RESUMO
INTRODUCTION: Heart failure (HF) patients discharged from a hospital are at a high risk of death and rehospitalization. Scarce data are available on the use of sacubitril / valsartan in this population in Poland. OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of sacubitril / valsartan in the group of Polish patients who participated in the TRANSITION study with the patients recruited at other sites. PATIENTS AND METHODS: This is a post hoc secondary analysis of the TRANSITION study comparing sacubitril / valsartan initiation pre- vs postdischarge in 991 patients hospitalized for acute decompensated HF with reduced ejection fraction (HFrEF). The Polish subgroup consisted of 104 patients. RESULTS: Significant differences were identified in the characteristics of Polish vs nonPolish populations. At baseline, the Polish population showed higher proportion of men, higher body mass index, lower heart rate, Nterminal pro-Btype natriuretic peptide and highsensitivity troponin T levels, and significantly lower New York Heart Association class. The Polish patients were better managed in terms of implanted electrotherapy devices, percutaneous coronary interventions, and drug therapy, and were more often hospitalized. The primary end point of achieving the target dose of sacubitril / valsartan at treatment week 10 was met by 45.6% of the Polish patients and 48.4% of the nonPolish population (P = 0.61). Approximately 90% of the Polish patients received and maintained any sacubitril / valsartan dose for 2 weeks over 10week treatment vs 87.5% of the nonPolish patients (P = 0.36). The rate of permanent sacubitril / valsartan treatment discontinuation was low in both Polish (3.9%) and nonPolish populations (6.4%) (P = 0.33). CONCLUSIONS: Sacubitril / valsartan can be used safely in the early period after an episode of acute HF both in the Polish and nonPolish patients with HFrEF, and the likelihood to achieve the maximum dose is the same despite significant differences between the studied populations.
Assuntos
Insuficiência Cardíaca , Masculino , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Tetrazóis , Polônia , Assistência ao Convalescente , Volume Sistólico/fisiologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Alta do Paciente , Valsartana/uso terapêuticoRESUMO
Both glutathione peroxidase and deiodinases are selenoproteins requiring selenium. Oxidative stress accompanying acute myocardial infarction (MI) may lead to activation of peroxidase and relative selenium deficiency. That may impair conversion of tetraiodothyronine (T4) to triiodothyronine (T3). AIM: The aim of the study was the evaluation of the prevalence of low T3 syndrome in MI, in relation to selenium deficiency. MATERIALS AND METHODS: The study group consisted of 59 consecutive patients hospitalized due to STEMI or NSTEMI, treated with primary percutaneous coronary intervention. Exclusion criteria: thyroid dysfunction, severe systemic disease, treatment with amiodarone, steroids or propranolol. Group A consisted of 7 patients with low fT3 concentration, Group B consisted of remaining 52 patients with normal fT3 levels. RESULTS: The prevalence of low T3 syndrome was 11.9%. The prevalence of selenium deficiency was 71.2%. Patients with low T3 syndrome had higher heart rate at admission and more often needed intravenous diuretics or inotropic agents. Low fT3 group presented higher levels of NT-proBNP, hsCRP, WBC, admission CKMB levels. There was a nonsignificant trend towards lower selenium levels in A group. We demonstrated correlations between fT3 and hsTnT, CKMB, NT-proBNP, hsCRP, MAPSE but we did not find correlation between fT3 and selenium or LVEF. CONCLUSIONS: Selenium deficiency was found in majority of MI patients, while low T3 was identified in 11.9% of patients. fT3 levels correlate with markers of infarction severity and inflammatory markers. Se deficiency alone does not explain the reason of low fT3 concentration.
Assuntos
Síndromes do Eutireóideo Doente , Hipotireoidismo , Infarto do Miocárdio , Selênio , Síndromes do Eutireóideo Doente/complicações , Humanos , Hipotireoidismo/complicações , Infarto do Miocárdio/complicações , Selênio/deficiência , Tiroxina , Tri-IodotironinaRESUMO
BACKGROUND: Selenium (Se) is incorporated in 25 enzymes, for example, glutathione peroxidase (activatedb by oxidative stress) and deiodinases (converting thyroid hormones). Oxidative stress present in heart failure (HF) and myocardial infarction (MI) might cause Se deficiency and decreased thyroxine to triiodothyronine conversion. AIMS: We sought to evaluate Se levels in Polish patients with MI, HF, and healthy volunteers in relation to thyroid hormone levels. METHODS: The study group consisted of 143 participants: 54 patients with MI, 59 patients with decompensated HF, and 30 healthy matched volunteers. The patients underwent echocardiography and laboratory tests on admission and 5 months later. RESULTS: Se levels were lower in patients with MI and HF than in controls (median [interquartile range, IQR], 65.9 [55.2-76.1] µg/l and 59.7 [47.7-70.7] µg/l vs 93.2 [84.2-99.1] µg/l, respectively; P <0.001). The Se deficiency was very common in patients with MI and HF, while it was rare in controls (70.37% and 74.58% vs 10%, respectively; P <0.001). Patients with MI and HF presented lower free triiodothyronine (FT3) levels and lower FT3 to free thyroxine (FT4) ratio in comparison with controls (median [IQR], 3.90 [3.60-4.38] pmol/l and 4.25 [3.57-4.60] pmol/l vs 4.92 [4.50-5.27] pmol/l; P <0.001; and 0.25 [0.23-0.29] and 0.25 [0.21-0.28] vs 0.32 [0.29-0.37]; P <0.001, respectively). There was a weak to moderate correlation between Se level, FT3 level, and the FT3/FT4 ratio. At followup, the FT3/FT4 ratio tended to normalize in patients with MI and remained decreased in patients with HF (mean [SD], 0.31 [0.06] vs 0.27 ([0.05]; P <0.001. CONCLUSIONS: Se deficiency is very common in Polish patients with MI and HF. Thyroid hormones disturbances were more transient in patients with MI, but more chronic in those with HF.
Assuntos
Insuficiência Cardíaca/metabolismo , Infarto do Miocárdio/metabolismo , Selênio/deficiência , Hormônios Tireóideos/sangue , Idoso , Feminino , Insuficiência Cardíaca/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Polônia , Tiroxina/sangue , Tri-Iodotironina/sangueRESUMO
BACKGROUND: The function of deiodinases - selenoproteins converting thyroid hormones may be disturbed by oxidative stress accompanying heart failure. Selenium (Se) may be used by glutathione peroxidase, leading to a lack of deiodinase and triiodothyronine (T3). The aim of the study was the evaluation of the prevalence and clinical significance of low T3 syndrome in heart failure and the assessment of the association of low fT3 and Se deficiency. METHODS: The study group consisted of 59 consecutive patients hospitalized due to decompensated HFrEF NYHA III or IV. Exclusion criteria were: thyroid dysfunction, severe systemic disease, treatment with amiodarone, steroids or propranolol. Group A included 9 patients with low free T3 (fT3) concentration below 3.1 pmol/L. Group B consisted of the remaining 50 patients with normal fT3 levels. RESULTS: The prevalence of low T3 syndrome was 15.3%. The prevalence of Se deficiency was 74.6%. We demonstrated correlations between fT3 and main clinical variables (i.e. NT-proBNP, LVEF, hsCRP), but we did not find correlation between fT3 and the Se level. Kaplan-Meier survival analysis showed lower survival probability in patients with low fT3 (p < 0.001). CONCLUSIONS: Low T3 syndrome is frequently found in patients with HFrEF and is associated with a poor outcome. We did not identify any significant correlation between Se and fT3 level.
Assuntos
Síndromes do Eutireóideo Doente/sangue , Insuficiência Cardíaca/sangue , Selênio/deficiência , Tri-Iodotironina/sangue , Idoso , Biomarcadores/sangue , Síndromes do Eutireóideo Doente/diagnóstico , Síndromes do Eutireóideo Doente/epidemiologia , Síndromes do Eutireóideo Doente/fisiopatologia , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Polônia/epidemiologia , Valor Preditivo dos Testes , Prevalência , Prognóstico , Estudos Prospectivos , Fatores de Risco , Selênio/sangueRESUMO
BACKGROUND AND AIMS: Numerous recent studies conducted in different clinical settings have focused on the benefits of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in the prevention of cardiovascular diseases. There is limited evidence that patients with type 2 diabetes (T2D) and very high cardiovascular risk can also benefit from a high dose of n-3PUFAs, especially those on optimal medical therapy as recommended by the guidelines. The aim of the present study was to assess the impact of high-dose n-3 PUFA treatment on endothelial function in patients with T2D and established atherosclerotic cardiovascular disease (ASCVD). METHODS: We conducted a prospective randomized double-blind, placebo-controlled, 2-center study, in which endothelial function was measured using flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD). Serum fatty acids composition was measured by gas chromatography. All measurements were done at baseline and after 3 months of treatment with PUFAs at a dose of 2â¯g/d (nâ¯=â¯36) or placebo (nâ¯=â¯38). RESULTS: The majority of the study population was treated with optimal medical therapy. Despite significantly higher concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid in the n-3 PUFA group after 3-month treatment, we did not observe significant changes in endothelial function indices (FMD and NMD). However, in regression analysis, only baseline FMD was associated with EPA concentration before 3 months of n-3 PUFA treatment. CONCLUSIONS: Three months of high-dose n-3 PUFA treatment in very high-risk patients with ASCVD and T2D did not improve the endothelial function indices.
Assuntos
Aterosclerose/tratamento farmacológico , Bebidas , Artéria Braquial/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácido Eicosapentaenoico/administração & dosagem , Endotélio Vascular/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Administração Oral , Idoso , Aterosclerose/diagnóstico , Aterosclerose/fisiopatologia , Artéria Braquial/diagnóstico por imagem , Artéria Braquial/fisiopatologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Suplementos Nutricionais/efeitos adversos , Ácidos Docosa-Hexaenoicos/efeitos adversos , Ácidos Docosa-Hexaenoicos/sangue , Método Duplo-Cego , Ácido Eicosapentaenoico/efeitos adversos , Ácido Eicosapentaenoico/sangue , Endotélio Vascular/diagnóstico por imagem , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polônia , Estudos Prospectivos , Recuperação de Função Fisiológica , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Despite numerous studies on cardioprotective effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs), there is limited evidence for n-3 PUFA-mediated effects, especially at its higher dose, on cardiovascular risk in patients with type 2 diabetes (DM2) and established atherosclerosis. PURPOSE: To investigate the effect of daily treatment with a higher dose (2 g) of n-3 PUFAs on platelet function, coagulation parameters, fibrin clot properties, markers of systemic inflammation and metabolic status, in patients with atherosclerotic vascular disease and DM2 who receive optimal medical therapy. METHODS: We conducted a prospective, double-blind, placebo-controlled, randomized, double-center study, in which thrombin generation (plasma thrombogenic potential from automated thrombogram), fibrin clot properties (plasma fibrin clot permeability; lysis time), platelet aggregation (light transmission aggregometry with adenosine diphosphate and arachidonic acid used as agonists), HbA1c, insulin level, lipid profiles, leptin and adiponectin levels, as well as markers of systemic inflammation (i.e., hsCRP, IL-6, TNF-α, ICAM-1, VCAM-1, and myeloperoxidase) were determined at baseline and at 3 months after treatment with 2 g/day of n-3 PUFAs (n = 36) or placebo (n = 38). Moreover, we assessed serum fatty acids of the phospholipid fraction by gas chromatography both at baseline and at the end of the study. RESULTS: Majority of patients were treated with optimal medical therapy and achieved recommended treatment targets. Despite higher serum levels of eicosapentaenoic acid (EPA) (by 204%; p < 0.001) and docosahexaenoic acid (DHA) (by 62%; p < 0.0001) in n-3 PUFA group at the end of treatment no changes in platelet aggregation, thrombin generation, fibrin clot properties or markers of systemic inflammation were observed. No intergroup differences in the insulin, HbA1c and lipid levels were found at the end of the study. There was no change in adiponectin and leptin in interventional group, however leptin increased in control group (p = 0.01), therefore after study period leptin levels were lower in the interventional group (p = 0.01). Additionally, resolvin D1 did not differ between interventional and control group. CONCLUSIONS: In conclusion, our study demonstrated that in patients with long-standing, well-controlled DM2 and atherosclerotic disease the treatment with a high dose of n-3 PUFAs (namely, 1 g/day of EPA and 1 g/day of DHA for 3 months) does not improve coagulation, metabolic, and inflammatory status when measured with the specified tests. The study was registered in ClinicalTrials.gov; identifier: NCT02178501. Registration date: April 12, 2014.
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Aterosclerose/tratamento farmacológico , Coagulação Sanguínea/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácido Eicosapentaenoico/administração & dosagem , Mediadores da Inflamação/sangue , Inflamação/tratamento farmacológico , Adiponectina/sangue , Idoso , Aterosclerose/sangue , Aterosclerose/diagnóstico , Biomarcadores/sangue , Plaquetas/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Suplementos Nutricionais/efeitos adversos , Ácidos Docosa-Hexaenoicos/efeitos adversos , Método Duplo-Cego , Ácido Eicosapentaenoico/efeitos adversos , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Insulina/sangue , Leptina/sangue , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Agregação Plaquetária/efeitos dos fármacos , Polônia , Estudos Prospectivos , Trombina/metabolismo , Fatores de Tempo , Resultado do TratamentoRESUMO
Calcified heart valves display a significant imbalance in tissue content of trace and essential elements. The valvular calcification is an age-related process and there are data suggesting involvement of lipids. We studied elemental composition and lipid distribution in three distinct regions of calcified human aortic valves, representing successive stages of the calcific degeneration: normal, thickened (early lesion) and calcified (late lesion), using SR-µXRF (Synchrotron Radiation Micro X-Ray Fluorescence) for elemental composition and Oil Red O (ORO) staining for demonstration of lipids. Two-dimensional SR-µXRF maps and precise point spectra were compared with histological stainings on consecutive valve sections to prove topographical localization and colocalization of the examined elements and lipids. In calcified valve areas, accumulation of calcium and phosphorus was accompanied by enhanced concentrations of strontium and zinc. Calcifications preferentially developed in lipid-rich areas of the valves. Calcium concentration ratio between lipid-rich and lipid-free areas was not age-dependent in early lesions, but showed a significant increase with age in late lesions, indicating age-dependent intensification of lipid involvement in calcification process. The results suggest that mechanisms of calcification change with progression of valve degeneration and with age.
Assuntos
Calcinose/patologia , Lipídeos/fisiologia , Fatores Etários , Idoso , Valva Aórtica/química , Valva Aórtica/metabolismo , Valva Aórtica/ultraestrutura , Doença da Válvula Aórtica Bicúspide , Calcinose/metabolismo , Estudos de Casos e Controles , Feminino , Cardiopatias Congênitas/metabolismo , Doenças das Valvas Cardíacas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Fósforo/análise , Espectrometria por Raios X/métodos , Estrôncio/análise , Zinco/análiseRESUMO
BACKGROUND AND AIMS: Increased consumption of omega-3 polyunsaturated fatty acids (PUFA) together with lifestyle measures and medications is recommended for the prevention of cardiovascular diseases. However, the exact mechanisms underlying observed benefits are not well defined. To this aim, we evaluated the effects of omega-3 PUFA in stable coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI) on lipoprotein associated phospholipase A2 (Lp-PLA2) mass and activity and their relation to oxidized low-density lipoproteins (oxy-LDL). METHODS AND RESULTS: In a prospective, double-blind, placebo-controlled, randomized study Lp-PLA2, oxy-LDL, myeloperoxidase and interleukin-6 were determined at baseline, 3-5 days and 30 days during administration of omega-3 PUFA 1 g/day (n = 30) or placebo (n = 24). Treatment with omega-3 PUFA resulted in reduction of Lp-PLA2 mass by 10.7%, activity by 9.3 (p = 0.026 for both) and oxy-LDL by 10.9% (p = 0.014) at 30 days, with no change in myeloperoxidase and interleukin-6. Compared with placebo, patients receiving omega-3 PUFA had lower Lp-PLA2 mass by 9.42%, activity by 9.2 (p = 0.041 for both) and oxy-LDL by 12.3% (p = 0.10) after one month, but not at 3-5 days. There were no correlations between Lp-PLA2 and both myeloperoxidase and oxy-LDL throughout the study. The multivariate model showed that only treatment with omega-3 PUFA and baseline myeloperoxidase levels were independent predictors of Lp-PLA2 mass changes at one month (R(2) = 0.37, P = 0.005). CONCLUSIONS: Administration of omega-3 PUFA can decrease Lp-PLA2 in patients with stable angina undergoing PCI. This novel effect may contribute to the benefits derived from omega-3 PUF.
Assuntos
1-Alquil-2-acetilglicerofosfocolina Esterase/sangue , Angina Estável/terapia , Doença da Artéria Coronariana/terapia , Suplementos Nutricionais , Ácidos Graxos Ômega-3/uso terapêutico , Idoso , Angina Estável/sangue , Angina Estável/diagnóstico , Angina Estável/enzimologia , Biomarcadores/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/enzimologia , Método Duplo-Cego , Regulação para Baixo , Feminino , Humanos , Mediadores da Inflamação/sangue , Interleucina-6/sangue , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estresse Oxidativo/efeitos dos fármacos , Intervenção Coronária Percutânea , Peroxidase/sangue , Polônia , Estudos Prospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Growing evidence suggests a cardioprotective role of omega-3 polyunsaturated fatty acids (PUFA). However, the exact mechanisms underlying the effects of omega-3 PUFA in humans have not yet been fully clarified. PURPOSE: We sought to evaluate omega-3 PUFA-mediated effects on adipokines in patients with stable coronary artery disease (CAD) undergoing elective percutaneous coronary intervention (PCI). METHODS: We conducted a prospective, double-blind, placebo-controlled, randomized study, in which adiponectin, leptin and resistin were determined at baseline, 3-5 days and 30 days during administration of omega-3 PUFA 1 g/day (n=20) or placebo (n=28). RESULTS: As compared to controls administration of omega-3 PUFA resulted in increase of adiponectin by 13.4% (P<0.0001), reduction of leptin by 22% (P<0.0001) and increase of adiponectin to leptin (A/L) ratio by 45.5% (P<0.0001) at 30 days, but not at 3-5 days. Compared with placebo adiponectin was 12.7% higher (P=0.0042), leptin was 16.7% lower (P<0.0001) and A/L ratio was 33.3% higher (P<0.0001) in the omega-3 PUFA group at 30 days. Resistin decreased similarly in both groups after 1 month, without intergroup differences (P=0.32). The multivariate model showed that the independent predictors of changes in adiponectin at 1 month (P<0.001) were: omega-3 PUFA treatment, baseline platelet count, total cholesterol and those in leptin (P<0.0001) were: omega-3 PUFA treatment and waist circumference. Independent predictors of A/L ratio changes (P<0.0001) were: assigned treatment, current smoking and hyperlipidemia. CONCLUSIONS: In high risk stable coronary patients after PCI omega-3 PUFA supplementation improves adipokine profile in circulating blood. This might be a novel, favourable mechanism of omega-3 PUFA action.
Assuntos
Adiponectina/sangue , Cardiotônicos/farmacologia , Doença da Artéria Coronariana/sangue , Ácidos Graxos Ômega-3/farmacologia , Leptina/sangue , Idoso , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/cirurgia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Resistina/sangueRESUMO
BACKGROUND: Dual antiplatelet therapy reduces the risk of thrombotic complications after primary percutaneous coronary intervention (PCI). AIM: To assess whether inhibition of platelet function attenuates microvascular damage in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: We studied 83 STEMI patients treated with primary PCI. Platelet aggregation was measured on admission (ADM) and 4 days later (D4) by light transmission aggregometry after stimulation with 0.5 mM of arachidonic acid and after stimulation with 5 and 20 µM of adenosine diphosphate (ADP) on treatment with dual antiplatelet therapy with aspirin and clopidogrel. Platelet-neutrophil aggregate (PNA) and platelet-monocyte aggregate (PMA) were analysed by flow cytometry. Contrast-enhanced magnetic resonance imaging was performed 2-4 days after STEMI to detect the area of perfusion defect at rest and to determine the size of microvascular obstruction. Microvascular obstruction was expressed as a percentage of infarct area. RESULTS: Perfusion defect at rest was found in 56 (67.5%) patients whereas microvascular obstruction in 63 (75.9%) patients. Patients with perfusion defect at rest had on admission a significantly higher level of both PMA (7.0 vs. 4.5%, p = 0.004) and PNA (4.1 vs. 2.2%, p = 0.016), however there were no significant differences at D4. Platelet aggregation after stimulation with 5 µM of ADP on ADM was correlated (r = 0.37, p = 0.004) with microvascular obstruction area. Moreover, the higher the concentration of PMA(ADM) (r = 0.31, p = 0.016), PNA(ADM) (r = 0.34, p = 0.006) and PM(AD4) (r = 0.35, p = 0.005) the larger the size of microvascular obstruction. Infarct size (ß = 0.43, 95% CI 0.19 to 0.67, p ã 0.0001), TIMI < 3 after PCI (ß = -0.27, 95% CI -1.90 to -0.11, p = 0.015) and PMA(D4) (ß = 0.21, 95% CI 0.13 to 1.86, p = 0.032) independently influenced the size of microvascular obstruction (R2 = 0.60, p ã 0.0001). CONCLUSIONS: Excessive platelet activation during reperfusion in STEMI patients despite dual antiplatelet therapy is associated with greater microvascular impairment.
Assuntos
Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/uso terapêutico , Agregação Plaquetária/efeitos dos fármacos , Lesões do Sistema Vascular/epidemiologia , Lesões do Sistema Vascular/prevenção & controle , Clopidogrel , Comorbidade , Angiografia Coronária , Eletrocardiografia , Feminino , Humanos , Magnetoterapia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/fisiopatologia , Reperfusão Miocárdica , Inibidores da Agregação Plaquetária/administração & dosagem , Fatores de Risco , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêutico , Lesões do Sistema Vascular/fisiopatologiaRESUMO
BACKGROUND: Antiplatelet properties of omega-3 polyunsaturated fatty acids (PUFA) have been demonstrated in patients with coronary artery disease (CAD). It is unknown whether omega-3 PUFA can enhance platelet inhibition on standard aspirin and clopidogrel treatment in the setting of CYP2C19 loss-of-function polymorphism. AIM: To investigate whether omega-3 PUFA are able to modify platelet responsiveness to clopidogrel therapy in patients with CYP2C19 loss-of-function polymorphism undergoing percutaneous coronary intervention (PCI). METHODS: 63 patients with stable CAD undergoing PCI (48 males, mean age 63.2 ± 9.6 years) were enrolled into an investigator- initiated, prospective, single-centre, double-blind, placebo-controlled, randomised study. Patients on standard dual antiplatelet therapy (aspirin 75 mg daily and clopidogrel 600 mg loading dose followed by 75 mg daily) were assigned to receive the addition of 1 g of omega-3 ethyl esters (n = 33) or placebo (n = 30) for 1 month. Platelet function was measured serially by light transmittance aggregometry in response to 5 and 20 µmol/L ADP at baseline, 12 h, 3-5 days and 30 days after randomisation. CYP2C19*2 was genotyped at baseline. RESULTS: No significant differences were found in baseline variables, including the frequency of CYP2C19 genetic variants. At least one loss-of-function variant of CYP2C19*2 was found in 19 (30.2%) patients. In patients with CYP2C19*1/*2 and *2/*2 variants, maximal platelet aggregation induced by 5 and 20 µmol/L ADP was reduced by 21.4% (p = 0.006) and 14.3% (p = 0.041), respectively, after 1 month of treatment with omega-3 PUFA as compared to placebo. The beneficial effect of omega-3 PUFA was demonstrated in carriers of CYP2C19 loss-of-function polymorphism, whereas no differences in platelet aggregation between the omega-3 PUFA and placebo groups were found in patients with the 1*/1* variant. CONCLUSIONS: The addition of omega-3 ethyl esters significantly potentiates platelet response to clopidogrel after PCI mostly in patients with CYP2C19 loss-of-function polymorphism.
Assuntos
Hidrocarboneto de Aril Hidroxilases/efeitos dos fármacos , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/genética , Ácidos Graxos Ômega-3/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Polimorfismo Genético , Ticlopidina/análogos & derivados , Administração Cutânea , Idoso , Aspirina/uso terapêutico , Clopidogrel , Citocromo P-450 CYP2C19 , Método Duplo-Cego , Sinergismo Farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Agregação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/genética , Polimorfismo Genético/efeitos dos fármacos , Estudos Prospectivos , Ticlopidina/uso terapêuticoRESUMO
OBJECTIVE: The goal of this study was to investigate whether omega-3 polyunsaturated fatty acids (n-3 PUFA) are able to alter plasma fibrin clot properties and reduce thrombin formation in stable coronary artery disease patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: In an investigator-initiated, prospective, double-blind, placebo-controlled, randomized study, patients undergoing PCI who received standard pharmacotherapy were assigned to the treatment with 1 g/day n-3 PUFA (n = 30) or placebo (n = 24) for 1 month. Plasma fibrin clot permeability (K(s)); lysis time (t(50%)); prothrombin fragment 1.2; and peak thrombin generation from automated thrombogram, 8-isoprostaglandin F(2α) (8-iso-PGF(2α), an oxidative stress marker), and C-reactive protein were determined at baseline, 3 to 5 days after randomization, and 30 days after randomization. At baseline, both treatment groups did not differ significantly. A 1-month treatment with n-3 PUFA compared with placebo was associated with 15.3% higher K(s), indicating larger pores in the fibrin network (P = 0.0005); 14.3% shorter t(50%), indicating increased susceptibility to fibrinolysis (P<0.0001); 33.8% lower prothrombin fragment 1.2 (P = 0.0013); 13.4% lower peak thrombin generation (P = 0.04); and 13.1% lower 8-iso-PGF(2α) (P = 0.009). Treatment with n-3 PUFA had no effect on fibrinogen and C-reactive protein. After 1 month of treatment, fibrinogen (r = -0.53, P<0.0001), treatment assignment (r = 0.29, P = 0.006) and 8-iso-PGF(2α) (r = -0.27, P = 0.015) were independently associated with clot permeability (P<0.0001, R(2) = 0.66). CONCLUSIONS: Adding n-3 PUFA to standard therapy in stable patients undergoing PCI significantly decreases thrombin formation and oxidative stress and favorably alters fibrin clot properties. These findings indicate novel antithrombotic effects induced by n-3 PUFA in humans.
Assuntos
Angioplastia Coronária com Balão , Aspirina/uso terapêutico , Doença da Artéria Coronariana/terapia , Ácidos Graxos Ômega-3/uso terapêutico , Fibrina/metabolismo , Inibidores da Agregação Plaquetária/uso terapêutico , Trombina/metabolismo , Trombose/prevenção & controle , Ticlopidina/análogos & derivados , Idoso , Análise de Variância , Angioplastia Coronária com Balão/efeitos adversos , Aspirina/efeitos adversos , Biomarcadores/sangue , Coagulação Sanguínea/efeitos dos fármacos , Proteína C-Reativa/metabolismo , Distribuição de Qui-Quadrado , Clopidogrel , Doença da Artéria Coronariana/sangue , Dinoprosta/análogos & derivados , Dinoprosta/sangue , Método Duplo-Cego , Regulação para Baixo , Quimioterapia Combinada , Ácidos Graxos Ômega-3/efeitos adversos , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Fragmentos de Peptídeos/sangue , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/efeitos adversos , Polônia , Estudos Prospectivos , Protrombina , Trombose/sangue , Ticlopidina/efeitos adversos , Ticlopidina/uso terapêutico , Fatores de Tempo , Resultado do TratamentoRESUMO
Magnesium deficiency has been proposed to be related to the mitral valve prolapse syndrome. However determinations of magnesium concentration in blood serum and hemolysates of red blood cells in this disease revealed divergent results. We investigated 49 patients with the mitral valve prolapse syndrome and 30 healthy individuals, matched by age and gender. The concentration of magnesium was measured in blood plasma and lysates of lymphocytes isolated from venous blood. The magnesium concentration in plasma was similar in both the patients and the healthy controls. By contrast, the magnesium concentration in lysates of lymphocytes was significantly lower (p < 0.03) in the patients with mitral valve prolapse syndrome than in the controls (range: 1.94-10.6 mmol/g of protein in Lymphocyte lysate; median 5.98 and 6.7-9.61 mmol/g of protein; median 7.22). The results obtained suggest that magnesium deficiency may be part of the mechanisms of the mitral valve prolapse syndrome.