Phenotypic changes in low-density lipoprotein particles as markers of adverse clinical outcomes in COVID-19.

BACKGROUND AND AIMS: Low-density lipoprotein (LDL) plasma concentration decline is a biomarker for acute inflammatory diseases, including coronavirus disease-2019 (COVID-19). Phenotypic changes in LDL during COVID-19 may be equally related to adverse clinical outcomes. METHODS: Individuals hospitalized due to COVID-19 (n = 40) were enrolled. Blood samples were collected on days 0, 2, 4, 6, and 30 (D0, D2, D4, D6, and D30). Oxidized LDL (ox-LDL), and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity were measured. In a consecutive series of cases (n = 13), LDL was isolated by gradient ultracentrifugation from D0 and D6 and was quantified by lipidomic analysis. Association between clinical outcomes and LDL phenotypic changes was investigated. RESULTS: In the first 30 days, 42.5% of participants died due to Covid-19. The serum ox-LDL increased from D0 to D6 (p < 0.005) and decreased at D30. Moreover, individuals who had an ox-LDL increase from D0 to D6 to over the 90th percentile died. The plasma Lp-PLA2 activity also increased progressively from D0 to D30 (p < 0.005), and the change from D0 to D6 in Lp-PLA2 and ox-LDL were positively correlated (r = 0.65, p < 0.0001). An exploratory untargeted lipidomic analysis uncovered 308 individual lipids in isolated LDL particles. Paired-test analysis from D0 and D6 revealed higher concentrations of 32 lipid species during disease progression, mainly represented by lysophosphatidyl choline and phosphatidylinositol. In addition, 69 lipid species were exclusively modulated in the LDL particles from non-survivors as compared to survivors. CONCLUSIONS: Phenotypic changes in LDL particles are associated with disease progression and adverse clinical outcomes in COVID-19 patients and could serve as a potential prognostic biomarker.

HDL-Targeted Therapies During Myocardial Infarction.

It is now apparent that a variety of deleterious mechanisms intrinsic to myocardial infarction (MI) exists and underlies its high residual lethality. Indeed, despite effective coronary patency therapies, ischemia and reperfusion (I/R) injury accounts for about 50% of the infarcted mass. In this context, recent studies in animal models have demonstrated that coronary reperfusion with high-density lipoproteins (HDL) may reduce MI size in up to 30%. A spectrum of mechanisms mediated by either HDL-related apolipoproteins or phospholipids attenuates myocardial cell death. Hence, promising therapeutic approaches such as infusion of reconstituted HDL particles, new HDL by genomic therapy, or the infusion of apoA-I mimetic peptides have been sought as a way of ensuring protection against I/R injury. In this review, we will explore the limitations and potential therapeutic effects of HDL therapies during the acute phase of MI.

No se requiere ayuno para la determinacion rutinaria del perfil lipidico: implicaciones clinicas y de laboratorio, incluyendo valores de corte deseables - Declaracion de consenso conjunta de la European Atherosclerosis Society y la European Federation of Clinical Chemistry and Laboratory Medicine / Fasting Is Not Routinely Required for Determination of a Lipid Profile: Clinical and Laboratory Implications Including Flagging at Desirable Concentration Cutpoints - A Joint Consensus Statement from the European Atherosclerosis Society and European Federation of Clinical Chemistry and Laboratory Medicine

Objetivos: Evaluar criticamente las implicaciones clinicas de la utilizacion del perfil lipidico sin ayuno en lugar de perfiles de lipidos con ayuno y proporcionar orientacion para la elaboracion de informes de laboratorio sobre perfiles lipidicos anormales con ayuno y sin ayuno. Metodos y Resultados: Abundantes datos observacionales, en los que perfiles lipidicos medidos aleatoriamente sin ayuno se han comparado con perfiles lipidicos determinados en condiciones de ayuno, indican que las variaciones medias maximas de 1-6 h despues de ingestas habituales no son clinicamente significativas [+0,3 mmol/L (+26 mg/dL) para trigliceridos; -0,2 mmol/L (-8 mg/dL) para colesterol total; -0,2 mmol/L (-8 mg/dL) para colesterol-LDL; +0,2 mmol/L (+8 mg/dL) para colesterol de remanentes calculado; -0,2 mmol/L (-8 mg/dL) para el colesterol no-HDL calculado]; las concentraciones de colesterol-HDL, apolipoproteina A1, apolipoproteina B, y lipoproteina(a) no se ven afectados por el estado de ayuno/ no ayuno. Ademas, las concentraciones en ayunas y sin ayuno varian de manera similar con el tiempo y son comparables en la prediccion de la enfermedad cardiovascular. Para mejorar el cumplimiento del paciente con las condiciones para la determinacion del perfil lipidico, por lo tanto, se recomienda el uso rutinario de los perfiles lipidicos sin ayuno, mientras que se puede considerar la toma de muestra en ayunas cuando los trigliceridos sin ayuno son >5 mmol/L (440 mg/dL). Para las muestras sin ayuno, los informes de laboratorio deberian marcar como concentraciones anormales a trigliceridos ≥2 mmol/L (175 mg/dL), colesterol total ≥5 mmol/L (190 mg/dL), colesterol-LDL ≥3 mmol/L (115 mg/dL), colesterol remanente calculado ≥0,9 mmol/L (35 mg/dL), colesterol no-HDL calculado ≥3.9 mmol/L (150 mg/dL), HDL colesterol ≤1 mmol/L (40 mg/dL), apolipoproteina A1 ≤1,25 g/L (125 mg/dL), apolipoproteina B ≥1,0 g/L (100 mg/dL), y lipoproteina(a) ≥50 mg/dL (percentil 80); para muestras con ayuno, las concentraciones anormales corresponden a trigliceridos ≥1,7 mmol/L (150 mg/dL). Aquellas concentraciones que ponen en peligro la vida requieren derivacion inmediata debido al riesgo de pancreatitis cuando los trigliceridos son >10 mmol/L (880 mg/dL), de hipercolesterolemia familiar homocigotica cuando el colesterol-LDL es >13 mmol/L (500 mg/dL) o hipercolesterolemia familiar heterocigota cuando el colesterol-LDL es >5 mmol/L (190 mg/dL), y debido al riesgo cardiovascular muy alto cuando la lipoproteina(a) es >150 mg/dL (percentil 99). Conclusiones: Recomendamos la utilizacion de rutina de muestras de sangre sin ayuno para la evaluacion del perfil lipidico plasmatico. Los informes de laboratorio deberian marcar resultados anormales basandose en valores de corte deseables. Las determinaciones con ayuno y sin ayuno deben ser complementarias, pero no se excluyen mutuamente.

Aims: To critically evaluate the clinical implications of the use of non-fasting rather than fasting lipid profiles and to provide guidance for the laboratory reporting of abnormal non-fasting or fasting lipid profiles. Methods and Results: Extensive observational data, in which random non-fasting lipid profiles have been compared with those determined under fasting conditions, indicate that the maximal mean changes at 1-6 h after habitual meals are not clinically significant [+0.3 mmol/L (26 mg/dL) for triglycerides; -0.2 mmol/L (8 mg/dL) for total cholesterol; -0.2 mmol/L (8 mg/dL) for LDL cholesterol; +0.2 mmol/L (8 mg/dL) for calculated remnant cholesterol; -0.2 mmol/L (8 mg/dL) for calculated non-HDL cholesterol]; concentrations of HDL cholesterol, apolipoprotein A1, apolipoprotein B, and lipoprotein(a) are not affected by fasting/nonfasting status. In addition, non-fasting and fasting concentrations vary similarly over time and are comparable in the prediction of cardiovascular disease. To improve patient compliance with lipid testing, we therefore recommend the routine use of non-fasting lipid profiles, whereas fasting sampling may be considered when non-fasting triglycerides are >5 mmol/L (440 mg/dL). For nonfasting samples, laboratory reports should flag abnormal concentrations as triglycerides ≥2 mmol/L (175 mg/dL), total cholesterol ≥5 mmol/L (190 mg/dL), LDL cholesterol ≥3 mmol/L (115 mg/dL), calculated remnant cholesterol ≥0.9 mmol/L (35 mg/dL), calculated non-HDL cholesterol ≥3.9 mmol/L (150 mg/dL), HDL cholesterol ≤1 mmol/L (40 mg/dL), apolipoprotein A1 ≤1.25 g/L (125 mg/dL), apolipoprotein B ≥1.0 g/L (100 mg/dL), and lipoprotein(a) ≥50 mg/dL (80th percentile); for fasting samples, abnormal concentrations correspond to triglycerides ≥1.7 mmol/L (150 mg/dL). Life-threatening concentrations require separate referral for the risk of pancreatitis when triglycerides are >10 mmol/L (880 mg/dL), for homozygous familial hypercholesterolemia when LDL cholesterol is >13 mmol/L (500 mg/dL), for heterozygous familial hypercholesterolemia when LDL cholesterol is >5 mmol/L (190 mg/dL), and for very high cardiovascular risk when lipoprotein(a) >150 mg/dL (99th percentile). Conclusions: We recommend that non-fasting blood samples be routinely used for the assessment of plasma lipid profiles. Laboratory reports should flag abnormal values on the basis of desirable concentration cutpoints. Non-fasting and fasting measurements should be complementary but not mutually exclusive.

SENP1, but not fetal hemoglobin, differentiates Andean highlanders with chronic mountain sickness from healthy individuals among Andean highlanders.

Chronic mountain sickness (CMS) results from chronic hypoxia. It is unclear why certain highlanders develop CMS. We hypothesized that modest increases in fetal hemoglobin (HbF) are associated with lower CMS severity. In this cross-sectional study, we found that HbF levels were normal (median = 0.4%) in all 153 adult Andean natives in Cerro de Pasco, Peru. Compared with healthy adults, the borderline elevated hemoglobin group frequently had symptoms (headaches, tinnitus, cyanosis, dilatation of veins) of CMS. Although the mean hemoglobin level differed between the healthy (17.1 g/dL) and CMS (22.3 g/dL) groups, mean plasma erythropoietin (EPO) levels were similar (healthy, 17.7 mIU/mL; CMS, 12.02 mIU/mL). Sanger sequencing determined that single-nucleotide polymorphisms in endothelial PAS domain 1 (EPAS1) and egl nine homolog 1 (EGLN1), associated with lower hemoglobin in Tibetans, were not identified in Andeans. Sanger sequencing of sentrin-specific protease 1 (SENP1) and acidic nuclear phosphoprotein 32 family, member D (ANP32D), in healthy and CMS individuals revealed that non-G/G genotypes were associated with higher CMS scores. No JAK2 V617F mutation was detected in CMS individuals. Thus, HbF and other classic erythropoietic parameters did not differ between healthy and CMS individuals. However, the non-G/G genotypes of SENP1 appeared to differentiate individuals with CMS from healthy Andean highlanders.