RESUMO
Mitochondrial DNA m.3243A > G mutation causes mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and its associated multi-organ disorders, including diabetes. To clarify associations between m.3243A > G organ heteroplasmy and clinical phenotypes, including the age at death, we combined genetic and pathological examinations from seven unreported and 36 literature cases of autopsied subjects. Clinical characteristics of subjects were as follows: male, 13; female, 28; unknown, 2; the age at death, 36.9 ± 20.2 [4-82] years; BMI, 16.0 ± 2.9 [13.0-22.3]; diabetes, N = 21 (49%), diabetes onset age 38.6 ± 14.2 years; deafness, N = 27 (63%); stroke-like episodes (StLEp), N = 25 (58%); congestive heart failure (CHF), N = 15 (35%); CHF onset age, 51.3 ± 14.5 years. Causes of death (N = 32) were as follows: cardiac, N = 13 (41%); infection, N = 8 (25%); StLEp, N = 4 (13%); gastrointestinal, N = 4 (13%); renal, N = 2 (6%); hepatic, N = 1 (2%). High and low heteroplasmies were confirmed in non-regenerative and regenerative organs, respectively. Heteroplasmy of the liver, spleen, leukocytes, and kidney for all subjects was significantly associated with the age at death. Furthermore, the age at death was related to juvenile-onset (any m.3243A > G-related symptoms appeared before 20) and stroke-like episodes. Multiple linear regression analysis with the age at death as an objective variable showed the significant contribution of liver heteroplasty and juvenile-onset to the age at death. m.3243A > G organ heteroplasmy levels, particularly hepatic heteroplasmy, are significantly associated with the age at death in deceased cases.
Assuntos
Diabetes Mellitus , Síndrome MELAS , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Idoso de 80 Anos ou mais , Heteroplasmia , DNA Mitocondrial/genética , Mutação , Acidente Vascular Cerebral/complicações , Fígado/patologia , Síndrome MELAS/genéticaRESUMO
Recent studies have reported that patients with autoimmune hyperchylomicronemia caused by glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) autoantibodies are associated with rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, Hashimoto's thyroiditis, Basedow's disease, and immune thrombocytopenia. We report a rare case of hyperchylomicronemia due to GPIHBP1 autoantibodies and fluctuating thyroid autoimmune disease. A 28-year-old woman, diagnosed with Hashimoto's thyroiditis at 26 years of age, started taking 50 µg/day of levothyroxine sodium. She had an episode of acute pancreatitis at 27 years of age; her serum triglyceride (TG) level was 1291 mg/dL at that time. The patient was referred to our hospital because her hyperchylomicronemia (hypertriglyceridemia) did not improve on treatment with pemafibrate and eicosapentaenoic acid (EPA). Serum total cholesterol and TG levels were 237 mg/dL and 2535 mg/dL, respectively, while plasma pre-heparin lipoprotein lipase (LPL) mass was 15 ng/mL (26.5-105.5 ng/mL). We diagnosed her as Basedow's disease based on autoimmune antibodies and ultrasound examination. Targeted exome sequencing revealed no pathogenic variants in the LPL or GPIHBP1 genes. The serum GPIHBP1 autoantibody level was 686.0 U/mL (<58.4 U/mL) and GPIHBP1 mass was 301.9 pg/mL (570.6-1625.6 pg/mL). The patient showed hyperchylomicronemia during periods of hypothyroidism and hyperthyroidism, whereas GPIHBP1 autoantibodies were positive during episode of hyperchylomicronemia but negative during periods of normal TG levels. Based on these findings, the patient was diagnosed with hyperchylomicronemia due to GPIHBP1 autoantibodies and treated with rituximab. GPIHBP1 autoantibodies remained undetectable and TG levels were controlled at approximately 200 mg/dL.
Assuntos
Doença de Graves , Hiperlipoproteinemia Tipo I , Pancreatite , Receptores de Lipoproteínas , Síndrome de Sjogren , Tireoidite , Humanos , Feminino , Adulto , Autoanticorpos , Doença Aguda , Pancreatite/complicações , Hiperlipoproteinemia Tipo I/genética , Lipase Lipoproteica/genética , Doença de Graves/complicações , Tireoidite/complicaçõesRESUMO
The coronavirus infection 2019 (COVID-19) pandemic has led to the development of mRNA vaccines with proven efficacy. However, it remains unclear whether patients who developed pericarditis after the first COVID-19 mRNA would be fit to receive the second vaccination. Herein, we present the case of a 64-year-old man who visited our emergency department with substernal chest discomfort that began 4 days after his first mRNA COVID-19 vaccination. Acute pericarditis was diagnosed based on symptoms and ST-segment elevation on an electrocardiogram. Chest pain improved 2 days after treatment.Since there are no guidelines on whether to administer an additional vaccination to a patient who developed pericarditis after the initial vaccination, we considered whether or not to administer the additional vaccination. We informed the patient about the risks and benefits and decided to administer the second dose. He did not experience any major adverse reactions. The indications for the second vaccination need to be thoroughly considered.
Assuntos
COVID-19 , Pericardite , Masculino , Humanos , Pessoa de Meia-Idade , RNA Mensageiro , COVID-19/diagnóstico , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Pericardite/diagnóstico , Pericardite/etiologia , Vacinação/efeitos adversosRESUMO
Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder, and a genetic analysis is important to make a definitive diagnosis. A comprehensive genetic analysis using next generation sequencing (NGS) and whole exome sequencing (WES) is feasible. However, the application of NGS in the assessment of genomic structural variations is generally limited, and a substantial number of control samples are needed for such assessments. Thus, NGS alone is unlikely to detect genomic structural variations in a "singleton." We present the case of a patient with compound HeFH (heterozygous FH), whose causative mutations in the LDLR gene could not be identified by WES, necessitating the application of the multiplex ligation-dependent probe amplification (MLPA) technique.
Assuntos
Hiperlipoproteinemia Tipo II , Receptores de LDL , Testes Genéticos/métodos , Heterozigoto , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Mutação , Receptores de LDL/genética , Sequenciamento do Exoma/métodosRESUMO
INTRODUCTION: Familial hypercholesterolaemia (FH) is an autosomal-dominant inherited genetic disease. It carries an extremely high cardiovascular risk associated with significantly elevated low-density lipoprotein (LDL) cholesterol. The diagnostic rate of this disease in some European nations is quite high, due to the presence of multiple prospective registries. On the other hand, few data-and in particular multicentre data-exist regarding this issue among Japanese subjects. Therefore, this study intends to assemble a multicentre registry that aims to comprehensively assess cardiovascular risk among Japanese FH patients while taking into account their genetic backgrounds. METHODS AND ANALYSIS: The Hokuriku-plus FH registry is a prospective, observational, multicentre cohort study, enrolling consecutive FH patients who fulfil the clinical criteria of FH in Japan from 37 participating hospitals mostly in Hokuriku region of Japan from April 2020 to March 2024. A total of 1000 patients will be enrolled into the study, and we plan to follow-up participants over 5 years. We will collect clinical parameters, including lipids, physical findings, genetic backgrounds and clinical events covering atherosclerotic and other important events, such as malignancies. The primary endpoint of this study is new atherosclerotic cardiovascular disease (ASCVD) events. The secondary endpoints are as follows: LDL cholesterol, secondary ASCVD events and the occurrence of other diseases including hypertension, diabetes and malignancies. ETHICS AND DISSEMINATION: This study is being conducted in compliance with the Declaration of Helsinki, the Ethical Guidelines for Medical and Health Research Involving Human Subjects, and all other applicable laws and guidelines in Japan. This study protocol has been approved by the Institutional Review Board at Kanazawa University. We will disseminate the final results at international conferences and in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: UMIN000038210.
Assuntos
Hiperlipoproteinemia Tipo II , Estudos de Coortes , Humanos , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/genética , Japão/epidemiologia , Estudos Prospectivos , Sistema de RegistrosRESUMO
A 69-year-old woman presented with appetite loss, fatigue, and a low-grade fever. She had been receiving certolizumab pegol for rheumatoid arthritis for six years. Computed tomography of the chest showed multiple micronodules in both lungs and bilateral hilar and mediastinal lymphadenopathy. An ophthalmic examination showed the findings of uveitis. Lymphocytosis with an increased CD4/CD8 ratio was seen in the bronchoalveolar lavage fluid. Video-assisted thoracoscopic biopsy specimens obtained from the right lung and a right hilar lymph node showed noncaseous epithelioid cell granulomas. Anti-tumor necrosis factor-α-induced sarcoidosis was diagnosed, and she was successfully treated with cessation of certolizumab pegol and systemic corticosteroid therapy.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Certolizumab Pegol/efeitos adversos , Sarcoidose/etiologia , Idoso , Líquido da Lavagem Broncoalveolar/citologia , Certolizumab Pegol/uso terapêutico , Feminino , Granuloma/patologia , Humanos , Pulmão/patologia , Linfonodos/patologia , Linfocitose/etiologia , Mediastino/patologia , Tomografia Computadorizada por Raios X , Uveíte/etiologiaRESUMO
A 71-year-old woman with congenital rubella syndrome (CRS) presented with prolonged cough. No physical findings suggested the presence of any connective tissue diseases. Chest computed tomography showed ground-glass opacities and consolidations in the bilateral lower lobes. She had elevated serum Krebs von den Lungen-6, hypoxemia and positive serum anti-Jo-1 antibody. Bronchoalveolar lavage fluid revealed lymphocytosis with a decreased CD4/CD8 ratio. A transbronchial lung biopsy specimen revealed organizing pneumonia. Based on a diagnosis of interstitial pneumonia with autoimmune features (IPAF), systemic corticosteroids were administered, and a good outcome was obtained. A possible relationship between CRS and IPAF is herein discussed.
Assuntos
Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/diagnóstico , Síndrome da Rubéola Congênita/complicações , Idoso , Anticorpos Antinucleares/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Tosse , Feminino , Humanos , Pulmão/patologia , Doenças Pulmonares Intersticiais/imunologia , Tomografia Computadorizada por Raios XRESUMO
An 81-year-old woman with rheumatoid arthritis (RA) who had been treated with bucillamine presented with dyspnea. Computed tomography of the chest showed ground-glass opacities and consolidations in both lungs and honeycombing in both basal lung areas. An elevation of the serum Krebs von den Lungen-6 level and hypoxemia were seen. Lymphocytosis with a decreased CD4/CD8 ratio was seen in the bronchoalveolar lavage fluid. A transbronchial lung biopsy specimen showed organizing pneumonia. Based on a diagnosis of bucillamine-induced pneumonitis (BIP) with RA-associated pre-existing interstitial pneumonia, she was successfully treated with the cessation of bucillamine and systemic corticosteroid therapy. The risk factors and prognosis of BIP are discussed.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Artrite Reumatoide/complicações , Cisteína/análogos & derivados , Doenças Pulmonares Intersticiais/complicações , Pneumonia/induzido quimicamente , Pneumonia/complicações , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Líquido da Lavagem Broncoalveolar/citologia , Cisteína/efeitos adversos , Cisteína/uso terapêutico , Dispneia/patologia , Feminino , Humanos , Hipóxia/complicações , Pulmão/patologia , Doenças Pulmonares Intersticiais/diagnóstico , Contagem de Linfócitos , Pneumonia/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
AIM: Coronary computed tomography angiography (CCTA)-derived fractional flow reserve (FFRCT) accurately diagnoses ischemic lesions of intermediate stenosis severity. However, significant determinants of FFRCT have not been fully evaluated. METHODS: This was a sub-analysis of the Treatment of Alogliptin on Coronary Atherosclerosis Evaluated by Computed Tomography-Based Fractional Flow Reserve trial. Thirty-nine diabetic patients (117 vessels) with intermediate coronary artery stenosis [percent diameter stenosis (%DS) ï¼70%] in whom FFRCT was measured were included in this study. CCTA-defined, vessel-based volumetric and morphological characteristics of plaques were examined to determine their ability to predict FFRCT. RESULTS: Patient-based, multivariate linear regression analysis showed that hemoglobinA1c, triglycerides, and the estimated glomerular filtration rate were significant independent factors associated with FFRCT. Vessel-based, univariate linear regression analysis showed that the total atheroma volume (r=ï¼0.233, p=0.01) and the percentage atheroma volume (PAV) (r=ï¼0.284, p=0.002) as well as %DS (r=ï¼0.316, p=0.006) were significant determinants of FFRCT. Among the plaque components, significant negative correlations were observed between FFRCT and low- (r=ï¼0.248, p=0.007) or intermediate-attenuation plaque volume (r=ï¼0.186, p=0.045), whereas calcified plaque volume was not associated with FFRCT. In the left anterior descending coronary artery (LAD), the plaque volume of each component was associated with FFRCT. CONCLUSIONS: Plaque volume, PAV, and %DS were significant determinants of FFRCT. Plaque morphology, particularly in LAD, was associated with FFRCT in diabetic patients with intermediate coronary artery stenosis.
Assuntos
Angiografia por Tomografia Computadorizada/métodos , Doença da Artéria Coronariana/patologia , Vasos Coronários/patologia , Reserva Fracionada de Fluxo Miocárdico , Placa Aterosclerótica/patologia , Idoso , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Masculino , Placa Aterosclerótica/diagnóstico por imagem , Prognóstico , Índice de Gravidade de DoençaRESUMO
Increasing the urine flow rate (UFR) reduces the toxic effect of contrast media. Use of the RenalGuard system enables the achievement of a high UFR by maintaining intravascular volume and prevents the development of contrast-induced acute kidney injury (CI-AKI). However, the efficacy and safety of RenalGuard system have not yet been evaluated in Japan. This multicenter prospective study evaluated the efficacy and safety of the RenalGuard therapy in preventing CI-AKI development in 60 Japanese patients with renal dysfunction [estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2] undergoing catheter procedures. Baseline eGFR and Mehran's CIN (contrast-induced nephropathy) risk score were 35.1 ± 8.5 mL/min/1.73 m2 and 11.7 ± 4.3, respectively. Regardless of this high-risk profile, the incidence of CI-AKI was 8.6% (5/58) compared with the 26.1% incidence estimated by the CIN risk score. Moreover, two-sided 95% (Fisher's) exact confidence interval was 2.9-19.0 and its upper limit (i.e., 19.0) was less than the prespecified threshold incidence of 25.0. Univariate logistic regression analysis demonstrated that the UFR during catheter procedure was one of the most important factor associated with CI-AKI (odds ratio 0.99, confidence interval 0.98-1.00, p = 0.03). In conclusion, RenalGuard therapy may prevent CI-AKI development in Japanese patients with renal dysfunction. Further large-scale prospective multicenter studies are necessary to confirm our findings.
Assuntos
Injúria Renal Aguda/prevenção & controle , Meios de Contraste/efeitos adversos , Hidratação/instrumentação , Insuficiência Renal Crônica/epidemiologia , Injúria Renal Aguda/induzido quimicamente , Idoso , Feminino , Taxa de Filtração Glomerular , Humanos , Japão/epidemiologia , Masculino , Estudos Prospectivos , Cloreto de Sódio/administração & dosagemRESUMO
Recently, fractional flow reserve (FFR) derived from coronary computed tomography angiography (CCTA) (FFRCT) has been developed. However, FFRCT cannot be calculated for all patients from CCTA datasets. The purpose of the present study, therefore, was to evaluate the predictors that results in cases being inappropriate for FFRCT processing. This study was a sub-analysis of the TRACT trial, from which 50 patients were divided into 2 groups according to FFRCT measurability (measurable [group M] or not measurable [group N]) using CCTA examination at baseline. Thirty-nine (78%) patients comprised group M and 11 (22%) comprised group N. Heart rate at CCTA examination (72 beats/min vs. 63 beats/min; p = 0.007) and Agatston score (665 vs. 33; p = 0.002) in group N were significantly higher than those in group M. Multivariate logistic regression analyses revealed that heart rate at CCTA examination (OR 1.348 [95% CI 1.167-1.556]; p < 0.001) and Agatston score (OR 1.002 [95% CI 1.000-1.003]; p = 0.004) were significant, independent factors associated with non-measurability of FFRCT. The frequency of poor image quality was highest in patients with heart rate > 65 beats/min and Agatston score > 400 (p < 0.0001). In conclusions, high heart rate at the time of CCTA examination and higher Agatston score were associated with poor image quality that resulted in cases being inappropriate for FFRCT processing. Heart rate control at CCTA examination is necessary to acquire good-quality images required for computing FFRCT.
Assuntos
Angiografia por Tomografia Computadorizada , Angiografia Coronária/métodos , Estenose Coronária/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/diagnóstico por imagem , Reserva Fracionada de Fluxo Miocárdico , Idoso , Idoso de 80 Anos ou mais , Estenose Coronária/etiologia , Estenose Coronária/fisiopatologia , Vasos Coronários/fisiopatologia , Diabetes Mellitus Tipo 2/diagnóstico , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/fisiopatologia , Feminino , Frequência Cardíaca , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Interpretação de Imagem Radiográfica Assistida por Computador , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Little data exist regarding the clinical application of whole exome sequencing (WES) for the molecular diagnosis of severe hypertriglyceridemia (HTG). METHODS: WES was performed for 28 probands exhibiting severe HTG (≥1000â¯mg/dl) without any transient causes. We evaluated recessive and dominant inheritance models in known monogenic HTG genes, followed by disease-network gene prioritization and copy number variation (CNV) analyses to identify causative variants and a novel genetic mechanism for severe HTG. RESULTS: We identified possible causative variants for severe HTG, including three novel variants, in nine probands (32%). In the recessive inheritance model, we identified two homozygous subjects with lipoprotein lipase (LPL) deficiency and one subject harboring compound heterozygous variants in both LPL and APOA5 genes (hyperchylomicronemia). In the dominant inheritance model, we identified probands harboring deleterious heterozygous variants in LPL, glucokinase regulatory protein, and solute carrier family 25 member 40 genes, possibly associated with this extreme HTG phenotype. However, gene prioritization and CNV analyses did not validate the novel genes associated with severe HTG. CONCLUSIONS: In 28 probands with severe HTG, we identified potential causative variants within nine genes associated with rare Mendelian dyslipidemias. Clinical WES may be feasible for such extreme cases, potentially leading to appropriate therapies.
Assuntos
Sequenciamento do Exoma , Hipertrigliceridemia/genética , Humanos , Hipertrigliceridemia/sangue , Hipertrigliceridemia/diagnóstico , Fenótipo , Índice de Gravidade de DoençaRESUMO
BACKGROUND: The use of coronary computed tomography angiography (CCTA) for noninvasive anatomic detection of coronary artery disease is increasing. Recently, fractional flow reserve (FFR) assessment using routinely acquired CCTA datasets (FFRCT) has been developed. However, there are no reports about changes in coronary atherosclerosis, composition, and FFRCT in patients with type 2 diabetes. METHODS: This prospective, multicenter, observational trial evaluated changes in coronary atherosclerosis after alogliptin therapy in patients with type 2 diabetes. Fifty-one patients with type 2 diabetes who underwent CCTA examination and having intermediate coronary artery stenosis were treated with 25â¯mg of alogliptin. After 48â¯weeks, CCTA examination was repeated. The primary endpoint was changes in FFRCT, and the secondary endpoint was changes in total atheroma volume (TAV) from the baseline to the 48-week follow-up. RESULTS: The FFRCT decreased from the baseline to follow-up, but not significantly. A significant increase in TAV (from 658.5â¯mm3 to 668.9â¯mm3, pâ¯=â¯0.048) was observed. Vessel volume tended to increase, whereas percentage atheroma volume and lumen volume did not change. A significant negative correlation was observed between percentage change in TAV and change in FFRCT (râ¯=â¯-0.185, pâ¯=â¯0.048). A significant increase in calcified plaques (pâ¯=â¯0.01) and a decrease in intermediate-attenuation plaques (pâ¯=â¯0.006) was observed. CONCLUSIONS: In Japanese patients with diabetes and intermediate coronary artery stenosis, alogliptin could not improve FFRCT or reduce atheroma volume, whereas the plaque composition changed. A progression of atheroma volume was associated with a reduction in FFRCT.
RESUMO
Hypercholesterolemia, particularly an increase in low-density lipoprotein cholesterol (LDL-C) levels, contributes substantially to the development of coronary artery disease and the risk for cardiovascular events. As the first-line pharmacotherapy, statins have been shown to reduce both LDL-C levels and cardiovascular events. However, despite intensive statin therapy, a sizable proportion of statin-treated patients are unable to achieve the recommended target LDL-C levels, and not all patients can avoid future cardiovascular events. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in cholesterol homeostasis by enhancing the degradation of hepatic low-density lipoprotein receptor (LDLR). Owing to its importance in lipid metabolism, PCSK9 has emerged as a novel pharmacological target for lowering LDL-C levels. In this review, the potential role of circulating PCSK9 as a new biomarker of lipid metabolism is described. Next, previous studies evaluating the effects of lipid-modifying pharmacological agents, particularly statins, on circulating PCSK9 concentrations are summarized. Statins decrease hepatic intracellular cholesterol, resulting in increased LDLRs as well as increased PCSK9 protein. There is a clear dose-response effect of statin treatment on PCSK9 level, as increasing doses of statins also increase the level of circulating PCSK9. Finally, the available therapeutic strategies to inhibit PCSK9 are present. Monoclonal antibodies against PCSK9, in combination with statins, are one of the most promising and novel approaches to achieve further reduction of LDL-C levels and reduce the risk of cardiovascular events.
Assuntos
Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Pró-Proteína Convertase 9/sangue , Anticorpos Monoclonais/uso terapêutico , Biomarcadores/sangue , LDL-Colesterol/sangue , Ezetimiba/uso terapêutico , Ácidos Fíbricos/uso terapêutico , Inativação Gênica , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/terapia , Metabolismo dos Lipídeos , Niacina/uso terapêutico , Inibidores de PCSK9 , Pró-Proteína Convertase 9/genéticaRESUMO
Activated factor-X (FXa) plays an important role not only in the coagulation cascade, but also in pro-inflammatory responses. However, few data exist regarding the anti-inflammatory effect of FXa inhibitors in clinical practice. The aim of this study was to evaluate the anti-inflammatory and anti-atherosclerotic effects of FXa inhibitors in Japanese patients with non-valvular atrial fibrillation (NVAF). Eighty-three patients with NVAF were treated with FXa inhibitors from March 2013 to March 2015 at our institution. Of these, 55 patients who were not pretreated with warfarin or dabigatran (rivarixaban in 23 patients and apixaban in 32) were included in this study. We measured various inflammatory and coagulation markers at baseline and at 6 months after treatment. Plasma concentrations of pentraxin 3 (PTX3) (from 2.45 ± 1.31 to 1.97 ± 1.00 ng/mL, p = 0.0009) and fibrin and fibrinogen degradation products (FDP) D-dimer (from 1.18 ± 0.70 to 0.74 ± 0.32 µg/mL, p < 0.0001) decreased, while those of TM (from 2.9 ± 0.8 to 3.2 ± 0.9 FU/mL, p = 0.003) increased significantly at 6 months. Interestingly, change of each marker denoted the same tendency in both rivaroxaban and apixaban. In conclusion, the present study suggests that FXa inhibitors have not only an anti-coagulant effect but also anti-inflammatory effects in patients with NVAF. Further large-scale prospective study is necessary to evaluate whether changes in these markers will be associated with a lower risk for future cardiovascular events.
Assuntos
Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Coagulação Sanguínea/efeitos dos fármacos , Inibidores do Fator Xa/farmacologia , Inflamação/tratamento farmacológico , Idoso , Anticoagulantes/farmacologia , Fibrilação Atrial/sangue , Feminino , Seguimentos , Humanos , Inflamação/sangue , Inflamação/complicações , Masculino , Estudos Prospectivos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do TratamentoRESUMO
BACKGROUND: Patients with type 2 diabetes are at high risk for developing coronary artery disease (CAD). Noninvasive anatomic assessment by coronary computed tomography angiography (CCTA) is being increasingly used for detecting or excluding CAD. Recently, fractional flow reserve (FFR) using routinely acquired CCTA datasets (FFRCT) has been developed. Although intensive glycemic control can reduce the risk of microvascular complications, intensive glucose control does not seem to be beneficial in preventing major cardiovascular events when compared with standard therapy. However, it has been reported that dipeptidyl peptidase-4 (DPP-4) inhibitors have anti-atherogenic effects in an animal model. In addition, DPP-4 inhibitors attenuate the progression of carotid intima-media thickness in patients with type 2 diabetes. Therefore, this study will be performed to evaluate the effects of alogliptin, a DPP-4 inhibitor, on coronary atherosclerosis using FFRCT in patients with type 2 diabetes. METHODS AND DESIGN: This study will be a prospective, non-randomized, multicenter trial performed in Japan. Patients with type 2 diabetes who have intermediate coronary artery stenosis (diameter stenosis <70%) as evaluated by CCTA will be treated with 25mg/day of alogliptin. After 48 weeks' treatment, CCTA will be repeated. The primary endpoint will be changes in FFRCT, and the secondary endpoint will be the change in plaque volume from baseline to the 48-week follow-up. CONCLUSION: This study will be the first multicenter trial to evaluate the effects of alogliptin on coronary atherosclerosis using the newly developed FFRCT as the primary endpoint, and the findings will clarify the anti-atherogenic effects of alogliptin.
Assuntos
Estenose Coronária/tratamento farmacológico , Estenose Coronária/fisiopatologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Reserva Fracionada de Fluxo Miocárdico/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Piperidinas/uso terapêutico , Uracila/análogos & derivados , Idoso , Espessura Intima-Media Carotídea , Angiografia por Tomografia Computadorizada , Angiografia Coronária/métodos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/tratamento farmacológico , Estudos Prospectivos , Uracila/uso terapêuticoRESUMO
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of serum low-density lipoprotein (LDL) cholesterol levels. Recently, PCSK9 has additionally been related to metabolic risk factors such as the levels of triglycerides, apolipoprotein B (apoB), insulin, and glucose, as well as body mass index. The purpose of this study was to investigate correlations between serum levels of PCSK9 and apoB-containing atherogenic lipoproteins in patients with coronary artery disease (CAD). METHODS: Serum levels of PCSK9 and lipoprotein(a) [Lp(a)]; small, dense LDL; and oxidized LDL were measured in 101 patients with CAD who were not receiving lipid-lowering therapy. RESULTS: Serum hetero-dimer PCSK9 levels were positively correlated with serum levels of Lp(a) (r = 0.195, p = 0.05); small, dense LDL (r = 0.336, p = 0.0006); and oxidized LDL (r = 0.268, p = 0.008). Multivariate regression analyses showed that serum hetero-dimer PCSK9 was a significant predictor of serum levels of Lp(a) (ß = 0.235, p = 0.01); small, dense LDL (ß = 0.143, p = 0.03); and oxidized LDL (ß = 0.268, p = 0.008). CONCLUSIONS: Serum PCSK9 levels were positively correlated with serum levels of Lp(a); small, dense LDL; and oxidized LDL in patients with CAD. This suggests that the interaction between serum PCSK9 and apoB-containing lipoproteins plays a role in establishing the atherosclerotic status of patients. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN ID: C000000311 .