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1.
ESC Heart Fail ; 7(1): 158-166, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31903729

RESUMO

AIMS: In the PARADIGM-heart failure trial, sacubitril-valsartan demonstrated a reduction in heart failure admissions and reduced all-cause mortality in patients with heart failure with reduced ejection fraction. Although real world data have shown similar benefits regarding efficacy and safety, there has been difficulty in achieving the target dose (TD). The factors preventing the achievement of TD remains unclear. This study assesses the tolerability, ability to achieve, and factors linked to attaining TD in a routine clinical population. METHODS AND RESULTS: This is a retrospective single-centre review of patients switched from angiotensin-converting enzyme inhibitors/angiotensin receptor blockers to sacubitril-valsartan between May 2016 and August 2018. Baseline and follow-up clinical characteristics and biomarker profiles were collected. Univariate and multivariate analyses were used to analyse predictors of achieving TD. Clinical response to sacubitril-valsartan was defined as a reduction in N terminal pro BNP of ≥30%, or an increase in left ventricular ejection fraction of ≥5% compared with baseline values. To date, a total of 322 patients (75% male patients) have been switched to sacubitril-valsartan. Those still in the titration phase were excluded (n = 25). Sacubitril-valsartan was not tolerated in 40 patients (12.4%). Those intolerant were older (73.4 years [68.3, 80.6] vs. 69.1 years [61.2, 76]; P = 0.003) and had worse renal function with estimated glomerular filtration rate (53.5 mL/min/1.72 m2 [36.8, 60.2] vs 60 mL/min/1.72 m2 [47, 77]; P ≤ 0.001). Of the remaining 257 patients, TD (97/103 mg BD) was achieved in 194 patients (75.5%), while 37 patients (11.4%) were maintained on 49/51 mg BD and 26 patients (8.1%) remained on 24/26 mg BD. Symptomatic hypotension (74.6%) was the main impediment to attaining TD, followed by renal deterioration (12.7%), and to a lesser extent hyperkalaemia and gastrointestinal symptoms (4.8% each). Diuretic dose decrease was achieved in 37.2% of patients, and this was the strongest independent predictor of achieving TD (odds ratio = 2.1; 95% confidence interval [1.16, 3.8]; P = 0.014). Responder status by N terminal pro BNP criterion was observed in 99 of 214 patients (46.3%) while 70 of 142 (49.3%) attained the left ventricular ejection fraction response status. Achieving this response was independently linked to achieving TD. CONCLUSIONS: Sacubitril-valsartan was well tolerated. Achievement of TD was possible in the majority of the cohort and was linked to response metrics. Reduction in diuretic was required in a large percentage of the population and was the strongest predictor of attaining TD. Therefore, careful clinical attention to volume status assessment is essential to maximising the benefits of sacubitril-valsartan.

4.
Cochrane Database Syst Rev ; 10: CD013015, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31613983

RESUMO

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. Early intervention for those with high cardiovascular risk is crucial in improving patient outcomes. Traditional prevention strategies for CVD have focused on conventional risk factors, such as overweight, dyslipidaemia, diabetes, and hypertension, which may reflect the potential for cardiovascular insult. Natriuretic peptides (NPs), including B-type natriuretic peptide (BNP) and N-terminal pro B-type natriuretic peptide (NT-proBNP), are well-established biomarkers for the detection and diagnostic evaluation of heart failure. They are of interest for CVD prevention because they are secreted by the heart as a protective response to cardiovascular stress, strain, and damage. Therefore, measuring NP levels in patients without heart failure may be valuable for risk stratification, to identify those at highest risk of CVD who would benefit most from intensive risk reduction measures. OBJECTIVES: To assess the effects of natriuretic peptide (NP)-guided treatment for people with cardiovascular risk factors and without heart failure. SEARCH METHODS: Searches of the following bibliographic databases were conducted up to 9 July 2019: CENTRAL, MEDLINE, Embase, and Web of Science. Three clinical trial registries were also searched in July 2019. SELECTION CRITERIA: We included randomised controlled trials enrolling adults with one or more cardiovascular risk factors and without heart failure, which compared NP-based screening and subsequent NP-guided treatment versus standard care in all settings (i.e. community, hospital). DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts and selected studies for inclusion, extracted data, and evaluated risk of bias. Risk ratios (RRs) were calculated for dichotomous data, and mean differences (MDs) with 95% confidence intervals (CIs) were calculated for continuous data. We contacted trial authors to obtain missing data and to verify crucial study characteristics. Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, two review authors independently assessed the quality of the evidence and GRADE profiler (GRADEPRO) was used to import data from Review Manager to create a 'Summary of findings' table. MAIN RESULTS: We included two randomised controlled trials (three reports) with 1674 participants, with mean age between 64.1 and 67.8 years. Follow-up ranged from 2 years to mean 4.3 years.For primary outcome measures, effect estimates from a single study showed uncertainty for the effect of NP-guided treatment on cardiovascular mortality in patients with cardiovascular risk factors and without heart failure (RR 0.33, 95% CI 0.04 to 3.17; 1 study; 300 participants; low-quality evidence). Pooled analysis demonstrated that in comparison to standard care, NP-guided treatment probably reduces the risk of cardiovascular hospitalisation (RR 0.52, 95% CI 0.40 to 0.68; 2 studies; 1674 participants; moderate-quality evidence). This corresponds to a risk of 163 per 1000 in the control group and 85 (95% CI 65 to 111) per 1000 in the NP-guided treatment group.When secondary outcome measures were evaluated, evidence from a pooled analysis showed uncertainty for the effect of NP-guided treatment on all-cause mortality (RR 0.90, 95% CI 0.60 to 1.35; 2 studies; 1354 participants; low-quality evidence). Pooled analysis indicates that NP-guided treatment probably reduces the risk of all-cause hospitalisation (RR 0.83, 95% CI 0.75 to 0.92; 2 studies; 1354 participants; moderate-quality evidence). This corresponds to a risk of 601 per 1000 in the control group and 499 (95% CI 457 to 553) per 1000 in the NP-guided treatment group. The effect estimate from a single study indicates that NP-guided treatment reduced the risk of ventricular dysfunction (RR 0.61, 95% CI 0.41 to 0.91; 1374 participants; high-quality evidence). The risk in this study's control group was 87 per 1000, compared with 53 (95% CI 36 to 79) per 1000 with NP-guided treatment. Results from the same study show that NP-guided treatment does not affect change in NP level at the end of follow-up, relative to standard care (MD -4.06 pg/mL, 95% CI -15.07 to 6.95; 1 study; 1374 participants; moderate-quality evidence). AUTHORS' CONCLUSIONS: This review shows that NP-guided treatment is likely to reduce ventricular dysfunction and cardiovascular and all-cause hospitalisation for patients who have cardiovascular risk factors and who do not have heart failure. Effects on mortality and natriuretic peptide levels are less certain. Neither of the included studies were powered to evaluate mortality. Available evidence shows uncertainty regarding the effects of NP-guided treatment on both cardiovascular mortality and all-cause mortality; very low event numbers resulted in a high degree of imprecision in these effect estimates. Evidence also shows that NP-guided treatment may not affect NP level at the end of follow-up.As both trials included in our review were pragmatic studies, non-blinding of patients and practices may have biased results towards a finding of equivalence. Further studies with more adequately powered sample sizes and longer duration of follow-up are required to evaluate the effect of NP-guided treatment on mortality. As two trials are ongoing, one of which is a large multi-centre trial, it is hoped that future iterations of this review will benefit from larger sample sizes across a wider geographical area.

5.
J Clin Sleep Med ; 15(7): 957-963, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31383232

RESUMO

STUDY OBJECTIVES: Systemic hypertension is highly prevalent in obstructive sleep apnea (OSA) but there are limited data on OSA prevalence in cohorts with hypertension comparing dippers and nondippers. We investigated this relationship in a clinic-based cohort of patients with hypertension who were not screened for any pretest possibility of OSA. METHODS: A total of 100 patients with hypertension aged (mean ± SD) 58 ± 10 years, body mass index 30.5 ± 6.1 kg/m2, and Epworth Sleepiness Scale score 6 ± 4 were included. All underwent overnight attended sleep studies and 24-hour ambulatory blood pressure monitoring. The primary study end-point was OSA prevalence based on the standard criteria of apnea-hypopnea index (AHI) ≥ 15 events/h in patients with dipping and nondipping nocturnal blood pressure. RESULTS: Results showed 10.5% of dippers and 43.5% of nondippers had an AHI ≥ 15 (chi-square P = .001). In univariate analysis, AHI correlated significantly with blood pressure dip (r = -.26, P < .05), as did ESS (r = -.28, P < .05). In linear regression, AHI predicted the magnitude of blood pressure dip (standardised ß = -.288, P = .03), whereas age, body mass index, systolic blood pressure and diastolic blood pressure did not. CONCLUSIONS: Patients with nondipping nocturnal blood pressure are at high risk of OSA, regardless of symptom profile, which supports the recommendation that such patients should be assessed for co-existing OSA.

6.
Expert Rev Cardiovasc Ther ; 17(4): 267-273, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30916595

RESUMO

INTRODUCTION: Heart failure is a highly prevalent condition affecting approximately 2% of people worldwide. Heart failure disease management programs (DMP) have shown a reduction in mortality and reduced hospitalization and are an established part of clinical guidelines; however, their presence is not widespread. Focusing on the application of proven therapies, patient education, diagnosis with work up of cause and easy access for clinical deterioration should be fundamental to the structure of the DMP. Multidisciplinary team care with early and timely recognition of potentially critical patients is essential, along with the inclusion of patients diagnosed in hospital as well as the community. Areas covered: The fundamental structure of a DMP along with the current gaps in evidence is outlined. Current challenges with the heart failure condition along with the current best evidence are covered. Articles were searched using MEDLINE containing the keywords; Chronic Heart Failure, Disease Management Program. We have also provided clinical opinion. Expert opinion: A multidisciplinary approach to disease management programs is essential to providing adequate care to patients. DMPs are an established part of current guidelines and should be a benchmark of treatment. Future resources should be focused on identifying patients at risk and early prevention.


Assuntos
Gerenciamento Clínico , Insuficiência Cardíaca/terapia , Humanos , Equipe de Assistência ao Paciente
7.
ESC Heart Fail ; 6(3): 499-508, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30854781

RESUMO

AIMS: This study sought to review the literature for clinical prediction models for the diagnosis of patients with chronic heart failure in the community and to validate the models in a novel cohort of patients with a suspected diagnosis of chronic heart failure. METHODS AND RESULTS: MEDLINE and Embase were searched from 1946 to Q4 2017. Studies were eligible if they contained at least one multivariable model for the diagnosis of chronic heart failure applicable to the primary care setting. The CHARMS checklist was used to evaluate models. We also validated models, where possible, in a novel cohort of patients with a suspected diagnosis of heart failure referred to a rapid access diagnostic clinic. In total, 5310 articles were identified with nine articles subsequently meeting the eligibility criteria. Three models had undergone internal validation, and four had undergone external validation. No clinical impact studies have been completed to date. Area under the curve (AUC) varied from 0.74 to 0.93 and from 0.60 to 0.65 in the novel cohort for clinical models alone with AUC up to 0.89 in combination with electrocardiogram and B-type natriuretic peptide (BNP). The AUC for BNP was 0.86 (95% confidence interval 83.3-88.6%). CONCLUSIONS: This review demonstrates that there are a number of clinical prediction rules relevant to the diagnosis of chronic heart failure in the literature. Clinical impact studies are required to compare the use of clinical prediction rules and biomarker strategies in this setting.


Assuntos
Diagnóstico por Computador , Insuficiência Cardíaca/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Doença Crônica , Feminino , Humanos , Masculino
8.
Circ Heart Fail ; 12(3): e005765, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30798618

RESUMO

BACKGROUND: Limited knowledge exists of the extent of epigenetic alterations, such as DNA methylation, in heart failure (HF). We conducted targeted DNA methylation sequencing to identify DNA methylation alterations in coding and noncoding RNA (ncRNA) across different etiological subtypes of HF. METHODS AND RESULTS: A targeted bisulfite sequence capture sequencing platform was applied to DNA extracted from cardiac interventricular septal tissue of 30 male HF patients encompassing causes including hypertrophic obstructive cardiomyopathy, ischemic cardiomyopathy, dilated cardiomyopathy, and 9 control patients with nonfailing hearts. We detected 62 678 differentially methylated regions in the studied HF cohort. By comparing each HF subgroup to the nonfailing control group, we identified 195 unique differentially methylated regions: 5 in hypertrophic obstructive cardiomyopathy, 151 in dilated cardiomyopathy, and 55 in ischemic cardiomyopathy. These translated to 4 genes/1 ncRNA in hypertrophic obstructive cardiomyopathy, 131 genes/17 ncRNA in dilated cardiomyopathy, and 51 genes/5 ncRNA in ischemic cardiomyopathy. Subsequent gene/ncRNA expression analysis was assessed using quantitative reverse transcription polymerase chain reaction and revealed 6 genes: 4 hypermethylated ( HEY2, MSR1, MYOM3, and COX17), 2 hypomethylated ( CTGF and MMP2); and 2 microRNA: 1 hypermethylated (miR-24-1), 1 hypomethylated (miR-155) with significantly upregulated or downregulated expression levels consistent with the direction of methylation in the particular HF subgroup. CONCLUSIONS: For the first time DNA methylation alterations and associated gene expression changes were identified in etiologically variant pathological HF tissue. The methylation-sensitive and disease-associated genes/ncRNA identified from this study represent a unique cohort of loci that demonstrate a plausible potential as a novel diagnostic and therapeutic target in HF and warrant further investigation.


Assuntos
Metilação de DNA/genética , Epigênese Genética/genética , Insuficiência Cardíaca/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Coração/fisiopatologia , Humanos , Masculino , Fenótipo
10.
Card Fail Rev ; 4(1): 21-24, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29892471

RESUMO

Heart failure is a growing problem in sub-Saharan Africa. This arises as the prevalence of risk factors for cardiovascular disease rises, life expectancy increases and causes of heart failure more common in Africa, such as rheumatic heart disease and endomyocardial fibrosis, continue to be a significant issue. Lack of access to diagnostics is an issue with the expense and technical expertise required for echocardiography limiting access. Biomarker strategies may play a role here. Access to essential medicines is also limited and requires a renewed focus by the international community to ensure that appropriate medications are readily available, similar to that which has been implemented for HIV and malaria.

11.
Am J Hypertens ; 31(2): 228-234, 2018 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-29036547

RESUMO

BACKGROUND: The prevalence and morbidity of hypertension continues to grow globally and improved methods of stratifying risk and identifying organ damage earlier are required. Methods such as echocardiography and population-based risk scores are suggested by guidelines as approaches to aid in risk stratification. However, biomarkers such as natriuretic peptides may help provide such an approach. METHODS: We analyzed data from the screening to prevent heart failure cohort including participants with hypertension with and without a history of a cardiovascular (CV) event at baseline. We investigated the ability of ventricular dysfunction on echocardiography at baseline and of B-type natriuretic peptide (BNP) levels in predicting future major adverse CV events (MACE) and death. We also investigated the use of Systematic COronary Risk Evaluation (SCORE) to predict these events in the uncomplicated cohort. RESULTS: In total, 572 patients (427 with uncomplicated hypertension) were included. Thirty-three patients had MACE or died during follow up. In a univariate analysis, BNP was predictive of MACE and death in all groups. Ventricular dysfunction was not predictive of MACE and death in any group. Both BNP and SCORE had predictive value in this category. However, the magnitude and strength of the continuous association between BNP and events is higher and BNP adds significantly to the predictive value of SCORE as determined by likelihood ratios. The net reclassification improvement for BNP compared to stage B heart failure was 0.20. CONCLUSION: This study demonstrates that in patients with hypertension, BNP is superior to ventricular dysfunction on echocardiography in the prediction of risk of MACE and death in a community-based cohort of patients with complicated and uncomplicated hypertension.


Assuntos
Pressão Sanguínea , Hipertensão/sangue , Peptídeo Natriurético Encefálico/sangue , Disfunção Ventricular Esquerda/sangue , Função Ventricular Esquerda , Idoso , Biomarcadores/sangue , Progressão da Doença , Ecocardiografia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/mortalidade , Hipertensão/fisiopatologia , Irlanda/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco , Fatores de Tempo , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/mortalidade , Disfunção Ventricular Esquerda/fisiopatologia
12.
Diabetes Res Clin Pract ; 137: 10-19, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29287838

RESUMO

Type 2 diabetes mellitus is no longer a disease of high income countries but a global health pandemic. With the continued and rapid increase in its prevalence worldwide it is forecasted that diabetes will be a leading cause of morbidity and mortality. A major concern stems from its role in development and progression of cardiovascular disease, including cardiac dysfunction and heart failure. Within low- and middle-income areas such as Sub-Saharan Africa the burden of diabetes is already significant driven by many factors, including, socioeconomic (urbanisation), nutritional (high-calorie "western-diet", obesity) and lifestyle (physical inactivity) changes. Insufficient economic and community resources, poor health care system development and chronic disease management, poor education, and a lack of preventative and diagnostic measures further aggravate the severity of the diabetes problem. This review outlines the burden of type 2 diabetes mellitus in Sub-Saharan Africa and highlights the need for improved community health care and regulations to reduce its epidemiological spread and devastating impact on health.


Assuntos
Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/complicações , Adolescente , Adulto , África ao Sul do Saara/epidemiologia , Idoso , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
13.
ESC Heart Fail ; 4(3): 252-258, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28772044

RESUMO

AIMS: We undertook a mixed-methods evaluation of a Web-based conferencing service (virtual consult) between general practitioners (GPs) and cardiologists in managing patients with heart failure in the community to determine its effect on use of specialist heart failure services and acceptability to GPs. METHODS AND RESULTS: All cases from June 2015 to October 2016 were recorded using a standardized recording template, which recorded patient demographics, medical history, medications, and outcome of the virtual consult for each case. Quantitative surveys and qualitative interviewing of 17 participating GPs were also undertaken. During this time, 142 cases were discussed-68 relating to a new diagnosis of heart failure, 53 relating to emerging deterioration in a known heart failure patient, and 21 relating to therapeutic issues. Only 17% required review in outpatient department following the virtual consultation. GPs reported increased confidence in heart failure management, a broadening of their knowledge base, and a perception of overall better patient outcomes. CONCLUSIONS: These data from an initial experience with Heart Failure Virtual Consultation present a very positive impact of this strategy on the provision of heart failure care in the community and acceptability to users. Further research on the implementation and expansion of this strategy is warranted.

14.
Eur J Obstet Gynecol Reprod Biol ; 210: 342-347, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28122315

RESUMO

OBJECTIVE: To determine the per cycle chance of a live birth and to identify factors that may support a more individualised application of IUI in view of National Institute for Health and Care Excellence (NICE) updated guideline on fertility 2013. STUDY DESIGN: A retrospective, cohort study of 851 couples (1688 cycles) with unexplained, mild endometriosis, one patent Fallopian tube (with ovulation occurring in the corresponding ovary), mild male factor or ovulatory dysfunction, who initiated their first cycle of IUI/COH during the study period 2009-2013 and completed up to 3 cycles. Exclusion criteria included donor sperm and diminished ovarian reserve. Success factors and probabilities were determined based on live birth rates. RESULTS: Mean age was 33.8±3.3years and mean duration of subfertility was 2.28±1.47years. Independent associates of successful outcome factors were lower age (AOR 0.93; 95%CI 0.89-0.98, p=0.007) and multiparity (AOR 1.72; 95%CI 1.17-2.52). Live-birth rates declined independently of other factors from 15.3% (n=130/851) in cycle 1-7.0% (n=19/273) in cycle 3 (AOR 0.76; 95%CI, 0.62-0.93, p=0.008). Per cycle probabilities of live birth ranged from 21.4% to 5.1% dependent on age, cycle number and previous parity. The unadjusted cumulative pregnancy rate for live birth per cycle started, over three cycles, was 34.9% with a multiple live birth rate per cycle started of 5.4%. The associates of live birth amongst those with unexplained sub-fertility only (n=632, first cycle attempt) were also analysed, yielding similar results. CONCLUSIONS: IUI/COH is a simple treatment that produces good live birth rates, especially in younger patients and/or those with previous parity. More than 90% of total live births with IUI/COH is achieved during the first two cycles. As a retrospective, observational study, there is no comparator group and therefore we cannot comment on the relative efficacy of up to three IUI cycles over expectant management in a similar cohort. Our study suggests that probabilities of success can be used to individualise treatment decisions and that there is merit in continuing to offer IUI before resorting to IVF for certain patients.


Assuntos
Inseminação Artificial/estatística & dados numéricos , Adulto , Feminino , Humanos , Masculino , Estudos Retrospectivos
15.
Acta Haematol ; 138(4): 223-232, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29301124

RESUMO

BACKGROUND: Iron food fortification and oral iron formulations are frequently limited by poor absorption, resulting in the widespread use of high-dose oral iron, which is poorly tolerated. METHODS: We evaluated novel iron-denatured whey protein (Iron-WP) microspheres on reactive oxygen species (ROS) and viability in gut epithelial (HT29) cells. We compared iron absorption from Iron-WP versus equimolar-dose (25 mg elemental iron) ferrous sulphate (FeSO4) in a prospective, randomised, cross-over study in fasting volunteers (n = 21 per group) dependent on relative iron depletion (a ferritin level ≤/>30 ng/mL). RESULTS: Iron-WP caused less ROS generation and better HT29 cell viability than equimolar FeSO4. Iron-WP also showed better absorption with a maximal 149 ± 39% increase in serum iron compared to 65 ± 14% for FeSO4 (p = 0.01). The response to both treatments was dependent on relative iron depletion, and multi-variable analysis showed that better absorption with Iron-WP was independent of baseline serum iron, ferritin, transferrin saturation, and haemoglobin in the overall group and in the sub-cohort with relative iron depletion at baseline (p < 0.01). CONCLUSIONS: Novel Iron-WP microspheres may protect gut epithelial cells and improve the absorption of iron versus FeSO4. Further evaluation of this approach to food fortification and supplementation with iron is warranted.


Assuntos
Ferro/administração & dosagem , Proteínas do Soro do Leite/administração & dosagem , Adulto , Estudos Cross-Over , Método Duplo-Cego , Portadores de Fármacos/administração & dosagem , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Jejum/sangue , Feminino , Ferritinas/sangue , Humanos , Absorção Intestinal/efeitos dos fármacos , Ferro/efeitos adversos , Ferro/deficiência , Masculino , Microesferas , Estresse Oxidativo/efeitos dos fármacos , Estudos Prospectivos , Substâncias Protetoras/administração & dosagem
16.
Card Fail Rev ; 3(2): 83-85, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29387458

RESUMO

There is increasing interest in the concept of personalised medicine, whereby conditions with common pathophysiologies are targeted together, and also using biomarkers to identify patients who will most benefit from certain interventions. Several data sets indicate that natriuretic peptides are effective in refining risk prediction for heart failure and cardiovascular disease and add predictive power to conventional risk factors. To date two trials have tested the approach of using natriuretic peptides as part of a strategy to identify those at highest risk of cardiovascular events: St. Vincent's Screening to Prevent Heart Failure (STOP-HF) and N-terminal Pro-brain Natriuretic Peptide Guided Primary Prevention of Cardiovascular Events in Diabetic Patients (PONTIAC). These have shown natriuretic peptide-based screening and targeted prevention can reduce heart failure and left ventricular dysfunction and other major cardiovascular events. This approach is now part of North American guidelines.

17.
Biomarkers ; 21(6): 538-43, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27049231

RESUMO

CONTEXT: Natriuretic peptide (NP) has been shown to be an effective screening tool to identify patients with Stage B heart failure and to have clinical value in preventing heart failure progression. The impact of associated metabolic confounders on the screening utility of NP needs clarification. OBJECTIVE: To assess the impact of diabetes mellitus (DM) on NP screening for asymptomatic Stage B heart failure. MATERIALS AND METHODS: The study population consisted of 1368 asymptomatic patients with cardiovascular risk factors recruited from general practice as part of the STOP-HF trial. B-type NP (BNP) was quantified at point-of-care. RESULTS: BNP was found to be as accurate for detecting Stage B heart failure in DM patients compared to non-DM patients (AUC 0.75 [0.71,0.78] and 0.77 [0.72,0.82], respectively). However, different BNP thresholds are required to achieve the same level of diagnostic sensitivity in DM compared with non-DM patients. To achieve 80% sensitivity a difference of 5-ng/L lower is required for patients with DM. CONCLUSION: Although a significantly different BNP threshold is detected for patients with DM, the BNP concentration difference is small and unlikely to warrant a clinically different diagnostic threshold.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Insuficiência Cardíaca/sangue , Peptídeo Natriurético Encefálico/sangue , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Insuficiência Cardíaca/diagnóstico , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Curva ROC , Fatores de Risco , Índice de Gravidade de Doença
18.
J Cardiovasc Pharmacol Ther ; 21(1): 127-37, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26130616

RESUMO

BACKGROUND: The development of heart failure is associated with changes in the size, shape, and structure of the heart that has a negative impact on cardiac function. These pathological changes involve excessive extracellular matrix deposition within the myocardial interstitium and myocyte hypertrophy. Alterations in fibroblast phenotype and myocyte activity are associated with reprogramming of gene transcriptional profiles that likely requires epigenetic alterations in chromatin structure. The aim of our work was to investigate the potential of a currently licensed anticancer epigenetic modifier as a treatment option for cardiac diseases associated with hypertension-induced cardiac hypertrophy and fibrosis. METHODS AND RESULTS: The effects of DNA methylation inhibition with 5-azacytidine (5-aza) were examined in a human primary fibroblast cell line and in a spontaneously hypertensive rat (SHR) model. The results from this work allude to novel in vivo antifibrotic and antihypertrophic actions of 5-aza. Administration of the DNA methylation inhibitor significantly improved several echocardiographic parameters associated with hypertrophy and diastolic dysfunction. Myocardial collagen levels and myocyte size were reduced in 5-aza-treated SHRs. These findings are supported by beneficial in vitro effects in cardiac fibroblasts. Collagen I, collagen III, and α-smooth muscle actin were reduced in a human ventricular cardiac fibroblast cell line treated with 5-aza. CONCLUSION: These findings suggest a role for epigenetic modifications in contributing to the profibrotic and hypertrophic changes evident during disease progression. Therapeutic intervention with 5-aza demonstrated favorable effects highlighting the potential use of this epigenetic modifier as a treatment option for cardiac pathologies associated with hypertrophy and fibrosis.


Assuntos
Azacitidina/farmacologia , Cardiomegalia/prevenção & controle , Metilação de DNA/efeitos dos fármacos , Metilases de Modificação do DNA/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Epigênese Genética/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Actinas/metabolismo , Animais , Cardiomegalia/enzimologia , Cardiomegalia/genética , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Células Cultivadas , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Metilases de Modificação do DNA/metabolismo , Modelos Animais de Doenças , Fibroblastos/enzimologia , Fibroblastos/patologia , Fibrose , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hipertensão/enzimologia , Hipertensão/genética , Hipertensão/patologia , Hipertensão/fisiopatologia , Masculino , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/patologia , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Fator de Crescimento Transformador beta1/farmacologia , Remodelação Ventricular/efeitos dos fármacos
19.
J Cardiovasc Pharmacol Ther ; 21(3): 245-61, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26519384

RESUMO

Heart failure (HF) is an increasingly prevalent and costly multifactorial syndrome with high morbidity and mortality rates. The exact pathophysiological mechanisms leading to the development of HF are not completely understood. Several emerging paradigms implicate cardiometabolic risk factors, inflammation, endothelial dysfunction, myocardial fibrosis, and myocyte dysfunction as key factors in the gradual progression from a healthy state to HF. Inflammation is now a recognized factor in disease progression in HF and a therapeutic target. Furthermore, the monocyte-platelet interaction has been highlighted as an important pathophysiological link between inflammation, thrombosis, endothelial activation, and myocardial malfunction. The contribution of monocytes and platelets to acute cardiovascular injury and acute HF is well established. However, their role and interaction in the pathogenesis of chronic HF are not well understood. In particular, the cross talk between monocytes and platelets in the peripheral circulation and in the vicinity of the vascular wall in the form of monocyte-platelet complexes (MPCs) may be a crucial element, which influences the pathophysiology and progression of chronic heart disease and HF. In this review, we discuss the role of monocytes and platelets as key mediators of cardiovascular inflammation in HF, the mechanisms of cell activation, and the importance of monocyte-platelet interaction and complexes in HF pathogenesis. Finally, we summarize recent information on pharmacological inhibition of inflammation and studies of antithrombotic strategies in the setting of HF that can inform opportunities for future work. We discuss recent data on monocyte-platelet interactions and the potential benefits of therapy directed at MPCs, particularly in the setting of HF with preserved ejection fraction.


Assuntos
Plaquetas/metabolismo , Células Endoteliais/metabolismo , Insuficiência Cardíaca/sangue , Mediadores da Inflamação/sangue , Inflamação/sangue , Monócitos/metabolismo , Adesividade Plaquetária , Animais , Anti-Inflamatórios/farmacologia , Plaquetas/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/epidemiologia , Inflamação/fisiopatologia , Monócitos/efeitos dos fármacos , Adesividade Plaquetária/efeitos dos fármacos , Transdução de Sinais
20.
J Cardiovasc Transl Res ; 8(9): 554-66, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26577946

RESUMO

The potential for serum amyloid P-component (SAP) to prevent cardiac remodeling and identify worsening diastolic dysfunction (DD) was investigated. The anti-fibrotic potential of SAP was tested in an animal model of hypertensive heart disease (spontaneously hypertensive rats treated with SAP [SHR - SAP] × 12 weeks). Biomarker analysis included a prospective study of 60 patients with asymptomatic progressive DD. Compared with vehicle-treated Wistar-Kyoto rats (WKY-V), the vehicle-treated SHRs (SHR-V) exhibited significant increases in left ventricular mass, perivascular collagen, cardiomyocyte size, and macrophage infiltration. SAP administration was associated with significantly lower left ventricular mass (p < 0.01), perivascular collagen (p < 0.01), and cardiomyocyte size (p < 0.01). Macrophage infiltration was significantly attenuated in the SHR-SAP group. Biomarker analysis showed significant decreases in SAP concentration over time in patients with progressive DD (p < 0.05). Our results indicate that SAP prevents cardiac remodeling by inhibiting recruitment of pro-fibrotic macrophages and that depleted SAP levels identify patients with advancing DD suggesting a role for SAP therapy.


Assuntos
Hipertensão/tratamento farmacológico , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Componente Amiloide P Sérico/administração & dosagem , Remodelação Ventricular/efeitos dos fármacos , Animais , Biópsia por Agulha , Células Cultivadas , Modelos Animais de Doenças , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/patologia , Imuno-Histoquímica , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Distribuição Aleatória , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Valores de Referência
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