Colesterol remanente, riesgo vascular y prevención de la arteriosclerosis / Remnant cholesterol, vascular risk, and prevention of atherosclerosis

En los pacientes que han alcanzado un control óptimo del c-LDL persiste un riesgo residual de enfermedad cardiovascular aterotrombótica (ECVA) relacionado con alteraciones del metabolismo lipídico, entre las que las alteraciones de las lipoproteínas ricas en triglicéridos y del colesterol que contienen, denominado colesterol remanente, juegan un papel principal. El colesterol remanente tiene una relación con el riesgo residual de ECVA que es independiente del c-LDL y ha sido demostrada en los estudios epidemiológicos y de aleatorización mendeliana, y en los análisis de los ensayos clínicos con fármacos hipolipidemiantes. Las partículas remanentes de las lipoproteínas ricas en triglicéridos son altamente aterogénicas, por su capacidad de entrar y ser retenidas en la pared arterial, su alto contenido en colesterol y su capacidad de generar células espumosas y una respuesta inflamatoria. La valoración del colesterol remanente puede aportar información sobre el riesgo residual de ECVA más allá de la información aportada por el c-LDL, el c-no HDL y la apoB, en particular en los individuos con hipertrigliceridemia, diabetes tipo 2 o síndrome metabólico. En el estudio REDUCE-IT se demostró que el icosapento de etilo tiene un efecto preventivo frente a la ECVA en los pacientes de muy alto riesgo cardiovascular con hipertrigliceridemia tratados con estatinas y con un c-LDL en objetivos. Los nuevos fármacos hipolipidemiantes contribuirán a definir la eficacia y los criterios en el tratamiento del exceso de colesterol remanente y de la hipertrigliceridemia en la prevención de la ECVA.(AU)

In patients who have achieved optimal LDL-C control, there remains a residual risk of atherothrombotic cardiovascular disease (ACVD) related to alterations in lipid metabolism, where alterations in triglyceride-rich lipoproteins and the cholesterol they contain, called remnant cholesterol, play a major role. Remnant cholesterol has an association with residual risk of ACVD that is independent of LDL-C and has been demonstrated in epidemiological and Mendelian randomisation studies, and in analyses of clinical trials of lipid-lowering drugs. Remnant triglyceride-rich lipoproteins particles are highly atherogenic, due to their ability to enter and be retained in the arterial wall, their high cholesterol content, and their ability to generate “foam cells” and an inflammatory response. Assessment of remnant cholesterol may provide information on residual risk of ACVD beyond the information provided by LDL-C, Non-HDL-C, and apoB, particularly in individuals with hypertriglyceridaemia, type 2 diabetes, or metabolic syndrome. In the REDUCE-IT study, icosapent ethyl was shown to have a preventive effect against ACVD in very high cardiovascular risk patients with hypertriglyceridaemia treated with statins and target LDL-C. New lipid-lowering drugs will help to define efficacy and criteria in the treatment of excess remnant cholesterol and hypertriglyceridaemia in the prevention of ACVD.(AU)

Remnant cholesterol, vascular risk, and prevention of atherosclerosis. / Colesterol remanente, riesgo vascular y prevención de la arteriosclerosis.

In patients who have achieved optimal LDL-C control, there remains a residual risk of atherothrombotic cardiovascular disease (ACVD) related to alterations in lipid metabolism, where alterations in triglyceride-rich lipoproteins and the cholesterol they contain, called remnant cholesterol, play a major role. Remnant cholesterol has an association with residual risk of ACVD that is independent of LDL-C and has been demonstrated in epidemiological and Mendelian randomisation studies, and in analyses of clinical trials of lipid-lowering drugs. Remnant triglyceride-rich lipoproteins particles are highly atherogenic, due to their ability to enter and be retained in the arterial wall, their high cholesterol content, and their ability to generate "foam cells" and an inflammatory response. Assessment of remnant cholesterol may provide information on residual risk of ACVD beyond the information provided by LDL-C, Non-HDL-C, and apoB, particularly in individuals with hypertriglyceridaemia, type 2 diabetes, or metabolic syndrome. In the REDUCE-IT study, icosapent ethyl was shown to have a preventive effect against ACVD in very high cardiovascular risk patients with hypertriglyceridaemia treated with statins and target LDL-C. New lipid-lowering drugs will help to define efficacy and criteria in the treatment of excess remnant cholesterol and hypertriglyceridaemia in the prevention of ACVD.

Beneficial effect of corticosteroids in preventing mortality in patients receiving tocilizumab to treat severe COVID-19 illness.

OBJECTIVES: To assess the characteristics and risk factors for mortality in patients with severe coronavirus disease-2019 (COVID-19) treated with tocilizumab (TCZ), alone or in combination with corticosteroids (CS). METHODS: From March 17 to April 7, 2020, a real-world observational retrospective analysis of consecutive hospitalized adult patients receiving TCZ to treat severe COVID-19 was conducted at our 750-bed university hospital. The main outcome was all-cause in-hospital mortality. RESULTS: A total of 1,092 patients with COVID-19 were admitted during the study period. Of them, 186 (17%) were treated with TCZ, of which 129 (87.8%) in combination with CS. Of the total 186 patients, 155 (83.3 %) patients were receiving noninvasive ventilation when TCZ was initiated. Mean time from symptoms onset and hospital admission to TCZ use was 12 (±4.3) and 4.3 days (±3.4), respectively. Overall, 147 (79%) survived and 39 (21%) died. By multivariate analysis, mortality was associated with older age (HR = 1.09, p < 0.001), chronic heart failure (HR = 4.4, p = 0.003), and chronic liver disease (HR = 4.69, p = 0.004). The use of CS, in combination with TCZ, was identified as a protective factor against mortality (HR = 0.26, p < 0.001) in such severe COVID-19 patients receiving TCZ. No serious superinfections were observed after a 30-day follow-up. CONCLUSIONS: In patients with severe COVID-19 receiving TCZ due to systemic host-immune inflammatory response syndrome, the use of CS in addition to TCZ therapy, showed a beneficial effect in preventing in-hospital mortality.