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1.
JACC Heart Fail ; 9(1): 28-38, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33309579

RESUMO

OBJECTIVES: The authors sought to evaluate the association of heart failure hospitalization (HFH) with guideline-directed medical therapy (GDMT) prescribing patterns among patients with heart failure with reduced ejection fraction (HFrEF). BACKGROUND: HFH represents an important opportunity to titrate GDMT among patients with HFrEF. METHODS: The CHAMP-HF (Change the Management of Patients With Heart Failure) registry is a prospective registry of adults with HFrEF (ejection fraction ≤40%). Using data from the CHAMP-HF registry (N = 4,365), adjusted time-to-event models were created to study the association of HFH with GDMT prescribing patterns. RESULTS: HFH (compared with no HFH) was positively associated with initiation of angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blocker (ARB), angiotensin receptor-neprilysin inhibitor, beta-blocker, and mineralocorticoid receptor antagonist (MRA). HFH positively associated with dose escalation of ACE inhibitor/ARB (probability ratio: 1.71, 95% confidence interval [CI]: 1.36 to 2.16) and MRA (probability ratio: 8.71, 95% CI: 4.19 to 18.10). In those on prior therapy, HFH was associated with discontinuation and de-escalation of all classes of GDMT. ACE inhibitor/ARB, angiotensin receptor-neprilysin inhibitor, beta-blocker, and MRA de-escalation/discontinuation after HFH was associated with increased risk of all-cause mortality with hazard ratios of 3.82 (95% CI: 2.42 to 6.03), 4.76 (95% CI: 2.06 to 11.03), 2.94 (95% CI: 2.04 to 4.25), and 4.81 (95% CI: 2.61 to 8.87), respectively. CONCLUSIONS: HFH positively associated with changes in GDMT, including initiation, dose escalation, discontinuation, and dose de-escalation. De-escalation/discontinuation of GDMT after HFH associated with increased risk of all-cause mortality. Educational endeavors are needed to ensure GDMT is not inappropriately held in the setting of HFH. For those in whom GDMT must be held/decreased, improvement tools at discharge and post-discharge titration clinics may help ensure lifesaving GDMT regimens remain optimized.

2.
J Endocr Soc ; 4(10): bvaa130, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32984743

RESUMO

SARS-CoV-2 infection is associated with significant lung and cardiac morbidity but there is a limited understanding of the endocrine manifestations of coronavirus disease 2019 (COVID-19). Although thyrotoxicosis due to subacute thyroiditis has been reported in COVID-19, it is unknown whether SARS-CoV-2 infection can also lead to decompensated hypothyroidism. We present the first case of myxedema coma (MC) in COVID-19 and we discuss how SARS-CoV-2 may have precipitated multiorgan damage and sudden cardiac arrest in our patient. A 69-year-old woman with a history of small cell lung cancer presented with hypothermia, hypotension, decreased respiratory rate, and a Glasgow Coma Scale score of 5. The patient was intubated and administered vasopressors. Laboratory investigation showed elevated thyrotropin, very low free thyroxine, elevated thyroid peroxidase antibody, and markedly elevated inflammatory markers. SARS-CoV-2 test was positive. Computed tomography showed pulmonary embolism and peripheral ground-glass opacities in the lungs. The patient was diagnosed with myxedema coma with concomitant COVID-19. While treatment with intravenous hydrocortisone and levothyroxine were begun the patient developed a junctional escape rhythm. Eight minutes later, the patient became pulseless and was eventually resuscitated. Echocardiogram following the arrest showed evidence of right heart dysfunction. She died 2 days later of multiorgan failure. This is the first report of SARS-CoV-2 infection with MC. Sudden cardiac arrest likely resulted from the presence of viral pneumonia, cardiac arrhythmia, pulmonary emboli, and MC-all of which were associated with the patient's SARS-CoV-2 infection.

3.
Curr Heart Fail Rep ; 17(1): 1-8, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31925667

RESUMO

PURPOSE OF REVIEW: To describe the epidemiology, pathophysiology, management, and prognosis of patients with heart failure with mid-range ejection fraction (HFmrEF). RECENT FINDINGS: In 2013, The American Heart Association (AHA)/American College of Cardiology (ACC) assigned an ejection fraction (EF) range to heart failure with reduced ejection fraction (HFrEF, EF ≤ 40%) and heart failure with preserved ejection fraction (HFpEF, EF ≥50%). This classification created a "gray zone" of patients with EFs between 41% and 49% that ultimately came to be known as heart failure with borderline or mid-range ejection fraction. HFmrEF patients represent a group with heterogeneous clinical characteristics that at times resembles HFrEF, at others HFpEF, and at others still a unique phenotype altogether. No randomized controlled trials exist in those with HFmrEF, though HFrEF and HFpEF studies that include overlap suggest some potential benefit of beta blockers, angiotensin receptor blockers, mineralocorticoid receptor antagonists, and angiotensin receptor-neprilysin inhibitors. Mortality rates among the HFmrEF population are significant, and are similar to those in patients with HFrEF and HFpEF. HFmrEF is a complex disorder that remains poorly understood. Future research is needed to better elucidate the pathophysiology, management, and prognosis of this condition.

4.
J Am Heart Assoc ; 8(21): e012831, 2019 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-31623505

RESUMO

Background Patient characteristics insufficiently explain disparities in cardiovascular outcomes among hospitalized patients, suggesting a role for community or hospital-level factors. Here, we evaluate the association of hospital racial composition and payer mix with all-cause inpatient mortality for patients hospitalized with acute coronary syndrome (ACS). Methods and Results Using the National Inpatient Sample, we identified adult hospitalizations from 2014 with a primary diagnosis of ACS (n=550 005). We divided National Inpatient Sample hospitals into quartiles based on percent of minority (black, Hispanic, Asian or Pacific Islander, Native American race/ethnicity) and low-income payer (Medicaid or uninsured) discharges in 2014. We utilized logistic regression to determine whether hospital minority or low-income payer makeup associated with all-cause inpatient mortality among those admitted for ACS . In adjusted models, ACS patients admitted to hospitals with >12.4% to 25.4% (Quartile 2), >25.4% to 44.3% (Q3), and >44.3% (Q4) minority discharges experienced a 14% (OR 1.14, 95% CI 1.06-1.23), 13% (OR 1.13, 95% CI 1.04-1.23), and 15% (OR 1.15, 95% CI 1.04-1.26) increased odds of all-cause inpatient mortality compared with hospitals with ≤12.4% (Q1) minority discharges. ACS patients admitted to hospitals with >18.7% to 25.7% (Q2) and >34.0% (Q4) low-income payer discharges experienced a 9% (OR 1.09, 1.01-1.17) and 9% (OR 1.09, 1.00-1.19) increased odds of all-cause inpatient mortality when compared with hospitals with ≤18.7% (Q1) low-income payer discharges. Conclusions Hospital minority and low-income payer makeup positively associate with odds of all-cause inpatient mortality among patients admitted for acute coronary syndrome.

6.
JAMA Cardiol ; 4(3): 195-196, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30810709
7.
JAMA Cardiol ; 3(12): 1226-1231, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30484837

RESUMO

Importance: The addition of receptor-neprilysin inhibition to standard therapy, including a renin-angiotensin system blocker, has been demonstrated to improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF) compared with standard therapy alone. The long-term absolute risk reduction from angiotensin receptor neprilysin inhibitor (ARNI) therapy, and whether it merits widespread use among diverse subpopulations, has not been well described. Objective: To calculate estimated 5-year number needed to treat (NNT) values overall and for different subpopulations for the Prospective Comparison of ARNI with Angiotensin-Converting Enzyme Inhibitor (ACEI) to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) cohort. Design, Setting, and Participants: Overall and subpopulation 5-year NNT values were estimated for different end points using data from PARADIGM-HF, a double-blind, randomized trial of sacubitril-valsartan vs enalapril. This multicenter, international study included 8399 men and women with HFrEF (ejection fraction, ≤40%). The study began in December 2009 and ended in March 2014. Analyses began in March 2018. Interventions: Random assignment to sacubitril-valsartan or enalapril. Main Outcomes and Measures: Cardiovascular death or HF hospitalization, cardiovascular death, and all-cause mortality. Results: The final cohort of 8399 individuals included 1832 women (21.8%) and 5544 white individuals (66.0%), with a mean (SD) age of 63.8 (11.4) years. The 5-year estimated NNT for the primary outcome of cardiovascular death or HF hospitalization with ARNI therapy incremental to ACEI therapy in the overall cohort was 14. The 5-year estimated NNT values were calculated for different clinically relevant subpopulations and ranged from 12 to 19. The 5-year estimated NNT for all-cause mortality in the overall cohort with ARNI incremental to ACEI was 21, with values ranging from 16 to 31 among different subgroups. Compared with imputed placebo, the 5-year estimated NNT for all-cause mortality with ARNI was 11. The 5-year estimated NNT values were also calculated for other HFrEF therapies compared with controls from landmark trials for all-cause mortality and were found to be 18 for ACEI, 24 for angiotensin receptor blockers, 8 for ß-blockers, 15 for mineralocorticoid antagonists, 14 for implantable cardioverter defibrillator, and 14 for cardiac resynchronization therapy. Conclusions and Relevance: The 5-year estimated NNT with ARNI therapy incremental to ACEI therapy overall and for clinically relevant subpopulations of patients with HFrEF are comparable with those for well-established HF therapeutics. These data further support guideline recommendations for use of ARNI therapy among eligible patients with HFrEF.


Assuntos
Aminobutiratos/uso terapêutico , Enalapril/uso terapêutico , Parada Cardíaca/prevenção & controle , Insuficiência Cardíaca/tratamento farmacológico , Neprilisina/antagonistas & inibidores , Volume Sistólico/fisiologia , Tetrazóis/uso terapêutico , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Causas de Morte/tendências , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Seguimentos , Parada Cardíaca/epidemiologia , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Hospitalização/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Quebeque/epidemiologia , Taxa de Sobrevida/tendências , Suécia/epidemiologia , Fatores de Tempo , Reino Unido/epidemiologia , Estados Unidos/epidemiologia
8.
Cardiovasc Revasc Med ; 19(3 Pt A): 268-272, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29454531

RESUMO

OBJECTIVES: We assessed the safety and efficacy of orbital atherectomy to modify severely calcified coronary plaque prior to stent implantation in patients with small vessel (2.5mm) disease. BACKGROUND: Severe coronary artery calcification increases the risk of adverse clinical events during percutaneous coronary intervention (PCI). Patients who undergo PCI of small vessels have worse clinical outcomes including higher rates of perforation and dissection. The outcomes of orbital atherectomy of small diameter vessels (2.5mm) are unknown. METHODS: ORBIT II was a single-arm, multicenter trial which prospectively enrolled patients with severely calcified coronary lesions treated with orbital atherectomy prior to stenting in 49U.S. sites. The primary endpoint was the 3year rate of major adverse cardiac events, which was the composite of cardiac death, myocardial infarction, and target vessel revascularization. RESULTS: Of the 443 patients, 55 (12.4%) had reference vessel diameters (RVD) of 2.5mm and 388 (87.6%) had RVD >2.5. The rates of severe angiographic complications were similar in both groups. The primary endpoint was similar in both groups (30.6% vs. 22.5%, p=0.22), as were the rates of cardiac death (9.8% vs. 6.3%, p=0.33) and myocardial infarction (12.8% vs. 10.9%, p=0.67). Target vessel revascularization was numerically higher in the small vessel group (16.8% vs. 9.3%, p=0.13). CONCLUSIONS: Patients with small coronary vessel disease had comparable clinical outcomes compared to the larger diameter group following orbital atherectomy. Subsequent studies are required to establish the optimal revascularization approach for such patients with small coronary vessel disease burdened by heavily calcified lesions.


Assuntos
Aterectomia Coronária/métodos , Doença da Artéria Coronariana/cirurgia , Vasos Coronários/cirurgia , Intervenção Coronária Percutânea , Calcificação Vascular/cirurgia , Idoso , Idoso de 80 Anos ou mais , Aterectomia Coronária/efeitos adversos , Aterectomia Coronária/mortalidade , Ensaios Clínicos como Assunto , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Vasos Coronários/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/mortalidade , Placa Aterosclerótica , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Stents , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/mortalidade
9.
J Invasive Cardiol ; 30(2): 77-80, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29378972

RESUMO

OBJECTIVES: We assessed the impact of intravascular ultrasound (IVUS)/optical coherence tomography (OCT) on outcomes of patients who underwent orbital atherectomy. BACKGROUND: Intravascular imaging provides enhanced lesion morphology assessment and optimization of percutaneous coronary intervention (PCI) outcomes. Severe coronary artery calcification increases the complexity of PCI and is associated with worse clinical outcomes. Orbital atherectomy modifies calcified plaque, facilitating stent delivery and optimizing stent expansion. The impact of IVUS/OCT on clinical outcomes after orbital atherectomy is unknown. METHODS: Of the 458 consecutive real-world patients in our retrospective multicenter registry, a total of 138 patients (30.1%) underwent orbital atherectomy with IVUS/OCT. The primary safety endpoint was the rate of 30-day major adverse cardiac and cerebrovascular events, comprised of death, myocardial infarction (MI), target-vessel revascularization (TVR), and stroke. RESULTS: The IVUS/OCT group and no-imaging group had similar rates of the primary endpoint (1.5% vs 2.5%; P=.48) as well as death (1.5% vs 1.3%; P=.86), MI (1.5% vs 0.9%; P=.63), TVR (0% vs 0%; P=NS), and stroke (0% vs 0.3%; P=.51). The 30-day stent thrombosis rates were low in both groups (0.7% vs 0.9%; P=.82). Emergent coronary artery bypass graft surgery was uncommonly performed in both groups (0.0% vs 0.9%; P=.25). CONCLUSION: Orbital atherectomy guided by intravascular imaging is feasible and safe. A large prospective randomized trial is needed to determine the clinical benefit of IVUS/OCT during PCI with orbital atherectomy.


Assuntos
Aterectomia Coronária , Doença da Artéria Coronariana , Vasos Coronários , Intervenção Coronária Percutânea , Complicações Pós-Operatórias , Stents/efeitos adversos , Acidente Vascular Cerebral , Cirurgia Assistida por Computador , Ultrassonografia de Intervenção/métodos , Idoso , Aterectomia Coronária/efeitos adversos , Aterectomia Coronária/métodos , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/cirurgia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Vasos Coronários/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/métodos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/prevenção & controle , Reoperação/métodos , Reoperação/estatística & dados numéricos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Cirurgia Assistida por Computador/efeitos adversos , Cirurgia Assistida por Computador/métodos , Estados Unidos/epidemiologia , Calcificação Vascular/diagnóstico , Calcificação Vascular/cirurgia
10.
J Interv Cardiol ; 31(1): 15-20, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28870003

RESUMO

OBJECTIVES: We assessed the feasibility and safety of orbital atherectomy in patients with severely calcified aorto-ostial coronary artery lesions. BACKGROUND: The treatment of calcified aorta-ostial coronary artery lesions is technically challenging. Orbital atherectomy can potentially damage the guiding catheter if it is not retracted sufficiently during treatment of ostial lesions. Orbital atherectomy can also excessively whip if the guiding catheter is not close enough to the ostium to provide sufficient support. Several techniques can be performed to successfully treat ostial lesions with orbital atherectomy. METHODS: Our retrospective multicenter registry included 548 real-world patients who underwent orbital atherectomy, 59 (10.8%) of whom underwent treatment for aorto-ostial coronary artery lesions (left main artery [n = 35] and right coronary artery [n = 24]). The primary endpoint was the rate of 30-day major adverse cardiac and cerebrovascular events (MACCE), defined as the occurrence of death, myocardial infarction, target vessel revascularization, and stroke. RESULTS: The primary endpoint was similar in patients with and without ostial lesions (3.4% vs 2.2%, P = 0.2), as were the 30-day rates of death (1.7% vs 1.4%, P = 0.7), myocardial infarction (1.7% vs 1.0%, P = 0.3), target vessel revascularization (0% vs 0%, P > 0.91), and stroke (0% vs 0.2%, P > 0.9). Angiographic complications and stent thrombosis did not occur in patients with ostial lesions. CONCLUSIONS: Despite its technical challenges, orbital atherectomy appears to be a feasible and safe treatment option for calcified aorto-ostial coronary lesions.


Assuntos
Aorta , Arteriopatias Oclusivas , Aterectomia Coronária , Vasos Coronários , Calcificação Vascular , Idoso , Aorta/diagnóstico por imagem , Aorta/patologia , Arteriopatias Oclusivas/diagnóstico , Arteriopatias Oclusivas/cirurgia , Aterectomia Coronária/efeitos adversos , Aterectomia Coronária/métodos , Angiografia Coronária/métodos , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos , Índice de Gravidade de Doença , Estados Unidos , Calcificação Vascular/diagnóstico , Calcificação Vascular/cirurgia
11.
Clin Chem ; 64(1): 10-12, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29158253

Assuntos
Coração , Miocárdio
12.
J Invasive Cardiol ; 30(5): 177-181, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29245154

RESUMO

OBJECTIVES: We compared the angiographic outcomes of patients treated with orbital atherectomy for profunda femoris artery (PFA) and superficial femoral artery (SFA) disease from the CONFIRM I-III registries. BACKGROUND: Endovascular revascularization of the PFA is considered a high-risk procedure given that it is an important collateral vessel when the SFA becomes occluded. Data on outcomes of endovascular revascularization of calcified PFA disease are limited. METHODS: The treatment of PFA disease with orbital atherectomy has not been previously reported. Patient demographics, lesion characteristics, and procedure data for all CONFIRM patients with at least one PFA lesion location (n = 33 patients; n = 33 lesions) were compared to patients with at least one SFA lesion location (n = 1574 patients; n = 1811 lesions). The primary endpoint was angiographic complication, defined as the composite of flow-limiting dissection, perforation, slow flow, vessel closure, spasm, embolism, or thrombosis. RESULTS: The PFA group had a shorter lesion length, larger residual stenosis, shorter total run time, and shorter inflation time. Adjunctive stenting was only performed in the SFA group (10%); no patient in the PFA group underwent stenting. The primary endpoint was low in the PFA group and compared favorably with the SFA group (3% vs 11%; P=.15). One patient in the PFA group had vessel spasm, while no patients had flow-limiting dissection, perforation, slow flow, vessel closure, embolism, or thrombus. CONCLUSIONS: Orbital atherectomy of the PFA was feasible and safe. A randomized trial is needed to determine the ideal treatment strategy for calcified PFA disease.


Assuntos
Aterectomia/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Artéria Femoral , Doença Arterial Periférica/cirurgia , Complicações Pós-Operatórias/epidemiologia , Sistema de Registros , Calcificação Vascular/cirurgia , Doença Aguda , Idoso , Feminino , Seguimentos , Humanos , Incidência , Masculino , Doença Arterial Periférica/diagnóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Estados Unidos/epidemiologia , Calcificação Vascular/diagnóstico
13.
J Am Heart Assoc ; 6(12)2017 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-29275373

RESUMO

BACKGROUND: Subclinical myocardial injury, as measured by high-sensitivity cardiac troponin T (hsTnT), and myocardial stress, as measured by N-terminal pro-B-type natriuretic peptide (NT-proBNP), are related to glycemic control in patients with type 2 diabetes mellitus, and are strong predictors of adverse cardiovascular outcomes. We sought to determine whether antihyperglycemic therapy improves measures of myocardial injury and myocardial stress in patients with type 2 diabetes mellitus. METHODS AND RESULTS: We randomized, in a 2×2 factorial fashion, 438 patients with type 2 diabetes mellitus to insulin glargine, metformin, the combination, or placebo and measured changes in NT-proBNP and hsTnT after 12 weeks of therapy. At baseline, the median (Q1-Q3) plasma concentration was 35.4 (15.7-86.3) ng/L for NT-proBNP and 6.7 (4.6-10.1) ng/L for hsTnT. The adjusted (95% confidence interval) change in NT-proBNP concentration was 20.7% (7.9-35.0) in the insulin arm compared with 0.13% (-10.8 to 12.5) in the no-insulin arm (P=0.03 for comparison). These changes were not related to changes in fasting or postprandial glucose, glycated hemoglobin, weight, blood pressure, or inflammation. In the metformin arm, the adjusted change in NT-proBNP was 7.8% (-3.7 to 20.7) compared with 13.0% (0.72-26.8) in the no-metformin arm (P=0.58). No significant changes in hsTnT concentrations were observed for any of the treatment arms. CONCLUSIONS: Insulin glargine was associated with a significant 20.7% increase in NT-proBNP, a marker of myocardial stress, after 12 weeks of therapy. No change in hsTnT, a marker of myocardial injury, was observed. The changes were independent of substantial improvements in glucose control. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00366301.


Assuntos
Doenças Cardiovasculares/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insulina Glargina/farmacologia , Metformina/farmacologia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Troponina T/sangue , Biomarcadores/sangue , Glicemia/metabolismo , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Quimioterapia Combinada , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemiantes/farmacologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco
14.
Matrix Biol ; 63: 69-90, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28126521

RESUMO

The HS3ST1 gene controls endothelial cell production of HSAT+ - a form of heparan sulfate containing a specific pentasaccharide motif that binds the anticoagulant protein antithrombin (AT). HSAT+ has long been thought to act as an endogenous anticoagulant; however, coagulation was normal in Hs3st1-/- mice that have greatly reduced HSAT+ (HajMohammadi et al., 2003). This finding indicates that HSAT+ is not essential for AT's anticoagulant activity. To determine if HSAT+ is involved in AT's poorly understood inflammomodulatory activities, Hs3st1-/- and Hs3st1+/+ mice were subjected to a model of acute septic shock. Compared with Hs3st1+/+ mice, Hs3st1-/- mice were more susceptible to LPS-induced death due to an increased sensitivity to TNF. For Hs3st1+/+ mice, AT treatment reduced LPS-lethality, reduced leukocyte firm adhesion to endothelial cells, and dilated isolated coronary arterioles. Conversely, for Hs3st1-/- mice, AT induced the opposite effects. Thus, in the context of acute inflammation, HSAT+ selectively mediates AT's anti-inflammatory activity; in the absence of HSAT+, AT's pro-inflammatory effects predominate. To explore if the anti-inflammatory action of HSAT+ also protects against a chronic vascular-inflammatory disease, atherosclerosis, we conducted a human candidate-gene association study on >2000 coronary catheterization patients. Bioinformatic analysis of the HS3ST1 gene identified an intronic SNP, rs16881446, in a putative transcriptional regulatory region. The rs16881446G/G genotype independently associated with the severity of coronary artery disease and atherosclerotic cardiovascular events. In primary endothelial cells, the rs16881446G allele associated with reduced HS3ST1 expression. Together with the mouse data, this leads us to conclude that the HS3ST1 gene is required for AT's anti-inflammatory activity that appears to protect against acute and chronic inflammatory disorders.


Assuntos
Antitrombinas/fisiologia , Aterosclerose/genética , Doenças das Artérias Carótidas/genética , Sulfotransferases/genética , Animais , Antitrombinas/farmacologia , Aterosclerose/enzimologia , Aterosclerose/imunologia , Doenças das Artérias Carótidas/enzimologia , Doenças das Artérias Carótidas/imunologia , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Imunomodulação , Desequilíbrio de Ligação , Lipopolissacarídeos/farmacologia , Masculino , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/fisiologia , Vasodilatação
15.
Am J Cardiol ; 117(3): 376-81, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26739393

RESUMO

Alcohol use, physical activity, diet, and cigarette smoking are modifiable cardiovascular risk factors that have a substantial impact on the risk of myocardial infarction, stroke, and cardiovascular death. We hypothesized that these behaviors may alter concentrations of cardiac troponin, a marker of myocyte injury, and B-type natriuretic peptide, a marker of myocyte stress. Both markers have shown strong association with adverse cardiovascular outcomes. In 519 women with no evidence of cardiovascular disease, we measured circulating concentrations of cardiac troponin T, using a high-sensitivity assay (hsTnT), and the N-terminal fragment of B-type natriuretic peptide (NT-proBNP). We used logistic regression to determine if these behaviors were associated with hsTnT ≥ 3 ng/l or with NT-proBNP in the highest quartile (≥ 127.3 ng/l). The median (Q1 to Q3) NT-proBNP of the cohort was 68.8 ng/l (40.3 to 127.3 ng/l), and 30.8% (160 of 519) of the cohort had circulating hsTnT ≥ 3 ng/l. In adjusted models, women who drank 1 to 6 drinks/week had lower odds of having a hsTnT ≥ 3 ng/l (odds ratio 0.58, 95% confidence interval 0.34 to 0.96) and lower odds of having an elevated NT-proBNP (odds ratio 0.55, 95% confidence interval 0.32 to 0.96). We were subsequently able to validate the results for B-type natriuretic peptide in a large independent cohort. In conclusion, our results suggest that regular alcohol consumption is associated with lower concentrations of hsTnT and NT-proBNP, 2 cardiovascular biomarkers associated with cardiovascular risk, and raise the hypothesis that the beneficial effects of alcohol consumption may be mediated by direct effects on the myocardium.


Assuntos
Aspirina/administração & dosagem , Doenças Cardiovasculares/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Medição de Risco/métodos , Troponina T/sangue , Vitamina E/administração & dosagem , Saúde da Mulher , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Incidência , Massachusetts/epidemiologia , Pessoa de Meia-Idade , Miocárdio/metabolismo , Neoplasias/epidemiologia , Neoplasias/prevenção & controle , Inibidores da Agregação de Plaquetas/administração & dosagem , Estudos Prospectivos , Fatores de Risco , Vitaminas/administração & dosagem
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