RESUMO
BACKGROUND: Aortic valve replacement in asymptomatic severe aortic stenosis is controversial. The Early valve replacement in severe ASYmptomatic Aortic Stenosis (EASY-AS) trial aims to determine whether early aortic valve replacement improves clinical outcomes, quality of life and cost-effectiveness compared to a guideline recommended strategy of 'watchful waiting'. METHODS: In a pragmatic international, open parallel group randomized controlled trial (NCT04204915), 2844 patients with severe aortic stenosis will be randomized 1:1 to either a strategy of early (surgical or transcatheter) aortic valve replacement or aortic valve replacement only if symptoms or impaired left ventricular function develop, or other cardiac surgery becomes nessessary. Exclusion criteria include other severe valvular disease, planned cardiac surgery, ejection fraction <50%, previous aortic valve replacement or life expectancy <2 years. The primary outcome is a composite of cardiovascular mortality or heart failure hospitalization. The primary analysis will be undertaken when 663 primary events have accrued, providing 90% power to detect a reduction in the primary endpoint from 27.7% to 21.6% (hazard ratio 0.75). Secondary endpoints include disability-free survival, days alive and out of hospital, major adverse cardiovascular events and quality of life. RESULTS: Recruitment commenced in March 2020 and is open in the UK, Australia, New Zealand, and Serbia. Feasibility requirements were met in July 2022, and the main phase opened in October 2022, with additional international centers in set-up. CONCLUSIONS: The EASY-AS trial will establish whether a strategy of early aortic valve replacement in asymptomatic patients with severe aortic stenosis reduces cardiovascular mortality or heart failure hospitalization and improves other important outcomes.
Assuntos
Estenose da Valva Aórtica , Implante de Prótese de Valva Cardíaca , Qualidade de Vida , Humanos , Estenose da Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca/métodos , Doenças Assintomáticas , Índice de Gravidade de Doença , Análise Custo-Benefício , Valva Aórtica/cirurgia , Masculino , Substituição da Valva Aórtica Transcateter/métodos , FemininoRESUMO
BACKGROUND: Patients at risk of statin non-adherence are often not identified during hospital admission with an acute coronary syndrome (ACS). METHODS: In 19,942 patients hospitalised for ACS, statin dispensing was determined from the national pharmaceutical dispensing database. A risk score for non-adherence was developed from a multivariable Poisson regression model of associations between risk factors and the statin Medication Possession Ratio (MPR) <0.8 6-18 months after hospital discharge. RESULTS: Statin MPR was <0.8 in 4,736 (24%) patients. MPR <0.8 was more likely in patients with a history of cardiovascular disease (CVD) (RR 3.79, CI 95% 3.42-4.20) and those without known CVD (RR 2.25, 95% CI 2.04-2.48) who were not taking a statin on ACS admission, compared to patients with low density lipoprotein (LDL) cholesterol <2 mmol/L who were on a statin. For patients taking a statin on admission, higher LDL was associated with MPR <0.8 (≥3 versus <2 mmol/L, RR 1.96, 95%CI 1.72-2.24). Other independent risk factors for MPR <0.8 were age <45 years, female, disadvantaged ethnic groups, and no coronary revascularisation during the ACS admission. The risk score, which included nine variables, had a C-statistic of 0.67. MPR was <0.8 in 12% of 5,348 patients with a score ≤5 (lowest quartile) and 45% of 5,858 patients with a score ≥11 (highest quartile). CONCLUSION: A risk score generated from routinely collected data predicts statin non-adherence in patients hospitalised with ACS. This may be used to target inpatient and outpatient interventions to improve medication adherence.
Assuntos
Síndrome Coronariana Aguda , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Feminino , Pessoa de Meia-Idade , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/epidemiologia , Estudos Retrospectivos , Hospitalização , Alta do PacienteRESUMO
RATIONALE: Transient myopericarditis has been recognised as an uncommon and usually mild adverse event predominantly linked to mRNA-based COVID-19 vaccines. These have mostly occurred in young males after the second dose of mRNA COVID-19 vaccines. OBJECTIVES: Fulminant necrotising eosinophilic myocarditis triggered by a variety of drugs or vaccines is an extremely rare hypersensitivity reaction carrying a substantial mortality risk. Early recognition of this medical emergency may facilitate urgent hospital admission for investigation and treatment. Timely intervention can lead to complete cardiac recovery, but the non-specific clinical features and rarity make early diagnosis challenging. FINDINGS: The clinical and pathological observations from a case of fatal fulminant necrotising myocarditis in a 57-year-old woman, following the first dose of the Pfizer-BioNTech vaccine, are described. Other causes have been discounted with reasonable certainty. CONCLUSION: These extremely rare vaccine-related adverse events are much less common than the risk of myocarditis and other lethal complications from COVID-19 infection. The benefits of vaccination far exceed the risks of COVID-19 infection.
Assuntos
COVID-19 , Hipersensibilidade , Transtornos Leucocíticos , Miocardite , Vacinas , Vacina BNT162 , COVID-19/diagnóstico , Vacinas contra COVID-19/efeitos adversos , Feminino , Humanos , Hipersensibilidade/complicações , Masculino , Pessoa de Meia-Idade , Miocardite/diagnóstico , Miocardite/etiologia , RNA MensageiroRESUMO
BACKGROUND: Circulating biomarkers are associated with the development of coronary heart disease (CHD) and its complications by reflecting pathophysiological pathways and/or organ dysfunction. We explored the associations between 157 cardiovascular (CV) and inflammatory biomarkers and CV death using proximity extension assays (PEA) in patients with chronic CHD. METHODS AND FINDINGS: The derivation cohort consisted of 605 cases with CV death and 2,788 randomly selected non-cases during 3-5 years follow-up included in the STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY (STABILITY) trial between 2008 and 2010. The replication cohort consisted of 245 cases and 1,042 non-cases during 12 years follow-up included in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study between 1997 and 2000. Biomarker levels were measured with conventional immunoassays and/or with the OLINK PEA panels CVD I and Inflammation. Associations with CV death were evaluated by Random Survival Forest (RF) and Cox regression analyses. Both cohorts had the same median age (65 years) and 20% smokers, while there were slight differences in male sex (82% and 76%), hypertension (70% and 78%), and diabetes (39% and 30%) in the respective STABILITY and LURIC cohorts. The analyses identified 18 biomarkers with confirmed independent association with CV death by Boruta analyses and statistical significance (all p < 0.0001) by Cox regression when adjusted for clinical characteristics in both cohorts. Most prognostic information was carried by N-terminal prohormone of brain natriuretic peptide (NTproBNP), hazard ratio (HR for 1 standard deviation [SD] increase of the log scale of the distribution of the biomarker in the replication cohort) 2.079 (95% confidence interval [CI] 1.799-2.402), and high-sensitivity troponin T (cTnT-hs) HR 1.715 (95% CI 1.491-1.973). The other proteins with independent associations were growth differentiation factor 15 (GDF-15) HR 1.728 (95% CI 1.527-1.955), transmembrane immunoglobulin and mucin domain protein (TIM-1) HR 1.555 (95% CI 1.362-1.775), renin HR 1.501 (95% CI 1.305-1.727), osteoprotegerin (OPG) HR 1.488 (95% CI 1.297-1.708), soluble suppression of tumorigenesis 2 protein (sST2) HR 1.478 (95% CI 1.307-1.672), cystatin-C (Cys-C) HR 1.370 (95% CI 1.243-1.510), tumor necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2) HR 1.205 (95% CI 1.131-1.285), carbohydrate antigen 125 (CA-125) HR 1.347 (95% CI 1.226-1.479), brain natriuretic peptide (BNP) HR 1.399 (95% CI 1.255-1.561), interleukin 6 (IL-6) HR 1.478 (95% CI 1.316-1.659), hepatocyte growth factor (HGF) HR 1.259 (95% CI 1.134-1.396), spondin-1 HR 1.295 (95% CI 1.156-1.450), fibroblast growth factor 23 (FGF-23) HR 1.349 (95% CI 1.237-1.472), chitinase-3 like protein 1 (CHI3L1) HR 1.284 (95% CI 1.129-1.461), tumor necrosis factor receptor 1 (TNF-R1) HR 1.486 (95% CI 1.307-1.689), and adrenomedullin (AM) HR 1.750 (95% CI 1.490-2.056). The study is limited by the differences in design, size, and length of follow-up of the 2 studies and the lack of results from coronary angiograms and follow-up of nonfatal events. CONCLUSIONS: Profiles of levels of multiple plasma proteins might be useful for the identification of different pathophysiological pathways associated with an increased risk of CV death in patients with chronic CHD. TRIAL REGISTRATION: ClinicalTrials.gov NCT00799903.
Assuntos
Biomarcadores/sangue , Proteínas Sanguíneas/análise , Doença das Coronárias/sangue , Doença das Coronárias/mortalidade , Idoso , Doença das Coronárias/fisiopatologia , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: In patients with coronary heart disease (CHD), atrial fibrillation (AF) is associated with increased morbidity and mortality. We investigated the associations between clinical risk factors and biomarkers with incident AF in patients with CHD. METHODS AND RESULTS: Around 13,153 patients with optimally treated CHD included in the STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY (STABILITY) trial with plasma samples obtained at randomization. Mean follow-up time was 3.5 years. The association between clinical risk factors and biomarkers with incident AF was estimated with Cox-regression models. Validation was performed in 1,894 patients with non-ST-elevation acute coronary syndrome included in the FRISC-II trial. The median (min-max) age was 64 years (range 26-92) and 2,514 (19.1%) were women. A total of 541 patients, annual incidence rate of 1.2%, developed AF during follow-up. In multivariable models, older age, higher levels of NT-proBNP, higher body mass index (BMI), male sex, geographic regions, low physical activity, and heart failure were independently associated with increased risk of incident AF with hazard ratios ranging from 1.04 to 1.79 (P ≤ .05). NT-proBNP improved the C-index from 0.70 to 0.71. In the validation cohort, age, BMI, and NT-proBNP were associated with increased risk of incident AF with similar hazard ratios. CONCLUSIONS: In patients with optimally treated CHD, the incidence of new AF was 1.2% per year. Age, NT-proBNP as a marker of impaired cardiac function, and BMI were the strongest factors, independently and consistently associated with incident AF. Male sex and low physical activity may also contribute to the risk of AF in patients with CHD.
Assuntos
Fibrilação Atrial/sangue , Doença das Coronárias/sangue , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Índice de Massa Corporal , Doença das Coronárias/tratamento farmacológico , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Comportamento Sedentário , Fatores SexuaisRESUMO
BACKGROUND: In patients with stable coronary heart disease, it is not known whether achievement of standard of care (SOC) targets in addition to evidence-based medicine (EBM) is associated with lower major adverse cardiovascular events (MACE): cardiovascular death, myocardial infarction, and stroke. METHODS: EBM use was recommended in the STabilisation of Atherosclerotic plaque By Initiation of darapLadIb TherapY trial. SOC targets were blood pressure (BP) <140/90â¯mm Hg and low-density lipoprotein-cholesterol (LDL-C)â¯<100 mg/dL and <70 mg/dL. In patients with diabetes, glycosylated hemoglobin A1c (HbA1c)â¯<â¯7% and BP of <130/80 mm Hg were recommended. Feedback to investigators about rates of EBM and SOC was provided regularly. RESULTS: In 13,623 patients, 1-year landmark analysis assessed the association between EBM, SOC targets, and MACE during follow-up of 2.7â¯years (median) after adjustment in a Cox proportional hazards model. At 1â¯year, aspirin was prescribed in 92.5% of patients, statins in 97.2%, ß-blockers in 79.0%, and angiotensin-converting enzyme inhibitors/angiotensin-II receptor blockers in 76.9%. MACE was lower with LDL-Câ¯<â¯100 mg/dL (70-99 mg/dL) compared with LDL-Câ¯≥â¯100 mg/dL (hazard ratio [HR] 0.694, 95% CI 0.594-0.811) and lower with LDL-Câ¯<â¯70 mg/dL compared with LDL-Câ¯<â¯100 mg/dL (70-99 mg/dL) (HR 0.834, 95% CI 0.708-0.983). MACE was lower with HbA1c <â¯7% compared with HbA1câ¯≥â¯7% (HR 0.705, 95% CI 0.573-0.866). There was no effect of BP targets on MACE. CONCLUSIONS: MACE was lower with LDL-Câ¯<â¯100 mg/dL (70-99 mg/dL) and even lower with LDL-Câ¯<â¯70 mg/dL. MACE in patients with diabetes was lower with HbA1c < 7%. Achievement of targets is associated with improved patient outcomes.
Assuntos
LDL-Colesterol/sangue , Doença das Coronárias/sangue , Hemoglobinas Glicadas/análise , Infarto do Miocárdio/etiologia , Acidente Vascular Cerebral/etiologia , Idoso , Doença das Coronárias/complicações , Doença das Coronárias/mortalidade , Medicina Baseada em Evidências , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Fatores de Risco , Acidente Vascular Cerebral/epidemiologiaRESUMO
BACKGROUND: Clinical Endpoint Classification (CEC) in clinical trials allows FOR standardized, systematic, blinded, and unbiased adjudication of investigator-reported events. We quantified the agreement rates in the STABILITY trial on 15,828 patients with stable coronary heart disease. METHODS: Investigators were instructed to report all potential events. Each reported event was reviewed independently by 2 reviewers according to prespecified processes and prespecified end point definitions. Concordance between reported and adjudicated cardiovascular (CV) events was evaluated, as well as event classification influence on final study results. RESULTS: In total, CEC reviewed 7,096 events: 1,064 deaths (696 CV deaths), 958 myocardial infarctions (MI), 433 strokes, 182 transient ischemic attacks, 2,052 coronary revascularizations, 1,407 hospitalizations for unstable angina, and 967 hospitalizations for heart failure. In total, 71.8% events were confirmed by CEC. Concordance was high (>80%) for cause of death and nonfatal MI and lower for hospitalization for unstable angina (25%) and heart failure (50%). For the primary outcome (composite of CV death, MI, and stroke), investigators reported 2,086 events with 82.5% confirmed by CEC. The STABILITY trial treatment effect of darapladib versus placebo on the primary outcome was consistent using investigator-reported events (hazard ratio 0.96 [95% CI 0.87-1.06]) or adjudicated events (hazard ratio 0.94 [95% CI 0.85-1.03]). CONCLUSIONS: The primary outcome results of the STABILITY trial were consistent whether using investigator-reported or CEC-adjudicated events. The proportion of investigator-reported events confirmed by CEC varied by type of event. These results should help improve event identification in clinical trials to optimize ascertainment and adjudication.
Assuntos
Benzaldeídos/uso terapêutico , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/mortalidade , Infarto do Miocárdio/epidemiologia , Oximas/uso terapêutico , Inibidores de Fosfolipase A2/uso terapêutico , Acidente Vascular Cerebral/epidemiologia , Angina Instável/epidemiologia , Doença das Coronárias/complicações , Determinação de Ponto Final , Insuficiência Cardíaca/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Ataque Isquêmico Transitório/epidemiologia , Ataque Isquêmico Transitório/etiologia , Estimativa de Kaplan-Meier , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/mortalidade , Intervenção Coronária Percutânea/estatística & dados numéricos , Placebos/uso terapêutico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidadeRESUMO
PURPOSE: Existing knowledge of medicines that increase the risk of an adverse event may be corroborated and augmented by population studies specifically assessing the risk associated with the concurrent use of these medicines and use by patients with existing comorbidity. An American Heart Association review recently identified a variety of medicines that may cause or exacerbate heart failure (HF), many with evidence from limited evaluation of population data. We assessed the risk of first-time HF associated with the use of 50 of these medicines by New Zealand's primary care population. METHODS: Case-control study utilising national pharmaceutical use and hospital admissions data 2007-2015; 22,989 patients with first-time HF 2008-2015 were matched with 114 498 control patients. The primary outcome was first-time HF and its association with medicine exposure in the prior 90 days, estimated using conditional logistic regression. We also assessed the risk associated with new use of medicines in the prior month, concurrent use, and in patients with existing comorbidity. RESULTS: Eleven medicines were significantly associated with HF with several other infrequently used medicines providing signals of increased risk. A high risk was associated with the use of salbutamol (adjusted odds ratio 2.63; 95% CI, 2.48-2.78), clozapine (2.70; 2.46-4.98), diltiazem (1.52; 1.44-1.60), indomethacin (2.51; 1.54-4.10), pioglitazone (1.50; 1.16-1.95), and antifungal medicines. New use of medicines and use of medicine combinations increased this risk in many cases. CONCLUSIONS: Our study provides further evidence to inform cautious use of these medicines in patients with HF or at risk of developing HF.
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Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Insuficiência Cardíaca/induzido quimicamente , Hospitalização/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Albuterol/administração & dosagem , Albuterol/efeitos adversos , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Estudos de Casos e Controles , Clozapina/administração & dosagem , Clozapina/efeitos adversos , Diltiazem/administração & dosagem , Diltiazem/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Seguimentos , Insuficiência Cardíaca/epidemiologia , Humanos , Indometacina/administração & dosagem , Indometacina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Pioglitazona/administração & dosagem , Pioglitazona/efeitos adversos , Pontuação de Propensão , Fatores de RiscoRESUMO
AIMS: To study the relation between visit-to-visit variability of blood pressure (BP) and cardiovascular risk in patients with stable coronary heart disease. METHODS AND RESULTS: In 15 828 patients from the STABILITY trial (darapladib vs. placebo in patients with established coronary heart disease), BP variability was assessed by the standard deviation (SD) of systolic BP, the SD of diastolic BP, maximum BP, and minimum BP, from 5 measurements (baseline and months 1, 3, 6, and 12) during the first year after randomisation. Mean (SD) average BP during the first year of study was 131.0 (13.7) mmHg over 78.3 (8.3) mmHg. Mean (SD) of the visit-to-visit SD was 9.8 (4.8) mmHg for systolic and 6.3 (3.0) mmHg for diastolic BP. During the subsequent median follow-up of 2.6 years, 1010 patients met the primary endpoint, a composite of time to cardiovascular death, myocardial infarction, or stroke. In Cox regression models adjusted for average BP during first year of study, baseline vascular disease, treatment, renal function and cardiovascular risk factors, the primary endpoint was associated with SD of systolic BP (hazard ratio for highest vs. lowest tertile, 1.30, 95% CI 1.10-1.53, P = 0.007), and with SD of diastolic BP (hazard ratio for highest vs. lowest tertile, 1.38, 95% CI 1.18-1.62, P < 0.001). Peaks and troughs in BP were also independently associated with adverse events. CONCLUSION: In patients with stable coronary heart disease, higher visit-to-visit variabilities of both systolic and diastolic BP are strong predictors of increased risk of cardiovascular events, independently of mean BP.
Assuntos
Pressão Sanguínea/fisiologia , Doença das Coronárias/fisiopatologia , Idoso , Doença das Coronárias/mortalidade , Diástole/fisiologia , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/fisiopatologia , Prognóstico , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/fisiopatologia , Sístole/fisiologiaRESUMO
BACKGROUND: Higher growth differentiation factor 15 (GDF-15) concentrations are associated with cardiovascular (CV) and non-CV morbidity and mortality. However, information on associations between GDF-15 and the risk of specific CV and non-CV events in stable coronary heart disease (CHD) patients is limited. METHODS: In 14 577 patients with stable CHD participating in the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial (STABILITY), GDF-15 and other prognostic biomarkers (N-terminal pro-B-type natriuretic peptide, high-sensitivity troponin T, cystatin C, and high-sensitivity C-reactive protein) were measured. In adjusted Cox regression models, the associations between GDF-15 and the composite CV end point [CV death, myocardial infarction (MI), and stroke], as well as other CV and non-CV events, were assessed. RESULTS: The median concentration (interquartile range) of GDF-15 at baseline was 1253 (915-1827) ng/L. The hazard ratio for the composite end point for the highest compared to the lowest quartile of GDF-15 was 1.8 (95% CI, 1.5-2.2); for CV death, 2.63 (1.9-3.6); for sudden death, 3.06 (1.9-4.8); for heart failure (HF) death, 4.3 (1.3-14); for cancer death, 2.5 (1.3-4.7); for hospitalization for HF, 5.8 (3.2-10); for MI 1.4 (95% CI, 1.1-1.9); and for stroke, 1.8 (95% CI, 1.1-2.8). After adjustment for other prognostic biomarkers, GDF-15 remained significantly associated with all outcomes except for MI. CONCLUSIONS: In stable CHD, GDF-15 was independently associated with CV, non-CV, and cancer mortality, as well as with MI and stroke. When also adjusting for other prognostic biomarkers, the associations to all fatal and nonfatal events were maintained except for MI. Information on GDF-15, therefore, might be helpful when assessing the risk of adverse outcomes in patients with stable CHD. ClinicalTrials.gov Identifier: NCT00799903.
Assuntos
Doença das Coronárias/sangue , Doença das Coronárias/mortalidade , Fator 15 de Diferenciação de Crescimento/sangue , Adulto , Idoso , Biomarcadores/sangue , Doença das Coronárias/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Estudos Prospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
AIMS: Atrial fibrillation (AF) is associated with an increased risk of stroke, which is currently estimated by clinical characteristics. The cardiac biomarkers N-terminal fragment B-type natriuretic peptide (NT-proBNP) and cardiac troponin high-sensitivity (cTn-hs) are independently associated with risk of stroke in AF. Our objective was to develop and validate a new biomarker-based risk score to improve prognostication of stroke in patients with AF. METHODS AND RESULTS: A new risk score was developed and internally validated in 14 701 patients with AF and biomarkers levels determined at baseline, median follow-up of 1.9 years. Biomarkers and clinical variables significantly contributing to predicting stroke or systemic embolism were assessed by Cox-regression and each variable obtained a weight proportional to the model coefficients. External validation was performed in 1400 patients with AF, median follow-up of 3.4 years. The most important predictors were prior stroke/transient ischaemic attack, NT-proBNP, cTn-hs, and age, which were included in the ABC (Age, Biomarkers, Clinical history) stroke risk score. The ABC-stroke score was well calibrated and yielded higher c-indices than the widely used CHA2DS2-VASc score in both the derivation cohort (0.68 vs. 0.62, P < 0.001) and the external validation cohort (0.66 vs. 0.58, P < 0.001). Moreover, the ABC-stroke score consistently provided higher c-indices in several important subgroups. CONCLUSION: A novel biomarker-based risk score for predicting stroke in AF was successfully developed and internally validated in a large cohort of patients with AF and further externally validated in an independent AF cohort. The ABC-stroke score performed better than the presently used clinically based risk score and may provide improved decision support in AF. CLINICALTRIALS GOV IDENTIFIER: NCT00412984, NCT00799903.
Assuntos
Acidente Vascular Cerebral , Fibrilação Atrial , Biomarcadores , Humanos , Anamnese , Peptídeo Natriurético Encefálico , Medição de Risco , Fatores de RiscoRESUMO
OBJECTIVES: To determine whether dietary pattern assessed by a simple self-administered food frequency questionnaire is associated with major adverse cardiovascular events (MACE) in high-risk patients with stable coronary artery disease. BACKGROUND: A Mediterranean dietary pattern has been associated with lower cardiovascular (CV) mortality. It is less certain whether foods common in western diets are associated with CV risk. METHODS: At baseline, 15 482 (97.8%) patients (mean age 67 ± 9 years) with stable coronary heart disease from 39 countries who participated in the Stabilisation of atherosclerotic plaque by initiation of darapladib therapy (STABILITY) trial completed a life style questionnaire which included questions on common foods. A Mediterranean diet score (MDS) was calculated for increasing consumption of whole grains, fruits, vegetables, legumes, fish, and alcohol, and for less meat, and a 'Western diet score' (WDS) for increasing consumption of refined grains, sweets and deserts, sugared drinks, and deep fried foods. A multi-variable Cox proportional hazards models assessed associations between MDS or WDS and MACE, defined as CV death, non-fatal myocardial infarction, or non-fatal stroke. RESULTS: After a median follow-up of 3.7 years MACE occurred in 7.3% of 2885 subjects with an MDS ≥15, 10.5% of 4018 subjects with an MDS of 13-14, and 10.8% of 8579 subjects with an MDS ≤12. A one unit increase in MDS >12 was associated with lower MACE after adjusting for all covariates (+1 category HR 0.95, 95% CI 0.91, 0.98, P = 0.002). There was no association between WDS (adjusted model +1 category HR 0.99, 95% CI 0.97, 1.01) and MACE. CONCLUSION: Greater consumption of healthy foods may be more important for secondary prevention of coronary artery disease than avoidance of less healthy foods typical of Western diets.
Assuntos
Doença das Coronárias , Idoso , Dieta Mediterrânea , Humanos , Infarto do Miocárdio , Modelos de Riscos Proporcionais , Fatores de RiscoAssuntos
Dieta Mediterrânea , Azeite de Oliva , Doenças Cardiovasculares , Humanos , Nozes , Óleos de Plantas , Prevenção Primária , Fatores de RiscoRESUMO
PURPOSE OF REVIEW: Regular exercise, physical fitness and sedentary behaviours are each known to be associated with cardiovascular and total mortality. This review evaluates recent research on these associations and its implications for guidelines on physical activity. RECENT FINDINGS: In several large cohort studies, modest levels of exercise, much less than recommended in current guidelines, were associated with lower mortality. Avoiding prolonged sitting has also been associated with lower mortality risk. Most research suggests graded decreases in long-term mortality with an increase in usual physical activity and fitness. However, at very high exercise levels, these benefits may be attenuated, particularly in patients with known coronary heart disease. SUMMARY: In sedentary persons, a modest increase in physical activity and avoiding prolonged sitting are likely to have important health benefits. Further research is needed to determine the most effective strategies for increasing physical activity.
Assuntos
Envelhecimento , Doenças Cardiovasculares/prevenção & controle , Atividade Motora/fisiologia , Aptidão Física , Comportamento de Redução do Risco , Envelhecimento/fisiologia , Envelhecimento/psicologia , Humanos , Aptidão Física/fisiologia , Aptidão Física/psicologia , Fatores de Risco , Comportamento SedentárioRESUMO
BACKGROUND: Pulse wave velocity (PWV), a measure of arterial stiffness, has been demonstrated to be an independent predictor of adverse cardiovascular outcomes. This can be derived non-invasively using cardiovascular magnetic resonance (CMR). Changes in PWV during exercise may reveal further information on vascular pathology. However, most known CMR methods for quantifying PWV are currently unsuitable for exercise stress testing. METHODS: A velocity-sensitive real-time acquisition and evaluation (RACE) pulse sequence was adapted to provide interleaved acquisition of two locations in the descending aorta (at the level of the pulmonary artery bifurcation and above the renal arteries) at 7.8 ms temporal resolution. An automated method was used to calculate the foot-to-foot transit time of the velocity pulse wave. The RACE method was validated against a standard gated phase contrast (STD) method in flexible tube phantoms using a pulsatile flow pump. The method was applied in 50 healthy volunteers (28 males) aged 22-75 years using a MR-compatible cycle ergometer to achieve moderate work rate (38 ± 22 W, with a 31 ± 12 bpm increase in heart rate) in the supine position. Central pulse pressures were estimated using a MR-compatible brachial device. Scan-rescan reproducibility was evaluated in nine volunteers. RESULTS: Phantom PWV was 22 m/s (STD) vs. 26 ± 5 m/s (RACE) for a butyl rubber tube, and 5.5 vs. 6.1 ± 0.3 m/s for a latex rubber tube. In healthy volunteers PWV increased with age at both rest (R(2) = 0.31 p < 0.001) and exercise (R(2) = 0.40, p < 0.001). PWV was significantly increased at exercise relative to rest (0.71 ± 2.2 m/s, p = 0.04). Scan-rescan reproducibility at rest was -0.21 ± 0.68 m/s (n = 9). CONCLUSIONS: This study demonstrates the validity of CMR in the evaluation of PWV during exercise in healthy subjects. The results support the feasibility of using this method in evaluating of patients with systemic aortic disease.
Assuntos
Aorta/fisiologia , Teste de Esforço , Imagem Cinética por Ressonância Magnética/métodos , Análise de Onda de Pulso/métodos , Rigidez Vascular , Adulto , Idoso , Automação , Ciclismo , Estudos de Viabilidade , Feminino , Voluntários Saudáveis , Frequência Cardíaca , Humanos , Interpretação de Imagem Assistida por Computador , Imagem Cinética por Ressonância Magnética/instrumentação , Masculino , Pessoa de Meia-Idade , Imagens de Fantasmas , Valor Preditivo dos Testes , Análise de Onda de Pulso/instrumentação , Reprodutibilidade dos Testes , Fatores de Tempo , Adulto JovemRESUMO
We evaluated statistical approaches to facilitate and improve multi-stage designs for clinical proteomic studies which plan to transit from laboratory discovery to clinical utility. To find the design with the greatest expected number of true discoveries under constraints on cost and false discovery, the operating characteristics of the multi-stage study were optimized as a function of sample sizes and nominal type-I error rates at each stage. A nested simulated annealing algorithm was used to find the best solution in the bounded spaces constructed by multiple design parameters. This approach is demonstrated to be feasible and lead to efficient designs. The use of biological grouping information in the study design was also investigated using synthetic datasets based on a cardiac proteomic study, and an actual dataset from a clinical immunology proteomic study. When different protein patterns presented, performance improved when the grouping was informative, with little loss in performance when the grouping was uninformative.
Assuntos
Estudos de Associação Genética/métodos , Estudos de Associação Genética/normas , Modelos Estatísticos , Proteômica , Projetos de Pesquisa , Algoritmos , Biomarcadores , Estudos de Casos e Controles , Imunodeficiência de Variável Comum/genética , Imunodeficiência de Variável Comum/metabolismo , Simulação por Computador , Humanos , Proteômica/métodosRESUMO
BACKGROUND: Dairy food is an important natural source of saturated and trans fatty acids in the human diet. This study evaluates the effect of dietary advice to change dairy food intake on plasma fatty acid levels known to be present in milk in healthy volunteers. METHODS: Twenty one samples of whole fat dairy milk were analyzed for fatty acids levels. Changes in levels of plasma phospholipid levels were evaluated in 180 healthy volunteers randomized to increase, not change or reduce dairy intake for one month. Fatty acids were measured by gas chromatography-mass spectrometry and levels are normalized to d-4 alanine. RESULTS: The long chain fatty acids palmitic (13.4%), stearic (16.7%) and myristic (18.9%) acid were most common saturated fats in milk. Four trans fatty acids constituted 3.7% of the total milk fat content. Increased dairy food intake by 3.0 (± 1.2) serves/ day for 1 month was associated with small increases in plasma levels of myristic (+0.05, 95% confidence level-0.08 to 0.13, p = 0.07), pentadecanoic (+0.014, 95% confidence level -0.016 to 0.048, p = 0.02) and margaric acid (+0.02, -0.03 to 0.05, p = 0.03). There was no significant change in plasma levels of 4 saturated, 4 trans and 10 unsaturated fatty acids. Decreasing dairy food intake by 2.5 (± 1.2) serves per day was not associated with change in levels of any plasma fatty acid levels. CONCLUSION: Dietary advice to change dairy food has a minor effect on plasma fatty acid levels. TRIAL REGISTRATION: ACTRN12612000574842.
Assuntos
Laticínios , Gorduras na Dieta/análise , Ácidos Graxos Insaturados/sangue , Ácidos Graxos/análise , Leite/química , Ácidos Graxos trans/sangue , Adulto , Animais , Doenças Cardiovasculares/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosfolipídeos/sangueRESUMO
BACKGROUND: EuroSCORE and the Society of Thoracic Surgeons' (STS) Score have been the most widely used risk scores for cardiac surgery. The revised EuroSCORE II and the AusSCORE, based on an Australasian population, were recently developed. We compared the prognostic utility of these four scores for mortality as well as morbidity in patients undergoing isolated coronary artery bypass grafting (CABG). METHODS: The scores were retrospectively calculated for isolated CABG patients at Auckland City Hospital during July 2010-June 2012. Discrimination and calibration of outcomes were assessed. RESULTS: 818 patients were followed for 1.6+/-0.6 years. Mortality at 30 days was 1.6% and 2.9% on follow up. Median predicted 30 day mortality (Interquartile range) for EuroSCORE I were 2.8% (1.6%, 5.2%), EuroSCORE II 1.6% (1.0%, 2.8%), STS Score 2.3% (1.3%, 4.5%) and AusSCORE 0.5% (0.2%, 1.1%). C-statistics and Hosmer-Lemeshow test p-values for these scores for 30-day mortality were Euro score I 0.675 (95%CI 0.531-0.819)/0.061, EuroSCORE II 0.642 (0.503-0.780)/0.150, STS Score 0.641 (0.507-0.775)/0.243 and AusSCORE 0.661 (0.516-0.807)/0.420. Only EuroSCORE I and STS scores were significant for predicting mortality at follow-up (c=0.639 and 0.666). All scores predicted composite morbidity. C-statistics were EuroSCORE I 0.678, EuroSCORE II 0.634, STS score 0.584 and AusSCORE 0.645. CONCLUSION: EuroSCORE II, STS Score and AusSCORE had slightly improved calibration but similar discrimination for 30-day mortality compared to EuroSCORE I. Revision of risk models to fit contemporary surgical outcomes is important, but there may only be modest room for improvement in discrimination.
Assuntos
Ponte de Artéria Coronária/mortalidade , Idoso , Austrália/epidemiologia , Ponte de Artéria Coronária/métodos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Fatores de TempoRESUMO
AIM: To investigate associations between psychosocial burden and biomarkers reflecting pathophysiological pathways in patients with chronic coronary syndrome. METHODS: Psychosocial (PS) factors were collected from self-assessed questionnaires and biomarkers representing inflammation (high-sensitivity [hs]-C-reactive protein [CRP], interleukin-6 [IL-6], lipoprotein-associated phospholipase A2 [Lp-PLA2]) and cardiac injury/stress (hs-troponin T [hs-TnT], N-terminal pro-B type natriuretic peptide [NT-proBNP]) were measured in 12,492 patients with chronic coronary syndrome in the STABILITY trial. Associations between level of each psychosocial factor (never-rarely (reference), sometimes, often-always) and biomarkers were evaluated using linear models with adjusted geometric mean ratios (GMR). A score comprising four factors ('feeling down', 'loss of interest', financial stress', 'living alone') that previously demonstrated association with cardiovascular (CV) outcome was created, and categorized into three levels: low, moderate and high PS burden. Associations between PS score and biomarkers were evaluated similarly. RESULTS: Greater PS burden was significantly associated with a gradual increase in inflammatory biomarkers (GMR [95% CI] for moderate vs low PS burden; and high vs low PS burden): hs-CRP (1.09 [1.04-1.14]; 1.12 [1.06-1.17]), IL-6 (1.05 [1.02-1.07]; 1.08 [1.05-1.11]), LpPLA2 (1.01 [1.00 - 1.02]; 1.02 [1.01-1.04]) and cardiac biomarkers hs-TnT (1.03 [1.01-1.06]; 1.06 [1.03-1.09]) and NT-proBNP (1.09 [1.04-1.13]; 1.21 [1.15-1.27]). CONCLUSIONS: In patients with chronic coronary syndrome, greater psychosocial burden was associated with increased levels of inflammatory and cardiac biomarkers. While this observational study does not establish causal nature of these associations, the findings suggest inflammation and cardiac injury/stress as plausible pathways linking psychosocial burden to an elevated CV risk, that needs to be further explored.
We studied the association between psychosocial factors and various circulating protein biomarkers, reflecting different underlying mechanisms of disease, with the hope of shedding light on the link between psychological factors like depression and stress and the risk of cardiovascular events in patients with chronic coronary syndrome. We analysed data from the global large-scale STABILITY trial, which included more than 12,000 patients with chronic coronary syndrome. Participants filled out a questionnaire assessing their level of psychosocial burden, including experiences of depressive symptoms, stress at home, at work and financial stress. Additionally, blood samples were collected in which biomarkers (NTproBNP, high-sensitive Troponin-T, Interleukin-6, CRP and LpPLA2) were analysed. Our findings revealed a significant association between higher psychosocial burden and increased concentrations of biomarkers in patients with chronic coronary syndrome. These biomarkers reflect both inflammatory processes and cardiac damage or dysfunction which could be potential disease mechanisms explaining the increased risk of adverse events in patients with chronic coronary syndrome and high psychosocial burden. Although causal relationships cannot be determined from this study, the findings suggest that inflammation and cardiac stress may play crucial roles in linking psychosocial factors to heightened cardiovascular risk in this patient population. These insights could pave the way for better understanding and managing cardiovascular health in individuals with chronic coronary syndrome, offering hope for more targeted interventions in the future.