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1.
Mayo Clin Proc ; 99(6): 940-952, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38530689

RESUMO

OBJECTIVE: To investigate whether hypotensive patients diagnosed with heart failure and reduced ejection fraction (HFrEF) might benefit from angiotensin receptor-neprilysin inhibitors (ARNis) in real-world practice because patients with baseline systolic blood pressure (SBP) of less than 100 mm Hg have been excluded from landmark trials. PATIENTS AND METHODS: In this multicenter study conducted between January 1, 2013, and December 31, 2021, a total of 7562 symptomatic patients with HFrEF were enrolled and grouped by SBP (hypotension was defined as an SBP of less than 100 mm Hg) and ARNi use as follows: group 1, hypotensive/non-ARNi users (n=484); group 2, hypotensive/ARNi users (n=308); group 3, nonhypotensive/non-ARNi users (n=4560); and group 4, nonhypotensive/ARNi users (n=2210). Inverse probability of treatment weighting was used to balance baseline characteristics for survival analysis. RESULTS: Diverse baseline characteristics and lower rates of medication use were found among non-ARNi users compared with ARNi users. Hypotensive/ARNi users had lower ARNi initiation doses than nonhypotensive/ARNi users. We observed significantly lower mortality, composite heart failure hospitalization, and CV death for hypotensive/ARNi and the other 2 nonhypotensive groups (groups 3 and 4) during a median follow-up of 3.43 years (all P<.05), with a similar effect on reverse remodeling for the hypotensive/ARNi group compared with the hypotensive/non-ARNi group. The event-free survival benefits of ARNi vs renin-angiotensin system inhibitors were consistent with the lower boundary of SBP for clinical benefits found until 88 mm Hg (spline curves) after inverse probability of treatment weighting. CONCLUSION: Patients with HFrEF and hypotension may still benefit from ARNi treatment. Patients with hypotensive HFrEF should not be routinely excluded from ARNi use in a real-world setting.


Assuntos
Aminobutiratos , Antagonistas de Receptores de Angiotensina , Compostos de Bifenilo , Combinação de Medicamentos , Insuficiência Cardíaca , Hipotensão , Volume Sistólico , Valsartana , Remodelação Ventricular , Humanos , Valsartana/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Masculino , Aminobutiratos/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Feminino , Volume Sistólico/efeitos dos fármacos , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Remodelação Ventricular/efeitos dos fármacos , Hipotensão/tratamento farmacológico , Hipotensão/mortalidade , Pessoa de Meia-Idade , Tetrazóis/uso terapêutico , Neprilisina/antagonistas & inibidores , Resultado do Tratamento
2.
Biosensors (Basel) ; 13(10)2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37887122

RESUMO

An effective early diagnosis is important for rheumatoid arthritis (RA) management. This study reveals a novel RA detection method using bacteriorhodopsin as a photoelectric transducer, a light-driven proton pump in purple membranes (PMs). It was devised by covalently conjugating a PM monolayer-coated electrode with a citrullinated-inter-alpha-trypsin inhibitor heavy chain 3 (ITIH3)542-556 peptide that recognizes the serum RA-associated autoantibodies. The direct serum coating decreased the photocurrents in the biosensor, with the reduction in the photocurrent caused by coating with an RA-patient serum that is significantly larger than that with a healthy-control serum (38.1% vs. 20.2%). The difference in the reduction in the photocurrent between those two serum groups widened after the serum-coated biosensor was further labeled with gold nanoparticle (AuNP)-conjugated anti-IgA (anti-IgA-AuNP) (53.6% vs. 30.6%). Both atomic force microscopic (AFM) and Raman analyses confirmed the sequential peptide, serum, and anti-IgA-AuNP coatings on the PM-coated substrates. The reductions in the photocurrent measured in both the serum and anti-IgA-AuNPs coating steps correlated well with the results using commercial enzyme-linked immunosorbent assay kits (Spearman rho = 0.805 and 0.787, respectively), with both a sensitivity and specificity close to 100% in both steps. It was shown that an RA diagnosis can be performed in either a single- or two-step mode using the developed biosensor.


Assuntos
Artrite Reumatoide , Bacteriorodopsinas , Técnicas Biossensoriais , Nanopartículas Metálicas , Humanos , Ouro , Artrite Reumatoide/diagnóstico , Peptídeos , Ensaio de Imunoadsorção Enzimática
3.
J Chin Med Assoc ; 86(8): 725-731, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37314316

RESUMO

BACKGROUND: Iron deficiency (ID) is a common comorbidity among patients with heart failure and reduced ejection fraction (HFrEF), and is associated with poorer outcomes independent of anemia. This study aimed to evaluate the prevalence and prognostic significance of ID in Taiwanese patients with HFrEF. METHODS: We included HFrEF patients from two multicenter cohorts at different periods. The multivariate Cox regression analysis was applied to assess the risk of outcomes associated with ID, accounting for the varying risk of death. RESULTS: Of the 3612 patients with HFrEF registered from 2013 to 2018, 665 patients (18.4%) had available baseline iron profile measurements. Of these, 290 patients (43.6%) were iron deficient; 20.2% had ID+/anemia+, 23.4% ID+/anemia-, 21.5% ID-/anemia+, and 34.9% ID-/anemia-. Regardless of anemia status, patients with coexisting ID had a higher risk than those without ID (all-cause mortality: 14.3 vs 9.5 per 100 patient-years, adjusted hazard ratio [HR] 1.33; 95% confidence interval [CI], 0.96-1.85; p = 0.091; cardiovascular mortality: 10.5 per 100 patient-years vs 6.1, adjusted HR 1.54 [95% CI, 1.03-2.30; p = 0.037]; cardiovascular mortality or first unplanned hospitalization for HF: 36.7 vs 19.7 per 100 patient-years, adjusted HR 1.57 [95% CI, 1.22-2.01; p < 0.001]). Among patients eligible for treatment in the IRONMAN trial design (43.9%), parenteral iron therapy was estimated to reduce heart failure hospitalizations and cardiovascular deaths by 13.7 per 100 patient-years. CONCLUSION: Iron profiles were tested in less than one-fifth of the Taiwanese HFrEF cohort. ID was present in 43.6% of tested patients and was independently associated with poor prognosis in these patients.


Assuntos
Anemia Ferropriva , Anemia , Insuficiência Cardíaca , Deficiências de Ferro , Disfunção Ventricular Esquerda , Humanos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/terapia , Volume Sistólico , Prognóstico , Anemia Ferropriva/etiologia , Ferro , Anemia/complicações , Hospitalização
4.
Int J Mol Sci ; 24(8)2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37108160

RESUMO

Tumor necrosis factor superfamily 14 (TNFSF14) is also known as the LT-related inducible ligand (LIGHT). It can bind to the herpesvirus invasion mediator and lymphotoxin-ß receptor to perform its biological activity. LIGHT has multiple physiological functions, including strengthening the synthesis of nitric oxide, reactive oxygen species, and cytokines. LIGHT also stimulates angiogenesis in tumors and induces the synthesis of high endothelial venules; degrades the extracellular matrix in thoracic aortic dissection, and induces the expression of interleukin-8, cyclooxygenase-2, and cell adhesion molecules in endothelial cells. While LIGHT induces tissue inflammation, its effects on angiogenesis after tissue ischemia are unclear. Thus, we analyzed these effects in the current study. In this study, the animal model of hind limb ischemia surgery in C57BL/6 mice was performed. Doppler ultrasound, immunohistochemical staining, and Western blotting were employed to analyze the situation of angiogenesis. In addition, human endothelial progenitor cells (EPCs) were used for in vitro studies to analyze the possible mechanisms. The results in the animal study showed that LIGHT injection inhibited angiogenesis in ischemic limbs. For the in vitro studies, LIGHT inhibited the expression of integrins and E-selectin; decreased migration and tube formation capabilities, mitochondrial respiration, and succinate dehydrogenase activity; and promoted senescence in EPCs. Western blotting revealed that the impairment of EPC function by LIGHT may be due to its effects on the proper functioning of the intracellular Akt signaling pathway, endothelial nitrite oxide synthase (eNOS), and mitochondrial respiration. In conclusion, LIGHT inhibits angiogenesis after tissue ischemia. This may be related to the clamped EPC function.


Assuntos
Células Progenitoras Endoteliais , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral , Animais , Humanos , Camundongos , Movimento Celular , Células Progenitoras Endoteliais/metabolismo , Isquemia/metabolismo , Camundongos Endogâmicos C57BL , Neovascularização Patológica/patologia , Neovascularização Fisiológica , Óxido Nítrico Sintase Tipo III/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo
5.
Mayo Clin Proc ; 98(1): 88-99, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36109207

RESUMO

OBJECTIVE: To investigate the effectiveness and safety of angiotensin receptor-neprilysin inhibitors (ARNIs) in real-world patients with heart failure with reduced ejection fraction (HFrEF) and advanced chronic kidney disease (estimated glomerular filtration rate [eGFR] < 30 mL/min per 1.73 m2), which have been excluded from the landmark trials. PATIENTS AND METHODS: This study examined 3281 patients pooled from two multicenter HFrEF cohorts, and 661 patients with baseline eGFR less than 30 mL/min per 1.73 m2 were further analyzed (the Taiwan Society of Cardiology - Heart Failure with reduced Ejection Fraction (TSOC-HFrEF) registry: May 1, 2013 to October 31, 2014, and the Treatment with Angiotensin Receptor neprilysin inhibitor fOr Taiwan Heart Failure patients (TAROT-HF) study: March 1, 2017, to December 31, 2018). Propensity score matching was performed to adjust for confounders. At 1-year follow-up, all-cause mortality, total heart failure hospitalizations, renal function, and left ventricular ejection fraction (LVEF) were used as the endpoints. RESULTS: After propensity score matching, 510 patients (age, 69.8±13.9 years; male, 61.0%; mean LVEF, 29.8±7.3%; mean eGFR, 19.8±9.0 mL/min per 1.73 m2) were included in the final analysis, including 278 patients receiving ARNI treatment (ARNI group) and 232 patients not on ARNI treatment (non-ARNI group). Baseline characteristics were comparable between the two groups. At 1 year, eGFR and LVEF measurements were significantly higher in the ARNI group than in the non-ARNI group (25.0±17.1 mL/min per 1.73 m2 vs 21.4±17.5 mL/min per 1.73 m2; P=.04; and 40.1±12.9% vs. 33.1±10.8%, P<.001, respectively). The ARNI group had significantly lower risks of 1-year all-cause mortality (19.4 vs 30.9 per 100-person year; P=.02), and total HF rehospitalizations (70.0 vs 110.4 per 100-person year; P=.01) than non-ARNI users. CONCLUSION: Our results show the effectiveness of ARNIs in HFrEF patients with advanced chronic kidney disease in a real-world setting.


Assuntos
Insuficiência Cardíaca , Insuficiência Renal Crônica , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Angiotensina/uso terapêutico , Angiotensinas , Combinação de Medicamentos , Insuficiência Cardíaca/tratamento farmacológico , Rim/fisiologia , Neprilisina , Receptores de Angiotensina , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Volume Sistólico/fisiologia , Resultado do Tratamento , Valsartana , Função Ventricular Esquerda , Feminino
6.
Biochem Pharmacol ; 198: 114978, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35218740

RESUMO

Abdominal aortic aneurysm (AAA) is a common inflammatory vascular disease. Angiotensin II (Ang II) involves in AAA progression by promoting the proliferation and migration of vascular smooth muscle cells, the degradation of extracellular matrices, and the generation of ROS to lead to vascular inflammation. Carbon monoxide releasing molecule-2 (CORM-2) is known to exert anti-inflammatory and antioxidant activities. However, it remains unclear whether CORM-2 can suppress Ang II-induced vascular inflammation to prevent AAA progression. Therefore, this study aimed to investigate the vasoprotective effects of CORM-2 against Ang II-induced inflammatory responses of human aortic smooth muscle cells (HASMCs) and the underlying mechanisms of those effects. The results showed that Ang II induced inflammatory responses of HASMCs via NADPH oxidase- and mitochondria-derived ROS/NF-κB/IL-6/Jak2/Stat3 pathway which was attenuated by the pretreatment with CORM-2. Additionally, CORM-2 further exhibited anti-inflammatory activities in Ang II-stimulated HASMCs, as indicated by the reduction of monocyte adhesion to HASMCs and migration of HASMCs via the suppression of ICAM-1 and VCAM-1 as well as MMP-2 and MMP-9 levels, respectively. Moreover, Ang II-induced COX-2-mediated PGE2 secretion was also inhibited by the pretreatment with CORM-2. Importantly, our data demonstrated that CORM-2 reversed Ang II-induced IL-6 overexpression dependent on Nrf2 activation and HO-1 expression. Taken together, the present study indicates that CORM-2-induced Nrf2/HO-1 alleviates IL-6/Jak2/Stat3-mediated inflammatory responses to Ang II by inhibiting NADPH oxidase- and mitochondria-derived ROS, suggesting that CORM-2 is a promising pharmacologic candidate to reverse the pathological changes involved in the inflammation of vessel wall for the prevention and treatment of AAA.


Assuntos
Angiotensina II , NADPH Oxidases , Angiotensina II/metabolismo , Anti-Inflamatórios/uso terapêutico , Monóxido de Carbono/metabolismo , Humanos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-6/metabolismo , Janus Quinase 2/metabolismo , Mitocôndrias/metabolismo , Miócitos de Músculo Liso , NADPH Oxidases/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Compostos Organometálicos , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição STAT3/metabolismo
7.
J Chin Med Assoc ; 84(9): 833-841, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34524212

RESUMO

BACKGROUND: This study used a real-world database to investigate the prescription patterns of sacubitril/valsartan (Sac/Val) among Taiwanese patients with heart failure with reduced ejection fraction (HFrEF). METHODS: The Treatment with Angiotensin Receptor neprilysin inhibitor fOr Taiwan Heart Failure patients (TAROT-HF) study is a principal investigator-initiated, multicenter, observational, retrospective study on Taiwanese HFrEF patients. A total of 1772 patients with HFrEF (mean age 62.5 years, 75.3% male, mean left ventricular ejection fraction [LVEF] 29.3%) who received Sac/Val at 10 hospitals between 2017 and 2018 were enrolled at the date of Sac/Val initiation. Among these patients, 585 (33%) initially received Sac/Val during acute decompensated heart failure (HF) hospitalization (TAROT-AHF arm), whereas 1187 (67%) initially received the same at the outpatient clinic (TAROT-CHF arm). RESULTS: A total of 1343 (75.8%) patients received an initial dose of 50 mg twice daily or fewer, whereas 422 (23.8%) received the standard initiation dose (100 mg twice daily). During outpatient Sac/Val initiation, the mean dosages were significantly higher than that following hospitalization (117 ± 55 mg vs 109 ± 57 mg; p = 0.014). Multivariate analysis identified younger age, higher systolic blood pressure, higher LVEF, prior use of renin-angiotensin system inhibitors, use of ivabradine, and a history of diabetes mellitus as independent factors for initiating a standard Sac/Val dose. Over a follow-up period of 18 months, incidences of cardiovascular death or first unplanned HF hospitalization were 18.69 and 33.11 per 100-person years for the TAROT-CHF and TAROT-AHF arms, respectively. CONCLUSION: The TAROT-HF study provided an opportunity to describe the clinical features of patients with HFrEF who received Sac/Val, assess the real-world utilization and efficacy of Sac/Val, and compare these patients with those included in prior registries.


Assuntos
Angiotensinas/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Neprilisina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neprilisina/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Sistema de Registros , Estudos Retrospectivos , Taiwan
8.
Oxid Med Cell Longev ; 2021: 2855042, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34336088

RESUMO

Particulate matter (PM), a major air pollutant, may be associated with adverse cardiovascular effects. Reactive oxygen species- (ROS-) dependent proinflammatory cytokine production, such as interleukin-6 (IL-6), is a possible underlying mechanism. Carbon monoxide- (CO-) releasing molecule-2 (CORM-2) which liberates exogenous CO can exert many beneficial effects, particularly anti-inflammation and antioxidant effects. The purpose of this study was to explore the protective effects and underpinning mechanisms of CORM-2 on PM-induced aorta inflammation. Here, human aortic vascular smooth muscle cells (HASMCs) were utilized as in vitro models for the assessment of signaling pathways behind CORM-2 activities against PM-induced inflammatory responses, including Toll-like receptors (TLRs), NADPH oxidase, ROS, nuclear factor-kappa B (NF-κB), and IL-6. The modulation of monocyte adherence and HASMC migration, that are two critical cellular events of inflammatory process, along with their regulators, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and matrix metalloproteinase-2 (MMP-2) and MMP-9, in response to PM by CORM-2, were further evaluated. Finally, mice experiments under different conditions were conducted for the in vivo evaluation of CORM-2 benefits on the expression of inflammatory molecules including IL-6, ICAM-1, VCAM-1, MMP-2, and MMP-9. Our results found that PM could induce aorta inflammation in vitro and in vivo, as evidenced by the increase of IL-6 expression that was regulated by the TLR2 and TLR4/NADPH oxidase/ROS/NF-κB signaling pathway, thereby promoting ICAM-1- and VCAM-1-dependent monocyte adhesion and MMP-2- and MMP-9-dependent HASMC migration. Importantly, our experimental models demonstrated that CORM-2-liberated CO effectively inhibited the whole identified PM-induced inflammatory cascade in HASMCs and tissues. In conclusion, CORM-2 treatment may elicit multiple beneficial effects on inflammatory responses of aorta due to PM exposure, thereby providing therapeutic value in the context of inflammatory diseases of the cardiovascular system.


Assuntos
Aorta/efeitos dos fármacos , Inflamação/tratamento farmacológico , Interleucina-6/metabolismo , NADPH Oxidases/efeitos dos fármacos , Compostos Organometálicos/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Animais , Aorta/patologia , Humanos , Masculino , Camundongos , Compostos Organometálicos/farmacologia
9.
JMIR Mhealth Uhealth ; 9(4): e26167, 2021 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-33835039

RESUMO

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. Early diagnosis of AF is crucial for preventing AF-related morbidity, mortality, and economic burden, yet the detection of the disease remains challenging. The 12-lead electrocardiogram (ECG) is the gold standard for the diagnosis of AF. Because of technological advances, ambulatory devices may serve as convenient screening tools for AF. OBJECTIVE: The objective of this review was to investigate the diagnostic accuracy of 2 relatively new technologies used in ambulatory devices, non-12-lead ECG and photoplethysmography (PPG), in detecting AF. We performed a meta-analysis to evaluate the diagnostic accuracy of non-12-lead ECG and PPG compared to the reference standard, 12-lead ECG. We also conducted a subgroup analysis to assess the impact of study design and participant recruitment on diagnostic accuracy. METHODS: This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. MEDLINE and EMBASE were systematically searched for articles published from January 1, 2015 to January 23, 2021. A bivariate model was used to pool estimates of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and area under the summary receiver operating curve (SROC) as the main diagnostic measures. Study quality was evaluated using the quality assessment of diagnostic accuracy studies (QUADAS-2) tool. RESULTS: Our search resulted in 16 studies using either non-12-lead ECG or PPG for detecting AF, comprising 3217 participants and 7623 assessments. The pooled estimates of sensitivity, specificity, PLR, NLR, and diagnostic odds ratio for the detection of AF were 89.7% (95% CI 83.2%-93.9%), 95.7% (95% CI 92.0%-97.7%), 20.64 (95% CI 10.10-42.15), 0.11 (95% CI 0.06-0.19), and 224.75 (95% CI 70.10-720.56), respectively, for the automatic interpretation of non-12-lead ECG measurements and 94.7% (95% CI 93.3%-95.8%), 97.6% (95% CI 94.5%-99.0%), 35.51 (95% CI 18.19-69.31), 0.05 (95% CI 0.04-0.07), and 730.79 (95% CI 309.33-1726.49), respectively, for the automatic interpretation of PPG measurements. CONCLUSIONS: Both non-12-lead ECG and PPG offered high diagnostic accuracies for AF. Detection employing automatic analysis techniques may serve as a useful preliminary screening tool before administering a gold standard test, which generally requires competent physician analyses. Subgroup analysis indicated variations of sensitivity and specificity between studies that recruited low-risk and high-risk populations, warranting future validity tests in the general population. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42020179937; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=179937.


Assuntos
Fibrilação Atrial , Fibrilação Atrial/diagnóstico , Eletrocardiografia , Humanos , Programas de Rastreamento , Fotopletismografia , Sensibilidade e Especificidade
10.
PLoS One ; 16(1): e0246029, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33493236

RESUMO

To examine the effect of de-escalation of P2Y12 inhibitor in dual antiplatelet therapy (DAPT) on major adverse cardiovascular events (MACE) and bleeding complications after acute myocardial infarction (AMI) in Taiwanese patients undergoing percutaneous coronary intervention (PCI). Patients who had received PCI during hospitalization for AMI (between 2013 and 2016) and were initially treated with aspirin and ticagrelor and without adverse events after 3 months of treatment were retrospectively evaluated. In total, 1,901 and 8,199 patients were identified as "de-escalated DAPT" (switched to aspirin and clopidogrel) and "unchanged DAPT" (continued on aspirin and ticagrelor) cohorts, respectively. With a mean follow-up of 8 months, the incidence rates (per 100 person-year) of death, AMI readmission and MACE were 2.89, 3.68, and 4.91 in the de-escalated cohort and 2.42, 3.28, and 4.72 in the unchanged cohort, respectively, based on an inverse probability of treatment weighted approach that adjusting for baseline characteristics of the patients. Multivariate Cox regression analyses showed the two groups had no significant differences in the hazard risk of death, AMI admission, and MACE. Additionally, there was no observed difference in the risk of bleeding, including major or clinically relevant non-major bleeding. The real-world data revealed that de-escalation of P2Y12 inhibitor in DAPT was not associated with a higher risk of death or AMI readmission in Taiwanese patients with AMI undergoing successful PCI.


Assuntos
Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ticagrelor/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aspirina/administração & dosagem , Aspirina/uso terapêutico , Clopidogrel/administração & dosagem , Clopidogrel/uso terapêutico , Substituição de Medicamentos , Terapia Antiplaquetária Dupla , Humanos , Pessoa de Meia-Idade , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Estudos Retrospectivos , Ticagrelor/administração & dosagem , Adulto Jovem
12.
Arterioscler Thromb Vasc Biol ; 39(6): 1240-1252, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30943772

RESUMO

Objective- Basic research indicates that TNFSF14 (tumor necrosis factor superfamily 14) may be involved in the pathogenesis of atherosclerosis. Given the requirements of new biomarkers for risk classification in coronary artery disease (CAD), we conducted a longitudinal analysis to investigate if TNFSF14 levels are associated with the risk of cardiovascular events among patients with stable CAD. Approach and Results- In total, 894 patients with CAD were enrolled in a multicenter prospective study. The primary outcome was the occurrence of cardiovascular death, nonfatal myocardial infarction, and stroke. The secondary outcome was the occurrence of all-cause death, nonfatal myocardial infarction, stroke, revascularization, and hospitalization because of angina or heart failure. During the mean follow-up period of 22±9 months, 32 patients reached the primary outcome and 166 patients reached the secondary outcome. Kaplan-Meier analysis showed that the event-free survival was significantly different in the first and fourth quartile groups in subjects categorized by TNFSF14 levels. In multivariate Cox proportional hazard regression analysis, TNFSF14 was independently associated with the risk of cardiovascular events after adjustment for various relevant factors (adjusted hazard ratio, 1.14; 95% CI, 1.04-1.25). In the validation cohort of 126 multivessel patients with CAD, TNFSF14 was confirmed to provide good prognostic predictive value for composite cardiovascular events (adjusted hazard ratio, 1.11; 95% CI, 1.04-1.19). Conclusions- This is the first study to demonstrate that increased TNFSF14 levels were independently associated with the occurrence of cardiovascular events in patients with stable CAD. Future studies are worthy to validate if TNFSF14 could be a novel prognostic biomarker for CAD outcomes over different populations.


Assuntos
Doença da Artéria Coronariana/sangue , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Causas de Morte , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/terapia , Progressão da Doença , Feminino , Hospitalização , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/mortalidade , Revascularização Miocárdica , Intervalo Livre de Progressão , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/mortalidade , Taiwan/epidemiologia , Fatores de Tempo , Regulação para Cima
13.
J Immunother Cancer ; 6(1): 72, 2018 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-30012209

RESUMO

BACKGROUND: Use of anti-programmed cell death-1 (anti-PD-1) has been successful in treating many types of cancers. Despite its promising efficacy, immune-related adverse events are still a major concern. Immune-related cardiotoxicity, which is rare but fatal, has recently become a focus of attention. Cardiotoxicities including myocarditis, cardiomyopathy, cardiac fibrosis, heart block and cardiac arrest have been reported. Of these toxicities, myocarditis is often accompanied by dysrhythmia. The presentation of sick sinus syndrome as an immune-related adverse event has not yet been reported. Here, we reported the first case of sick sinus syndrome, a rare toxicity induced by anti-PD-1. CASE PRESENTATION: A 42-year-old male patient who had metastatic hepatocellular carcinoma failed treatment with sorafenib. Pembrolizumab at a fixed dose of 100 mg every three weeks was given. His heart rate gradually slowed down and he presented sick sinus syndrome with a lowest heart rate of 38 bpm after six cycles of pembrolizumab. He denied chest tightness, cold sweating, palpitation and dyspnea. Lab data including cardiac enzyme, electrolytes and thyroid function were all within a normal range. Simultaneously, he complained of fatigue, dizziness and anorexia with hypotension. Lab data revealed low cortisol and ACTH levels. Anti-PD-1 induced adrenal insufficiency was suspected. Low-dose cortisone (12.5 mg) was prescribed, and the patient's symptoms, hypotension and sick sinus syndrome showed rapid improvement. Cortisone was gradually titrated and discontinued three weeks later. His sick sinus syndrome did not relapse and the cortisol and ACTH level returned to normal. CONCLUSIONS: Sick sinus syndrome caused by anti-PD-1 treatment is a rare adverse event. With the development of sick sinus syndrome, myocarditis should be the first differential diagnosis because of its lethality. From this case, we learned that sick sinus syndrome may be a presentation of immune- or adrenal insufficiency-mediated sinus node dysfunction, both could be reversed with a glucocorticoid supplement.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Síndrome do Nó Sinusal/induzido quimicamente , Adulto , Humanos , Masculino
14.
Sci Rep ; 6: 33953, 2016 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-27650781

RESUMO

Fibroblast growth factor 21 (FGF21), a polypeptide ligand promoted glucose homeostasis and lipids metabolism, was recently reported to attenuate cardiac hypertrophy. The aim of this study was to investigate the impact of FGF21 in diastolic heart failure. Subjects admitted for coronary angiogram were screened for heart failure, and those with left ventricular (LV) ejection fraction < 45% were excluded. Diastolic dysfunction was defined as functional abnormalities that exist during LV relaxation and filling by echocardiographic criteria. Plasma levels of FGF21 and N-terminal Pro-Brain Natriuretic Peptide (NT-pro-BNP) were determined. All patients were followed up for 1 year, or till the occurrence of heart failure readmission or death. Totally 95 patients with diastolic dysfunction and 143 controls were enrolled. Circulating FGF21 level was correlated with echocardiographic parameters of diastolic function and LV end-diastolic pressure (LVEDP). In multivariate logistic analysis, FGF21 was significantly associated with diastolic dysfunction, either identified by echocardiographic criteria (odds ratio: 2.97, p = 0.012) or confirmed with LVEDP level (odds ratio: 3.73, p = 0.030). Both plasma FGF21 (log rank p < 0.0001) and NT-pro-BNP levels (log rank p = 0.0057) showed good predictive power to the 1-year adverse cardiac events. This finding suggested FGF21 could be involved in the pathophysiology of diastolic heart failure.


Assuntos
Fatores de Crescimento de Fibroblastos/sangue , Insuficiência Cardíaca Diastólica/sangue , Insuficiência Cardíaca Diastólica/fisiopatologia , Volume Sistólico , Idoso , Idoso de 80 Anos ou mais , Angiografia Coronária , Ecocardiografia , Feminino , Seguimentos , Insuficiência Cardíaca Diastólica/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue
15.
J Formos Med Assoc ; 115(7): 501-9, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26830105

RESUMO

BACKGROUND/PURPOSE: To investigate the correlation between the CHADS2 score and risk of contrast-induced nephropathy (CIN), we conducted a retrospective study in patients who underwent elective percutaneous coronary intervention (PCI) and compared its accuracy with previous scoring systems. METHODS: A total of 539 patients who underwent elective PCI were enrolled. Based on their underlying diseases, such as hypertension, diabetes, and kidney disease, CHADS2 score, R2CHADS2 score, and Mehran's risk score were calculated for each patient. Incidence of CIN was defined as a rise in serum creatinine >0.5 mg/dL or >25% increase in baseline within 48 hours after PCI. All study participants were followed up until October 2014, or until the occurrence of major adverse cardiovascular events (MACEs). RESULTS: Overall, 55 cases (10.2%) of CIN and 90 cases (16.7%) of MACEs were identified after participants were followed up for 1.57 ± 1.46 years. The study cohort was divided into three groups according to CHADS2 scores: score 0, score 1-2, and score 3-6. In multivariate analysis, an increase of 1 point in the CHADS2 score was independently associated with a 37% increase in the risk of CIN (odds ratio, 1.37; 95% confidence interval, 1.00-1.87; p = 0.048) and a 49% increase in MACEs (hazard ratio, 1.49; 95% confidence interval, 1.18-1.88, p = 0.001). In pairwise comparison, the discriminatory performance of CHADS2 score was not inferior to either R2CHADS2 score (p = 0.226) or Mehran's risk score (p = 0.075). CONCLUSION: CHADS2 score could be a simple and useful predictor for CIN in patients undergoing elective PCI.


Assuntos
Injúria Renal Aguda/epidemiologia , Meios de Contraste/efeitos adversos , Angiografia Coronária/efeitos adversos , Doença da Artéria Coronariana/cirurgia , Índice de Gravidade de Doença , Injúria Renal Aguda/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Creatinina/sangue , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Intervenção Coronária Percutânea , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Taiwan
16.
Psychosom Med ; 77(7): 743-51, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26355726

RESUMO

OBJECTIVES: Insomnia may increase the risk of cardiovascular disease (CVD), but the reported magnitude of the associations between sleep characteristics and CVD is inconsistent. We investigated the association between insomnia and the risk of developing acute myocardial infarction (AMI) and/or stroke by using a nationwide, population-based cohort database in Taiwan. METHODS: The analyses were conducted using information from a random sample of 1 million people enrolled in the nationally representative Taiwan National Health Insurance Research Database. A total of 44,080 individuals who were 20 years or older, including 22,040 people who had diagnosis of insomnia during the study period and an age-, sex-, comorbidity-matched group of 22,040 people without insomnia, were enrolled in our study. The study end points were the occurrence of cardiovascular events including AMI or stroke during follow-up. RESULTS: During a 10-year follow-up, 302 AMI events and 1049 stroke events were identified. The insomnia group had a higher incidence of AMI (2.25 versus 1.08 per 1000 person-years) and stroke (8.01 versus 3.69 per 1000 person-years, p < .001). Cox proportional hazard regression model analysis showed that insomnia was independently associated with a higher risk of future AMI (hazard ratio [HR] = 1.68, 95% confidence interval [CI] = 1.31-2.16, p < .001), stroke (HR = 1.85, 95% CI = 1.62-2.12, p < .001), and the composite event index (HR = 1.81, 95% CI = 1.61-2.05, p < .001), after adjusting for age, sex, and comorbidities. CONCLUSIONS: Insomnia is associated with an increased risk of future cardiovascular events.


Assuntos
Infarto do Miocárdio/etiologia , Distúrbios do Início e da Manutenção do Sono/complicações , Acidente Vascular Cerebral/etiologia , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Programas Nacionais de Saúde/estatística & dados numéricos , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Taiwan/epidemiologia
17.
Am J Cardiol ; 116(7): 1028-33, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-26254707

RESUMO

Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor superfamily, is an antiapoptotic soluble receptor considered to play an important role in immune modulation and has pro-inflammatory functions. This study was designed to test whether circulating DcR3 levels are associated with coronary artery disease (CAD) severity and predict future major adverse cardiovascular events (MACEs) in patients with CAD. Circulating DcR3 levels and the Syntax score (SXscore) were determined in patients with multivessel CAD. The primary end point was the MACE within 12 months. In total, 152 consecutive patients with angiographically confirmed multivessel CAD who had received percutaneous coronary intervention were enrolled and were divided into 3 groups according to CAD lesion severity. Group 1 was defined as low SXscore (≤13), group 2 as intermediate SXscore (>13 and ≤22), and group 3 as high SXscore (>22). DcR3 levels were significantly higher in the high SXscore group than the other 2 groups (13,602 ± 7,256 vs 8,025 ± 7,789 vs 4,637 ± 4,403 pg/ml, p <0.001). By multivariate analysis, circulating DcR3 levels were identified as an independent predictor for high SXscore (adjusted odds ratio 1.15, 95% confidence interval 1.09 to 1.21; p <0.001). The Kaplan-Meier analysis showed that increased circulating DcR3 levels are associated with enhanced 1-year MACE in patients with multivessel CAD (log-rank p <0.001). In conclusion, increased circulating DcR3 levels are associated with CAD severity and predict future MACE in patients with multivessel CAD.


Assuntos
Doença da Artéria Coronariana/sangue , Membro 6b de Receptores do Fator de Necrose Tumoral/sangue , Medição de Risco/métodos , Idoso , Biomarcadores/sangue , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Índice de Gravidade de Doença , Taxa de Sobrevida/tendências , Taiwan/epidemiologia
18.
PLoS One ; 9(3): e89942, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24646509

RESUMO

OBJECTIVES: Reduced number and impaired function of circulating endothelial progenitor cells (EPCs) in patients with chronic kidney disease have been reported. However, there is little data about the association between circulating EPC levels and risk of contrast-induced nephropathy (CIN). The aim of this study was to investigate the relationship between circulating EPCs and CIN in patients after angiography. METHODS AND RESULTS: A total of 77 consecutive patients undergoing elective percutaneous coronary intervention (PCI) and percutaneous transluminal angioplasty (PTA) were enrolled. Flow cytometry with quantification of EPC markers (defined as CD34+, CD34+KDR+, and CD34+KDR+CD133+) in peripheral blood samples was used to assess EPC number before the procedure. CIN was defined as an absolute increase ≧0.5 mg/dl or a relative increase ≧25% in the serum creatinine level at 48 hours after the procedure. Eighteen (24%) of the study subjects developed CIN. Circulating EPC levels were significantly lower in patients who developed CIN than in those without CIN (CD34+KDR+, 4.11±2.59 vs. 9.25±6.30 cells/105 events, P<0.001). The incidence of CIN was significantly greater in patients in the lowest EPC tertile (CD34+KDR+; from lowest to highest, 52%, 15%, and 4%, P<0.001). Using univariate logistic regression, circulating EPC number (CD34+KDR+) was a significant negative predictor for development of CIN (odds ratio 0.69, 95% CI 0.54-0.87, P = 0.002). Over a two-year follow-up, patients with CIN had a higher incidence of major adverse cardiovascular events including myocardial infarction, stroke, revascularization of treated vessels, and death (66.7% vs. 25.4%, P = 0.004) than did patients without CIN. CONCLUSIONS: Decreased EPC level is associated with a greater risk of CIN, which may explain part of the pathophysiology of CIN and the poor prognosis in CIN patients.


Assuntos
Angioplastia/efeitos adversos , Meios de Contraste/efeitos adversos , Células Progenitoras Endoteliais/patologia , Nefrose/diagnóstico , Intervenção Coronária Percutânea/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/metabolismo , Biomarcadores/análise , Contagem de Células , Creatinina/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nefrose/induzido quimicamente , Nefrose/mortalidade , Nefrose/patologia , Análise de Sobrevida
19.
Asia Pac J Clin Oncol ; 10(2): e118-21, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23384412

RESUMO

A 73-year-old woman was admitted to hospital because of progressive dyspnea on exertion. Computed tomography revealed a large hepatic tumor, which was proved to be a hepatic epithelioid hemangioendothelioma (EHE). Echocardiography demonstrated high cardiac output, for which the tumor was considered to be the leading cause. A transcatheter arterial chemoembolization (TACE) was performed sequentially at 1-month intervals to reduce the size of the hepatic tumor, and this temporarily improved the patient's cardiac condition and quality of life. In this case, we successfully used TACE in the treatment of hepatic EHE with high-output heart failure. TACE is a reasonable choice of treatment both for managing malignant hepatic tumors and resolving low systemic vascular resistance by embolization of the abnormal neoangiogenic vessels. Nevertheless, clinicians should be aware of the potential adverse effect of hepatic decompensation induced by TACE, especially when the tumor involvement is widespread and poorly preserved hepatic function is encountered.


Assuntos
Quimioembolização Terapêutica/métodos , Insuficiência Cardíaca/terapia , Hemangioendotelioma Epitelioide/terapia , Neoplasias Hepáticas/terapia , Idoso , Gerenciamento Clínico , Feminino , Insuficiência Cardíaca/etiologia , Hemangioendotelioma Epitelioide/complicações , Humanos , Neoplasias Hepáticas/complicações , Qualidade de Vida
20.
Coron Artery Dis ; 24(1): 23-8, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23151854

RESUMO

OBJECTIVES: This study aims to determine whether plasma levels of matrix metalloproteinases (MMPs) and inflammatory markers can predict the long-term prognosis of coronary revascularization in patients after acute myocardial infarction (AMI). BACKGROUND: MMPs have been implicated in the development of atherosclerosis and plaque rupture in acute coronary syndrome. METHODS: Ninety-six consecutive patients (63±11 years) diagnosed with myocardial infarction were enrolled. All patients were followed up for 43±12 months. Plasma levels of MMP-2 and MMP-9 were determined from blood samples collected immediately after hospitalization. Coronary revascularization was defined as having received a percutaneous coronary intervention or a coronary artery bypass graft surgery. RESULTS: A total of 29 patients (30%) had undergone coronary revascularization during the follow-up period, including 27 percutaneous coronary intervention and two coronary artery bypass graft surgery. The baseline characteristics were similar between groups with or without revascularization. Patients with coronary revascularization had significantly higher MMP-9 levels (P=0.048), but not MMP-2 levels. In addition, a positive correlation was found between circulating MMP-9 level and total cholesterol (r=0.250, P=0.016) and low-density lipoprotein-cholesterol (r=0.284, P=0.009). All patients were divided into a high-MMP-9 group (highest tertile≥1.10 ng/ml) and a low-MMP-9 group (<1.10 ng/ml). The incidence of coronary revascularization was significantly increased in the high-MMP-9 group (P=0.034). In a multivariate Cox regression analysis that included MMP-9 and classical risk factors, the MMP-9 level was an independent predictor of coronary revascularization in patients after AMI (hazard ratio, 2.72; 95% confidence interval, 1.24-5.98; P=0.026). CONCLUSION: Increased plasma levels of MMP-9 but not MMP-2 or inflammatory markers predict future coronary revascularization, and a significant association was observed with MMP-9 and low-density lipoprotein-cholesterol. These findings suggest a pivotal role of MMP-9 in atherothrombosis in AMI patients.


Assuntos
Ponte de Artéria Coronária , Metaloproteinase 9 da Matriz/sangue , Infarto do Miocárdio/enzimologia , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea , Idoso , Biomarcadores/sangue , Proteína C-Reativa/análise , Colesterol/sangue , LDL-Colesterol/sangue , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/mortalidade , Feminino , Humanos , Mediadores da Inflamação/sangue , Estimativa de Kaplan-Meier , Masculino , Metaloproteinase 2 da Matriz/sangue , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/sangue , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/cirurgia , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue , Regulação para Cima
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