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1.
Coron Artery Dis ; 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32897898

RESUMO

OBJECTIVES: The SYNTAX score and SYNTAX score II have a high predictive capacity for adverse cardiovascular events. We aimed to demonstrate that both scores were good predictors of long-term adverse outcomes in an 'all-comers' population treated with a percutaneous coronary intervention (PCI). METHODS: In the study, we included 785 patients who received an angioplasty at our center between January 2011 and December 2012. The patients were distributed in tertiles according to the SYNTAX score and SYNTAX score II values; for the SYNTAX score - low ≤6.5 (n = 225); mid >6.5, <11.5 (n = 229); high ≥11.5 (n = 221); and for the SYNTAX score II PCI: low ≤20.5 (n = 226); mid >20.5, < 29.6 (n = 221); and high ≥29.6 (n = 218). RESULTS: The rates of major adverse cardiovascular events, death, cardiac death and new revascularizations at 3 years were significantly higher in the highest tertile of both the scores. For SYNTAX score: major adverse cardiovascular events, 12-15.3-21.7%, P < 0.001; death, 7.6-8.3-14%, P = 0.04; cardiac death, 3.2-2.7-7.5%, P = 0.03; new revascularizations, 4.5-8.6-10.4%, P = 0.001. For SYNTAX score II PCI: major adverse cardiovascular events, 8-10.9-28.9%, P < 0.001; death, 3.1-3.6-21.5%, P < 0.001; cardiac death, 0.9-0.5-11.4%, P < 0.001; new revascularizations, 4.5-8.2-11.3%, P = 0.03. CONCLUSION: The SYNTAX score II showed better predictive capacity than the SYNTAX score for major adverse cardiovascular events, death and cardiac death, with no difference noted for new revascularizations, and it was an independent predictor for these events in an 'all-comers' population.

2.
Eur Heart J Acute Cardiovasc Care ; : 2048872620924198, 2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32700543

RESUMO

BACKGROUND: Most studies assessing the diagnostic value of high-sensitivity troponin in the diagnosis of myocardial infarction used batch-wise analyses of frozen samples for high-sensitivity troponin measurements. Whether the accuracy of these batch-wise high-sensitivity troponin measurements described in diagnostic studies is comparable to clinical routine is unknown. METHODS: We enrolled 937 patients presenting with suspected myocardial infarction in this prospective cohort study. Measurements of high-sensitivity troponin I (Abbott Architect) and high-sensitivity troponin T (Roche) were performed in two settings: (a) on-demand in clinical routine using fresh blood samples; and (b) in batches using frozen blood samples from the same individuals at three timepoints (0 hours, 1 hour and 3 hours after presentation). RESULTS: Median troponin levels were not different between on-demand and batch-wise measurements. Troponin levels in the range of 0 to 40 ng/L showed a very high correlation between the on-demand and batch setting (Pearson correlation coefficient (r) was 0.92-0.95 for high-sensitivity troponin I and 0.96 for high-sensitivity troponin T). However, at very low troponin levels (0 to 10 ng/L) correlation between the two settings was moderate (r for high-sensitivity troponin I 0.59-0.66 and 0.65-0.69 for high-sensitivity troponin T). Application of guideline-recommended rapid diagnostic algorithms showed similar diagnostic performance with both methods. CONCLUSIONS: Overall on-demand and batch-wise measurements of high-sensitivity troponin provided similar results, but their correlation was moderate, when focusing on very low troponin levels. The application of rapid diagnostic algorithms was safe in both settings.Trial Registration: www.clinicaltrials.gov (NCT02355457).

3.
J Cell Physiol ; 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32542704

RESUMO

Training induces a number of healthy effects including a rise in skeletal muscle (SKM) glucose uptake. These adaptations are at least in part due to the reactive oxygen species produced within SKM, which is in agreement with the notion that antioxidant supplementation blunts some training-induced adaptations. Here, we tested whether hydroxytyrosol (HT), the main polyphenol of olive oil, would modify the molecular regulators of glucose uptake when HT is supplemented during exercise. Rats were included into sedentary and exercised (EXE) groups. EXE group was further divided into a group consuming a low HT dose (0.31 mg·kg·d; EXElow), a moderate HT dose (4.61 mg·kg·d; EXEmid), and a control group (EXE). EXE raised glucose transporter type 4 (GLUT4) protein content, Ras-related C3 botulinum toxin substrate 1 (Rac1) activity, and protein kinase b (AKT) phosphorylation in SKM. Furthermore, EXElow blunted GLUT4 protein content and AKT phosphorylation while EXEmid showed a downregulation of the GLUT4/AKT/Rac1 axis. Hence, a low-to-moderate dose of HT, when it is supplemented as an isolated compound, might alter the beneficial effect of training on basal AKT phosphorylation and Rac1 activity in rats.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32386768

RESUMO

OBJECTIVE: We aimed to analyze the association among flow patterns, gene expression, and histologic alterations of the proximal aorta in patients with aortic valve disease. METHODS: A total of 131 patients referred for aortic valve replacement were grouped by valve dysfunction (aortic stenosis vs aortic regurgitation) and valve morphology (bicuspid vs tricuspid). On the basis of magnetic resonance imaging, aortic tissue from outer and inner curvature was collected for gene expression and histologic analysis. To identify differences in aortic remodeling, age- and sex-adjusted data for inflammation (CCL2, VCAM1, inflammation and atherosclerosis) and medial degeneration (COL1A1, ELN, fibrosis, elastin fragmentation, and cystic medial necrosis) were compared. RESULTS: First, we compared all patients with aortic regurgitation (n = 64) and patients with aortic stenosis (n = 67). In patients with aortic regurgitation, COL1A1 expression and all histologic markers were significantly increased. With respect to aortic diameter, all subsequent analyses were refined by considering only individuals with aortic diameter 40 mm or greater. Second, patients with bicuspid aortic valve were compared, resulting in a similar aortic diameter. Although patients with aortic regurgitation were younger, no differences were found in gene expression or histologic level. Third, valve morphology was compared in patients with aortic regurgitation. Although aortic diameter was similar, patients with regurgitant bicuspid aortic valve were younger than patients with regurgitant tricuspid aortic valve. Inflammatory markers were similar, whereas markers for medial degeneration were increased in patients with regurgitant tricuspid aortic valve. CONCLUSIONS: Our results indicate that the proximal aorta in patients with aortic regurgitation showed an increased inflammation and medial degeneration compared with patients with aortic stenosis. Refining both groups by valve morphology, in patients with bicuspid aortic valve, no difference except age was detected between aortic regurgitation and aortic stenosis. In patients with aortic regurgitation, tricuspid aortic valve revealed increased markers for medial degeneration but no differences regarding inflammatory markers.

7.
J Am Heart Assoc ; 9(9): e015218, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32351154

RESUMO

Background Differences in risk factors for atrial fibrillation (AF) and heart failure (HF) are incompletely understood. Aim of this study was to understand whether risk factors and biomarkers show different associations with incident AF and HF and to investigate predictors of subsequent onset and mortality. Methods and Results In N=58 693 individuals free of AF/HF from 5 population-based European cohorts, Cox regressions were used to find predictors for AF, HF, subsequent onset, and mortality. Differences between associations were estimated using bootstrapping. Median follow-up time was 13.8 years, with a mortality of 15.7%. AF and HF occurred in 5.0% and 5.4% of the participants, respectively, with 1.8% showing subsequent onset. Age, male sex, myocardial infarction, body mass index, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) showed similar associations with both diseases. Antihypertensive medication and smoking were stronger predictors of HF than AF. Cholesterol, diabetes mellitus, and hsCRP (high-sensitivity C-reactive protein) were associated with HF, but not with AF. No variable was exclusively associated with AF. Population-attributable risks were higher for HF (75.6%) than for AF (30.9%). Age, male sex, body mass index, diabetes mellitus, and NT-proBNP were associated with subsequent onset, which was associated with the highest all-cause mortality risk. Conclusions Common risk factors and biomarkers showed different associations with AF and HF, and explained a higher proportion of HF than AF risk. As the subsequent onset of both diseases was strongly associated with mortality, prevention needs to be rigorously addressed and remains challenging, as conventional risk factors explained only 31% of AF risk.

10.
Nutrients ; 12(4)2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32326137

RESUMO

Sweeteners that are a hundred thousand times sweeter than sucrose are being consumed as sugar substitutes. The effects of sweeteners on gut microbiota composition have not been completely elucidated yet, and numerous gaps related to the effects of nonnutritive sweeteners (NNS) on health still remain. The NNS aspartame and acesulfame-K do not interact with the colonic microbiota, and, as a result, potentially expected shifts in the gut microbiota are relatively limited, although acesulfame-K intake increases Firmicutes and depletes Akkermansia muciniphila populations. On the other hand, saccharin and sucralose provoke changes in the gut microbiota populations, while no health effects, either positive or negative, have been described; hence, further studies are needed to clarify these observations. Steviol glycosides might directly interact with the intestinal microbiota and need bacteria for their metabolization, thus they could potentially alter the bacterial population. Finally, the effects of polyols, which are sugar alcohols that can reach the colonic microbiota, are not completely understood; polyols have some prebiotics properties, with laxative effects, especially in patients with inflammatory bowel syndrome. In this review, we aimed to update the current evidence about sweeteners' effects on and their plausible biological interactions with the gut microbiota.

11.
J Am Heart Assoc ; 9(8): e015452, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32299288

RESUMO

Background Risk stratification among patients with coronary artery disease (CAD) is of considerable interest due to the potential to guide secondary preventive therapies. Thus, we evaluated the predictive value of soluble urokinase-type plasminogen activator receptor (suPAR) levels for cardiovascular mortality and nonfatal myocardial infarction in patients with CAD. Methods and Results Plasma levels of suPAR were measured in a cohort of 1703 patients with documented CAD as evidenced by coronary angiography-including 626 patients with acute coronary syndrome and 1077 patients with stable angina pectoris. Cardiovascular death and/or nonfatal myocardial infarction were defined as main outcome measures. During a median follow-up of 3.5 years, suPAR levels reliably predicted cardiovascular death or myocardial infarction in CAD, evidenced by survival curves stratified for tertiles of suPAR levels. In Cox regression analyses, the hazard ratio for the prediction of cardiovascular death and/or myocardial infarction was 2.19 (P<0.001) in the overall cohort and 2.56 in the acute coronary syndrome cohort (P<0.001). Even after adjustment for common cardiovascular risk factors, renal function and the biomarkers C-reactive protein, N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin I suPAR still enabled a reliable prediction of cardiovascular death or myocardial infarction with a hazard ratio of 1.61 (P=0.022) in the overall cohort and 2.22 (P=0.005) in the acute coronary syndrome cohort. Conclusions SuPAR has a strong and independent prognostic value in secondary prevention settings, and thereby might represent a valuable biomarker for risk estimation in CAD.

12.
Adv Ther ; 37(Suppl 2): 80-88, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32236875

RESUMO

Hypophosphataemic rickets (HR) is a group of rare disorders caused by excessive renal phosphate wasting in which the participation of fibroblast growth factor 23 (FGF23) can be prominent. These diseases pose therapeutic challenges with important consequences for growth and bone development in childhood, with higher risk of fractures and poorer bone healing, dental problems, and nephrolithiasis or nephrocalcinosis. In some cases, the diagnostic delay can be very long; laboratory findings and an exhaustive anamnesis could help distinguish between various pathologies, and FGF23 values-although currently not routinely measured-have implications for the differential diagnosis. Genetic testing is encouraged, especially in sporadic or insidious cases. In this review we discuss the clinical features of HR, with a particular emphasis on the differential diagnosis and the therapeutic implications.

14.
Biomolecules ; 10(3)2020 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-32143410

RESUMO

Risk stratification among patients with coronary artery disease (CAD) is of considerable interest to potentially guide secondary preventive therapies. Cardiac troponins as well as C-reactive protein (hsCRP) and natriuretic peptides have emerged as biomarkers for risk stratification. The question remains if one of these biomarkers is superior in predicting adverse outcomes. Thus, we perform a head-to-head comparison between high-sensitivity troponin I (hsTnI), hsCRP, and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with CAD. Plasma levels were measured in a cohort of 2193 patients with documented CAD. The main outcome measures were cardiovascular (CV) death and/or nonfatal myocardial infarction (MI). During a median follow-up of 3.8 years, all three biomarkers were associated with cardiovascular death and/or MI. After adjustments for conventional cardiovascular risk factors, the hazard ratio (HR) per standard deviation (SD) for the prediction of CV death and/or nonfatal MI was 1.39 [95% CI: 1.24-1.57, p < 0.001] for hsTnI, 1.41 [95% CI: 1.24-1.60, p < 0.001] for hsCRP, and 1.64 [95% CI: 1.39-1.92, p < 0.001] for NT-proBNP. However, upon further adjustments for the other two biomarkers, only NT-proBNP was still associated with the combined endpoint with an HR of 1.47 [95% CI: 1.19-1.82, p < 0.001]. Conclusively, NT-proBNP is reliably linked to CV death and MI in patients with CAD and provides incremental value beyond hsCRP and hsTnI.

15.
Phys Med ; 70: 169-175, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32032801

RESUMO

The aim of this study is to propose national diagnostic reference levels (DRL) for updating in the field of interventional cardiology and to include technical details to help plan optimization. Medical physics experts and interventional cardiologists from 14 hospitals provided patient dose indicators from coronary angiography and percutaneous coronary interventions. Information about X-ray system dose settings and image quality was also provided. The dose values from 30,024 procedures and 26 interventional laboratories were recorded. The national DRLs proposed for coronary angiography and percutaneous coronary interventions were respectively 39 and 78 Gy·cm2 for air kerma area product (PKA), 530 and 1300 mGy for air kerma at reference point (Ka,r), 6.7 and 15 min of fluoroscopy time and 760 and 1300 cine images. 36% of the KAP meters required correction factors from 10 to 35%. The dose management systems should allow these corrections to be included automatically. The dose per image in cine in reference conditions differed in a factor of 5.5. Including X-ray system dose settings in the methodology provides an insight into the differences between hospitals. The DRLs proposed for Spain in this work were similar to those proposed in the last European survey. The poor correlation between X-ray systems dose settings and patient dose indicators highlights that other factors such as operation protocols and complexity may have more impact in patient dose indicators, which allows a wide margin for optimization. Dose reduction technology together with appropriate training programs will be determinant in the future reduction of patient dose indicators.

16.
Europace ; 22(4): 522-529, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31740944

RESUMO

AIMS: Limited evidence is available on the temporal relationship between atrial fibrillation (AF) and ischaemic stroke and their impact on mortality in the community. We sought to understand the temporal relationship of AF and ischaemic stroke and to determine the sequence of disease onset in relation to mortality. METHODS AND RESULTS: Across five prospective community cohorts of the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project we assessed baseline cardiovascular risk factors in 100 132 individuals, median age 46.1 (25th-75th percentile 35.8-57.5) years, 48.4% men. We followed them for incident ischaemic stroke and AF and determined the relation of subsequent disease diagnosis with overall mortality. Over a median follow-up of 16.1 years, N = 4555 individuals were diagnosed solely with AF, N = 2269 had an ischaemic stroke but no AF diagnosed, and N = 898 developed both, ischaemic stroke and AF. Temporal relationships showed a clustering of diagnosis of both diseases within the years around the diagnosis of the other disease. In multivariable-adjusted Cox regression analyses with time-dependent covariates subsequent diagnosis of AF after ischaemic stroke was associated with increased mortality [hazard ratio (HR) 4.05, 95% confidence interval (CI) 2.17-7.54; P < 0.001] which was also apparent when ischaemic stroke followed after the diagnosis of AF (HR 3.08, 95% CI 1.90-5.00; P < 0.001). CONCLUSION: The temporal relations of ischaemic stroke and AF appear to be bidirectional. Ischaemic stroke may precede detection of AF by years. The subsequent diagnosis of both diseases significantly increases mortality risk. Future research needs to investigate the common underlying systemic disease processes.

17.
Lancet ; 394(10215): 2173-2183, 2019 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-31810609

RESUMO

BACKGROUND: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment. METHODS: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol. FINDINGS: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7-59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0-20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0-1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6-2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0-1·3 to 2·3, 2·0-2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced. INTERPRETATION: Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician-patient communication about primary prevention strategies. FUNDING: EU Framework Programme, UK Medical Research Council, and German Centre for Cardiovascular Research.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , LDL-Colesterol/sangue , Medição de Risco/métodos , Adulto , Idoso , Austrália/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estados Unidos/epidemiologia
18.
Eur J Prev Cardiol ; : 2047487319885458, 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31707846

RESUMO

BACKGROUND: Modifiable lifestyle risk factors (modRF) of coronary artery disease (CAD) are associated with increased inflammation represented by elevated C-reactive protein (CRP) levels. Lifestyle changes may influence the inflammatory burden in patients with CAD, relevantly modifying the target population for emerging anti-inflammatory compounds. AIMS: The aims of this study were to analyse the association of modRF and CRP levels in CAD patients, and to define a potential target population for anti-inflammatory treatment with and without the optimisation of modRF. METHODS: We included all patients with angiographically documented CAD from the observational cohort study INTERCATH. Patients with recent myocardial infarction, malignancy, infectious disease, and pre-existing immunosuppressive medication including a history of solid organ transplantation were excluded. Overweight (body mass index (BMI) ≥ 25 kg/m2), smoking, lack of physical activity (PA; <1.5 h/week), and poor diet (≤12 points of an established Mediterranean diet score (MDS), range 0-28 points) were considered as modRF. CRP was measured by a high-sensitivity assay (hsCRP) at baseline. We performed multivariable linear regressions with log-transformed hsCRP as the dependent variable. Based on these associations, we calculated potential hsCRP levels for each patient, assuming optimisation of the individual modRF. RESULTS: Of 1014 patients, 737 (73%) were male, the mean age was 69 years, and 483 (48%) had an hsCRP ≥ 2 mg/l. ModRF were significantly overrepresented in patients with hsCRP ≥ 2 mg/l compared to patients with an hsCRP < 2 mg/l (BMI ≥ 25 kg/m2: 76% vs 61%; PA < 1.5 h/week: 69% vs 57%; MDS ≤ 12: 46% vs 37%; smoking: 61% vs 54%; p < 0.05 for all). hsCRP increased with the incremental number of modRF present (median hsCRP values for N = 0, 1, 2, 3, and 4 modRF: 1.1, 1.0, 1.6, 2.4, 2.8 mg/l, p < 0.001). Multivariable linear regression adjusting for age, sex, intake of lipid-lowering medication, and diabetes mellitus revealed independent associations between log-transformed hsCRP and all modRF (BMI ≥ 25 kg/m2: exp(ß) = 1.55, p < 0.001; PA < 1.5 h/week: exp(ß) = 1.33, p < 0.001; MDS ≤ 12: exp(ß) = 1.18, p = 0.018; smoking: exp(ß) = 1.18, p = 0.019). Individual recalculation of hsCRP levels assuming optimisation of modRF identified 183 out of 483 (38%) patients with hsCRP ≥ 2 mg/l who could achieve an hsCRP < 2 mg/l via lifestyle changes. CONCLUSION: modRF are strongly and independently associated with CRP levels in patients with CAD. A relevant portion of CAD patients with high inflammatory burden could achieve an hsCRP < 2 mg/l by lifestyle changes alone. This should be considered both in view of the cost and side-effects of pharmacological anti-inflammatory treatment and for the design of future clinical trials in this field.

19.
Clin Chem ; 65(12): 1592-1601, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31699700

RESUMO

BACKGROUND: Increasing numbers of patients are presenting worldwide to emergency departments with suspected myocardial infarction. The use of point-of-care troponin assays might enable faster decision-making in this high-risk population and reduce the burden on emergency facilities. Here, we evaluate the diagnostic performance of a point-of-care high-sensitivity troponin I assay. METHODS: We conducted a prospective cohort study including patients presenting to the emergency department with suspected myocardial infarction from July 2013 to July 2016. A diagnostic algorithm for a high-sensitivity troponin I point-of-care assay was developed in a derivation data set with 669 patients and validated in an additional 610 patients. RESULTS: The derived 0/1 h algorithm for the point-of-care assay consisted of an admission troponin I <4 ng/L and a δ from 0 h to 1 h <3 ng/L for rule out and an admission troponin I ≥90 ng/L or a δ from 0 h to 1 h ≥20 ng/L for rule in of non-ST-elevation myocardial infarction. Application to the validation cohort showed a negative predictive value of 99.7% (95% CI, 98.1%-100.0%) and 48.0% of patients ruled out, whereas 14.6% were ruled in with a positive predictive value of 86.5% (95% CI, 77.6%-92.8%). The diagnostic performance of the point-of-care high-sensitivity assay was highly comparable to guideline-recommended use of a laboratory-based high-sensitivity troponin assay. CONCLUSIONS: The clinical application of a 0/1 h diagnostic algorithm based on a high-sensitivity troponin I point-of-care assay is safe, and diagnostic performance is comparable to a laboratory-based high-sensitivity troponin I assay.


Assuntos
Infarto do Miocárdio/diagnóstico , Troponina I/análise , Idoso , Algoritmos , Biomarcadores , Estudos de Coortes , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito/tendências , Testes Imediatos/tendências , Estudos Prospectivos , Fatores de Risco , Sensibilidade e Especificidade , Fatores de Tempo , Troponina I/metabolismo , Troponina T/análise , Troponina T/metabolismo
20.
JAMA Cardiol ; 4(12): 1270-1279, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31664431

RESUMO

Importance: Risk stratification for coronary heart disease (CHD) remains challenging because of the complex causative mechanism of the disease. Metabolomic profiling offers the potential to detect new biomarkers and improve CHD risk assessment. Objective: To evaluate the association between circulating metabolites and incident CHD in a large European cohort. Design, Setting, and Participants: This population-based study used the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) case-cohort to measure circulating metabolites using a targeted approach in serum samples from 10 741 individuals without prevalent CHD. The cohort consisted of a weighted, random subcohort of the original cohort of more than 70 000 individuals. The case-cohort design was applied to 6 European cohorts: FINRISK97 (Finland), Monitoring of Trends and Determinants in Cardiovascular Diseases/Cooperative Health Research in the Region of Augsburg (MONICA/KORA; Germany), MONICA-Brianza and Moli-sani (Italy), DanMONICA (Denmark), and the Scottish Heart Health Extended Cohort (United Kingdom). Main Outcomes and Measures: Associations with time to CHD onset were assessed individually by applying weighted and adjusted Cox proportional hazard models. The association of metabolites with CHD onset was examined by C indices. Results: In 10 741 individuals (4157 women [38.7%]; median [interquartile range] age, 56.5 [49.2-62.2] years), 2166 incident CHD events (20.2%) occurred over a median (interquartile range) follow-up time of 9.2 (4.5-15.0) years. Among the 141 metabolites analyzed, 24 were significantly associated with incident CHD at a nominal P value of .05, including phosphatidylcholines (PCs), lysoPCs, amino acids, and sphingolipids. Five PCs remained significant after correction for multiple testing: acyl-alkyl-PC C40:6 (hazard ratio [HR], 1.13 [95% CI, 1.07-1.18]), diacyl-PC C40:6 (HR, 1.10 [95% CI, 1.04-1.15]), acyl-alkyl-PC C38:6 (HR, 1.11 [95% CI, 1.05-1.16]), diacyl-PC C38:6 (HR, 1.09 [95% CI, 1.04-1.14]) and diacyl-PC C38:5 (HR, 1.10 [95% CI, 1.05-1.16]). Lower levels of these metabolites were associated with increased risk of incident CHD. The strength of the associations competes with those of classic risk factors (C statistics: acyl-alkyl-PC C40:6, 0.756 [95% CI, 0.738-0.774], diacyl-PC C40:6, 0.754 [95% CI, 0.736-0.772], acyl-alkyl-PC C38:6, 0.755 [95% CI, 0.736-0.773], diacyl-PC C38:6, 0.754 [95% CI, 0.736-0.772]), diacyl-PC C38:5, 0.754 [95% CI, 0.736-0.772]). Adding metabolites to a base risk model including classic risk factors high-sensitivity C-reactive protein and high-sensitivity troponin I did not improve discrimination by C statistics. Conclusions and Relevance: Five PCs were significantly associated with increased risk of incident CHD and showed comparable discrimination with individual classic risk factors. Although these metabolites do not improve CHD risk assessment beyond that of classic risk factors, these findings hold promise for an improved understanding of the pathophysiology of CHD.

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