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1.
Blood Press ; : 1-8, 2020 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-32586143

RESUMO

Purpose: Hypertensive patients are at increased risk of atrial fibrillation (AF). Although low baseline high density lipoprotein (HDL) cholesterol has been associated with a higher risk of AF, this has not been verified in recent population-based studies. Whether changing levels of HDL over time are more strongly related to the risk of new AF in hypertensive patients has not been examined.Material and methods: Incident AF was examined in relation to baseline and on-treatment HDL levels in 8267 hypertensive patients with no history of AF, in sinus rhythm on their baseline electrocardiogram, randomly assigned to losartan- or atenolol-based treatment. HDL levels at baseline and each year of testing were categorised into quartiles according to baseline HDL levels.Results: During 4.7 ± 1.10 years of follow-up, 645 patients (7.8%) developed new AF. In univariate Cox analyses, compared with the highest quartile of HDL levels (>1.78 mmol/l), patients with on-treatment HDL in the lowest quartile (≤ 1.21 mmol/l) had a 53% greater risk of new AF. Patients with on-treatment HDL in the second and third quartiles had intermediate increased risks of AF. Baseline HDL in the lowest quartile was not a significant predictor of new AF (hazard ratio (HR): 1.14, 95% confidence interval (CI): 0.90-1.43). In multivariable Cox analyses adjusting for multiple baseline and time-varying covariates, the lowest quartile of on-treatment HDL remained associated with a nearly 54% increased risk of new AF (HR: 1.54, 95% CI: 1.16-2.05) whereas a baseline HDL≤ ⩽1.21 mmol/l was not predictive of new AF (HR: 1.01, 95% CI: 0.78-1.31).Conclusion: Lower on-treatment HDL is strongly associated with risk of new AF. These findings suggest that serial assessment of HDL can estimate AF risk better than baseline HDL in hypertensive patients with left ventricular hypertrophy. Future studies may investigate whether therapies that increase HDL can lower risk of developing AF.Clinical Trials Registration: http://clinicaltrials.gov/ct/show/NCT00338260?order=1.

2.
Hypertension ; 75(1): 23-32, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31786973

RESUMO

Current cardiovascular pharmacotherapy targets maladaptive overactivation of the renin-angiotensin-aldosterone system (RAAS), which occurs throughout the continuum of cardiovascular disease spanning from hypertension to heart failure with reduced ejection fraction. Over the past 16 years, 4 prospective, randomized, placebo-controlled clinical trials using candesartan, perindopril, irbesartan, and spironolactone in patients with heart failure with preserved ejection fraction (HFpEF) failed to demonstrate increased efficacy of RAAS blockade added to guideline-directed medical therapy. We reappraise these trials and their weaknesses, which precluded statistically significant findings. Recently, dual-acting RAAS blockade with sacubitril-valsartan relative to stand-alone valsartan failed to improve outcome in the PARAGON-HF trial (Efficacy and Safety of LCZ696 Compared with Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction). The majority of patients with HFpEF experience hypertension, frequently with subclinical left ventricular dysfunction, contributed to by comorbidities such as coronary disease, diabetes mellitus, overweight, and atrial fibrillation. Contrasting the findings in HFpEF, trials evaluating RAAS blockade on either side of HFpEF on the cardiovascular continuum in patients with high-risk hypertension and heart failure with reduced ejection fraction, respectively, showed positive outcomes. We do not have a biologically plausible explanation for such divergent efficacy of RAAS blockade. Based on considerations of well-established clinical efficacy in hypertension and heart failure with reduced ejection fraction and the shortcomings of aforementioned clinical trials in HFpEF, we argue that RAAS blockers including MRAs (mineralocorticoid receptor antagonists; aldosterone antagonists) should be used in the treatment of patients with HFpEF.

3.
Am J Cardiol ; 124(11): 1736-1740, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31586530

RESUMO

In this study, we aimed to determine if pretreatment low-density lipoprotein (LDL) levels and aortic stenosis (AS) severity alter the efficacy of lipid-lowering therapy on reducing aortic valve replacement (AVR). We used 1,687 patients with asymptomatic mild-to-moderate AS, who were randomly assigned (1:1) to 40/10 mg simvastatin/ezetimibe combination versus. placebo in the simvastatin and ezetimibe in aortic stenosis (SEAS) trial. Pretreatment LDL levels (>4 mmol/L) and peak aortic jet velocity (3 m/s) were used to partition study participants into 4 groups, which were followed for a primary endpoint of AVR. Cox regression with tests for interaction was used to study the effect of randomized treatment in each subgroup. During a median follow-up of 4.3 years (IQR 4.2 to 4.7 years; total 7,396 patient-years of follow-up), 478 (28%) patients underwent AVR and 146 (9%) died. A significant risk dependency was detected between simvastatin/ezetimibe combination, LDL levels and mild versus moderate AS on rates of AVR (p = 0.01 for interaction). In stratified analyses, randomized treatment, therefore, reduced the rate of AVR in patients with LDL levels >4 mmol and mild AS at baseline (HR 0.4; 95% CI: 0.2 to 0.9). There was no detectable effect of randomized treatment on the need for AVR in the 3 other participants subgroups. We conclude, that in a secondary analysis from a prospective randomized clinical trial, treatment with simvastatin/ezetimibe combination reduced the need for AVR in a subset of patients with mild AS and high pretreatment LDL levels (Unique identifier on clinicaltrials.gov: NCT00092677).


Assuntos
Estenose da Valva Aórtica/terapia , Valva Aórtica/cirurgia , Ezetimiba/uso terapêutico , Implante de Prótese de Valva Cardíaca/tendências , Lipoproteínas LDL/sangue , Sinvastatina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anticolesterolemiantes/uso terapêutico , Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/diagnóstico , Doenças Assintomáticas , Biomarcadores/sangue , Progressão da Doença , Método Duplo-Cego , Quimioterapia Combinada , Dislipidemias/sangue , Dislipidemias/complicações , Dislipidemias/tratamento farmacológico , Ecocardiografia Doppler , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
4.
Blood Press ; 28(5): 317-326, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31259628

RESUMO

Aims: Atrial fibrillation (AF) is associated with increased cardiovascular risk and the incidence increases with age, hypertension and left ventricular hypertrophy (LVH). Reducing in-treatment systolic blood pressure (SBP) prevents new-onset AF but has previously not been studied in patients with isolated systolic hypertension (ISH). We aimed to investigate the effect on preventing new-onset AF by decreased in-treatment SBP in patients with ISH compared to patients with non-ISH. Methods and results: Double-blind, randomized, parallel-group study of 1320 patients with ISH and electrocardiographic (ECG) LVH, included among the 9193 patients in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Annual ECGs were Minnesota coded centrally, and new-onset AF was evaluated in 1248 ISH patients and compared with 7583 non-ISH patients during mean 4.8 ± 0.9 years follow-up. Cox regression analyses were used to assess the effect of reduced in-treatment SBP. New-onset AF occurred in 61 (4.9%) ISH patients and 292 (3.9%) non-ISH patients. In multivariate analysis lower in-treatment SBP was associated with 17% risk reduction (p = 0.008) for new-onset AF in ISH patients and 9% risk reduction (p = 0.006) in non-ISH patients per 10 mmHg decrease in in-treatment SBP, independent of treatment modality, baseline risk factors, baseline SBP and in-treatment heart rate and ECG-LVH. There was a significant interaction (p = 0.041) in favor of SBP reduction and AF prevention in ISH vs. non-ISH patients. Conclusion: Our data suggest that the effect of in-treatment SBP reduction in preventing new-onset AF is stronger in ISH compared to non-ISH patients with hypertension and ECG-LVH. However, the principal findings were the same in ISH and non-ISH patients.


Assuntos
Anti-Hipertensivos/uso terapêutico , Fibrilação Atrial/prevenção & controle , Hipertensão/tratamento farmacológico , Hipertensão do Jaleco Branco/complicações , Eletrocardiografia , Feminino , Seguimentos , Humanos , Hipertensão/complicações , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Sístole , Hipertensão do Jaleco Branco/tratamento farmacológico
5.
Am Heart J ; 214: 60-68, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31176289

RESUMO

OBJECTIVE: The DanGer Shock trial test the hypothesis that left ventricular (LV) mechanical circulatory support with Impella CP transvalvular microaxial flow pump improves survival in patients with ST segment elevation acute myocardial infarction complicated by cardiogenic shock (AMICS) compared to conventional guideline-driven treatment. This paper describes the rationale and design of the randomized trial, in addition to the baseline characteristics of the population screened and enrolled so far. METHODS: The DanGer Shock study is a prospective, multicenter, open-label trial in patients with AMICS randomized 1:1 to Impella CP or current guideline-driven therapy with planned enrollment of 360 patients. Patients comatose after out of hospital cardiac arrest are excluded. Eligible patients are randomized immediately following shock diagnosis. Among patients randomized to receive Impella CP, the device is placed prior to angioplasty. The primary endpoint is all-cause mortality at 180 days. Baseline characteristics of patients screened and randomized in the DanGer Shock as of June 2018 are compared with 2 contemporary AMICS studies. RESULTS: As of end of June 2018, 314 patients were screened and 100 patients were randomized. Patients had median arterial lactate of 5.5 mmol/L (interquartile range 3.7-8.8 mmol/L), median systolic blood pressure of 76 mmHg (interquartile range 70-88 mmHg), and median LV ejection fraction of 20% (interquartile range 10%-30%). CONCLUSION: The DanGer Shock trial will be the first adequately powered randomized trial to address whether mechanical circulatory LV support with Impella CP can improve survival in AMICS. Baseline characteristics of the first 100 randomized patients indicate a population in profound cardiogenic shock.


Assuntos
Fidelidade a Diretrizes , Coração Auxiliar , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Choque Cardiogênico/terapia , Idoso , Pressão Sanguínea , Causas de Morte , Feminino , Humanos , Ácido Láctico/sangue , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Intervenção Coronária Percutânea , Estudos Prospectivos , Projetos de Pesquisa , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Choque Cardiogênico/sangue , Choque Cardiogênico/complicações , Choque Cardiogênico/fisiopatologia , Volume Sistólico , Fatores de Tempo
6.
Int J Cardiol ; 287: 1-6, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31006595

RESUMO

BACKGROUND: Exercise stress test (EST) has a moderate precision for diagnosis of CAD and could potentially obtain improved accuracy if adding a reliable cardiac biomarker to the test. OBJECTIVE: We aimed to investigate resting levels and change in hs-cTnT during EST in patients with and without angiographically significant CAD. Moreover, we intended to explore the additive value of hs-cTnT to EST results in diagnosis of stable CAD. We hypothesized that hs-cTnT would be higher in CAD patients and increase diagnostic precision of EST. METHOD: Patients presenting with symptoms of stable CAD, performed a maximal EST on a bicycle ergometer. Venous blood samples were taken at rest and within 5 min post-exercise. All patients underwent coronary angiography. Significant CAD was defined as having ≥75% stenosis in one or more segments of the coronary arteries. RESULTS: Out of the 297 participants, significant CAD was found in 111 (37%) patients. Patients with significant CAD compared to without, had higher resting levels of hs-cTnT (median 8.1 vs 5.0 ng/L) and no significant difference in exercise-induced change (median 0.5 vs 0.3 ng/L), p < 0.001 and p = 0.086 respectively. Combined resting hs-cTnT with EST had higher predictive value for significant CAD than EST alone, AUC = 0.751 vs. AUC = 0.637. In an adjusted multivariable regression analysis, resting hs-cTnT >6.0 ng/L was predictive for having significant CAD, OR 2.55 (CI 95% 1.40, 4.65 p = 0.002). CONCLUSION: In patients with suspected stable CAD, hs-cTnT has a predictive value alone, as well as added to a diagnostic EST for CAD.


Assuntos
Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico , Teste de Esforço/métodos , Troponina T/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Doença da Artéria Coronariana/sangue , Eletrocardiografia/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Índice de Gravidade de Doença
7.
Blood Press ; 28(2): 84-92, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30698038

RESUMO

AIMS: We aimed to investigate whether left bundle branch block (LBBB) is related to new-onset left ventricle (LV) wall motion abnormalities during treatment in hypertensive patients with electrocardiographic (ECG) defined left ventricular hypertrophy (LVH). METHODS AND RESULTS: 960 patients with essential hypertension and ECG-LVH participating in the LIFE Echo Sub-study were investigated at baseline and annually with echocardiography, during randomized antihypertensive therapy. After excluding patients with LV wall motion abnormalities at baseline and patients developing new-onset LBBB during study time, we investigated 784 patients. The participants with (n = 32) and without (n = 752) LBBB were similar regarding most baseline variables. Logistic regression models controlling for LV mass index, Framingham risk score, and randomized treatment assignment were used to assess the odds ratio of developing new-onset abnormal LV wall motion on annual follow-up echocardiograms. The likelihood of developing new global LV wall motion abnormalities in patients with LBBB was not higher compared to those without LBBB except at year 5 (p = .002). The likelihood of developing new segmental LV wall motion abnormalities in patients with LBBB was however higher compared to patients without LBBB after 1 year (OR = 3.1, 95% CI = 0.7-14.2, p = .173); 2 years (OR = 6.9, 2.1-22.4, p = .003); 3 years (OR = 5.3, 2.0-14.3, p < .001), 4 years (OR = 4.0, 1.6-10.3, p = .003 and 5 years (OR = 4.1, 1.0-16.2, p = .394) of treatment. CONCLUSION: Among patients with ECG-LVH, undergoing antihypertensive treatment, the presence of LBBB independently identifies individuals with ∼3- to 7-fold greater odds of developing new segmental abnormal LV wall motion. These findings suggest that LBBB may be a marker for progressive myocardial disease.


Assuntos
Bloqueio de Ramo/complicações , Ventrículos do Coração/fisiopatologia , Hipertensão/complicações , Hipertrofia Ventricular Esquerda/diagnóstico , Idoso , Anti-Hipertensivos/uso terapêutico , Cardiomiopatias , Progressão da Doença , Ecocardiografia , Eletrocardiografia , Feminino , Ventrículos do Coração/patologia , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Prognóstico
10.
Atherosclerosis ; 272: 129-136, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29602140

RESUMO

BACKGROUND AND AIMS: Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory marker associated with cardiovascular disease. Statins lower both low-density lipoprotein (LDL)-cholesterol and C-reactive protein (CRP), resulting in improved outcomes. However, whether lipid-lowering therapy also lowers suPAR levels is unknown. METHODS: We investigated whether treatment with Simvastatin 40 mg and Ezetimibe 10 mg lowered plasma suPAR levels in 1838 patients with mild-moderate, asymptomatic aortic stenosis, included in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study, using a pattern mixture model. A 1-year Cox analysis, adjusted for established cardiovascular risk factors, allocation to study treatment, peak aortic valve velocity and baseline suPAR, was performed to evaluate relationships between change in suPAR with all-cause mortality and the composite endpoint of major cardiovascular events (MCE) composed of ischemic cardiovascular events (ICE) and aortic valve related events (AVE). RESULTS: After 4.3 years of follow-up, suPAR levels had increased by 9.2% (95% confidence interval [CI]: 7.0%-11.5%) in the placebo group, but only by 4.1% (1.9%-6.2%) in the group with lipid-lowering treatment (p<0.001). In a multivariate 1-year analysis, 1-year suPAR was strongly associated with all-cause mortality, hazard ratio (HR) = 2.05 (1.17-3.61); MCE 1.40 (1.01-1.92); and AVE 1.42 (1.02-1.99) (all p<0.042) for each doubling of suPAR; but was not associated with ICE. CONCLUSIONS: Simvastatin and Ezetimibe treatment impeded the progression of the time-related increase in plasma suPAR levels. Year-1 suPAR was associated with all-cause mortality, MCE, and AVE irrespective of baseline levels (SEAS study: NCT00092677).


Assuntos
Aorta/patologia , Ezetimiba/uso terapêutico , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Sinvastatina/uso terapêutico , Idoso , Anticolesterolemiantes/uso terapêutico , Estenose da Valva Aórtica/complicações , Biomarcadores/sangue , Proteína C-Reativa/análise , LDL-Colesterol/sangue , Constrição Patológica , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco
11.
Open Heart ; 5(1): e000743, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29387432

RESUMO

Background: We evaluated whether early measurement of soluble urokinase plasminogen activator receptor (suPAR) could predict future risk of postoperative complications in initially asymptomatic patients with mild-moderate aortic stenosis (AS) undergoing aortic valve replacement (AVR) surgery. Methods: Baseline plasma suPAR levels were available in 411 patients who underwent AVR surgery during follow-up in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Cox analyses were used to evaluate suPAR in relation to all-cause mortality and the composite endpoint of postoperative complications (all-cause mortality, congestive heart failure, stroke and renal impairment) occurring in the 30-day postoperative period. Results: Patients with initially higher levels of suPAR were at increased risk of postoperative mortality with a HR of 3.5 (95% CI 1.4 to 9.0, P=0.008) and postoperative complications with a HR of 2.7 (95% CI 1.5 to 5.1, P=0.002), per doubling in suPAR. After adjusting for the European System for Cardiac Operative Risk Evaluation or Society of Thoracic Surgeons risk score, suPAR remained associated with postoperative mortality with a HR 3.2 (95% CI 1.2 to 8.6, P=0.025) and 2.7 (95% CI 1.0 to 7.8, P=0.061); and postoperative complications with a HR of 2.5 (95% CI 1.3 to 5.0, P=0.007) and 2.4 (95% CI 1.2 to 4.8, P=0.011), respectively. Conclusion: Higher baseline suPAR levels are associated with an increased risk for postoperative complications and mortality in patients with mild-moderate, asymptomatic AS undergoing later AVR surgery. Further validation in other subsets of AS individuals are warranted. Trial registration number: NCT00092677; Post-results.

12.
Am J Cardiol ; 121(6): 739-745, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29361285

RESUMO

Observational studies indicate that low-density lipoprotein (LDL) cholesterol acts as a primary contributor to an active process leading to aortic stenosis (AS) development. However, randomized clinical trials have failed to demonstrate an effect of lipid lowering on impeding AS progression. This study explored if pretreatment LDL levels and AS severity altered the efficacy of lipid-lowering therapy. The study goal was evaluated in the analysis of surviving patients with baseline data in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial of 1,873 asymptomatic patients with mild-to-moderate AS. Serially measured peak aortic jet velocity was the primary effect estimate. Linear mixed model analysis adjusted by baseline peak jet velocity and pretreatment LDL levels was used to assess effect modifications of treatment. Data were available in 1,579 (84%) patients. In adjusted analyses, lower baseline peak aortic jet velocity and higher pretreatment LDL levels increased the effect of randomized treatment (p = 0.04 for interaction). As such, treatment impeded progression of AS in the highest quartile of LDL among patients with mild AS at baseline (0.06 m/s per year slower progression vs placebo in peak aortic jet velocity, 95% confidence interval 0.01 to 0.11, p = 0.03), but not in the 3 other quartiles of LDL. Conversely, among patients with moderate AS, there was no detectable effect of treatment in any of the pretreatment LDL quartiles (all p ≥0.14). In conclusion, in a non-prespecified post hoc analysis, the efficacy of lipid-lowering therapy on impeding AS progression increased with higher pretreatment LDL and lower peak aortic jet velocity (SEAS study: NCT00092677).


Assuntos
Anticolesterolemiantes/uso terapêutico , Estenose da Valva Aórtica/tratamento farmacológico , Estenose da Valva Aórtica/fisiopatologia , Ezetimiba/uso terapêutico , Sinvastatina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/diagnóstico por imagem , Progressão da Doença , Método Duplo-Cego , Combinação de Medicamentos , Ecocardiografia Doppler , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Resultado do Tratamento
13.
J Am Heart Assoc ; 6(12)2017 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-29180457

RESUMO

BACKGROUND: Patients with aortic stenosis (AS) often have concomitant hypertension. Antihypertensive treatment with a ß-blocker (Bbl) is frequently avoided because of fear of depression of left ventricular function. However, it remains unclear whether antihypertensive treatment with a Bbl is associated with increased risk of cardiovascular events in patients with asymptomatic mild to moderate AS. METHODS AND RESULTS: We did a post hoc analysis of 1873 asymptomatic patients with mild to moderate AS and preserved left ventricular ejection fraction in the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) study. Propensity-matched Cox regression and competing risk analyses were used to assess risk ratios for all-cause mortality, sudden cardiac death, and cardiovascular death. A total of 932 (50%) patients received Bbl at baseline. During a median follow-up of 4.3±0.9 years, 545 underwent aortic valve replacement, and 205 died; of those, 101 were cardiovascular deaths, including 40 sudden cardiovascular deaths. In adjusted analyses, Bbl use was associated with lower risk of all-cause mortality (hazard ratio 0.5, 95% confidence interval 0.3-0.7, P<0.001), cardiovascular death (hazard ratio 0.4, 95% confidence interval 0.2-0.7, P<0.001), and sudden cardiac death (hazard ratio 0.2, 95% confidence interval 0.1-0.6, P=0.004). This was confirmed in competing risk analyses (all P<0.004). No interaction was detected with AS severity (all P>0.1). CONCLUSIONS: In post hoc analyses Bbl therapy did not increase the risk of all-cause mortality, sudden cardiac death, or cardiovascular death in patients with asymptomatic mild to moderate AS. A prospective study may be warranted to determine if Bbl therapy is in fact beneficial. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00092677.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/administração & dosagem , Estenose da Valva Aórtica/complicações , Pressão Sanguínea/fisiologia , Ezetimiba/administração & dosagem , Ventrículos do Coração/fisiopatologia , Hipertensão/tratamento farmacológico , Sinvastatina/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Anticolesterolemiantes/administração & dosagem , Estenose da Valva Aórtica/mortalidade , Estenose da Valva Aórtica/fisiopatologia , Doenças Assintomáticas , Pressão Sanguínea/efeitos dos fármacos , Causas de Morte/tendências , Relação Dose-Resposta a Droga , Método Duplo-Cego , Quimioterapia Combinada , Ecocardiografia Doppler/métodos , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hipertensão/epidemiologia , Hipertensão/etiologia , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Pontuação de Propensão , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia
15.
Thromb J ; 15: 3, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28115916

RESUMO

BACKGROUND: Strenuous exercise may trigger myocardial infarction through increased pro-coagulant activity. We aimed to investigate whether patients referred for exercise testing, who were found to have angiographically verified coronary artery disease (CAD), have a more hypercoagulable profile during exercise testing than those without CAD. METHODS: Patients with symptoms of stable CAD were examined with exercise electrocardiography on bicycle ergometer. Venous blood samples were taken at rest and within 5 min after end of exercise. The following haemostatic variables were analyzed: tissue factor pathway inhibitor (TFPI) activity and antigen, prothrombin fragment 1 + 2 (F1 + 2), D-dimer and endogenous thrombin potential (ETP). All participants underwent conventional coronary angiography. CAD was defined as having any degree of atherosclerosis. RESULTS: Out of the 106 patients enrolled, 70 were found to have CAD. Mean exercise duration was 10:06 ± 4:11 min, with no significant differences between the groups. A significant increase from baseline to after exercise testing was observed in all measured markers in the total population (p ≤ 0.002 for all). In patients with angiographically verified CAD, total TFPI was significantly lower at baseline compared to patients without CAD (median value 67.4 and 76.6 ng/ml respectively, p = 0.027). However, no significant differences in changes of any of the measured markers during exercise were observed between the two groups. CONCLUSION: Pro-coagulant activity increased during short-term strenuous exercise testing in patients with symptoms suggestive of CAD. However the hypercoagulable state observed, was not more pronounced in patients with angiographically verified CAD compared to patients without CAD. NCT01495091.

16.
Blood Press ; 26(3): 150-155, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27710139

RESUMO

We tested the prognostic impact of a marker of arterial stiffness, pulse pressure/stroke volume index (PP/SVi), in patients with hypertension and left ventricular (LV) hypertrophy. We used data from 866 patients randomized to losartan or atenolol-based antihypertensive treatment, over a median of 4.8 years, in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. The association of PP/SVi with outcomes was tested in Cox regression analyses and reported as hazard ratio (HR) and 95% confidence intervals (CI). In multivariate regression, reduction of PP/SVi was independently associated with male gender, reduction in systolic blood pressure (BP) and relative wall thickness and with an increase in left ventricular ejection fraction (all p < .05). After adjusting for confounders, higher baseline PP/SVi predicted a 38% higher hazard of combined major fatal and non-fatal cardiovascular events (95% CI 1.04-1.84), and higher hazard of cardiovascular mortality (HR 2.35 (95% CI 1.59-3.48) and stroke (HR 1.45 (95% CI 1.06-1.99) (all p < .05). Higher PP/SVi also predicts higher rate of hospitalization for HF (HR 2.15 (95% CI 1.48-3.12) and a 52% higher hazard of all-cause mortality (95% CI 1.10-2.09) (both p < .05). In hypertensive patients with electrocardiographic LV hypertrophy, higher PP/SVi was associated with increased cardiovascular morbidity and mortality.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Volume Sistólico/efeitos dos fármacos , Acidente Vascular Cerebral/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Atenolol/uso terapêutico , Eletrocardiografia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertensão/mortalidade , Hipertrofia Ventricular Esquerda/complicações , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Hipertrofia Ventricular Esquerda/mortalidade , Losartan/uso terapêutico , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores Sexuais , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade , Rigidez Vascular
19.
Can J Cardiol ; 32(12): 1462-1469, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27499378

RESUMO

BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory marker associated with subclinical cardiovascular damage and cardiovascular events. Whether suPAR is of prognostic value in asymptomatic patients with aortic stenosis (AS) remains unknown. METHODS: Plasma suPAR levels were measured in 1503 patients with a mean age of 68 years who were recruited in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Cox regression analysis was performed to evaluate associations between suPAR and the composite end points of ischemic cardiovascular events (ICEs), aortic valve events (AVEs), cardiovascular and all-cause mortality after adjusting for traditional cardiovascular risk factors, and allocation to treatment. RESULTS: The multivariate adjusted hazard ratio (HR) (95% confidence interval [CI]) per unit log2 ng/mL increase in suPAR was HR, 1.5; 95% CI, 1.2-1.9; P = 0.002 for ICEs; HR, 1.2; 95% CI, 0.9-1.5; P = 0.071) for AVEs; HR, 2.0; 95% CI, 1.2-3.3; P = 0.007) for cardiovascular mortality, and HR, 2.0; 95% CI, 1.4-2.9; P < 0.001 for all-cause mortality. CONCLUSIONS: In patients with mild-moderate AS, suPAR is independently associated with the incidence of ICEs, cardiovascular mortality, and all-cause mortality.


Assuntos
Estenose da Valva Aórtica , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Idoso , Estenose da Valva Aórtica/sangue , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/mortalidade , Doenças Assintomáticas , Biomarcadores/sangue , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/epidemiologia , Isquemia Miocárdica/etiologia , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco
20.
Circulation ; 134(6): 455-68, 2016 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-27486164

RESUMO

BACKGROUND: Evidence for treating hypertension in patients with asymptomatic aortic valve stenosis is scarce. We used data from the SEAS trial (Simvastatin Ezetimibe in Aortic Stenosis) to assess what blood pressure (BP) would be optimal. METHODS: A total of 1767 patients with asymptomatic aortic stenosis and no manifest atherosclerotic disease were analyzed. Outcomes were all-cause mortality, cardiovascular death, heart failure, stroke, myocardial infarction, and aortic valve replacement. BP was analyzed in Cox models as the cumulative average of serially measured BP and a time-varying covariate. RESULTS: The incidence of all-cause mortality was highest for average follow-up systolic BP ≥160 mm Hg (4.3 per 100 person-years; 95% confidence interval [CI], 3.1-6.0) and lowest for average systolic BP of 120 to 139 mm Hg (2.0 per 100 person-years; 95% CI, 1.6-2.6). In multivariable analysis, all-cause mortality was associated with average systolic BP <120 mm Hg (hazard ratio [HR], 3.4; 95% CI, 1.9-6.1), diastolic BP ≥90 mm Hg (HR, 1.8; 95% CI, 1.1-2.9), and pulse pressure <50 mm Hg (HR, 1.8; 95% CI, 1.1-2.9), with systolic BP of 120 to 139 mm Hg, diastolic BP of 70 to 79 mm Hg, and pulse pressure of 60 to 69 mm Hg taken as reference. Low systolic and diastolic BPs increased risk in patients with moderate aortic stenosis. With a time-varying systolic BP from 130 to 139 mm Hg used as reference, mortality was increased for systolic BP ≥160 mm Hg (HR, 1.7; P=0.033) and BP of 120 to 129 mm Hg (HR, 1.6; P=0.039). CONCLUSIONS: Optimal BP seems to be systolic BP of 130 to 139 mm Hg and diastolic BP of 70 to 90 mm Hg in these patients with asymptomatic aortic stenosis and no manifest atherosclerotic disease or diabetes mellitus. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00092677.


Assuntos
Anticolesterolemiantes/administração & dosagem , Estenose da Valva Aórtica/tratamento farmacológico , Pressão Sanguínea/efeitos dos fármacos , Ezetimiba/administração & dosagem , Hipertensão/tratamento farmacológico , Sinvastatina/administração & dosagem , Idoso , Estenose da Valva Aórtica/diagnóstico por imagem , Pressão Sanguínea/fisiologia , Método Duplo-Cego , Seguimentos , Humanos , Hipertensão/diagnóstico por imagem , Pessoa de Meia-Idade
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