Marcadores de inflamación e insulinorresistencia en la hiperlipemia familiar combinada

La hiperlipemia familiar combinada (HFC) es un modelo genético de dislipemia mixta con resistencia a la insulina (RI) y elevado riesgo de cardiopatía isquémica por el desarrollo precoz de arteriosclerosis. La RI es independiente del grado de obesidad y del fenotipo lipoproteico. Constituye, además, factor de riesgo cardiovascular en estos pacientes. Actualmente existe una gran evidencia de que en el desarrollo y progresión de la aterosclerosis subyacen mecanismos inmunológicos e inflamatorios. Algunos estudios han demostrado que proteínas de fase aguda y algunas interleucinas fueron factores predictivos de progresión y gravedad de enfermedad coronaria. Recientemente, en modelos animales y humanos, la inflamación crónica y el grado de estrés oxidativo se han relacionado con la obesidad y el desarrollo de RI y en la HFC se ha demostrado relación entre el grado de estrés oxidativo y la RI. En modelos humanos de dislipemia primaria y arteriosclerosis precoz se ha demostrado un aumento de la actividad inflamatoria y su relación con la RI, sin embargo, no se ha demostrado la relación entre inflamación y grado de RI en la HFC. Hipótesis En la HFC la RI debe estar relacionada con el grado de inflamación crónica y estado protrombótico. Objetivos a) Estudiar el nivel de inflamación en sujetos afectos de HFC y su relación con la RI. b) Estudiar el estado protrombótico en sujetos con HFC y su relación con la RI Utilidad práctica Este conocimiento podría permitir desarrollar nuevos procedimientos diagnósticos de riesgo cardiovascular y diseñar nuevas dianas terapéuticas. Sujetos y métodos Estudio de casos (n=36) y controles (GC, n=36). Los pacientes fueron seleccionados por muestreo consecutivo en la Unidad de Lípidos y Arteriosclerosis del Servicio de Endocrinología del Hospital Clínico Universitario de Valencia (HCUV). Tanto para casos como controles se exigió el cumplimiento de rigurosos criterios de inclusión y exclusión y la firma del consentimiento informado. Se han determinado los parámetros de metabolismo lipídico CT, cHDL, cLDL, TG, ApoA, ApoB100, los de RI Glucosa, Insulina e Índice HOMA, los marcadores de inflamación TNF, IL-1, IL-6, IL-8, IL-10 y PCR y los de evaluación del riesgo aterotrombótico Adiponectina, ICAM, VCAM, MMP9, MPO y PAI-1 en los laboratorios del HCUV y de su Instituto de Investigación Sanitaria (INCLIVA). Resultados Los sujetos HFC tienen mayor grado de RI frente al GC a igualdad de IMC y perímetro de cintura. No hay diferencias significativas entre los marcadores de inflamación entre ambos grupos aunque sí se observan al comparar GC sin obesidad ni RI (IL-8 e IL-10) con sujetos HFC con RI y entre HFC sin y con RI (IL-10). La MPO se correlaciona en los sujetos con HFC con insulina, índice HOMA, apoB100 y perímetro de cintura. Son significativamente superiores las concentraciones de PAI-1 en el grupo HFC y las de PAI-1 y MPO del grupo HFC con RI frente al GC y HFC sin RI. Es superior significativamente PAI-1 incluso en el grupo HFC sin RI frente al GC sin RI. Los niveles de PAI-1 se correlacionan en los sujetos afectos de HFC con TG, insulina, HOMA, MPO, IL-8 y de forma inversa con IL-10. Conclusión Este estudio confirma la hipotesis planteada, demostrando en los sujetos con HFC que la existencia de RI se relaciona con un aumento de la inflamación crónica (IL-8, MPO y, de forma inversa, con IL-10) y del estado protrombótico (PAI-1

Laboratory test requesting appropriateness and patient safety

Patient Safety emphasizes the reporting, analysis and prevention of medical errors that very often leads to adverse healthcare situations.1 in 10 patients are impacted by medical errors.The WHO calls the patient safety issue an endemic concern. A number of well-known experts of all areas in the medical field have collectedvery valuable information for a better patient treatment and higher safety culture in all medical disciplines

Procalcitonin and long-term prognosis after an admission for acute heart failure

Background Traditionally, procalcitonin (PCT) is considered a diagnostic marker of bacterial infections. However, slightly elevated levels of PCT have also been found in patients with heart failure. In this context, it has been suggested that PCT may serve as a proxy for underrecognized infection, endotoxemia, or heightened proinflammatory activity. Nevertheless, the clinical utility of PCT in this setting is scarce. We aimed to evaluate the association between PCT and the risk of long-term outcomes. Methods and results We measured at admission PCT of 261 consecutive patients admitted for acute heart failure (AHF) after excluding active infection. Cox and negative binomial regression methods were used to evaluate the association between PCT and the risk of death and recurrent rehospitalizations, respectively. At a median follow-up of 2 years (IQR: 1.0–2.8), 108 deaths, 170 all-cause rehospitalizations and 96 AHF-rehospitalizations were registered. In an adjusted analysis, including well-established risk factors such as natriuretic peptides and indices of renal function, the logarithm of PCT was associated with a higher risk of death (HR = 1.43, CI 95%: 1.12–1.82; p = 0.004), all-cause rehospitalizations (IRR = 1.22, CI 95% 1.02–1.44; p = 0.025) and AHF-rehospitalizations (IRR = 1.28, CI 95%: 1.02–1.61; p = 0.032). The association with these endpoints persisted after adjustment for other inflammatory biomarkers such as white blood cells, C-reactive protein and interleukins. Conclusion In patients with AHF and no evidence of infection, PCT was independently and positively associated with the risk of long-term death and recurrent rehospitalizations

Long-Term Potassium Monitoring and Dynamics in Heart Failure and Risk of Mortality

Background -The prognostic value of long-term potassium monitoring and dynamics in heart failure (HF) has not been characterized completely. We sought to determine the association between serum potassium values collected at follow-up with all-cause mortality in a prospective and consecutive cohort of patients discharged from a previous acute HF admission. Methods -Serum potassium was measured at every physician-patient encounter, including hospital admissions and ambulatory settings. The multivariable-adjusted association of serum potassium with mortality was assessed using comprehensive state-of-the-art regression methods that can accommodate time-dependent exposure modeling. Results -The study sample included 2164 patients with a total of 16,116 potassium observations. Mean potassium at discharge was 4.3±0.48 mEq/L. Hypokalemia (5 mEq/L) were observed at the index admission in 77 (3.6%), 1965 (90.8%), and 122 (5.6%) patients, respectively. At a median follow-up of 2.8 years (range=0.03-12.8 years), 1090 patients died (50.4%). On a continuous scale, the multivariable-adjusted association of potassium values and mortality revealed a non-linear association (U-shaped) with higher risk at both ends of its distribution (omnibus p-value=0.001). Likewise, the adjusted hazard ratios (HRs) for hypokalemia and hyperkalemia - normokalemia as reference - were 2.35 (95% confidence interval [CI]:1.40-3.93; p=0.001) and 1.55 (95% CI:1.11-2.16; p=0.011), respectively (omnibus p-value=0.0003). Furthermore, dynamic changes in potassium were independently associated with substantial differences in mortality risk. Potassium normalization was independently associated with lower mortality risk (p=0.001). Conclusions -Either modeled continuously or categorically, serum potassium levels during long-term monitoring were independently associated with mortality in patients with HF. Likewise, persistence of abnormal potassium levels was linked to higher risk of death compared with patients who maintained or returned to normal values

Similar Clinical Course and Significance of Circulating Innate and Adaptive Immune Cell Counts in STEMI and COVID-19

This study aimed to assess the time course of circulating neutrophil and lymphocyte counts and their ratio (NLR) in ST-segment elevation myocardial infarction (STEMI) and coronavirus disease (COVID)-19 and explore their associations with clinical events and structural damage. Circulating neutrophil, lymphocyte and NLR were sequentially measured in 659 patients admitted for STEMI and in 103 COVID-19 patients. The dynamics detected in STEMI (within a few hours) were replicated in COVID-19 (within a few days). In both entities patients with events and with severe structural damage displayed higher neutrophil and lower lymphocyte counts. In both scenarios, higher maximum neutrophil and lower minimum lymphocyte counts were associated with more events and more severe organ damage. NLR was higher in STEMI and COVID-19 patients with the worst clinical and structural outcomes. A canonical deregulation of the immune response occurs in STEMI and COVID-19 patients. Boosted circulating innate (neutrophilia) and depressed circulating adaptive immunity (lymphopenia) is associated with more events and severe organ damage. A greater understanding of these critical illnesses is pivotal to explore novel alternative therapies

Optimal carbohydrate antigen 125 cutpoint for identifying low-risk patients after admission for acute heart failure

Introduction and objectivesCarbohydrate antigen 125 (CA125) has been shown to be useful for risk stratification in patients admitted with acute heart failure (AHF). We sought to determine a CA125 cutpoint for identifying patients at low risk of 1-month death or the composite of death/HF readmission following admission for AHF.MethodsThe derivation cohort included 3231 consecutive patients with AHF. CA125 cutoff values with 90% negative predictive value (NPV) and sensitivity up to 85% were identified. The adequacy of these cutpoints and the risk of 1-month death/HF readmission was then tested using the Royston-Parmar method. The best cutpoint was selected and externally validated in a cohort of patients hospitalized from BIOSTAT-CHF (n=1583).ResultsIn the derivation cohort, the median [IQR] CA125 was 57 [25.3-157] U/mL. The optimal cutoff value was ConclusionsIn patients admitted with AHF, CA125 <23 U/mL identified a subgroup at low risk of short-term adverse events, a population that may not require intense postdischarge monitoring