RESUMEN
BACKGROUND: Proenkephalin (PENK), a stable endogenous opioid biomarker related to renal function, has prognostic utility in acute and chronic heart failure. We investigated the prognostic utility of PENK in heart failure with preserved ejection fraction (HFpEF), and its relationship to renal function, Body Mass Index (BMI), and imaging measures of diastolic dysfunction. METHODS: In this multicentre study, PENK was measured in 522 HFpEF patients (ejection fraction > 50%, 253 male, mean age 76.13 ± 10.73 years) and compared to 47 age and sex-matched controls. The primary endpoint was 2-years composite of all-cause mortality and/or heart failure rehospitalisation (HF). A subset (n = 163) received detailed imaging studies. RESULTS: PENK levels were raised in HFpEF (median [interquartile range] 88.9 [62.1-132.0]) compared to normal controls (56.3 [47.9-70.5]). PENK was correlated to urea, eGFR, Body Mass Index and E/e' (rs 0.635, - 0.741, - 0.275, 0.476, respectively, p < 0.0005). During 2 years follow-up 144 patients died and 220 had death/HF endpoints. Multivariable Cox regression models showed PENK independently predicted 2 year death/HF [hazard ratio (for 1 SD increment of log-transformed biomarker) HR 1.45 [95% CI 1.12-1.88, p = 0.005]], even after adjustment for troponin (HR 1.59 [1.14-2.20, p = 0.006]), and Body Mass Index (HR 1.63 [1.13-2.33, p = 0.009]). PENK showed no interaction with ejection fraction status for prediction of poor outcomes. Net reclassification analyses showed PENK significantly improved classification of death/HF outcomes for multivariable models containing natriuretic peptide, troponin and Body Mass Index (p < 0.05 for all). CONCLUSIONS: In HFpEF, PENK levels are related to BMI, and measures of diastolic dysfunction and are prognostic for all-cause mortality and heart failure rehospitalisation.
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Encefalinas/sangre , Insuficiencia Cardíaca/sangre , Ventrículos Cardíacos/diagnóstico por imagen , Precursores de Proteínas/sangre , Volumen Sistólico/fisiología , Anciano , Biomarcadores/sangre , Causas de Muerte/tendencias , Ecocardiografía Doppler , Femenino , Tasa de Filtración Glomerular/fisiología , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Ventrículos Cardíacos/fisiopatología , Humanos , Imagen por Resonancia Cinemagnética , Masculino , Pronóstico , Tasa de Supervivencia/tendencias , Suiza/epidemiologíaRESUMEN
BACKGROUND: Proenkephalin A (PENK) and its receptors are widely distributed. Enkephalins are cardiodepressive and difficult to measure directly. PENK is a stable surrogate analyte of labile enkephalins that is correlated inversely with renal function. Cardiorenal syndrome is common in acute heart failure (HF) and portends poor prognosis. OBJECTIVES: This study assessed the prognostic value of PENK in acute HF, by identifying levels that may be useful in clinical decisions, and evaluated its utility for predicting cardiorenal syndrome. METHODS: This multicenter study measured PENK in 1,908 patients with acute HF (1,186 male; mean age 75.66 ± 11.74 years). The primary endpoint was 1-year all-cause mortality; secondary endpoints were in-hospital mortality, all-cause mortality or HF rehospitalization within 1 year, and in-hospital worsening renal function, defined as a rise in plasma creatinine ≥26.5 µmol/l or 50% higher than the admission value within 5 days of presentation. RESULTS: During 1-year follow-up, 518 patients died. Measures of renal function were the major determinants of PENK levels. PENK independently predicted worsening renal function (odds ratio: 1.58; 95% confidence interval [CI]: 1.24 to 2.00; p < 0.0005) with a model receiver-operating characteristic area of 0.69. PENK was associated with the degree of worsening renal function. Multivariable Cox regression models showed that PENK level was an independent predictor of 1-year mortality (p < 0.0005) and 1-year death and/or HF (hazard ratio: 1.27; 95% CI: 1.10 to 1.45; p = 0.001). PENK levels independently predicted outcomes at 3 or 6 months and were independent predictors of in-hospital mortality, predominantly down-classifying risk in survivors when added to clinical scores; levels <133.3 pmol/l and >211.3 pmol/l detected low-risk and high-risk patients, respectively. CONCLUSIONS: PENK levels reflect cardiorenal status in acute HF and are prognostic for worsening renal function and in-hospital mortality as well as mortality during follow-up.
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Síndrome Cardiorrenal/etiología , Encefalinas/sangre , Tasa de Filtración Glomerular/fisiología , Insuficiencia Cardíaca/sangre , Precursores de Proteínas/sangre , Medición de Riesgo/métodos , Enfermedad Aguda , Anciano , Biomarcadores/sangre , Síndrome Cardiorrenal/mortalidad , Síndrome Cardiorrenal/fisiopatología , Causas de Muerte/tendencias , Femenino , Estudios de Seguimiento , Francia/epidemiología , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/mortalidad , Humanos , Pruebas de Función Renal , Masculino , Pronóstico , Modelos de Riesgos Proporcionales , Tasa de Supervivencia/tendencias , Suiza/epidemiología , Factores de Tiempo , Reino Unido/epidemiologíaRESUMEN
CONTEXT: Excess growth hormone (GH) is associated with early mortality. OBJECTIVES: We assessed the association of GH with prognosis after acute myocardial infarction (AMI), and the effects of secondary prevention therapies. METHODS: GH was measured using a high-sensitivity assay in 953 AMI patients (687 males, mean age 66.1 ± 12.8 years). RESULTS: During 2 years follow-up, there were 281 major adverse cardiac events (MACE). Patients with MACE had higher GH levels (median [range], 0.91 [0.04-26.28] µg/L) compared to event-free survivors (0.59 [0.02-21.6], p < 0.0005). In multivariate Cox survival analysis, GH was a significant predictor of MACE (hazard ratios 1.43, p = 0.026 and 1.49, p = 0.01, respectively) with significant interactions with beta blocker therapy (p = 0.047) and angiotensin converting enzyme inhibitor or angiotensin receptor blocker (ACE/ARB) therapy (p = 0.016). CONCLUSIONS: GH levels post-AMI are prognostic for MACE and may indicate those patients who benefit from beta blocker and ACE/ARB therapy.
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Biomarcadores/sangre , Hormona del Crecimiento/sangre , Infarto del Miocardio/sangre , Infarto del Miocardio/tratamiento farmacológico , Antagonistas Adrenérgicos beta/uso terapéutico , Anciano , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Estudios de Cohortes , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Evaluación de Resultado en la Atención de Salud/métodos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Pronóstico , Modelos de Riesgos Proporcionales , Factores de RiesgoRESUMEN
BACKGROUND: Pro-substance P (ProSP) is a stable surrogate marker for labile substance P, which has pro-inflammatory effects, increases platelet aggregation and clot strength, and reduces fibrinolysis. OBJECTIVES: This study assessed whether ProSP was associated with poor prognosis after acute myocardial infarction (AMI) to identify novel pathophysiological mechanisms. METHODS: ProSP was measured in 1,148 AMI patients (825 men, mean age 66.2 ± 12.8 years). Endpoints were major adverse cardiac events (composite of death, reinfarction, and heart failure [HF] hospitalization), death/reinfarction, and death/HF. GRACE (Global Registry of Acute Coronary Events) scores were compared with ProSP for death and/or reinfarction at 6 months. RESULTS: During 2-year follow-up, there were 140 deaths, 112 HF hospitalizations, and 149 re-AMI. ProSP levels were highest on the first 2 days after admission and related to estimated glomerular filtration rate, age, history of diabetes, ischemic heart disease or hypertension, Killip class, left ventricular wall motion index, and sex. Multivariate Cox regression models showed ProSP level was a predictor of major adverse events (hazard ratio [HR]: 1.30; 95% confidence interval [CI]: 1.10 to 1.54; p < 0.002), death and/or AMI (HR: 1.42; 95% CI: 1.20 to 1.68; p < 0.0005), death and/or HF (HR: 1.38; 95% CI: 1.14 to 1.67; p < 0.001). ProSP levels with GRACE scores were independent predictors of 6-month death and/or reinfarction (p < 0.0005 for both). ProSP-adjusted GRACE scores reclassified patients significantly (overall category-free net reclassification improvement of 31.6 (95% CI: 14.3 to 49.0; p < 0.0005) mainly by down-classifying those without endpoints. CONCLUSIONS: ProSP levels post-AMI are prognostic for death, recurrent AMI, or HF, and they improve risk prediction of GRACE scores, predominantly by down-classifying risk in those without events.
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Infarto del Miocardio/sangre , Infarto del Miocardio/diagnóstico , Sustancia P/sangre , Anciano , Biomarcadores/sangre , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Método Simple CiegoRESUMEN
OBJECTIVES: The goal of this research was to assess the prognostic value of proenkephalin (PENK) levels in acute myocardial infarction (AMI) by using N-terminal pro-B-type natriuretic peptide and Global Registry of Acute Coronary Events (GRACE) scores as comparators and to identify levels that might be valuable in clinical decision making. BACKGROUND: PENK is a stable analyte of labile enkephalins. Few biomarkers predict recurrent AMI. METHODS: We measured PENK in 1,141 patients (820 male subjects; mean age 66.2 ± 12.8 years) with AMI. Endpoints were major adverse events (composite of death, myocardial infarction [MI], and heart failure [HF] hospitalization) and recurrent MI at 2 years. GRACE scoring was used for comparisons with PENK for the death and/or MI endpoint at 6 months. RESULTS: During follow-up, 139 patients died, and there were 112 HF hospitalizations and 149 recurrent AMIs. PENK levels were highest on admission and were related to estimated glomerular filtration rate, left ventricular wall motion index, sex, blood pressure, and age. Multivariable Cox regression models found that the PENK level was a predictor of major adverse events (hazard ratio [HR]: 1.52 [95% confidence interval (CI): 1.19 to 1.94]), death and/or AMI (HR: 1.76 [95% CI: 1.34 to 2.30]), and death and/or HF (HR: 1.67 [95% CI: 1.24 to 2.25]) (all comparisons p < 0.001), as well as recurrent AMI (HR: 1.43 [95% CI: 1.07 to 1.91]; p < 0.01). PENK levels were independent predictors of 6-month death and/or MI compared with GRACE scores. PENK-adjusted GRACE scores reclassified patients significantly (overall category-free net reclassification improvement [>0] of 21.9 [95% CI: 4.5 to 39.4]; p < 0.014). PENK levels <48.3 pmol/l and >91 pmol/l detected low- and high-risk patients, respectively. CONCLUSIONS: PENK levels reflect cardiorenal status post-AMI and are prognostic for death, recurrent AMI, or HF. Cutoff values define low- and high-risk groups and improve risk prediction of GRACE scores.
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Electrocardiografía , Encefalinas/sangre , Infarto del Miocardio/sangre , Precursores de Proteínas/sangre , Sistema de Registros , Medición de Riesgo/métodos , Anciano , Femenino , Estudios de Seguimiento , Humanos , Inmunoensayo , Incidencia , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Infarto del Miocardio/fisiopatología , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Vitamin D status (VDS) has been linked to mortality and incident acute myocardial infarction (AMI) in healthy cohorts. Associations with recurrent adverse cardiovascular events in those with cardiovascular disease are less clear. Our objective was to assess the prevalence and prognostic impact of VDS on patients presenting with AMI. METHODS: We measured plasma 25-(OH)D3 and 25-(OH)D2 using isotope dilution tandem mass spectrometry, in 1259 AMI patients (908 men, mean age 65.7 ± 12.8 years). The primary endpoint was major adverse events (MACE), a composite of death (n=141), heart failure hospitalisation (n=111) and recurrent AMI (n=147) over median follow-up of 550 days (range 131-1095). Secondary endpoints were fatal and non-fatal MACE. RESULTS: Almost 74% of the patients were vitamin D deficient (<20 ng/ml 25-(OH)D). Plasma 25-(OH)D existed mainly as 25-(OH)D3 which varied with month of recruitment. Multivariable survival Cox regression models stratified by recruitment month (adjusted for age, gender, past history of AMI/angina, hypertension, diabetes, hypercholesterolaemia, ECG ST change, Killip class, eGFR, smoking, plasma NTproBNP), showed 25-(OH)D3 quartile as an independent predictor of MACE(P<0.001) and non-fatal MACE(P<0.01), but not death. Using the lowest 25-(OH)D3 quartile(<7.3 ng/ml) as reference for MACE prediction, the 2nd, 3rd and 4th quartiles showed significantly lower hazard ratios (HR 0.59(P<0.002), 0.58(P<0.001), and 0.59(P<0.003) respectively). For non-fatal MACE prediction, the 2nd, 3rd and 4th 25-(OH)D3 quartiles were all significantly different from the lowest reference quartile (HR 0.69(P<0.05), 0.54(P<0.003) and 0.59(P<0.014) respectively). CONCLUSIONS: VDS is prognostic for MACE (predominantly non-fatal MACE) post-AMI, with approximate 40% risk reduction for 25-(OH)D3 levels above 7.3 ng/ml.
Asunto(s)
Electrocardiografía , Infarto del Miocardio/sangre , Vitamina D/sangre , Anciano , Biomarcadores/sangre , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Infarto del Miocardio/epidemiología , Valor Predictivo de las Pruebas , Prevalencia , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia/tendencias , Espectrometría de Masas en Tándem , Factores de Tiempo , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: In patients being considered for aortic valve replacement, there remains controversy over which design or tissue offers the best performance. We aimed to evaluate in a single study the haemodynamic performances of five different widely used aortic valve prostheses: stentless porcine xenograft (Elan), stentless bovine pericardium (Pericarbon Freedom), stented porcine xenograft (Aspire), stented bovine pericardium (More) and mechanical (Ultracor). We also compared them with normal aortic valves and stenosed valves of variable severity. METHODS AND RESULTS: Preoperative echocardiography and dobutamine stress echocardiography at 1 year postoperatively were undertaken in 106 patients (n=18-24 from each group). Stentless bioprostheses, whether porcine or bovine, displayed superior haemodynamics across nearly all echocardiographic parameters: lower gradients, larger effective orifice area, higher dimensionless severity index (DSI) and lower resistance, when compared with stented or mechanical prostheses. Comparing both stented designs, bovine tissue performed the worst at rest, but with stress, there was no difference. The stress performances of the stentless bioprostheses were similar to the mildly stenosed native aortic valve, whereas the performances of the stented and mechanical prostheses resembled that of native valves with mild-to-moderate stenoses. Haemodynamic differences, however, did not translate into differences in left ventricular mass reduction at 1 year. CONCLUSIONS: Stentless bioprostheses displayed haemodynamics superior to stented or mechanical prostheses and had the closest performance to a normal, native aortic valve. Stress DSI data, least reliant on variable annulus/valve sizes and flow rates, provided the best haemodynamic discrimination.
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Estenosis de la Válvula Aórtica/fisiopatología , Válvula Aórtica/cirugía , Bioprótesis , Ecocardiografía de Estrés/métodos , Prótesis Valvulares Cardíacas , Hemodinámica/fisiología , Anciano , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/fisiopatología , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Diseño de Prótesis , Stents , Resultado del TratamientoRESUMEN
BACKGROUND: Soluble ST2 is a marker of cellular stress and injury whose natural ligand is interleukin-33. We investigate, for the first time, the relationship of IL-33 and ST2 with death at 30-days, 1-year and beyond in unselected STEMI patients. We assess the incremental value they offer over GRACE score and NT-proBNP. Secondary endpoints were heart failure readmission and re-infarction. METHODS: ST2 and IL-33 were measured in 677 patients 3-5 days after admission. Median follow-up was 587 (134-2818) days during which 101 (15%) patients died. RESULTS: ST2 was higher in those who died when compared to event-free survivors (median [range] 1125 [123-15781] vs. 630 [59-11729] pg/ml, p<0.001) as was IL-33 (75 [5.4-17893] vs. 5.4 [5.4-16466] pg/mL, p=0.006). Multivariate Cox regression analysis reveals that elevated ST2 is associated with increased risk of mortality at 30-days (HR 9.34, p<0.001) and 1-year (HR 3.15, p=0.001). These relationships continued after further adjustment for GRACE-RS and NT-proBNP. Combining ST2 (c-statistic 0.82, p<0.001), GRACE-RS (0.82, p<0.001) and NT-proBNP (0.84, p<0.001) leads to a significant improvement in the c-statistic for 30-day mortality to 0.90 (p=0.01). IL-33 above 5.4 pg/ml was independently associated with increased mortality at 30-days (HR 4.16, p=0.007) and 1-year (HR 2.29, p=0.008) but, did not add incremental prognostic value over using GRACE-RS and NT-proBNP. The ratio IL-33/ST2 was not associated with events. CONCLUSIONS: Elevated ST2 and IL-33 were both associated with increased mortality. ST2 demonstrated incremental value over contemporary risk markers but, IL-33 did not. ST2 has a potential role in risk stratification using a multi-marker approach.
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Interleucinas/fisiología , Infarto del Miocardio/sangre , Infarto del Miocardio/mortalidad , Alta del Paciente/tendencias , Receptores de Superficie Celular/fisiología , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Femenino , Estudios de Seguimiento , Humanos , Proteína 1 Similar al Receptor de Interleucina-1 , Interleucina-33 , Interleucinas/sangre , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Receptores de Superficie Celular/sangre , Medición de RiesgoRESUMEN
BACKGROUND: Soluble ST2 is a marker of biomechanical strain for which the natural ligand is interleukin 33 (IL-33). They have not been studied together in non-ST-elevation myocardial infarction (NSTEMI). We investigated their relationship with death, heart failure (HF) readmission, and reinfarction combined (termed major adverse cardiac events [MACE]) and, separately, in unselected patients using Global Registry of Acute Coronary Events Risk Scoring (GRACE-RS) and n terminal pro B type natriuretic peptide (NT-proBNP) as benchmark comparators. METHODS: ST2 and IL-33 were measured in 577 patients 3 to 5 days after admission. Mean follow-up was 532 (150-1059) days, during which 156 patients (27%) reached the primary end point. RESULTS: ST2 was higher in those who experienced MACE when compared with event-free survivors (median 782 pg/mL vs 596, P < .001), but there was no difference in IL-33 levels across any end point. Multivariate Cox regression analysis reveals that elevated ST2 is independently associated with increased risk of MACE during the long term (hazard ratio [HR] 2.01, P = .005). This relationship continues on further adjustment for either GRACE risk score or NT-proBNP individually but not on adjustment for both. ST2 also independently predicts reinfarction (HR 2.48, P = .03) and 30-day mortality (HR 4.43, P = .02, c-statistic 0.73, P < .001). Adding ST2 to GRACE or to NT-proBNP did not lead to significant improvements in the c-statistic for MACE for long-term follow-up (P = .27 and P = .57, respectively) or the net reclassification index. Neither IL-33 nor its ratio with ST2 was associated with study end points. CONCLUSIONS: Elevated ST2 predicts adverse outcome in non-ST-elevation myocardial infarction but does not significantly improve risk stratification for established markers. Interleukin 33 was not related to adverse events.
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Interleucinas/sangre , Infarto del Miocardio/sangre , Receptores de Superficie Celular/sangre , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Femenino , Insuficiencia Cardíaca/etiología , Humanos , Proteína 1 Similar al Receptor de Interleucina-1 , Interleucina-33 , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Infarto del Miocardio/complicaciones , Infarto del Miocardio/mortalidad , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Pronóstico , Curva ROC , Medición de RiesgoRESUMEN
Copeptin, the 39-amino-acid C-terminal portion of provasopressin, has been shown to be an independent predictor for adverse events following STEMI (ST elevation myocardial infarction). We hypothesized that plasma copeptin was an independent predictor for adverse outcomes following acute NSTEMI (non-STEMI) and evaluated whether copeptin added prognostic information to the GRACE (Global Registry of Acute Coronary Events) score compared with NT-proBNP (N-terminal pro-B-type natriuretic peptide). Plasma copeptin and NT-proBNP were measured in 754 consecutive patients admitted to the hospital with chest pain and diagnosed as having NSTEMI in this prospective observational study. The end point was all-cause mortality at 6 months. Upper median levels of copeptin were strongly associated with all-cause mortality at 6 months. Copeptin was a significant predictor of time to mortality {HR (hazard ratio), 5.98 [95% CI (confidence interval, 3.75-9.53]; P < 0.0005} in univariate analysis and remained a significant predictor in multivariate analysis [HR, 3.03 (05% CI, 1.32-6.98); P = 0.009]. There were no significant differences between the area under ROC (receiver operating characteristic) curves of copeptin, NT-proBNP and the GRACE score. Copeptin improved accuracy of risk classification when used in combination with the GRACE score as determined by net reclassification improvement, whereas NT-proBNP did not. The relative utility of the GRACE score was increased more by copeptin than by NT-proBNP over a wide range of risks. Plasma copeptin is elevated after NSTEMI, and higher levels are associated with worse outcomes. Copeptin used in conjunction with the GRACE score improves risk stratification enabling more accurate identification of high-risk individuals.
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Glicopéptidos/sangre , Infarto del Miocardio/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Inglaterra/epidemiología , Métodos Epidemiológicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/mortalidad , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , PronósticoRESUMEN
A multimarker approach may be useful for risk stratification in AMI (acute myocardial infarction) patients, particularly utilizing pathways that are pathophysiologically distinct. Our aim was to assess the prognostic value of PR3 (proteinase 3) in patients post-AMI. We compared the prognostic value of PR3, an inflammatory marker, with an established marker NT-proBNP (N-terminal pro-B-type natriuretic peptide) post-AMI. We recruited 900 consecutive post-AMI patients (700 men; age, 64.6±12.4 years) in a prospective study with follow-up over 347 (0-764) days. Plasma PR3 was significantly higher in patients who died [666.2 (226.8-4035.5) ng/ml; P<0.001] or were readmitted with heart failure [598 (231.6-1803.9) ng/ml, P<0.004] compared with event-free survivors [486.9 (29.3-3118.2) ng/ml]. Using Cox modelling, log10 PR3 [HR (hazard ratio), 3.80] and log10 NT-proBNP (HR, 2.51) were significant independent predictors of death or heart failure. When patients were stratified by plasma NT-proBNP (median, 1023 pmol/l), PR3 gave additional predictive value for death or heart failure, in both the patients in whom NT-proBNP level was above the median (log rank for trend, 12.54; P<0.0004) and those with NT-proBNP level below the median (log rank for trend, 3.83; P<0.05). Neither marker predicted recurrent AMI. In conclusion, this is the first report showing a potential role for the serine protease PR3 in determining mortality and incidence of heart failure following AMI, independent of established conventional risk factors. PR3 may represent a clinically useful marker of prognosis after an AMI as part of a multimarker strategy.
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Mieloblastina/sangre , Infarto del Miocardio/diagnóstico , Anciano , Biomarcadores/sangre , Pruebas Enzimáticas Clínicas/métodos , Métodos Epidemiológicos , Femenino , Insuficiencia Cardíaca/etiología , Humanos , Mediadores de Inflamación/sangre , Masculino , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Peroxidasa/sangre , Pronóstico , alfa 1-Antitripsina/sangreRESUMEN
Alterations in the balance of matrix metalloproteinase to tissue inhibitor of metalloproteinase (TIMP) are seen after acute myocardial infarction (AMI) and are associated with adverse left ventricular remodeling and prognosis in this setting. We aimed to investigate the association between TIMP levels and the occurrence of major adverse cardiac events (MACEs) after AMI. We measured plasma TIMP-1, -2, and -4 levels in 1,313 patients presenting with AMI. Subjects were followed over a median period of 520 days for the occurrence of MACEs. Clinical risk was assessed using the Global Registry of Acute Coronary Events (GRACE) score. All TIMP levels correlated with patient age and inversely with estimated glomerular filtration rate (all p values <0.001). Levels were higher in women versus men (p <0.001) and in subjects with a history of diabetes (TIMP-1, p <0.001; TIMP-2, p = 0.002; TIMP-4, p <0.001) or hypertension (TIMP-1, p = 0.031; TIMP-2, p <0.001; TIMP-4, p <0.001). TIMP-1 and TIMP-4 were higher in subjects with previous MI or angina (p <0.001). TIMP levels increased incrementally with quartiles of GRACE score (p <0.001). All TIMPs showed univariate association with the occurrence of MACEs (p <0.001). Areas under the receiver operator characteristic curve for prediction of MACE at 1 year were 0.61 for TIMP-1, 0.57 for TIMP-2, and 0.64 for TIMP-4. Combination of TIMPs with GRACE risk score revealed a greater area under the curve than GRACE score alone (0.72 vs 0.69, p = 0.0015). On multivariable Cox proportional hazards analysis, GRACE score (p <0.001) and plasma TIMPs (log TIMP-1, p = 0.017; log TIMP-2, p <0.001; log TIMP-4, p = 0.011) independently predicted MACEs. Using Kaplan-Meier analysis, the risk of MACEs increased incrementally with the number of TIMPs above their respective median (p <0.001 for all comparisons, log-rank test). In conclusion, higher plasma TIMP-1, -2, and -4 after AMI are associated with MACEs and provide additional prognostic information to that obtained from GRACE clinical risk scores alone.
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Infarto del Miocardio/sangre , Inhibidores Tisulares de Metaloproteinasas/sangre , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Medición de Riesgo , Inhibidor Tisular de Metaloproteinasa-1/sangre , Inhibidor Tisular de Metaloproteinasa-2/sangre , Adulto Joven , Inhibidor Tisular de Metaloproteinasa-4RESUMEN
OBJECTIVES: The purpose of this study was to assess the prognostic value of admission and discharge mid-regional pro-adrenomedullin (sAM) levels in non-ST-elevation myocardial infarction (MI) and identify values to aid clinical decision making. N-terminal pro-B-type natriuretic peptide and GRACE (Global Registry of Acute Coronary Events) score were used as comparators. BACKGROUND: sAM is a stable precursor of adrenomedullin. METHODS: We measured plasma sAM on admission and discharge in 745 non-ST-elevation MI patients (514 men, median age 70.0 +/- 12.7 years). The primary end point was a composite of death, heart failure, hospitalization, and recurrent acute MI over mean follow-up of 760 days (range 150 to 2,837 days), with each event assessed individually as secondary end points. RESULTS: During follow-up, 120 (16.1%) patients died, and there were 65 (8.7%) hospitalizations for heart failure and 77 (10.3%) recurrent acute MIs. Both admission and discharge levels were increased (median 0.81 nmol/l [range 0.06 to 5.75 nmol/l] and 0.76 nmol/l [range 0.25 to 6.95 nmol/l], respectively) compared with established normal ranges. Multivariate adjusted Cox regression models revealed that both were associated with the primary end point (hazard ratio: 9.75 on admission and 7.54 on discharge; both p < 0.001). Admission sAM was particularly associated with early (<30 days) mortality (c-statistic = 0.90, p < 0.001), and when compared with N-terminal pro-B-type natriuretic peptide and GRACE score, it was the only independent predictor of this end point. Admission sAM >1.11 nmol/l identified those at highest risk of death (p < 0.001). Patients with above-median admission sAM may benefit from revascularization. CONCLUSIONS: sAM level is prognostic for death or heart failure. Admission levels are a strong predictor of early mortality and, when >1.11 nmol/l, complements the GRACE score to improve risk stratification.
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Adrenomedulina/sangre , Infarto del Miocardio/sangre , Precursores de Proteínas/sangre , Anciano , Electrocardiografía , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/mortalidad , Humanos , Masculino , Infarto del Miocardio/fisiopatología , Péptido Natriurético Encefálico/sangre , Admisión del Paciente , Alta del Paciente , Fragmentos de Péptidos/sangre , PronósticoRESUMEN
OBJECTIVE: To consider whether patients most likely to benefit from ACE inhibition in routine practice after acute coronary syndrome (ACS) may be identified from plasma natriuretic peptide concentrations. DESIGN: Observational cohort study. SETTING: Teaching hospital coronary care unit. PATIENTS: 1725 patients admitted with acute coronary syndrome (56.3% ST elevation ACS; median age 67, range 24-97 years). MEASUREMENTS: Using Cox proportional hazards analysis, we assessed the adjusted predictive value for major adverse cardiac events (MACE) of prescription of an ACE inhibitor, of plasma N-terminal pro B-type natriuretic peptide (NT-proBNP) and for interaction between these factors. To adjust for demographic differences between patients prescribed or not prescribed an ACE inhibitor, a factor correcting for likelihood of ACE inhibitor prescription (propensity score) was included in the analysis. OUTCOME MEASURES: The primary end point was the occurrence of MACE (death, recurrent myocardial infarction or hospitalisation with heart failure). RESULTS: During the index admission ACE inhibitor was prescribed for 1267/1725 (73.4%) patients. During follow-up (median 528 days, range 0-3873 days), 534/1725 patients experienced MACE. After covariable adjustment, NT-proBNP showed linear association with risk of MACE (p<0.005), strongest for patients with NT-proBNP in the top quartile of observed values (HR=2.768, p<0.001). Only for patients with NT-proBNP in the top quartile was prescription of ACE inhibitor associated with reduction in risk of MACE (HR=0.532, p=0.003). This association was maintained after correction for propensity scores (HR=0.599, p=0.003). CONCLUSIONS: Prognostic benefit from ACE inhibition was seen only in patients with the most marked elevation of plasma NT-proBNP. Plasma NT-proBNP may be a useful indicator of the appropriateness of individual prescription of ACE inhibitor treatment across the spectrum of ACS.
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Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/tratamiento farmacológico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Infarto del Miocardio/sangre , Infarto del Miocardio/tratamiento farmacológico , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Métodos Epidemiológicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Procalcitonin is involved in the inflammatory response and is associated with adverse prognosis in certain conditions. AIMS: To investigate the association between procalcitonin and major adverse cardiac events (MACE), left ventricular (LV) function and remodelling following acute myocardial infarction (AMI). METHODS: Plasma procalcitonin was measured in 977 patients with AMI. Subjects were followed for MACE (median 671 days). A subgroup underwent echocardiography at discharge and follow-up LV function and volume assessment. RESULTS: Procalcitonin was associated with MACE on uni- and multivariable analysis. Kaplan-Meier assessment revealed an adverse outcome in subjects with procalcitonin above the median. Procalcitonin was related to markers of LV dysfunction and remodelling. CONCLUSION: Procalcitonin is associated with MACE, LV dysfunction and remodelling post-AMI.
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Calcitonina/sangre , Infarto del Miocardio/diagnóstico , Precursores de Proteínas/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Péptido Relacionado con Gen de Calcitonina , Ecocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/epidemiologíaRESUMEN
Left ventricular hypertrophy (LVH) is a risk factor for cardiovascular disease. Elevated natriuretic peptides in LVH have spurred interest that biomarkers may play a role in screening programs. Adrenomedullin (ADM) is a 52-amino acid peptide mediating vasorelaxation, natriuresis, and diuresis. The midregional portion of proADM (MRproADM) is secreted stoichiometrically with ADM; hence, it can be used as a surrogate marker of ADM. We compared the diagnostic performance of MRproADM for the detection of LVH with N-terminal pro-B-type natriuretic peptide (NTproBNP). Two hundred fifty-three hypertensive patients were derived from a local screening study. The MRproADM and NTproBNP levels were assayed using immunoluminometric assays. The MRproADM levels were significantly elevated in patients with LVH than those without (mean [SD]: 0.73 [0.25] vs 0.59 [0.18] nmol/L, P < .001). In multivariate analyses, male sex (P < .001) and log MRproADM (P = .003) retained significance for detecting LVH. Receiver operating characteristic curve for MRproADM yielded an area under the curve of 0.71; confidence interval, 0.62-0.81; P < .001, superior to NTproBNP. An optimal cutoff value for MRproADM as an indicator of LVH was 0.50 nmol/L, with a sensitivity, specificity, and negative predictive value of 90.5%, 36.5%, and 95.1%, respectively. The high negative predictive value of the MRproADM assay allows it to be used as a rule-out test for LVH when stratifying patients into high or low risk. Patients who test positive would necessitate echocardiography, enabling better resource allocation.
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Adrenomedulina/metabolismo , Ventrículos Cardíacos/patología , Hipertensión/patología , Precursores de Proteínas/metabolismo , Anciano , Cardiomegalia/metabolismo , Cardiomegalia/patología , Cardiomegalia/fisiopatología , Electrocardiografía , Femenino , Ventrículos Cardíacos/metabolismo , Ventrículos Cardíacos/fisiopatología , Humanos , Hipertensión/metabolismo , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Tamaño de los ÓrganosRESUMEN
Proguanylin and prouroguanylin are the inactive precursors of guanylin and uroguanylin, natriuretic peptides involved in the regulation of sodium balance. Urinary uroguanylin levels have been found previously to be elevated in patients with HF (heart failure). The aim of the present study was to investigate whether plasma proguanylin and prouroguanylin levels are increased in patients with HF and to evaluate their relationship with cardiac and renal function. In this prospective observational study, we recruited 243 patients with HF (151 men) and 72 healthy controls. In patients with HF, plasma levels of proguanylin [median, 7.2 (range, 0.9-79.0) microg/l] and prouroguanylin [8.3 (1.7-53.0 microg/l)] were both significantly (P<0.0005) higher compared with levels in healthy controls [5.5 (0.4-22.3 microg/l) for proguanylin and 6.3 (2.5-16.9) microg/l for prouroguanylin]. In patients with HF, increased age, a history of hypertension, diabetes and atrial fibrillation, use of diuretics, a higher NYHA (New York Heart Association) class and a lower eGFR (estimated glomerular filtration rate) were significant univariate predictors of proguanylin and prouroguanylin levels. In multivariate analysis, a history of hypertension and low eGFR both had strong independent associations with proguanylin and prouroguanylin levels. Proguanylin and prouroguanylin varied significantly between NYHA class with a trend of increasing plasma concentrations with worsening severity of symptoms. In conclusion, plasma proguanylin and prouroguanylin are elevated in patients with HF. Elevated plasma proguanylin and prouroguanylin levels are associated with hypertension, renal impairment and increasing severity of HF. This novel endocrine system may contribute to the pathophysiology of HF.
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Hormonas Gastrointestinales/sangre , Insuficiencia Cardíaca/sangre , Precursores de Proteínas/sangre , Adulto , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/sangre , Diabetes Mellitus/sangre , Diuréticos/uso terapéutico , Femenino , Tasa de Filtración Glomerular , Insuficiencia Cardíaca/fisiopatología , Humanos , Hipertensión/sangre , Masculino , Persona de Mediana Edad , Natriuresis/fisiología , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
The aim of the present study was to investigate the predictive value of MMP (matrix metalloproteinase)-2, MMP-3 and MMP-9 levels in patients with acute coronary syndrome for death, readmission with HF (heart failure) or recurrent MI (myocardial infarction) and to compare them with established markers, NT-proBNP (N-terminal pro-B-type natriuretic peptide) and the GRACE (Global Registry of Acute Coronary Events) score. A single blood test was taken 4 days after admission in 1024 consecutive patients with acute MI with end points observed over 519 (134-1059) days [value is median (range)]. MMP-2 and MMP-3 were increased in patients who died (n=111) compared with survivors (P<0.006 and P=0.01 respectively), but were similar in patients with HF (n=106) or MI (n=138). MMP-9 levels were similar across study end points. Using Cox proportional hazards modelling, MMP-2 demonstrated an independent prediction of death [HR (hazard ratio) 6.60, P=0.001], along with NT-proBNP (HR 4.62, P<0.001) and the GRACE score (HR 1.03, P<0.001), but MMP-3, MMP-9 or log10-troponin I did not. For 1 year mortality, the areas under the receiver operating characteristic curves were 0.60 and 0.58 for MMP-2 and MMP-3 respectively, compared with 0.82 for NT-proBNP and 0.84 for the GRACE score (all P<0.001). Kaplan-Meier analysis revealed that MMP-2 levels in the top quartile were associated with higher mortality rates (log rank 12.49, P=0.006). On univariate analysis, MMP-2 and MMP-3 had a weak association with HF readmission, which was lost after adjustment for clinical factors. None of the MMPs tested predicted MI. In conclusion, this is the first single centre study that identifies MMP2 as an independent predictor of all-cause mortality post-ACS (acute coronary syndrome); however, NT-proBNP and the GRACE score are superior for risk stratification in this cohort.
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Síndrome Coronario Agudo/diagnóstico , Metaloproteinasa 2 de la Matriz/sangre , Síndrome Coronario Agudo/mortalidad , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Pruebas Enzimáticas Clínicas/métodos , Inglaterra/epidemiología , Femenino , Insuficiencia Cardíaca/diagnóstico , Humanos , Masculino , Metaloproteinasa 3 de la Matriz/sangre , Metaloproteinasa 9 de la Matriz/sangre , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/mortalidad , Péptido Natriurético Encefálico/sangre , Readmisión del Paciente/estadística & datos numéricos , Fragmentos de Péptidos/sangre , Pronóstico , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Ultrasonografía , Disfunción Ventricular Izquierda/diagnóstico , Disfunción Ventricular Izquierda/diagnóstico por imagenRESUMEN
BACKGROUND AND AIM OF THE STUDY: Aortic stentless bioprostheses provide good clinical and hemodynamic results, but may be difficult to implant. Their use is also contraindicated in the presence of a severely calcified aortic root. The study aim was to assess the mid-term results of a simplified implant technique of the Sorin Pericarbon Freedom stentless bioprosthesis (SPF), that allows its use in the presence of severe aortic root calcification. METHODS: Between 2001 and 2007, a total of 51 patients underwent aortic valve replacement (AVR) with the SPF, using a new technique which consisted of standard annular fixation and the fixation of each strut with a single 'U' stitch. The perioperative characteristics, early and late mortality and occurrence of valve-related events were evaluated. The overall mean cross-clamp and cardiopulmonary bypass times were 91.5 +/- 30.2 and 125.3 +/- 44.9 min, respectively, and 77.8 +/- 17.7 and 105.6 +/- 22.8 min, respectively, for AVR (these times were comparable to those required in patients receiving stented valve bioprostheses). The mean follow up period was 40.5 months (range: 3-75 months), and was 100% complete. RESULTS: Hospital mortality was 4% and survival 76.5 +/- 14.5% at six years. Late deaths occurred in eight patients; in four cases this was valve-related (1.9%/patient-year). Freedom from valve-related death and reoperation was 91 +/- 9% and 98 +/- 2% respectively, at six years. The mean transprosthetic gradients were 12.0 +/- 3.4, 9.9 +/- 2.6, 8.7 +/- 4.2, 5.2 +/- 3.9, 4.5 +/- 3.0 and 3.2 +/- 2.7 mmHg for the 19, 21, 23, 25, 27 and 29 mm valve sizes, respectively. No valvular or paravalvular regurgitation was recorded. CONCLUSION: This new implantation technique for the aortic SPF stentless bioprosthesis is simple, effective and versatile, and showed good early results. It may be applicable to other stentless bioprostheses, and also be particularly useful in patients with small aortic annulus and in those with a calcified aortic root.
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Válvula Aórtica/cirugía , Bioprótesis , Implantación de Prótesis de Válvulas Cardíacas/métodos , Prótesis Valvulares Cardíacas , Adulto , Anciano , Anciano de 80 o más Años , Ecocardiografía Doppler , Femenino , Implantación de Prótesis de Válvulas Cardíacas/mortalidad , Hemodinámica , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Diseño de Prótesis , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
The GRACE (Global Registry of Acute Coronary Events) risk score has been shown to offer predictive power with regard to death and AMI (acute myocardial infarction) in patients with ACS (acute coronary syndromes). NT-proBNP (N-terminal pro-B-type natriuretic peptide) has also been found to be useful in predicting mortality following ACS. In the present study, we sought to investigate the use of the GRACE score and NT-proBNP levels at predicting risk of early and late deaths following ACS. We studied 1033 patients (740 men, mean age 66.5+/-12.7 years) with AMI. Blood was drawn once within 24 h following the onset of chest pain. The plasma concentration of NT-proBNP was determined using an in-house non-competitive immunoassay. Patients were GRACE risk scored. The 30-day mortality was 3.7% and the 6-month mortality was 7.8%, and all were related to higher GRACE risk scores (P=0.001 for trend). Higher NT-proBNP levels were also related to increased mortality (P<0.0001). In a Cox proportional hazards model, independent predictors of 30-day and 6-month mortality included NT-proBNP levels and the GRACE risk score. The receiver-operating curve for the GRACE risk score was complemented by NT-proBNP levels for prediction of 30-day mortality [AUC (area under the curve), 0.85] and 6-month mortality (AUC, 0.81). NT-proBNP gives complementary information to the GRACE risk score for predicting early and late mortality. The inclusion of the NT-proBNP blood test is useful in risk-stratifying patients after ACS.