble nuclear factor-ΚB receptor activator ligand (sRANKL) and the incidence of coronary heart disease (CHD). METHODS: 528 patients in Tianjin suspected of CHD and underwent coronary angiography (CAG) who admitted to the department of cardiology of Tianjin Chest Hospital from April 2017 to December 2018 were enrolled. According to the CAG results, they were divided into two groups: CHD group (n = 302) and non-CHD group (n = 226). The gender, age, history of hypertension, family history of CHD, diabetes, levels of blood lipid parameters in serum and other clinical data of patients were recorded. The levels of serum OPG and sRANKL were measured by enzyme-linked immunosorbent assay (ELISA). T149C and T950C gene polymorphisms were analyzed by polymerase chain reaction-restriction endonuclease fragment length polymorphism (PCR-RFLP) methods. Hardy-Weinberg genetic balance test was performed for alleles. Binomial classification multivariate non-conditional Logistic regression method was used to analyze the relationship between T149C and T950C gene polymorphisms, serum levels of OPG and sRANKL and CHD. RESULTS: All patients were enrolled in the final analysis. The serum level of OPG in CHD group was significantly higher than that in non-CHD group (µg/L: 1.76±0.49 vs. 1.47±0.29, P < 0.01), the serum level of sRANKL was significantly lower than that in non-CHD group (ng/L: 342.14±121.38 vs. 376.63±108.66, P < 0.05). Logistic regression analysis showed that after adjusting for age, gender, blood lipid parameters, diabetes and other factors, the increase in serum OPG level was an independent risk factor for CHD [odds ratio (OR) = 1.995, 95% confidence interval (95%CI) = 1.935-2.066, P = 0.012]. PCR-RFLP results showed that TT, TC and CC genotypes were found in T149C and T950C of OPG promoter. According to Hardy-Weinberg equilibrium test, the polymorphisms of OPG T149C and T950C accorded with Hardy-Weinberg law, achieving genetic balance with representative of the population. The frequencies of TT, TC, CC and alleles T and C in T149C genotypes of non-CHD group were 53.5%, 42.9%, 3.6%, 75.0% and 25.0%, respectively, and they were 43.1%, 50.3%, 6.6%, 68.2% and 31.8%, respectively in CHD group. There were statistically significant differences in genotype and allele frequencies between the two groups (all P < 0.05). It was shown by Logistic regression analysis that the risk of CHD in TC+CC genotype of T149C was 1.86 of TT genotype (OR = 1.86, 95%CI = 1.24-2.78, P = 0.003). It was suggested that C allele might be a susceptible gene for CHD. In non-CHD group, the frequencies of TT, TC, CC, and alleles T and C in T950C genotypes were 39.8%, 46.5%, 13.7%, 63.1% and 36.9%, respectively. They were 39.4%, 43.4%, 17.2%, 61.1% and 38.9%, respectively in CHD group. There were no significant differences in genotype and allele frequencies between the two groups (all P > 0.05). Logistic regression analysis showed that TC+CC genotype of T950C was not related with CHD. CONCLUSIONS: The increased level of serum OPG was closely related with CHD and could be used as a risk factor for CHD. The cases carried OPG T149C TC+CC genotype might have the risk suffering CHD. C allele is might be a susceptible gene.


Assuntos
Doença das Coronárias/sangue , Osteoprotegerina/sangue , Osteoprotegerina/genética , Polimorfismo Genético , Regiões Promotoras Genéticas/genética , China/epidemiologia , Doença das Coronárias/epidemiologia , Feminino , Humanos , Masculino , Fatores de Risco
8.
Medicine (Baltimore) ; 98(5): e14216, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30702576

RESUMO

Patients with coronary heart disease (CHD) frequently have cardiovascular complications after undergoing PCI. Angiopoietin-2 (Ang-2) is an important proangiogenic factor that also plays an important role in atherosclerosis. This study aimed to evaluate the value of Ang-2 in predicting cardiovascular events after elective PCI.This prospective study enrolled 97 patients with CHD who underwent elective PCI from 2013 to 2014. Blood samples were collected in the first morning after admission and within 24 to 48 h after PCI. The primary endpoint was cardiovascular events, defined as a composite of cardiac death, nonfatal myocardial infarction/repeat revascularization, readmission for severe deterioration of angina and readmission for new onset heart failure. Based on the median level of pre-PCI or post-PCI Ang-2, the patients were divided into a low level group and a high level group.During the whole follow-up period (mean, 53 ±â€Š13 months), Kaplan-Meier curves of cardiovascular events showed that there was no significant difference between the two pre-PCI groups (χ = 2.22, P = .137, and log-rank test) or the two post-PCI groups (χ = 2.83, P = .093, and log-rank test). However, in a multivariable Cox regression model, landmark analysis showed that the patients in high level group of post-PCI, not pre-PCI, were associated with remarkable higher risks of cardiovascular events compared to the low level group during the first 1.5 years of follow-up (adjusted HR = 9.99, 95%CI = 1.99-50.13, P = .005). However, that was of no significance from 1.5 years to maximum follow-up years (adjusted HR = 0.82, 95%CI = 0.26-2.59, P = .733).High Ang-2 levels of post-PCI can predict the occurrence of cardiovascular events in the short to medium term.


Assuntos
Angiopoietina-2/sangue , Doença das Coronárias/sangue , Doença das Coronárias/cirurgia , Intervenção Coronária Percutânea/métodos , Idoso , Angiopoietina-2/biossíntese , Doença das Coronárias/complicações , Feminino , Cardiopatias/etiologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Prognóstico , Reoperação/estatística & dados numéricos , Fatores de Risco
9.
Ecotoxicol Environ Saf ; 173: 37-44, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-30753939

RESUMO

Cross-sectional studies have described an association between exposure to phthalate esters and cardiovascular risk factors. However, the association with coronary heart disease (CHD) is still unclear. A total of 180 subjects randomly selected from 336 CHD patients, and 360 age- and sex-matched non-CHD controls were included from 2008 to 2011. Urinary metabolites of phthalate esters were measured by liquid chromatography-tandem mass spectrometry. The geometric means of urinary phthalates metabolites were significantly higher for the three Di-(2-ethylhexyl)-phthalate (DEHP) metabolites, mono-2-ethylhexyl phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate, and mono-(2-ethyl-5-oxohexyl) phthalate among CHD patients in-hospital than those of being discharged. Excluding 89 CHD patients of in-hospital and hospital discharge within 2 days, we found the urinary concentrations of MEHP, mono-n-butyl phthalate (MnBP), and mono-isobutyl phthalate (MiBP) of 91 CHD patients discharged ≥ 3 days were higher than those of controls. Among 451 participants, those with higher tertile levels of urinary MEHP, MnBP, and MiBP showed an increased risk for CHD compared to those with lowest tertile levels; the corresponding odds ratios (95% CI) were 2.77 (1.22-6.28), 2.90 (1.32-6.4), and 3.19 (1.41-7.21), respectively, after adjustment for confounders. Higher levels of hs-CRP, fibrinogen, and D-dimer were linked with increased levels of all DEHP metabolites in CHD patients. In conclusion, exposure to DEHP and dibutyl phthalates was positively associated with CHD and this relationship may be probably mediated via atherothrombosis.


Assuntos
Doença das Coronárias/sangue , Doença das Coronárias/urina , Exposição Ambiental/análise , Poluentes Ambientais/urina , Ácidos Ftálicos/urina , Adulto , Biomarcadores/sangue , Estudos Transversais , Poluentes Ambientais/química , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ácidos Ftálicos/química , Fatores de Risco
10.
Braz J Cardiovasc Surg ; 34(1): 17-21, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30810669

RESUMO

OBJECTIVE: To investigate the clinical significance of serum cystatin C (Cys-C) and high-sensitivity C-reactive protein (hs-CRP) in coronary heart disease (CHD) patients undergoing percutaneous coronary intervention (PCI). METHODS: One hundred and twenty-eight CHD patients were divided into drug treatment (56 cases) and PCI treatment (72 cases) groups, receiving conventional drug treatment and PCI plus conventional drug treatment, respectively. At admission time and 4 weeks after treatment, the left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter, and left ventricular end systolic diameter were measured. At admission time and 24h, 72h, 1 week, and 4 weeks after treatment, the serum levels of Cys-C and hs-CRP were determined. RESULTS: After 4 weeks of treatment, LVEF in the PCI treatment group was significantly higher than that before treatment (P<0.01) and it was significantly higher than in the drug treatment group at the same time (P<0.01). Cys-C and hs-CRP level in the PCI treatment group were significantly higher than in the drug treatment group 72h and 1 week after treatment (P<0.05 or P<0.01), respectively, but they were significantly lower than in the drug treatment group 4 weeks after treatment (P<0.01). There were obvious interaction effects between grouping factor and time factor in Cys-C (F=3.62, P<0.05) and hs-CRP (F=17.85, P<0.01). CONCLUSION: Serum levels of Cys-C and hs-CRP are closely related to the heart function in CHD patients undergoing PCI, and they may be used for predicting the outcome of PCI.


Assuntos
Proteína C-Reativa/análise , Doença das Coronárias/sangue , Doença das Coronárias/cirurgia , Cistatina C/sangue , Intervenção Coronária Percutânea/métodos , Idoso , Índice de Massa Corporal , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Volume Sistólico/fisiologia , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Esquerda/fisiopatologia
11.
Clin Biochem ; 65: 21-23, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30659791

RESUMO

OBJECTIVES: Low serum PON1 activities (paraoxon, phenyl-acetate or lactone substrates) are associated with coronary heart disease (CHD). We investigated the rate of diazoxon hydrolysis by PON1 in a population with CHD. DESIGN & METHODS: Case- control study of 410 subjects with CHD and 274 controls. PON1 activity towards paraoxon and diazoxon, PON1 serum concentration and the PON1-55 and 192 polymorphisms were determined. RESULTS: There were no differences in the distribution of the PON1-55 or PON1-192 genotypes between the CHD and controls, however, PON1 activity towards diazoxon (DIAZ) was significantly (+160%) higher in CHD. In the control population, DIAZ was significantly different between the PON1-192 genotypes in the order QQ > QR > RR (P < .001). However, in CHD the order was QQ > QR = RR. In CHD DIAZ was significantly higher in all the PON1-192 and 55 genotypes compared to controls. In both populations DIAZ was significantly different between the PON1-55 genotypes in the order LL > LM > MM (P < .001). CONCLUSION: If this result can be replicated in other studies and/or with other PON1 substrates, there may be major diagnostic and mechanistic implications for the relationship of PON1 and CHD.


Assuntos
Arildialquilfosfatase/sangue , Doença das Coronárias/sangue , Doença das Coronárias/enzimologia , Compostos Organofosforados/metabolismo , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Oxirredução
12.
Nutr Metab Cardiovasc Dis ; 29(2): 152-158, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30642791

RESUMO

BACKGROUND AND AIMS: Diet is known to play a decisive role in the development of coronary heart disease (CHD). One factor believed to decrease lifetime risk of CHD is the consumption of omega-3 fatty acids. Yet, conclusive evidence regarding the potential cardioprotective effects of fatty acids is far from being reached. The present study aimed to provide further evidence on the association of serum fatty acid profiles with CHD risk. METHODS AND RESULTS: The CARdio-vascular Disease, Living and Ageing in Halle study (CARLA study) is an observational cohort study comprising an older adult's general population with a high level of cardiovascular risk factors. In a matched case-control design the serum fatty acid concentrations of 73 subjects with an incident fatal or nonfatal CHD event were compared to 146 controls matched for sex and age. Our data show that the participants of the CARLA study are underserved in unsaturated fatty acids with respect to current dietary recommendations. In addition, the ratio of omega-6 to omega-3 fatty acids was determined to be 8:1 which underlines the consumption of a Western-style diet enriched in omega-6 fatty acids. There were no significant differences in fatty acid patterns between cases and controls. Thus, no clear association of particular serum fatty acid levels with cardiovascular risk was found. CONCLUSION: Our results support the conclusion that in populations with a homogenous low level of omega-3 polyunsaturated fatty acids consumption, serum fatty acid levels are not associated with CHD risk.


Assuntos
Doença das Coronárias/sangue , Doença das Coronárias/epidemiologia , Ácidos Graxos Ômega-3/sangue , Dieta Saudável , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Doença das Coronárias/diagnóstico , Doença das Coronárias/prevenção & controle , Ácidos Graxos Ômega-3/administração & dosagem , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Proteção , Medição de Risco , Fatores de Risco , Fatores de Tempo
13.
Life Sci ; 219: 329-335, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30658102

RESUMO

OBJECTIVE: The aim of this study was to evaluate the association between serum soluble semaphorin4D (sSema4D) and coronary heart disease (CHD) and the extent of coronary artery stenosis. METHODS: The study included 188 cases that underwent coronary angiography because of precordial pain. One hundred and twenty-eight cases were diagnosed with CHD; 60 cases with negative coronary angiography served as controls. Coronary stenosis was evaluated by the number of diseased coronary artery and Gensini scoring system. Serum sSema4D and C-reactive protein (CRP) levels were measured. RESULTS: Serum sSema4D levels in CHD patients were significantly higher than those of controls (p < 0.001) and the levels in those with acute coronary syndrome (ACS) were significantly higher than those with stable angina pectoris (p < 0.05) and controls (p < 0.05). Higher levels of serum sSema4D were observed in the group with high Gensini scores. Serum sSema4D concentration was positively correlated with the Gensini score (r = 0.735, p < 0.001) and was the only independent factor that significantly influenced the Gensini score (p < 0.001). Serum sSema4D levels were positively correlated with CRP levels in all subjects (r = 0.182, p = 0.013). Elevated sSema4D and CRP levels were independently associated with the presence of CHD. CONCLUSION: Serum sSema4D levels were increased in CHD patients, especially in those with ACS. Serum sSema4D may be an independent risk factor for CHD and reflect the extent of coronary artery stenosis to some extent.


Assuntos
Antígenos CD/sangue , Doença das Coronárias/sangue , Estenose Coronária/sangue , Semaforinas/sangue , Proteína C-Reativa/análise , Estudos de Casos e Controles , Angiografia Coronária , Doença das Coronárias/diagnóstico por imagem , Estenose Coronária/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Índice de Gravidade de Doença
14.
Lipids Health Dis ; 18(1): 22, 2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-30670045

RESUMO

PURPOSE: This study was designed to explore the value of monitoring miR-92a in T2DM patients with coronary heart disease (CHD). MATERIALS AND METHODS: 40 ACS patients with prior history of CHD and diabetes while the onset time of diabetes preceded that of CHD by more than 2 years were enrolled as the DACS group(diabetic ACS group). 40 ACS subjects who had had a definite diagnosis of CHD for more than 2 years with no history of T2DM were recuited as the CACS group(chronic CHD with ACS group). All enrolled subjects from DACS and CACS group came from an emergency basis and diagnosed with ACS by coronary angiography. Another 68 age- and sex-matched volunteers with chronic stable CHD without diabetes history were assigned as the control group (CHD group). We examined the serum levels of miR-92a and analyzed their correlations with blood pressure, glucose level, and lipid level. RESULTS: The levels of miR-92a were significantly elevated in the DACS group compared with those of the CACS and CHD groups. Multivariate analysis showed that miR-92a, systolic blood pressure (SBP), and glycosylated hemoglobin (HbA1c) were significantly related to ACS events in patients with T2DM. Forward stepwise binary logistic regression analysis identified miR-92a as an independent predictive factor for ACS events in the patients with T2DM. CONCLUSION: An elevated circulating miR-92a level was associated with an increased risk of ACS in CHD patients with T2DM. Thus the level of miR-92a, especially combined with elevated SBP and HbA1c, may be helpful in the detection of ACS in patients with T2DM.


Assuntos
Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/genética , MicroRNA Circulante/sangue , Doença das Coronárias/sangue , Doença das Coronárias/genética , Diabetes Mellitus Tipo 2/complicações , MicroRNAs/sangue , Síndrome Coronariana Aguda/complicações , Adulto , Doença das Coronárias/complicações , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Análise Multivariada , Curva ROC , Análise de Regressão
15.
Clin Sci (Lond) ; 133(2): 205-224, 2019 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-30670671

RESUMO

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a hepatic enzyme that regulates the low-density lipoprotein cholesterol (LDL-c) receptor and thus circulating LDL-c levels. With overwhelming evidence now supporting the reduction in LDL-c to lower the risk of cardiovascular disease, PCSK9 inhibitors represent an important therapeutic target, particularly in high-risk populations. Here, we summarise and update the science of PCSK9, including its discovery and the development of various inhibitors, including the now approved monoclonal antibodies. In addition, we summarise the clinical applications of PCSK9 inhibitors in a range of patient populations, as well as the major randomised controlled trials investigating their use in coronary prevention.


Assuntos
Anticolesterolemiantes/uso terapêutico , LDL-Colesterol/sangue , Doença das Coronárias/prevenção & controle , Dislipidemias/tratamento farmacológico , Serviços Preventivos de Saúde/métodos , Pró-Proteína Convertase 9/antagonistas & inibidores , Inibidores de Serino Proteinase/uso terapêutico , Animais , Anticolesterolemiantes/efeitos adversos , Biomarcadores/sangue , Doença das Coronárias/sangue , Doença das Coronárias/enzimologia , Dislipidemias/sangue , Dislipidemias/enzimologia , Humanos , Pró-Proteína Convertase 9/metabolismo , Fatores de Risco , Inibidores de Serino Proteinase/efeitos adversos , Resultado do Tratamento
16.
JAMA ; 321(4): 364-373, 2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30694319

RESUMO

Importance: Triglycerides and cholesterol are both carried in plasma by apolipoprotein B (ApoB)-containing lipoprotein particles. It is unknown whether lowering plasma triglyceride levels reduces the risk of cardiovascular events to the same extent as lowering low-density lipoprotein cholesterol (LDL-C) levels. Objective: To compare the association of triglyceride-lowering variants in the lipoprotein lipase (LPL) gene and LDL-C-lowering variants in the LDL receptor gene (LDLR) with the risk of cardiovascular disease per unit change in ApoB. Design, Setting, and Participants: Mendelian randomization analyses evaluating the associations of genetic scores composed of triglyceride-lowering variants in the LPL gene and LDL-C-lowering variants in the LDLR gene, respectively, with the risk of cardiovascular events among participants enrolled in 63 cohort or case-control studies conducted in North America or Europe between 1948 and 2017. Exposures: Differences in plasma triglyceride, LDL-C, and ApoB levels associated with the LPL and LDLR genetic scores. Main Outcomes and Measures: Odds ratio (OR) for coronary heart disease (CHD)-defined as coronary death, myocardial infarction, or coronary revascularization-per 10-mg/dL lower concentration of ApoB-containing lipoproteins. Results: A total of 654 783 participants, including 91 129 cases of CHD, were included (mean age, 62.7 years; 51.4% women). For each 10-mg/dL lower level of ApoB-containing lipoproteins, the LPL score was associated with 69.9-mg/dL (95% CI, 68.1-71.6; P = 7.1 × 10-1363) lower triglyceride levels and 0.7-mg/dL (95% CI, 0.03-1.4; P = .04) higher LDL-C levels; while the LDLR score was associated with 14.2-mg/dL (95% CI, 13.6-14.8; P = 1.4 × 10-465) lower LDL-C and 1.9-mg/dL (95% CI, 0.1-3.9; P = .04) lower triglyceride levels. Despite these differences in associated lipid levels, the LPL and LDLR scores were associated with similar lower risk of CHD per 10-mg/dL lower level of ApoB-containing lipoproteins (OR, 0.771 [95% CI, 0.741-0.802], P = 3.9 × 10-38 and OR, 0.773 [95% CI, 0.747-0.801], P = 1.1 × 10-46, respectively). In multivariable mendelian randomization analyses, the associations between triglyceride and LDL-C levels with the risk of CHD became null after adjusting for differences in ApoB (triglycerides: OR, 1.014 [95% CI, 0.965-1.065], P = .19; LDL-C: OR, 1.010 [95% CI, 0.967-1.055], P = .19; ApoB: OR, 0.761 [95% CI, 0.723-0.798], P = 7.51 × 10-20). Conclusions and Relevance: Triglyceride-lowering LPL variants and LDL-C-lowering LDLR variants were associated with similar lower risk of CHD per unit difference in ApoB. Therefore, the clinical benefit of lowering triglyceride and LDL-C levels may be proportional to the absolute change in ApoB.


Assuntos
Apolipoproteínas B/sangue , LDL-Colesterol/sangue , Doença das Coronárias/genética , Predisposição Genética para Doença , Variação Genética , Lipase Lipoproteica/genética , Receptores de LDL/genética , Triglicerídeos/sangue , Estudos de Casos e Controles , Doença das Coronárias/sangue , Feminino , Humanos , Lipase Lipoproteica/metabolismo , Mutação com Perda de Função , Masculino , Análise da Randomização Mendeliana , Redes e Vias Metabólicas , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
17.
PLoS One ; 14(1): e0210909, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30673762

RESUMO

Circulating biomarkers available in clinical practice do not allow to stratify patients with coronary heart disease (CHD) prior the onset of a clinically relevant event. We evaluated the methylation status of specific genomic segments and gene expression in peripheral blood of patients undergoing Cardiac Computed Tomography (CCT) for CHD (n = 95). We choose to investigate cholesterol metabolism. Methylation and gene expression of low density lipoprotein receptor (LDLR), sterol regulatory element-binding factor 2 (SREBF2) and ATP-binding cassette transporter 1 (ABCA1) were evaluated by qRT-PCR. Calcium score (CACS), stenosis degree, total plaque volume (TPV), calcified plaque volume (CPV), non-calcified plaque volume (NCPV) and plaque burden (PB) were assessed in all CHD patients (n = 65). The percentage of methylation at the specific analyzed segment of LDLR promoter was higher in CHD patients vs healthy subjects (HS) (n = 30) (p = 0.001). LDLR, SREBF2 and ABCA1 mRNAs were up-regulated in CHD patients vs HS (p = 0.02; p = 0.019; p = 0.008). SREBF2 was overexpressed in patients with coronary stenosis ≥50% vs subjects with stenosis <50% (p = 0.036). After adjustment for risk factors and clinical features, ABCA1 (p = 0.005) and SREBF2 (p = 0.010) gene expression were identified as independent predictors of CHD and severity. ROC curve analysis revealed a good performance of ABCA1 on predicting CHD (AUC = 0.768; p<0.001) and of SREBF2 for the prediction of disease severity (AUC = 0.815; p<0.001). Moreover, adjusted multivariate analysis demonstrated SREBF2 as independent predictor of CPV, NCPV and TPV (p = 0.022; p = 0.002 and p = 0.006) and ABCA1 as independent predictor of NCPV and TPV (p = 0.002 and p = 0.013). CHD presence and characteristics are related to selected circulating transcriptional and epigenetic-sensitive biomarkers linked to cholesterol pathway. More extensive analysis of CHD phenotypes and circulating biomarkers might improve and personalize cardiovascular risk stratification in the clinical settings.


Assuntos
Doença das Coronárias/sangue , Doença das Coronárias/genética , Epigênese Genética , Transportador 1 de Cassete de Ligação de ATP/genética , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Angiografia por Tomografia Computadorizada , Doença das Coronárias/diagnóstico por imagem , Metilação de DNA , Feminino , Expressão Gênica , Marcadores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/genética , Regiões Promotoras Genéticas , Receptores de LDL/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/genética
18.
Diabetes Care ; 42(3): 457-465, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30617142

RESUMO

OBJECTIVE: To estimate the long-term absolute risk for cardiovascular disease (CVD) according to fasting glucose (FG) levels below the threshold of diabetes. RESEARCH DESIGN AND METHODS: We pooled data from seven observational cohorts of U.S. black and white men and women followed from 1960 to 2015. We categorized FG as follows: <5.0, 5.0-5.5, 5.6-6.2, 6.3-6.9 mmol/L, and diabetes (FG ≥7.0 mmol/L or use of diabetes medications). CVD was defined as fatal/nonfatal coronary heart disease and fatal/nonfatal stroke. We estimated the risk of CVD by FG category at index age 55 years using a modified Kaplan-Meier survival analysis, adjusted for the competing risk of non-CVD death. We also assessed risk for incident CVD according to change in FG before 50 years of age, specifically among the categories <5.6 mmol/L, 5.6-6.9 mmol/L, and diabetes. RESULTS: Our sample included 19,630 individuals (6,197 blacks and 11,015 women) without a prior CVD event. Risk for CVD through 85 years of age ranged from 15.3% (<5.0 mmol/L) to 38.6% (diabetes levels) among women and from 21.5% (5.0-5.5 mmol/L) to 47.7% (diabetes levels) among men. An FG of 6.3-6.9 mmol/L was associated with higher long-term CVD risk compared with the lowest FG among men but not women. Increases in glucose during midlife with conversion to diabetes were associated with higher cardiovascular risk (1.3- to 3.6-fold) than increases in glucose below the diabetes threshold. CONCLUSIONS: Middle-age individuals with diabetes have high long-term absolute risk for CVD. These data strongly support the importance of blood glucose monitoring in midlife for CVD prevention.


Assuntos
Glicemia/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Diabetes Mellitus/sangue , Angiopatias Diabéticas/sangue , Adulto , Idoso , Glicemia/análise , Automonitorização da Glicemia , Doenças Cardiovasculares/classificação , Doenças Cardiovasculares/epidemiologia , Doença das Coronárias/sangue , Doença das Coronárias/epidemiologia , Diabetes Mellitus/epidemiologia , Angiopatias Diabéticas/classificação , Angiopatias Diabéticas/epidemiologia , Jejum , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estados Unidos/epidemiologia
19.
Diabetes Care ; 42(3): 486-493, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30659073

RESUMO

OBJECTIVE: The prognostic value of long-term glycemic variability is incompletely understood. We evaluated the influence of visit-to-visit variability (VVV) of fasting blood glucose (FBG) on incident cardiovascular disease (CVD) and mortality. RESEARCH DESIGN AND METHODS: We conducted a prospective cohort analysis including 4,982 participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) who attended the baseline, 24-month, and 48-month visits. VVV of FBG was defined as the SD or variability independent of the mean (VIM) across FBG measurements obtained at the three visits. Participants free of CVD during the first 48 months of the study were followed for incident CVD (coronary heart disease [CHD], stroke, and heart failure [HF]) and all-cause mortality. RESULTS: Over a median follow-up of 5 years, there were 305 CVD events (189 CHD, 45 stroke, and 81 HF) and 154 deaths. The adjusted hazard ratio (HR) comparing participants in the highest versus lowest quartile of SD of FBG (≥26.4 vs. <5.5 mg/dL) was 1.43 (95% CI 0.93-2.19) for CVD and 2.22 (95% CI 1.22-4.04) for all-cause mortality. HR for VIM was 1.17 (95% CI 0.84-1.62) for CVD and 1.89 (95% CI 1.21-2.93) for all-cause mortality. Among individuals without diabetes, the highest quartile of SD of FBG (HR 2.67 [95% CI 0.14-6.25]) or VIM (HR 2.50 [95% CI 1.40-4.46]) conferred a higher risk of death. CONCLUSIONS: Greater VVV of FBG is associated with increased mortality risk. Our data highlight the importance of achieving normal and consistent glycemic levels for improving clinical outcomes.


Assuntos
Anti-Hipertensivos/uso terapêutico , Glicemia/metabolismo , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/mortalidade , Hipolipemiantes/uso terapêutico , Visita a Consultório Médico/estatística & dados numéricos , Idoso , Glicemia/análise , Doenças Cardiovasculares/sangue , Causas de Morte , Doença das Coronárias/sangue , Doença das Coronárias/mortalidade , Doença das Coronárias/prevenção & controle , Diabetes Mellitus/sangue , Quimioterapia Combinada , Feminino , Seguimentos , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/mortalidade , Variações Dependentes do Observador , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/prevenção & controle , Fatores de Tempo
20.
Vascul Pharmacol ; 115: 1-12, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30685502

RESUMO

Platelet P2Y12 receptors play a key role in platelet activation and thrombus formation. Accordingly, P2Y12 receptor antagonists are the cornerstone of secondary prevention of atherothrombotic events in patients undergoing percutaneous coronary intervention (PCI). The availability of different oral P2Y12 antagonists (clopidogrel, prasugrel, ticagrelor) along with the introduction of the first intravenous P2Y12 antagonist cangrelor offer an opportunity to individualize antiplatelet therapy according to the changing clinical setting. The recent International Expert Consensus provided the first recommendations on switching between the P2Y12 antagonists. While the consensus greatly helps to guide switching between P2Y12 antagonists, a number of controversial clinical scenarios remain where the evidence regarding the optimal switch strategy is scarce. In such clinical scenarios, understanding of the (i) pharmacological properties of P2Y12 antagonists, (ii) recent evidence from pharmacodynamics studies, clinical trials and registries, and (iii) factors affecting the efficacy and safety of the P2Y12 antagonists, all summarized below, are crucial to choose the optimal switch strategy.


Assuntos
Doença das Coronárias/terapia , Substituição de Medicamentos , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Animais , Tomada de Decisão Clínica , Doença das Coronárias/sangue , Doença das Coronárias/diagnóstico , Técnicas de Apoio para a Decisão , Árvores de Decisões , Esquema de Medicação , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação de Plaquetas/efeitos adversos , Inibidores da Agregação de Plaquetas/farmacocinética , Guias de Prática Clínica como Assunto , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/farmacocinética , Fatores de Risco , Resultado do Tratamento
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