Lipoproteínas ricas en triglicéridos y riesgo cardiovascular residual / Triglyceride rich lipoproteins and residual cardiovascular risk / Lipoproteínas ricas em triglicerídeos e risco cardiovascular residual / Reconocimiento a la trayectoria del Prof. Dr. Juan Miguel Castagnino†

Resumen Una vasta evidencia científica de resultados de ensayos clínicos, preclínicos, epidemiológicos y genéticos, mostraron una asociación causal entre el aumento de triglicéridos (TG), lipoproteínas ricas en TG (LRT) y sus remanentes para la enfermedad cardiovascular aterosclerótica (ECA). La acumulación de LRT circulantes puede explicar, en parte, el riesgo cardiovascular residual que se observa en pacientes eficazmente tratados para reducir sus niveles de LDL; sin embargo, persiste el riesgo de ECA. Es imprescindible que en el estudio del perfil lipídico se considere la determinación o estimación de estas lipoproteínas, sumada a la medida de TG plasmáticos. El objetivo de la presente revisión fue actualizar el conocimiento acerca de los niveles incrementados de TG, de LRT y sus remanentes, brindar alternativas para su determinación y comprender los mecanismos que involucran a las LRT en el desarrollo acelerado de la aterosclerosis. La actualización de los diferentes parámetros asociados al aumento de TG y sus valores de corte o límites de decisión clínica según la clasificación del riesgo de ECA para cada paciente, permitirá el rediseño de un informe de resultados que será de gran utilidad para el médico y el paciente con respecto a las conductas preventivas y terapéuticas de la ECA.

Abstract Vast scientific evidence from clinical, preclinical, epidemiological, and genetic trial results show a causal association between increased triglycerides (TG), TG-rich lipoproteins (TRL), and their remnants for atherosclerotic cardiovascular disease (ASCVD). The accumulation of circulating LRT may explain, in part, the residual cardiovascular risk observed in patients successfully treated to reduce their LDL levels, however, the risk of ASCVD still persists. It is essential that in the assessment of the lipid profile, the determination or estimation of these lipoproteins be considered, added to the measurement of plasmatic TG. The objective of this review is to update the knowledge about the increased levels of TG, LRT and their remnants, proprovide alternatives for their determination and understand the mechanisms that involve LRT in the accelerated development of atherosclerosis. Updating the different parameters associated with increased TG and their cut-off values or clinical decision limits according to the ASCVD risk classification for each patient will allow for the redesign of a results report that will be very useful for the physician and the patient regarding the preventive and therapeutic behaviours of the ASCVD.

Resumo Vastas evidências científicas de resultados de ensaios clínicos, pré-clínicos, epidemiológicos e genéticos mostraram uma associação causal entre o aumento de triglicerídeos (TG), lipoproteínas ricas em TG (LRT) e seus remanescentes para doença cardiovascular aterosclerótica (DCA). O acúmulo de LRT circulante pode explicar, em parte, o risco cardiovascular residual observado em pacientes tratados de maneira eficaz para reduzir seus níveis de LDL, no entanto, o risco de DCA persiste. É fundamental que no estudo do perfil lipídico seja considerada a determinação ou estimativa dessas lipoproteínas, somada à dosagem de TG plasmáticos. O objetivo desta revisão foi atualizar o conhecimento sobre os níveis aumentados de TG, LRT e seus remanescentes, fornecer alternativas para sua determinação e compreender os mecanismos que envolvem as LRT no desenvolvimento acelerado da aterosclerose. A atualização dos diferentes parâmetros associados ao aumento de TG, e seus valores de corte ou limites de decisão clínica de acordo com a classificação do risco de DCE para cada paciente, permitirá o redesenho de um relatório de resultados que será muito útil para o médico e o paciente quanto às condutas preventivas e terapêuticas da DCE.

Residual risk of hepatitis C virus in blood screening among voluntary blood donors in Zhengzhou / 中国输血杂志

【Objective】 To evaluate the residual risk of hepatitis C virus (HCV) in blood screening among voluntary blood donors in Zhengzhou. 【Methods】 The ELISA and NAT screening results of 497 171 voluntary blood donors in Zhengzhou from January 2019 to December 2020 were collected through the information management system of our blood center.The residual risk of HCV was assessed using the Prevalence-Window Period Residual Risk Model. 【Results】 The residual risk among repeated and first-time blood donors was 1∶132 280 (95% CI: 1∶95 520~1∶188 820) and 1∶44 090 (95% CI: 1∶31 840~1∶62 940), respectively. The overall residual risk of blood donors screening was 1∶68 540 (95% CI: 1∶65 910~1∶130 290). The reactive rate of HCV screening in first-time blood donors (0.144%, 334/231 168) was significantly higher than that in repeated blood donors (0.014%, 36/266 003) (P<0.05), and the reactive rate of repeated blood donors in 2019 (0.019%, 26/135 267) was significantly higher than that in repeat blood donors in 2020 (0.008%, 10/130 736) (P<0.05). 【Conclusion】 The residual risk of HCV among voluntary blood donors in Zhengzhou is low.The publicity and recruitment should be further strengthened to establish a stable team of voluntary blood donation, and health consultation and physical examination should also be strengthened to further reduce the residual risk of blood transfusion.

Assessment of residual risk of hepatitis C virus transmission by blood transfusion in Taiyuan / 中国输血杂志

【Objective】 To analyze the epidemic of hepatitis C virus (HCV) in voluntary blood donors , and to assess the residual risk of HCV transmission by blood transfusion in Taiyuan. 【Methods】 The HCV screening results of voluntary blood donors in Taiyuan from 2016 to 2021 were collected by blood center information system, and the epidemiologic feature of first-time and repeated donors were analyzed. The incidence-window period model was used to assess the residual risk of HCV transmission by transfusion in first-time/repeated donors as well as that in repeated donors under different blood screening modes. 【Results】 Of the 662 705 samples in Taiyuan from 2016 to 2021, the HCV positive rate of the first-time donors was 1.83‰(595/325 009) and the residual risk of HCV transmission was 14.91/100 000. The HCV positive rate of the repeated donors was 0.04‰ (13/337 696) and the residual risk was 0.31/1 000 000. The total residual risk of HCV transmission was 7.47/1 000 000. A total of 337 696 blood samples of repeated blood donors were tested, the repeated blood donors’ residual risk of transfusion-transmitted HCV was 0.31/100 000 after dual ELISA tests , and 0.06/100 000 after dual ELISA and once NAT, which reduce by 80.65% since NAT were adopted. 【Conclusion】 The residual risk of HCV transmission from repeated donors was less than that from first-time donors. The blood screening mode of HCV by dual ELISA and once NAT can effectively reduce the residual risk of transfusion-transmitted HCV and improve blood safety. The rate of repeat blood donation needs to be increased by continuously optimizing the recruitment strategy of blood donors.

Prevalence of hepatitis B virus infection and residual transmission risk among volunteer blood donors in Hangzhou City / 预防医学

Objective @#To investigate the prevalence of hepatitis B virus ( HBV ) infection among volunteer blood donors in Hangzhou City, and to evaluate the residual risk of transfusion-transmitted HBV infections. @*Methods @#Data pertaining to volunteer blood donors in Hangzhou City from 2016 to 2019 were retrieved from the blood donor management system. Hepatitis B surface antigen ( HBsAg ) was detected by enzyme-linked immunosorbent assay ( ELISA ) and HBV DNA was detected using nucleic acid testing. The incidence/window period model was employed to assess the residual risk of HBV transmitted through transfusion from donors. @*Results @#The prevalence of HBV infections was 0.56% among the 320 755 first-time donors and 0.13% among the 279 816 repeat donors in Hangzhou City from 2016 to 2019, and a higher prevalence of HBV infection was detected among first-time donors than among repeat donors ( P<0.05 ). The residual risks of transfusion-transmitted HBV infection were 296.38 per million person-times ( 95%CI: 277.57 to 315.19 per million person-times ) and 98.79 per million person-times ( 95%CI: 87.15 to 110.43 per million person-times ) among first-time and repeat donors with positive HBsAg, and were 86.79 per million person-times ( 95%CI: 76.60 to 96.98 per million person-times ) and 28.93 per million person-times ( 95%CI: 22.63 to 35.23 per million person-times ) among first-time and repeat donors tested positive for HBV DNA, respectively.@*Conclusions @#There is still a residual risk of HBV infection transmitted through transfusion from blood donors in Hangzhou City. Nucleic acid testing may remarkably reduce the residual risk of transfusion-transmitted HBV infection in blood donors.

HBV infection in window period among repeated blood donors: Residual risk assessment and trend analysis / 中国输血杂志

【Objective】 To investigate the status of blood safety and the effectiveness of preventive measures. 【Methods】 The data of Fengxian Blood Bank from 2018 to 2020 were extracted from Shanghai blood collection and supply information system. HBsAg sero-conversion samples of repeated blood donors were confirmed, and HBV serologic supplemental test were performed to obtain the number of new infections during the blood donation interval. The incidence and residual risk of HBV infection were evaluated by the sero-conversion model in donation intervals for repeated donors, and residual risk trend between the study period of 2002 to 2005, 2007 to 2011, 2011 to 2013 and 2018 to 2020 was compared. 【Results】 During 2018~2020, nine new HBV infections occurred among repeated donors during blood donation interval, with an incidence rate of 2.71 per 10 000. The residual risk of window period HBV transmission by transfusion could be reduced by 58.33% using HBsAg test plus NAT (HBsAg test 1∶30 637 vs HBsAg test plus NAT 1∶73 529). The residual risk of HBV transmission was decreasing when stratifying by periods, especially one order of magnitude dropped in 2018~2020 as in comparison of 2002 to 2005. 【Conclusion】 The residual risk of HBV transmission by transfusion showed a decrease trend. Although NAT could greatly reduce the risk, comprehensive preventive measures are needed to further reduce the risk.

Progress of residual inflammatory cardiovascular risk / 医学研究生学报

Coronary artery disease (CAD) remains a leading cause of morbidity and mortality in the world. Although the comprehensive control of cardiovascular disease risk factors has achieved remarkable progress in recent years, the incidence of cardiovascular events is still high after the control of traditional risk factors such as low density lipoprotein cholesterol, blood pressure and blood glucose, collectively referred to as cardiovascular residual risk. Inflammation is a central driver of atherosclerosis and the ultimate rupture of plaque, as well as an important cause of residual cardiovascular risk. Therefore, this article reviews the formation, assessment and treatment of residual inflammatory cardiovascular risk.

Correlation of lipoprotein(a) with clinical stability and severity of coronary artery lesions in patients with coronary artery disease / 南方医科大学学报

OBJECTIVE@#To analyze the correlation of lipoprotein(a) [Lp(a)] with the clinical stability and severity of coronary artery stenosis in patients with coronary artery disease (CAD).@*METHODS@#A total of 531 patients undergoing coronary angiography in Nanfang Hospital between January, 2013 and December, 2016 were enrolled in this study. At the cutoff Lp(a) concentration of 300 mg/L, the patients were divided into high Lp(a) group (=191) and low Lp(a) group (=340). In each group, the patients with an established diagnosis of CAD based on coronary angiography findings were further divided into stable angina pectoris (SAP) group and acute coronary syndrome (ACS) group. The correlation between the severity of coronary artery stenosis and Lp(a) was evaluated.@*RESULTS@#The patients in high and low Lp(a) groups showed no significant differences in age, gender, body mass index, smoking status, hypertension, or diabetes (>0.05). Multivariate logistic regression analysis revealed that age, gender, and serum levels of low-density lipoprotein cholesterol (LDL-C) and Lp(a) were independent risk factors for CAD in these patients. A high Lp(a) level was associated with an increased risk of CAD (OR=2.443, 95%CI: 1.205-4.951, =0.013). The patients with a high Lp(a) level were at a significantly higher risk of CAD than those with a low Lp(a) level irrespective of a low or high level of LDL-C (=0.006 and 0.020). In the patients with CAD, the ACS group had a significantly higher Lp(a) level than the SAP group ( < 0.001); the proportion of the patients with high Gensini scores was significantly greater in high Lp(a) group than in low Lp(a) group (17.3% vs 5.6%, =0.026), and a linear relationship was found between Lp(a) level and Gensini score (R=0.130, =0.006).@*CONCLUSIONS@#Serum level of Lp(a) is an independent risk factor for CAD, and an increased Lp(a) is the residual risk for CAD. In patients with CAD, a high Lp(a) level is associated with the clinical instability and severity of coronary artery stenosis.

Estimation of the Residual Risk of Transfusion-Transmissible Infectious Agents in Korea / 대한수혈학회지

BACKGROUND: The risk of transfusion-transmissible infections (TTIs) of HBV, HCV, and HIV in Korea has been reduced significantly by strengthening the blood safety policies. On the other hand, the risk of TTI still exists due to the diagnostic window period or viral variants. METHODS: The residual risks of TTI of HBV, HCV, and HIV were calculated from July 1, 2012 to June 30, 2018 by dividing the data into two year sets. The residual risk was conducted by separating the donors who donated only once and those who donated more than once during each period. RESULTS: In the first two years, the residual risks of HBV, HCV, and HIV were calculated to be 17.54/106, 0.42/106, and 0.30/106 respectively. The residual risk of HBV and HCV over the last two years was calculated to be 9.41/106 and 0.27/106, showing a tendency to decrease with time. On the other hand, the residual risk of HIV over the last two years was calculated to be 0.29/106, showing no significant difference. The residual risk in the donors who donated only once was higher than that in the donors who donated more than once during each period. CONCLUSION: The real transfusion-transmitted infection can be different from the estimated residual risk in this study because this study was based on the thesis that all NAT-reactive blood components cause infection. Because the residual risk of HBV is higher than HCV and HIV, it was considered that the safety measures for the HBV need to be improved continuously.

Preliminary evaluation of reducing residual risk of blood transfusion-transmitted infection by using HBV DNA detection / 中华实验和临床病毒学杂志

Objective@#To evaluate the reduction of the residual risk of blood transfusion- transmitted hepatitis B virus (HBV), using nucleic acid detection(NAT)test for enzyme linked immunosorbent assay (ELISA) qualified volunteer-donor bloods in Quzhou area after NAT was developed.@*Methods@#Specimens were collected from March 2016 to March 2017, detected by ELISA twice with two different reagents and NAT only once. The residual risks of blood transfusion-transmitted HBV infection were calculated by mathematical model of risk evaluation.@*Results@#Totally 27 646 specimens were collected from March 2016 to March 2017, which included 76 specimens that were both ELISA and NAT positive, 31 specimens were ELISA negative but NAT positive.The total number of NAT positive specimens was 107.The residual risk of HBV by ELISA test was 28.2×10 -5and NAT test was 13.0×10-5.@*Conclusions@#NAT detection can greatly reduce the residual risk of blood transfusion-transmitted HBV infection, and provide effective value for bloods safety in practice.

Residual Risk of Transfusion-Transmitted Infection with Hepatitis C Virus since the Introduction of Nucleic Acid Testing in Korea / 대한수혈학회지

BACKGROUND: In 2005, the Korean Red cross introduced mini-pool nucleic acid testing (NAT) for human immunodeficiency virus (HIV) and hepatitis C virus (HCV), which upgraded to individual donation (ID) NAT including HBV in 2012. In this study, we analyzed the trend of HCV infection among blood donors after introduction of NAT by estimating the residual risk (RR) of transfusion transmitted infection (TTI) of HCV. METHODS: Donation data from 2003 to 2014 were analyzed using the Blood Information Management System (BIMS). Each donation was tested for antibodies and viral RNA for HCV. Prevalence and incidence rate (IR) among repeat donors were determined. RR was determined using the incidence rate/window period model. RESULTS: During the 12-year period, a total of 29,058,436 donations were screened with 34 HCV NAT yield donations. Calculated RR per million donations for HCV was significantly reduced from 13.41 in the pre-NAT period (2003~2004) to 0.52 in the post NAT period (2006~2007) (P<0.001). Most recently (2013~2014), RR for HCV with TTI was estimated by 0.16 per million donations (1:6,289,308). CONCLUSION: RR of TTI with HCV was remarkably decreased since introduction of NAT. However, the prevalence and IR of HCV RNA among first time donors was still high and yield cases were more frequent among repeat donors. Therefore, establishment of a sensitive and accurate screening system and measures for maintaining healthy donors should be considered in order to ensure blood safety.

Changes in the prevalence, incidence and residual risk for HIV and hepatitis C virus in Southern Brazilian blood donors since the implementation of NAT screening

Introduction Previous studies have shown high residual risk of transfusing a blood donation contaminated by human immunodeficiency virus (HIV) or hepatitis C virus (HCV) in Brazil and motivated the development of a Brazilian platform for simultaneous detection of both viruses by nucleic acid amplification test (NAT) denominated HIV/HCV Bio-Manguinhos/Fundação Oswaldo Cruz (FIOCRUZ). The objective of this study was to verify seroprevalence, incidence and residual risk for both viruses before and after the implementation of NAT. Methods Over 700,000 blood samples from all blood banks in the southern Brazilian State of Santa Catarina were analyzed during the period between January 2007 and July 2013. Results Compared with the period preceding the NAT screening, HIV prevalence increased from 1.38 to 1.58 per 1,000 donors, HIV incidence rate increased from 1.22 to 1.35 per 1,000 donor-years, and HIV residual risk dropped almost 2.5 times during the NAT period. For HCV, seroprevalence increased from 1.22 to 1.35 per 1,000 donors, incidence dropped from 0.12 to 0.06 per 1,000 donor-years, and residual risk decreased more than 3 times after the NAT implementation. Conclusions NAT reduced the duration of the immunologic window for HIV and HCV, thus corresponding to approximately 2.5- and 3-fold respective residual risk reductions. .

Dislipidemias: Controversias del riesgo residual

Las estatinas son el principal tratamiento para la reducción del colesterol LDL habiendo demostrado un claro beneficio en la reducción de enfermedad cardiovascular (ECV). Sin embargo, a pesar de los pacientes alcanzar la meta de colesterol LDL, queda un remanente de riesgo relativo de ECV entre un 60% a 70%, el cual ha sido denominado Riesgo Residual. Por ello, el enfoque actual se inclina sobre objetivos adicionales al colesterol LDL, siendo el colesterol HDL bajo y/o triglicéridos elevados los objetivos terapéuticos para reducir el riesgo residual. Se han empleado diversas combinaciones de hipolipemiantes asociados a las estatinas para optimizar el perfil lipídico. La mayorías de estas drogas clásicas (fibratos, niacina y ácidos grasos omega-3), así como un nuevo grupo de moléculas inhibidoras de la Proteína Transportadora de Esteres de Colesterol, son capaces de mejorar las concentraciones de colesterol HDL y triglicéridos en asociación con estatinas, sin embargo, dichas combinaciones en la mayoría de los casos, no han demostrado beneficios en reducir la presencia de ECV, incluso, en el caso de la niacina, se observan efectos deletéreos en las combinaciones a pesar de la optimización del perfil lipídico. Estos hechos nos hacen replantear el conocimiento que tenemos sobre la dislipidemia y su tratamiento, por lo que se presenta la siguiente revisión.

Statins are the principal treatment for highest levels of LDL cholesterol, with clear benefits in reduction of cardiovascular disease (CVD). However, although patients reach LDL cholesterol goal, 60% to 70% have a relative risk remnant of CVD, named Residual Risk. By this, the discussion is focused in other objectives beside LDL cholesterol, being the low HDL cholesterol and/or elevated triglycerides a relevant therapeutic target to reduce the residual risk. Many combinations of drugs have been associated to statins to optimize lipid profile. Most of these classics drugs (fibratos, niacin, and fatty acids omega-3) and the new drugs of Cholesteryl Ester Transfer Proteins inhibitors, increase HDL cholesterol and reduce triglycerides combined with statins, however, in mostly of cases these combinations have not reduced CVD; in studies with niacin, the combination increase deleterious effects despite the optimization of lipid profile. These facts make us reconsider the knowledge we have on dyslipidemia and its treatment, so we present the following review.

Association of lipoprotein particles with cardiovascular risk in diabetes / 中华内分泌代谢杂志

Type 2 diabetic patients are usually accompanied by dyslipidemia.The cardiovascular residual risk is still high in these patients,even with glycemia,blood pressure,and plasma lipids well controlled.In this review,the relationship of plasma lipids and changes in lipoprotein particles with cardiovascular risk is discussed.

Comportamiento de marcadores serológicos en donantes de sangre del territorio de Colón, 1998-2007 / Behavior of the serologic markers in blood donors in the territory of Colon, 1998-2007

En el laboratorio de Sistema Ultra-Micro-Analítico, del banco de sangre del Hospital Territorial Universitario Dr Mario Muñoz Monroy, del municipio Colón, provincia Matanzas, se realizó un estudio descriptivo prospectivo longitudinal, sobre el comportamiento de marcadores serológicos, donde se determinó la incidencia y prevalencia del antígeno de superficie del virus de la hepatitis B (VHB, HBsAg) y de los anticuerpos contra los virus de la hepatitis C (VHC, anti-VHC) y de la inmunodeficiencia humana 1 y 2 (VIH 1 y 2, anti-VIH 1+2), en donantes de sangre del territorio, y el estimado de infección potencial no detectada transmisible por sangre o riesgo residual (RR) en la sangre donada, en el tiempo comprendido del 1 de enero de 1998 al 31 de diciembre de 2007. La investigación se realizó con todo el universo de donantes útiles y sus respectivas donaciones de sangre, y quedó constituido por 49 749 donantes y 84 932 bolsas de sangre. Los índices de prevalencia (x 100 000 donantes), incidencia (x 100 000 donantes), y estimado de riesgo residual (x 1 000 000 de unidades de sangre donada) en el citado período de tiempo fueron: para el VHB 0,81; 0,17 y 0,20; para el VHC 0,55; 0,12 y 0,23; y para los VIH 1y2 0,005; 0,01x10-2 y 0,02 x10-3, respectivamente, índices bajos según la clasificación internacional; pero no para Cuba con respecto al HBsAg.

We carried out a prospective descriptive longitudinal study on the behavior of the serologic markers in the Ultra-Micro-Analytic System laboratory, of the blood bank of the territorial university hospital Dr Mario Muñoz Monroy, of the municipality of Colon, province of Matanzas. We determined the incidence and prevalence of the surface Hepatitis B virus antigen (HBV, HBsAg) and of the antibodies against the Hepatitis C (HCV, anti HCV) and the human immunodeficiency virus 1 and 2 (HIV 1 and 2, anti-HIV 1+2) in blood donors of the territory, and the estimate of non-detected potential infection transmissible by blood or residual risk (RR) in the donated blood, in the period from January 1st 1998 to December 31st 2007. The research was made with all the universe of utile donors and their respective blood donations, and was formed by 49 749 donors and 84 932 blood bags. The prevalence rates (x 100 000 donors), incidence (x 100 000 donors), and estimated residual risk (x 1 000 000 units of donated blood) in the quoted time period were: for the HBV 0,81; 0,17 and 0,20; for the HCV 0,55; 0,12 and 0,23, and for the HIV 1 and 2 0,005; 0,01x10-2 and 0,02x10-3 respectively, low rates according to the international classification, but not for Cuba with respect of the HBsAg.

Joint application of mathematic models in assessing the residual risk of hepatitis C virus transmitted through blood transfusion / 中华流行病学杂志

The practicable and effective methods for residual risk assessment on transfusion-transmitted disease was to establish the mathematic models. Based on the characteristics of the repeat donors which donated their blood on a regular base, a model of sero-conversion during the interval of donations was established to assess the incidence of the repeat donors. Based on the characteristics of the prevalence in the population, a model of ‘prevalence increased with the age of the donor' was established to assess the incidence of those first-time donors. And based on the impact of the windows period through blood screening program, a model of residual risk associated with the incidence and the length of the windows period was established to assess the residual risk of blood transfusion. In this paper, above said 3 kinds of mathematic models were jointly applied to assess the residual risk of hepatitis C virus (HCV) which was transmitted through blood transfusion in Shanghai,based on data from the routine blood collection and screening program. All the anti-HCV unqualified blood donations were confirmed before assessment. Results showed that the residual risk of HCV transmitted through blood transfusion during Jan. 1st,2007 to Dec. 31st,2008 in Shanghai was 1∶101 000. Data showed that the results of residual risk assessment with mathematic models was valuable. The residual risk of transfusion-transmitted HCV in Shanghai was at a safe level, according to the results in this paper.