RESUMEN
BACKGROUND: The intensity of inflammation during COVID-19 is related to adverse outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in low-density lipoprotein receptor homeostasis, with potential influence on vascular inflammation and on COVID-19 inflammatory response. OBJECTIVES: The goal of this study was to investigate the impact of PCSK9 inhibition vs placebo on clinical and laboratory outcomes in patients with severe COVID-19. METHODS: In this double-blind, placebo-controlled, multicenter pilot trial, 60 patients hospitalized for severe COVID-19, with ground-glass opacity pneumonia and arterial partial oxygen pressure to fraction of inspired oxygen ratio ≤300 mm Hg, were randomized 1:1 to receive a single 140-mg subcutaneous injection of evolocumab or placebo. The primary endpoint was death or need for intubation at 30 days. The main secondary endpoint was change in circulating interleukin (IL)-6 at 7 and 30 days from baseline. RESULTS: Patients randomized to receive the PCSK9 inhibitor had lower rates of death or need for intubation within 30 days vs placebo (23.3% vs 53.3%, risk difference: -30%; 95% CI: -53.40% to -6.59%). Serum IL-6 across time was lower with the PCSK9 inhibitor than with placebo (30-day decline: -56% vs -21%). Patients with baseline IL-6 above the median had lower mortality with PCSK9 inhibition vs placebo (risk difference: -37.50%; 95% CI: -68.20% to -6.70%). CONCLUSIONS: PCSK9 inhibition compared with placebo reduced the primary endpoint of death or need for intubation and IL-6 levels in severe COVID-19. Patients with more intense inflammation at randomization had better survival with PCSK9 inhibition vs placebo, indicating that inflammatory intensity may drive therapeutic benefits. (Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19 [IMPACT-SIRIO 5]; NCT04941105).
Asunto(s)
COVID-19 , Proproteína Convertasa 9 , Humanos , Interleucina-6 , LDL-Colesterol , SARS-CoV-2 , Inflamación , Resultado del Tratamiento , Método Doble CiegoRESUMEN
Inflammatory activation during acute ST-elevation myocardial infarction (STEMI) can contribute to post-infarct heart failure (HF). This study aimed to determine prognostic value of high-sensitivity C-reactive protein concentration (CRP) for HF over a long-term follow-up in 204 patients with a first STEMI undergoing guideline-based therapies including percutaneous coronary intervention. CRP was measured at admission, 24 h (CRP24), discharge (CRPDC), and one month (CRP1M) after index hospitalization for STEMI. Within a median period of 5.6 years post-index hospitalization for STEMI, hospitalization for HF (HFH) which is a primary endpoint, occurred in 24 patients (11.8%, HF+ group). During the study, 8.3% of HF+ patients died vs. 1.7% of patients without HFH (HF- group) (p = 0.047). CRP24, CRPDC, and CRP1M were significantly higher in HF+ compared to HF- group. The median CRP1M in HF+ group was 2.57 mg/L indicating low-grade systemic inflammation, in contrast to 1.54 mg/L in HF- group. CRP1M ≥ 2 mg/L occurred in 58.3% of HF+ vs. 42.8% of HF- group (p = 0.01). Kaplan-Meier analysis showed decreased probability of survival free from HFH in patients with CRP24 (p < 0.001), CRPDC (p < 0.001), and CRP1M (p = 0.03) in quartile IV compared to lower quartiles. In multivariable analysis, CRPDC significantly improved prediction of HFH over a multi-year period post-STEMI. Persistent elevation in CRP post STEMI aids in risk stratification for long-term HF and suggests that ongoing cardiac and low-grade systemic inflammation promote HF development despite guideline-based therapies.
Asunto(s)
Biomarcadores , Proteína C-Reactiva/metabolismo , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/metabolismo , Infarto del Miocardio/complicaciones , Causas de Muerte , Ecocardiografía , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/mortalidad , Hospitalización , Humanos , Estimación de Kaplan-Meier , Infarto del Miocardio/etiología , Pronóstico , Factores de Tiempo , Remodelación VentricularRESUMEN
Acute ST-segment elevation myocardial infarction (STEMI) activates inflammation that can contribute to left ventricular systolic dysfunction (LVSD) and heart failure (HF). The objective of this study was to examine whether high-sensitivity C-reactive protein (CRP) concentration is predictive of long-term post-infarct LVSD and HF. In 204 patients with a first STEMI, CRP was measured at hospital admission, 24 h (CRP24), discharge (CRPDC), and 1 month after discharge (CRP1M). LVSD at 6 months after discharge (LVSD6M) and hospitalization for HF in long-term multi-year follow-up were prospectively evaluated. LVSD6M occurred in 17.6% of patients. HF hospitalization within a median follow-up of 5.6 years occurred in 45.7% of patients with LVSD6M vs. 4.9% without LVSD6M (p < 0.0001). Compared to patients without LVSD6M, the patients with LVSD6M had higher CRP24 and CRPDC and persistent CRP1M ≥ 2 mg/L. CRP levels were also higher in patients in whom LVSD persisted at 6 months (51% of all patients who had LVSD at discharge upon index STEMI) vs. patients in whom LVSD resolved. In multivariable analysis, CRP24 ≥ 19.67 mg/L improved the prediction of LVSD6M with an increased odds ratio of 1.47 (p < 0.01). Patients with LVSD6M who developed HF had the highest CRP during index STEMI. Elevated CRP concentration during STEMI can serve as a synergistic marker for risk of long-term LVSD and HF.
Asunto(s)
Proteína C-Reactiva/metabolismo , Insuficiencia Cardíaca , Infarto del Miocardio con Elevación del ST , Disfunción Ventricular Izquierda , Anciano , Biomarcadores/sangre , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/etiología , Humanos , Inflamación/sangre , Inflamación/epidemiología , Inflamación/etiología , Masculino , Persona de Mediana Edad , Infarto del Miocardio con Elevación del ST/sangre , Infarto del Miocardio con Elevación del ST/complicaciones , Infarto del Miocardio con Elevación del ST/epidemiología , Infarto del Miocardio con Elevación del ST/terapia , Disfunción Ventricular Izquierda/sangre , Disfunción Ventricular Izquierda/epidemiología , Disfunción Ventricular Izquierda/etiologíaRESUMEN
OBJECTIVE: To assess the value of C-reactive protein (CRP) in predicting postinfarct left ventricular remodelling (LVR). METHODS: We measured in-hospital plasma CRP concentrations in patients with a first ST-segment elevation myocardial infarction (STEMI). RESULTS: LVR was present at 6 months in 27.8% of 198 patients. CRP concentration rose during the first 24 h, mainly in LVR group. The prevalence of LVR was higher in patients from the highest quartile of CRP concentrations at 24 h as compared to those from any other quartile (odds ratio (OR) 3.48, 95% confidence interval (95% CI) 1.76-6.88). Multivariate analysis identified CRP concentration at 24 h (OR for a 10 mg/L increase 1.29, 95% CI 1.04-1.60), B-type natriuretic peptide at discharge (OR for a 100 pg/mL increase 1.21, 95% CI 1.05-1.39), body mass index (OR for a 1 kg/m(2) increase 1.10, 95% CI 1.01-1.21), and left ventricular end-diastolic volume (OR for a 1 mL increase 0.98, 95% CI 0.96-0.99) as independent predictors of LVR. The ROC analysis revealed a limited discriminative value of CRP (area under the curve 0.61; 95% CI 0.54-0.68) in terms of LVR prediction. CONCLUSIONS: Measurement of CRP concentration at 24 h after admission possesses a significant but modest value in predicting LVR after a first STEMI.
Asunto(s)
Proteína C-Reactiva/metabolismo , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Remodelación Ventricular/fisiología , Ecocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND: Post-ST-segment elevation myocardial infarction (STEMI) left ventricular systolic dysfunction (LVSD) has been identified as an important marker of poor prognosis. AIM: To assess the prevalence and course of LVSD at hospital discharge and in long-term follow-up in STEMI patients treated with primary percutaneous coronary intervention (pPCI). METHODS: We enrolled 205 patients (157 male, 48 female) with a first STEMI. Echocardiography was performed before hospital discharge and 12 months after STEMI. Left ventricular systolic function (LVSF) parameters were assessed: left ventricular ejection fraction (LVEF), wall motion score index (WMSI), and average peak systolic mitral annular velocity (S') by tissue Doppler echocardiography (TDE). B-type natriuretic peptide plasma concentration was measured at admission (BNP(admission)) and at discharge (BNP(discharge)). RESULTS: We found moderate LVSD, both at hospital discharge and after 12 months. Significant global LVSD (LVEF ≤ 40%) was observed in 34% of patients at discharge, and 21% after 12 months (p ã 0.001). Significant regional LVSD (WMSI ≥ 1.7) after 12 months was less frequent than at discharge (21% vs 33%; p ã 0.001). More patients had significant longitudinal LVSD (S' ≤ 6.0 cm/s) after 12 months compared to discharge (28% vs 23%; p ã 0.001). Severe global LVSD (LVEF ≤ 30%) was rare. Univariate logistic regression analysis revealed the predictors of significant global LVSD at 12 months after STEMI to be: anterior location of STEMI; pre-discharge echocardiographic parameters of LVSF and left ventricle size and mass; prepPCI angiographic indices; ratio of the difference of BNP(discharge) and BNPa(dmission) to BNP(admission) expressed as % (BNP(delta) %); time from onset of pain to balloon, and the use of abciximab. Multivariate logistic regression analysis found independent predictors of significant global LVSD at 12 months to be: BNP(delta) % and LVEF at discharge with optimal cut-off values of 728.2% for BNP(delta) % and 37% for LVEF. CONCLUSIONS: Patients with a first STEMI treated with pPCI present moderate LVSD, both at hospital discharge and after 12 months. In long-term follow-up, we found an improvement in global LVSF, and, albeit a smaller, improvement in regional LVSF. No improvement in longitudinal LVSF was observed. The increase of BNP during hospitalisation, and LVEF at discharge, are independent predictors of significant global LVSD at 12 months after a first STEMI treated with pPCI. Pre-discharge peak systolic mitral annular velocity obtained by TDE may be useful in predicting LVEF in long-term follow-up in this group of patients.
Asunto(s)
Infarto del Miocardio/fisiopatología , Péptido Natriurético Encefálico/sangre , Disfunción Ventricular Izquierda/fisiopatología , Adulto , Anciano , Angioplastia Coronaria con Balón/métodos , Biomarcadores/sangre , Ecocardiografía Doppler , Femenino , Estudios de Seguimiento , Hospitalización , Humanos , Modelos Logísticos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/diagnóstico por imagen , Alta del Paciente , Valor Predictivo de las Pruebas , Pronóstico , Índice de Severidad de la Enfermedad , Factores de Tiempo , Disfunción Ventricular Izquierda/sangre , Disfunción Ventricular Izquierda/diagnóstico por imagenRESUMEN
OBJECTIVE: To assess the usefulness of in-hospital measurement of C-reactive protein (CRP) concentration in comparison to well-established risk factors as a marker of post-infarct left ventricular systolic dysfunction (LVSD) at discharge. MATERIALS AND METHODS: Two hundred and four consecutive patients with ST-segment-elevation myocardial infarction (STEMI) were prospectively enrolled into the study. CRP plasma concentrations were measured before reperfusion, 24 h after admission and at discharge with an ultra-sensitive latex immunoassay. RESULTS: CRP concentration increased significantly during the first 24 h of hospitalization (2.4 ± 1.9 vs. 15.7 ± 17.0 mg/L; p < 0.001) and persisted elevated at discharge (14.7 ± 14.7 mg/L), mainly in 57 patients with LVSD (2.4 ± 1.8 vs. 25.0 ± 23.4 mg/L; p < 0.001; CRP at discharge 21.9 ± 18.6 mg/L). The prevalence of LVSD was significantly increased across increasing tertiles of CRP concentration both at 24 h after admission (13.2 vs. 19.1 vs. 51.5 %; p < 0.0001) and at discharge (14.7 vs. 23.5 vs. 45.6 %; p < 0.0001). Multivariate analysis demonstrated CRP concentration at discharge to be an independent marker of early LVSD (odds ratio of 1.38 for a 10 mg/L increase, 95 % confidence interval 1.01-1.87; p < 0.04). CONCLUSION: Measurement of CRP plasma concentration at discharge may be useful as a marker of early LVSD in patients after a first STEMI.
Asunto(s)
Proteína C-Reactiva/análisis , Infarto del Miocardio/sangre , Disfunción Ventricular Izquierda/sangre , Anciano , Angioplastia Coronaria con Balón , Antiarrítmicos/uso terapéutico , Antihipertensivos/uso terapéutico , Aspirina/uso terapéutico , Biomarcadores/sangre , Clopidogrel , Femenino , Heparina/uso terapéutico , Humanos , Masculino , Metoprolol/uso terapéutico , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/terapia , Perindopril/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Estudios Prospectivos , Factores de Riesgo , Ticlopidina/análogos & derivados , Ticlopidina/uso terapéutico , Disfunción Ventricular Izquierda/diagnóstico , Disfunción Ventricular Izquierda/terapiaRESUMEN
BACKGROUND: Although European guidelines advise oral glucose tolerance test (OGTT) in patients with acute myocardial infarction (AMI) before or shortly after hospital discharge, data supporting this recommendation are inconclusive. We aimed to analyze whether disturbances in glucose metabolism diagnosed before hospital discharge in AMI patients represents a latent pre-existing condition or rather temporary finding. Additionally, we planned to investigate the value of pre-selected glycemic control parameters as predictors of long-term glucometabolic state. METHODS: We assessed admission glycemia, glycated hemoglobin, mean blood glucose concentration on days 1 and 2 in 200 patients with a first AMI but without overt disturbances of glucose metabolism. We also performed OGTT at discharge and 3 months after discharge. RESULTS: The prevalence of disturbances in glucose metabolism (as assessed by OGTT) at 3 months was significantly lower than at discharge (29% vs. 48%, p = 0.0001). Disturbances in glucose metabolism were not confirmed in 63% of patients with impaired glucose tolerance and in 36% of patients with diabetes mellitus diagnosed during the acute phase of AMI. Age >77 years, glucose ≥ 12.06 mmol/l at 120 minutes during OGTT before discharge and mean blood glucose level on day 2 >7.5 mmol/l were identified as independent predictors of disturbances in glucose metabolism at the 3-month follow-up. CONCLUSIONS: Disturbances in glucose metabolism observed in patients with a first AMI are predominantly transient. Elderly age, high plasma glucose concentration at 120 minutes during OGTT at discharge and elevated mean blood glucose level on day 2 were associated with sustained disturbances in glucose metabolism.