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1.
Clin Chim Acta ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32061575

RESUMO

The early concentration kinetic profiles of cardiac troponin in patients with non-ST-elevated myocardial infarction (NSTEMI) measured by high-sensitivity cardiac troponin I (hs-cTnI) and T (hs-cTnT) assays have not been described. In intermediate-to-high-risk of NSTEMI patients we measured serial cTn concentrations on ED arrival, at 1, 2, 3, 6-12, 24 and 48-hours with hs-cTnI and hs-cTnT assays. Log-normal curves were fitted to concentrations from time from symptom onset, and the time to rule-out decision thresholds estimated (hs-cTnI: 2ng/L and 5ng/L; hs-cTnT: 5ng/L). Among 164 patients there were 58 NSTEMI. The hs-cTnI to hs-cTnT ratio increased linearly over the first 6-12 hours following symptom onset. The estimated times from symptom onset to the 2ng/L and 5ng/L thresholds for hs-cTnI were 1.8h (0.1-3.1) and 1.9h (1.1-3.5) hours, and to the 5ng/L threshold for hs-cTnT 1.9h (1.1-3.8). The estimated time to exceed 5ng/L was ≥3 hours in 32.6% (95%CI: 20.0% to 48.1%) cases for hs-cTnI and 33.3% (19.6% to 50.0%) for hs-cTnT. cTnI concentrations increased at a much more rapid rate than cTnT concentrations in patients with NSTEMI. Concentrations of a high proportion of patients took longer than 3 hours from symptom onset to exceed the 5ng/L rule-out decision threshold.

2.
Clin Biochem ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32032568

RESUMO

BACKGROUND: Erythroferrone (ERFE) is an erythroid hormone putatively involved in stress erythropoiesis. Its regional clearance and circulating form in humans, as well as levels in normal health and coronary disease remain unclear. METHODS: To establish a reference interval, ERFE was measured in 155 healthy volunteers using the Intrinsic LifeSciences ELISA. To identify trans-organ gradients in ERFE, regional blood sampling was undertaken in patients (n = 13) undergoing clinically indicated cardiac catheterisation. The Intrinsic ELISA was assessed for reproducibility, stability, linearity and possible cross-reactivity, interference and anticoagulant effects. Circulating forms of ERFE were evaluated by HPLC. RESULTS: In healthy individuals, the median concentration of ERFE was 0.51 ng/mL (IQR: 0.12-1.25), with men (n = 78) having higher levels than women (n = 77) (0.67 vs 0.32 ng/mL, p = 0.0001). ERFE concentrations in trans-organ sampling revealed no clear organ of clearance or production. Samples with high endogenous ERFE levels were suppressed by haemoglobin (≥2 g/L), bilirubin (≥200 µmol/L), lipaemia (>1 g/L), and freeze thawing (≥2 cycles), but this was not observed with low ERFE concentrations. Endogenous ERFE immunoreactivity was 46% higher in EDTA plasma compared with serum and lithium heparin plasma. On SE-HPLC, ERFE eluted as intact and cleaved forms. CONCLUSION: We provide a useful reference range for ERFE in EDTA plasma. We found no specific site of secretion or clearance. The Intrinsic ELISA performed adequately but is limited by interference and stability when endogenous levels are high. Circulating forms are multiple and complex.

3.
Heart ; 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31822573

RESUMO

OBJECTIVE: Following acute coronary syndrome (ACS), patients are managed long-term in the community, yet few tools are available to guide patient-clinician communication about risk management in that setting. We developed a score for predicting cardiovascular disease (CVD) risk among patients managed in the community after ACS. METHODS: Adults aged 30-79 years with prior ACS were identified from a New Zealand primary care CVD risk management database (PREDICT) with linkage to national mortality, hospitalisation, pharmaceutical dispensing and regional laboratory data. A Cox model incorporating clinically relevant factors was developed to estimate the time to a subsequent fatal or non-fatal CVD event and transformed into a 5-year risk score. External validation was performed in patients (Coronary Disease Cohort Study) assessed 4 months post-ACS. RESULTS: The PREDICT-ACS cohort included 13 703 patients with prior hospitalisation for ACS (median 1.9 years prior), 69% men, 58% European, median age 63 years, who experienced 3142 CVD events in the subsequent 5 years. Median estimated 5 year CVD risk was 24% (IQR 17%-35%). The validation cohort consisted of 2014 patients, 72% men, 92% European, median age 67 years, with 712 CVD events in the subsequent 5 years. Median estimated 5-year risk was 33% (IQR 24%-51%). The risk score was well calibrated in the derivation and validation cohorts, and Harrell's c-statistic was 0.69 and 0.68, respectively. CONCLUSIONS: The PREDICT-ACS risk score uses data routinely available in community care to predict the risk of recurrent clinical events. It was derived and validated in real-world contemporary populations and can inform management decisions with patients living in the community after experiencing an ACS.

4.
Sci Rep ; 9(1): 12108, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31431677

RESUMO

Natriuretic Peptides (NP) are important in maintaining normal cardiac and metabolic status and have been used to predict cardiovascular events. Whether plasma concentrations of NP products within the normal range reflect cardio-metabolic health is unknown. Plasma NTproANP, NTproBNP and NTproCNP and their bioactive counterparts were measured in a random sample of 348 community dwellers aged 49-51 yr without heart disease and associations sought with established vascular risk factors, echocardiographic indices and a genetic variant previously linked with BNP. Stratified by sex, each of ten vascular risk factors were positively associated with NTproCNP whereas associations with NTproBNP and NTproANP were all negative. In both sexes, higher plasma NTproCNP was associated with higher arterial elastance, lower LV stroke volume and lower LV end diastolic volume. Exactly opposite associations were found with plasma NTproBNP or NTproANP. Sex specific differences were identified: positive association of NTproBNP with LV end systolic volume and the negative association with LV elastance were found only in males. The genetic variant rs198358 was independently associated with NTproBNP but not with NTproANP. In conclusion, higher NTproCNP is likely to be an adaptive response to impaired LV relaxation whereas genetic factors likely contribute to higher NTproBNP and improved cardio-metabolic health at midlife.

5.
Heart ; 105(22): 1717-1724, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31337669

RESUMO

OBJECTIVES: High-sensitivity cardiac troponin testing is used in the diagnosis of acute coronary syndromes but its role during convalescence is unknown. We investigated the long-term prognostic significance of serial convalescent high-sensitivity cardiac troponin concentrations following acute coronary syndrome. METHODS: In a prospective multicentre observational cohort study of 2140 patients with acute coronary syndrome, cardiac troponin I concentrations were measured in 1776 patients at 4 and 12 months following the index event. Patients were stratified into three groups according to the troponin concentration at 4 months using the 99th centile (women>16 ng/L, men>34 ng/L) and median concentration of those within the reference range. The primary outcome was cardiovascular death. RESULTS: Troponin concentrations at 4 months were measurable in 99.0% (1759/1776) of patients (67±12 years, 72% male), and were ≤5 ng/L (median) and >99th centile in 44.8% (795) and 9.3% (166), respectively. There were 202 (11.4%) cardiovascular deaths after a median of 4.8 years. After adjusting for the Global Registry of Acute Coronary Events score, troponin remained an independent predictor of cardiovascular death (HR 1.4, 95% CI 1.3 to 1.5 per doubling) with the highest risk observed in those with increasing concentrations at 12 months. Patients with 4-month troponin concentrations >99th centile were at increased risk of cardiovascular death compared with those ≤5 ng/L (29.5% (49/166) vs 4.3% (34/795); adjusted HR 4.9, 95% CI 3.8 to 23.7). CONCLUSIONS: Convalescent cardiac troponin concentrations predict long-term cardiovascular death following acute coronary syndrome. Recognising this risk by monitoring troponin may improve targeting of therapeutic interventions. TRIAL REGISTRATION NUMBER: ACTRN12605000431628;Results.

6.
Arthritis Rheumatol ; 71(10): 1733-1738, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31162825

RESUMO

OBJECTIVE: To determine whether gout and serum urate (SU) levels are associated with increased risk of death, time to first readmission for any cardiovascular event, or incident heart failure in individuals with cardiovascular disease. METHODS: Individuals presenting with an acute coronary syndrome (ACS) were enrolled in the Coronary Disease Cohort Study. Clinical data were collected from the medical records at the index hospital admission, and clinical, echocardiographic, and biochemical data were collected postdischarge. Gout was defined by self-report, use of urate-lowering therapy, or use of colchicine with evidence of gout on review of the medical record. The primary end points were all-cause mortality, time to readmission for a cardiac ischemic event, and time to readmission for heart failure. RESULTS: Data from 1,514 participants were available. During the follow-up period, 53 of 160 participants with gout (33.1%) and 298 of 1,354 participants without gout (22.0%) died. After adjustment for other factors known to be associated with mortality, there was no gout-specific increase in risk of mortality (adjusted hazard ratio 0.98 [95% confidence interval 0.69-1.38]). Time to readmission for heart failure was significantly briefer in those with, compared to those without, gout (adjusted hazard ratio 1.42 [95% confidence interval 1.02-1.97]). Irrespective of whether a participant had gout or not, as SU level increased, there was an increased risk of death and readmission for either a cardiovascular event or heart failure. CONCLUSION: Survival post-ACS is similar with and without the presence of gout. People with gout are at an increased risk of readmission for heart failure and have longer hospital stays. Risk of these events increases in parallel with increases in SU levels.

7.
N Engl J Med ; 380(26): 2529-2540, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31242362

RESUMO

BACKGROUND: Data regarding high-sensitivity troponin concentrations in patients presenting to the emergency department with symptoms suggestive of myocardial infarction may be useful in determining the probability of myocardial infarction and subsequent 30-day outcomes. METHODS: In 15 international cohorts of patients presenting to the emergency department with symptoms suggestive of myocardial infarction, we determined the concentrations of high-sensitivity troponin I or high-sensitivity troponin T at presentation and after early or late serial sampling. The diagnostic and prognostic performance of multiple high-sensitivity troponin cutoff combinations was assessed with the use of a derivation-validation design. A risk-assessment tool that was based on these data was developed to estimate the risk of index myocardial infarction and of subsequent myocardial infarction or death at 30 days. RESULTS: Among 22,651 patients (9604 in the derivation data set and 13,047 in the validation data set), the prevalence of myocardial infarction was 15.3%. Lower high-sensitivity troponin concentrations at presentation and smaller absolute changes during serial sampling were associated with a lower likelihood of myocardial infarction and a lower short-term risk of cardiovascular events. For example, high-sensitivity troponin I concentrations of less than 6 ng per liter and an absolute change of less than 4 ng per liter after 45 to 120 minutes (early serial sampling) resulted in a negative predictive value of 99.5% for myocardial infarction, with an associated 30-day risk of subsequent myocardial infarction or death of 0.2%; a total of 56.5% of the patients would be classified as being at low risk. These findings were confirmed in an external validation data set. CONCLUSIONS: A risk-assessment tool, which we developed to integrate the high-sensitivity troponin I or troponin T concentration at emergency department presentation, its dynamic change during serial sampling, and the time between the obtaining of samples, was used to estimate the probability of myocardial infarction on emergency department presentation and 30-day outcomes. (Funded by the German Center for Cardiovascular Research [DZHK]; ClinicalTrials.gov numbers, NCT00470587, NCT02355457, NCT01852123, NCT01994577, and NCT03227159; and Australian New Zealand Clinical Trials Registry numbers, ACTRN12611001069943, ACTRN12610000766011, ACTRN12613000745741, and ACTRN12611000206921.).


Assuntos
Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Medição de Risco/métodos , Troponina/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos de Coortes , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Sensibilidade e Especificidade , Troponina I/sangue
8.
Clin Biochem ; 69: 36-44, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31129182

RESUMO

BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) is an emerging marker of cardiovascular disease burden. Appropriate assessment of assay performance and reference interval are required to enable interpretation of results to facilitate its clinical application. METHODS: suPAR was measured using the suPARnostic® ELISA in 155 healthy volunteers. Assay performance was assessed for anticoagulant effect, recovery, interference, linearity and cross-reactivity. The identity of immunoreactive suPAR was confirmed by size-exclusion HPLC. To establish anatomical sites of release and uptake, we measured suPAR in regional samples from subjects undergoing cardiac catheterization. RESULTS: The median concentration of suPAR was 2.1 ng/mL (IQR:1.7-2.3) in health. In comparison with EDTA, suPAR measurements were affected by lithium heparin (>10% change) and increased with serum usage. suPAR reactivity also increased in the presence of haemolysis (10 g/L), but was suppressed with urokinase and lipids (4 g/L). In multiple regression analyses, suPAR associated independently with body weight, NT-proBNP and MR-proADM (P = .03) for healthy individuals. Regional plasma sampling showed lower suPAR concentrations in the coronary sinus and renal vein compared with concentrations in femoral arterial samples. Immunoreactive circulating suPAR species had Mr of 10-39 kDa. CONCLUSION: The suPARnostic® assay performs acceptably for a clinical assay but is limited in the presence of high levels of hemolysis, lipids and urokinase. We provide the first evidence for the heart and kidneys as organs of suPAR clearance in humans. Additional investigations are warranted to determine whether there is a need to compare the marker performance of differing circulating forms of suPAR.


Assuntos
Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Adulto , Cromatografia em Gel/métodos , Cromatografia Líquida de Alta Pressão/métodos , Ensaio de Imunoadsorção Enzimática , Feminino , Voluntários Saudáveis , Humanos , Limite de Detecção , Masculino , Pessoa de Meia-Idade , Peso Molecular , Receptores de Ativador de Plasminogênio Tipo Uroquinase/química , Padrões de Referência
9.
J Card Fail ; 25(9): 703-711, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30953792

RESUMO

BACKGROUND: Amino-terminal pro-B-type natriuretic peptide (NTproBNP) is closely associated with prognosis in acute decompensated heart failure (ADHF). As a result, there has been great interest measuring it during the course of treatment. The prognostic implications in both short-term and follow-up changes in NTproBNP need further clarification. METHODS: Baseline, 48-72 hour, and 30-day NTproBNP levels were measured in 795 subjects in the ASCEND-HF trial. Multivariable logistic and Cox-proportional hazards models were used to test the association between static, relative, and absolute changes in NTproBNP with outcomes during and after ADHF. RESULTS: The median NTproBNP at baseline was 5773 (2981-11,579) pg/mL; at 48-72 hours was 3036 (1191-6479) pg/mL; and at 30 days was 2914 (1364-6667) pg/mL. Absolute changes in NTproBNP by 48-72 hours were not associated with 30-day heart failure rehospitalization or mortality (P = .065), relative changes in NTproBNP were nominally associated (P = .046). In contrast, both absolute and relative changes in NTproBNP from baseline to 48-72 hours and to 30 days were closely associated with 180-day mortality (P < .02 for all) with increased discrimination compared to the multivariable models with baseline NTproBNP (P <.05 for models with relative and absolute change at both time points). CONCLUSIONS: Although the degree of absolute change in NTproBNP was dependent on baseline levels, both short-term absolute and relative changes in NTproBNP were independently and incrementally associated with long-term clinical outcomes. Changes in NTproBNP levels at 30-days were particularly well associated with long-term clinical outcomes.

10.
Heart ; 105(11): 842-847, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30661038

RESUMO

OBJECTIVE: Ethnic differences in the prevalence of atrial fibrillation (AF) in heart failure (HF) remain unclear. We compared the prevalence and clinical correlates of AF among different ethnicities in an Asian-Pacific population with HF. METHODS: Patients with validated HF were prospectively studied across Singapore and New Zealand (NZ). RESULTS: Among 1746 patients with HF (62% Asian, 26% women, mean age 66 (SD 13) years, mean ejection fraction (EF) 37 (SD 16%), 39% had AF. The prevalence of AF was markedly lower in Singapore-Asians than NZ-Europeans (24% vs 63%; p<0.001), even after adjusting for age, clinical and echocardiographic covariates, regardless of EF group (pinteraction for EF=0.39). Patients with AF were older, had higher body mass index and were more likely to have a history of hypertension, stroke, peripheral vascular disease, renal disease, chronic respiratory disease and increased alcohol intake, but less likely to have diabetes. Clinical correlates were similar for Asians and NZ-Europeans, except diabetes: Asian diabetic patients with HF had less AF compared with Asian patients without diabetes (OR 0.66, 95% CI 0.50 to 0.88), whereas among NZ-Europeans there was no significant association between diabetes and AF (OR 1.22, 95% CI 0.85 to 1.75) (pinteraction for ethnicity=0.01). AF was associated with a higher crude composite outcome of mortality and HF hospitalisations at 2 years (HR 1.19, 95% CI 1.02 to 1.38). CONCLUSION: There is a strikingly lower prevalence of AF among Asian compared with NZ-European patients with HF. The underlying mechanisms for the lower prevalence of AF among Asians, particularly in the presence of diabetes, deserve further study. TRIAL REGISTRATION NUMBER: ACTRN12610000374066.

11.
JAMA Cardiol ; 3(11): 1108-1112, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30347004

RESUMO

Importance: Emergency department (ED) investigations of patients with suspected acute myocardial infarction (AMI) are time consuming, partly because of the turnaround time of laboratory tests. Current point-of-care troponin assays shorten test turnaround times but lack precision at lower concentrations. Development of point-of-care troponin assays with greater analytical precision could reduce the decision-making time in EDs for ruling out AMI. Objective: To determine the clinical accuracy for AMI of a single troponin concentration measured on arrival to ED with a new-generation, higher precision point-of-care assay with a 15-minute turnaround time. Design, Setting, and Participants: This observational study occurred at a single urban regional ED. Adults presenting acutely from the community to the ED with symptoms suggestive of AMI were included. Troponin concentrations were measured on ED arrival with both a novel point-of-care assay (i-STAT TnI-Nx; Abbott Point of Care) and a high-sensitivity troponin I assay (Architect hs-cTnI; Abbott Diagnostics). Main Outcomes and Measures: The primary outcome was type 1 AMI during index presentation. We compared the discrimination ability of the TnI-Nx assay with the hs-cTnI assay using the area under receiver operator characteristic curve (AUC) and sensitivity, negative predictive value, and the proportion of negative test results at thresholds with 100% sensitivity. Results: Of 354 patients (255 [72.0%] men; mean [SD] age, 62 [12] years), 57 (16.1%) experienced an AMI. Eighty-five patients (24.0%) presented to the ED less than 3 hours after symptom onset. No difference was found between the AUC of the TnI-Nx assay (0.975 [95% CI, 0.958-0.993]) and the hs-cTnI assay (0.970 [95% CI, 0.949 to 0.990]; P = .46). A TnI-Nx assay result of less than 11 ng/L identified 201 patients (56.7%) as low risk, with a sensitivity of 100% (95% CI, 93.7%-100%) and a negative predictive value of 100% (95% CI, 98.2%-100%). In comparison, an hs-cTnI assay result of less than 3 ng/L identified 154 patients (43.5%) as low risk, with a sensitivity of 100% (95% CI, 93.7%-100%) and a negative predictive value of 100% (95% CI, 97.6%-100%). Conclusions and Relevance: A novel point-of-care troponin assay that can produce a result 15 minutes after blood sampling had comparable discrimination ability to an hs-cTnI assay for ruling out AMI after a single blood test. Use in the ED may facilitate earlier decision making and could expedite the safe discharge of a large proportion of low-risk patients.


Assuntos
Infarto do Miocárdio/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito , Troponina I/análise , Idoso , Área Sob a Curva , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/metabolismo , Nova Zelândia , Sensibilidade e Especificidade , Fatores de Tempo
12.
BMC Cardiovasc Disord ; 18(1): 169, 2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-30111293

RESUMO

BACKGROUND: Development of collateral circulation in coronary artery disease is cardio-protective. A key process in forming new blood vessels is attraction to occluded arteries of monocytes with their subsequent activation as macrophages. In patients from a prospectively recruited post-acute coronary syndromes cohort we investigated the prognostic performance of three products of activated macrophages, soluble vascular endothelial growth factor (VEGF) receptors (sFlt-1 and sKDR) and pterins, alongside genetic variants in VEGF receptor genes, VEGFR-1 and VEGFR-2. METHODS: Baseline levels of sFlt-1 (VEGFR1), sKDR (VEGFR2) and pterins were measured in plasma samples from subgroups (n = 513; 211; 144, respectively) of the Coronary Disease Cohort Study (CDCS, n = 2067). DNA samples from the cohort were genotyped for polymorphisms from the VEGFR-1 gene SNPs (rs748252 n = 2027, rs9513070 n = 2048) and VEGFR-2 gene SNPs (rs2071559 n = 2050, rs2305948 n = 2066, rs1870377 n = 2042). RESULTS: At baseline, levels of sFlt-1 were significantly correlated with age, alcohol consumption, NTproBNP, BNP and other covariates relevant to cardiovascular pathophysiology. Total neopterin levels were associated with alcohol consumption at baseline. 7,8 dihydroneopterin was associated with BMI. The A allele of VEGFR-2 variant rs1870377 was associated with higher plasma sFlt-1 and lower levels of sKDR at baseline. Baseline plasma sFlt-1 was univariately associated with all cause mortality with (p < 0.001) and in a Cox's proportional hazards regression model sFlt-1 and pterins were both associated with mortality independent of established predictors (p < 0.027). CONCLUSIONS: sFlt-1 and pterins may have potential as prognostic biomarkers in acute coronary syndromes patients. Genetic markers from VEGF system genes warrant further investigation as markers of levels of VEGF system components in these patients. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry. ACTRN12605000431628 . 16 September 2005, Retrospectively registered.


Assuntos
Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/genética , Polimorfismo de Nucleotídeo Único , Pterinas/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/sangue , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/mortalidade , Fatores Etários , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Angiografia Coronária , Feminino , Estudos de Associação Genética , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Ativação de Macrófagos , Macrófagos/metabolismo , Masculino , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco
13.
JACC Basic Transl Sci ; 3(2): 163-175, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30062203

RESUMO

We identified a plasma signature of 11 C14 to C26 ceramides and 1 C16 dihydroceramide predictive of major adverse cardiovascular events in patients with acute myocardial infarction (AMI). Among patients undergoing coronary artery bypass surgery, those with recent AMI, compared with those without recent AMI, showed a significant increase in 5 of the signature's 12 ceramides in plasma but not simultaneously-biopsied aortic tissue. In contrast, a rat AMI model, compared with sham control, showed a significant increase in myocardial concentrations of all 12 ceramides and up-regulation of 3 ceramide-producing enzymes, suggesting ischemic myocardium as a possible source of this ceramide signature.

14.
Clin Chem ; 64(7): 1044-1053, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29760219

RESUMO

BACKGROUND: Increased cardiac troponin I or T detected by high-sensitivity assays (hs-cTnI or hs-cTnT) confers an increased risk of adverse prognosis. We determined whether patients presenting with putatively normal, detectable cTn concentrations [> limit of detection and < upper reference limit (URL)] have increased risk of major adverse cardiovascular events (MACE) or all-cause mortality. METHODS: A prospective 5-year follow-up of patients recruited in the emergency department with possible acute coronary syndrome (ACS) and cTn concentrations measured with hs-cTnI (Abbott) and hs-cTnT (Roche) assays. Cox regression models were generated with adjustment for covariates in those without MACE on presentation. Hazard ratios (HRs) for hs-cTn were calculated relative to the HRs at the median concentration. RESULTS: Of 1113 patients, 836 were without presentation MACE. Of these, 138 incurred a MACE and 169 died during a median 5.8-year follow-up. HRs for MACE at the URLs were 2.3 (95% CI, 1.7-3.2) for hs-cTnI and 1.8 (95% CI, 1.3-2.4) for hs-cTnT. Corresponding HRs for mortality were 1.7 (95% CI, 1.2-2.2) for hs-cTnI and 2.3 (95 % CI, 1.7-3.1) for hs-cTnT. The HR for MACE increased with increasing hs-cTn concentration similarly for both assays, but the HR for mortality increased at approximately twice the rate for hs-cTnT than hs-cTnI. Patients with hs-cTnI ≥10 ng/L or hs-cTnT ≥16 ng/L had the same percentage of MACE at 5-year follow-up (33%) as patients with presentation MACE. CONCLUSIONS: Many patients with ACS ruled out and putatively normal but detectable hs-cTnI concentrations are at similar long-term risk as those with MACE. hs-cTnT concentrations are more strongly associated with 5-year mortality than hs-cTnI.


Assuntos
Troponina I/sangue , Troponina T/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Humanos , Limite de Detecção , Padrões de Referência , Fatores de Risco
16.
Clin Chem ; 64(2): 363-373, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29097512

RESUMO

BACKGROUND: In community studies, plasma B-type natriuretic peptide (BNP) is positively associated with cardiovascular disorders. Those born with very low birth weight (VLBW) have increased risk of metabolic and vascular disorders in later life, but plasma concentrations of natriuretic peptides have not been studied. The objectives here were to evaluate BNP and C-type natriuretic peptide (CNP)-a putative marker of vascular risk-in young adults born with VLBW. METHODS: In all, 220 VLBW cases and 97 matched controls were studied 28 years after birth during a 2-day period at 1 research center. Aminoterminal (NT) products (NTproBNP, NTproCNP) and a range of conventional vascular risk factors including echocardiographic indices were measured along with genetic polymorphisms known to increase plasma NTproBNP. RESULTS: VLBW individuals were smaller, had smaller hearts, reduced stroke volume and endothelial function, and higher systolic blood pressure and arterial elastance. Of the many humoral vascular and metabolic risk factors measured, including NTproBNP, only plasma NTproCNP (higher in VLBW individuals) differed significantly. Across all individuals, associations of NTproCNP with each of 7 conventional risk factors, as well as with arterial elastance, were positive, whereas associations of NTproBNP with risk were all inverse. In multivariate analysis, the genetic variant rs198358 was independently associated with NTproBNP. CONCLUSIONS: In young adults at increased risk of cardiovascular disease, higher NTproCNP likely reflects a compensatory vascular response to vascular stress, whereas the negative link with NTproBNP likely reflects beneficial genetic mutations. The ratio of NTproBNP to NTproCNP may provide a novel index of ideal cardiovascular health.


Assuntos
Recém-Nascido de muito Baixo Peso , Peptídeo Natriurético Encefálico/sangue , Peptídeo Natriurético Tipo C/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Ecocardiografia , Feminino , Humanos , Recém-Nascido , Masculino , Síndrome Metabólica/sangue , Peptídeo Natriurético Encefálico/genética , Peptídeo Natriurético Encefálico/metabolismo , Peptídeo Natriurético Tipo C/genética , Peptídeo Natriurético Tipo C/metabolismo , Estudos Prospectivos , Fatores de Risco , Transdução de Sinais/genética
17.
Circulation ; 137(4): 354-363, 2018 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-29138293

RESUMO

BACKGROUND: Efforts to safely reduce length of stay for emergency department patients with symptoms suggestive of acute coronary syndrome (ACS) have had mixed success. Few system-wide efforts affecting multiple hospital emergency departments have ever been evaluated. We evaluated the effectiveness of a nationwide implementation of clinical pathways for potential ACS in disparate hospitals. METHODS: This was a multicenter pragmatic stepped-wedge before-and-after trial in 7 New Zealand acute care hospitals with 31 332 patients investigated for suspected ACS with serial troponin measurements. The implementation was a clinical pathway for the assessment of patients with suspected ACS that included a clinical pathway document in paper or electronic format, structured risk stratification, specified time points for electrocardiographic and serial troponin testing within 3 hours of arrival, and directions for combining risk stratification and electrocardiographic and troponin testing in an accelerated diagnostic protocol. Implementation was monitored for >4 months and compared with usual care over the preceding 6 months. The main outcome measure was the odds of discharge within 6 hours of presentation RESULTS: There were 11 529 participants in the preimplementation phase (range, 284-3465) and 19 803 in the postimplementation phase (range, 395-5039). Overall, the mean 6-hour discharge rate increased from 8.3% (range, 2.7%-37.7%) to 18.4% (6.8%-43.8%). The odds of being discharged within 6 hours increased after clinical pathway implementation. The odds ratio was 2.4 (95% confidence interval, 2.3-2.6). In patients without ACS, the median length of hospital stays decreased by 2.9 hours (95% confidence interval, 2.4-3.4). For patients discharged within 6 hours, there was no change in 30-day major adverse cardiac event rates (0.52% versus 0.44%; P=0.96). In these patients, no adverse event occurred when clinical pathways were correctly followed. CONCLUSIONS: Implementation of clinical pathways for suspected ACS reduced the length of stay and increased the proportions of patients safely discharged within 6 hours. CLINICAL TRIAL REGISTRATION: URL: https://www.anzctr.org.au/ (Australian and New Zealand Clinical Trials Registry). Unique identifier: ACTRN12617000381381.


Assuntos
Síndrome Coronariana Aguda/diagnóstico , Serviço Hospitalar de Cardiologia/normas , Procedimentos Clínicos/normas , Serviço Hospitalar de Emergência/normas , Hospitalização , Melhoria de Qualidade/normas , Indicadores de Qualidade em Assistência à Saúde/normas , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/epidemiologia , Síndrome Coronariana Aguda/terapia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Tomada de Decisão Clínica , Eletrocardiografia , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Valor Preditivo dos Testes , Prevalência , Prognóstico , Medição de Risco , Fatores de Risco , Fatores de Tempo , Troponina/sangue
19.
Clin Chem ; 63(1): 316-324, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28062626

RESUMO

AIMS: C-type natriuretic peptide (CNP) is a paracrine growth factor expressed in the vascular endothelium. Although upregulated in atheromatous arteries, the predictive value of plasma CNP products for outcome in coronary disease is unknown. This study aimed to compare the prognostic value of plasma CNP products with those of other natriuretic peptides in individuals with coronary artery disease, and investigate their associations with cardiac and renal function. METHODS AND RESULTS: Plasma concentrations of CNP and amino-terminal proCNP (NT-proCNP) were measured at baseline in 2129 individuals after an index acute coronary syndrome admission and related to cardiac and renal function, other natriuretic peptides [atrial NP (ANP) and B-type NP (BNP)] and prognosis (primary end point, mortality; secondary end point, cardiac readmission). Median follow-up was 4 years. At baseline, and in contrast to CNP, ANP, and BNP, plasma NT-proCNP was higher in males and weakly related to cardiac function but strongly correlated to plasma creatinine. All NPs were univariately associated with mortality. Resampling at 4 and 12 months in survivors showed stable concentrations of NT-proCNP whereas all other peptides declined. When studied by diagnosis (myocardial infarction, unstable angina) at index admission using a multivariate model, NT-proBNP predicted mortality and readmission in myocardial infarction. In unstable angina, only NT-proCNP predicted both mortality and cardiac readmission. CONCLUSIONS: In contrast to the close association of NT-proBNP with cardiac function, and predictive value for outcome after myocardial infarction, plasma NT-proCNP is highly correlated with renal function and is an independent predictor of mortality and cardiac readmission in individuals with unstable angina.


Assuntos
Doença da Artéria Coronariana/sangue , Peptídeo Natriurético Tipo C/sangue , Idoso , Biomarcadores/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
20.
Endocrinology ; 157(12): 4865-4874, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27754786

RESUMO

Corticotropin-releasing factor (CRF) and the CRF-related peptides, urocortin (Ucn)-1, Ucn2, and Ucn3 signal through receptors CRFR1 and CRFR2 to restore homeostasis in response to stress. The Ucns exert potent cardioprotective effects and may have clinical utility in heart failure. To explore the activity of this system in the heart, we measured the levels of myocardial gene expression of the CRF/Ucn family of ligands/receptors and investigated genetic variation and alternative splicing of CRFR1 in 110 heart failure patients and 108 heart donors. Using quantitative real-time PCR, we detected CRFR1, CRFR2, CRF, Ucn1, Ucn2, and Ucn3 in all samples. CRFR2α was the most abundant receptor and Ucn3 the most abundant ligand, both in patients and donors. Compared with donors, cardiac expression of CRFR1, CRF, and Ucn3 was higher (P < .001) and CRFR2α lower (P = .012) in patients. In patients and donors, genetic variation within CRFR1, represented by the chromosome 17q21.31 inversion polymorphism, was associated with markedly higher CRFR1 expression (P < .001), making CRFR1 and CRFR2α expression almost equivalent in some patients. A novel, truncated splice variant of CRFR1, designated CRFR1j, was identified and shown to exert a dominant-negative effect on CRFR1 signaling in vitro. The novel variant was expressed in a greater proportion of patients (60%) than donors (3%, P < .001). In summary, cardiac expression of CRFR1, CRF, and Ucn3 genes is elevated in heart failure and may contribute to the activation of the CRF/Ucn system in these patients. A common variant within the CRFR1 gene and a novel CRFR1 splice variant may modulate CRFR1 expression and signaling.


Assuntos
Processamento Alternativo , Variação Genética , Insuficiência Cardíaca/metabolismo , Miocárdio/metabolismo , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Adulto , Idoso , Hormônio Liberador da Corticotropina/genética , Hormônio Liberador da Corticotropina/metabolismo , Feminino , Insuficiência Cardíaca/genética , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Hormônio Liberador da Corticotropina/genética , Transdução de Sinais/fisiologia , Urocortinas/genética , Urocortinas/metabolismo
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