Limitaciones de los puntajes de riesgo cardiovascular en prevención primaria. ¿Una oportunidad para los moduladores de riesgo? / Limitations of cardiovascular risk scores in primary prevention. An opportunity for risk modulators?

RESUMEN Introducción : Los puntajes de riesgo cardiovascular tienen limitaciones relacionadas con la calibración, la discriminación y la baja sensibilidad. Se han identificado diferentes "moduladores de riesgo" que permiten mejorar la estratificación del riesgo cardiovascular: placa aterosclerótica carotídea (PAC), puntaje de calcio arterial coronario (pCAC) y lipoproteína(a) [Lp(a)]. Objetivos : 1) determinar la prevalencia de los moduladores de riesgo citados en una población en prevención primaria; 2) determinar la concordancia entre los 2 métodos de detección de aterosclerosis subclínica; 3) establecer qué proporción de pacientes deberían recibir estatinas inicialmente, según su puntaje de riesgo, y posteriormente con el conocimiento de los moduladores de riesgo. Material y métodos : Se incluyeron individuos de 18 a 79 años, que asistieron para una evaluación de riesgo cardiovascular y que no estaban recibiendo tratamiento hipolipemiante. Se calculó el puntaje de riesgo (ASCVD Risk Estimator) en cada paciente. Se evaluó la presencia de PAC, el pCAC y el nivel plasmático de Lp(a). Resultados : Se incluyeron 348 pacientes (edad media 55,6 ± 12,2 años, 45,4% hombres). En la población total, 29,8%, 36,8% y 53,2% de los pacientes mostraron un valor de Lp(a) ≥ 50 mg/dL, PAC o un pCAC > 0, respectivamente. La prevalencia de PAC y pCAC fue progresivamente mayor según la categoría de riesgo cardiovascular; sin embargo, la proporción de sujetos de bajo riesgo que tenían moduladores de riesgo fue considerable (Lp(a) ≥ 50 mg/dl: 25,7%; PAC: 22%; pCAC > 0: 33%). En los 60 individuos menores de 45 años la prevalencia de pCAC > 0 y PAC fue de 18,3% y 10%, respectivamente. La concordancia entre los dos métodos para determinar la presencia de ateromatosis subclínica fue discreta (kappa 0,33). La indicación del tratamiento con estatinas aumentó un 31,6% luego de evaluar la presencia de moduladores. Conclusión : La presencia de moduladores de riesgo fue frecuente en esta población en prevención primaria, incluso en sujetos de bajo riesgo o menores de 45 años. La detección de moduladores de riesgo podría mejorar la estratificación inicial y llevar a reconsiderar el tratamiento con estatinas.

ABSTRACT Background : Cardiovascular risk scores have limitations related to calibration, discrimination, and low sensitivity. Different "risk modulators" have been identified to improve cardiovascular risk stratification: carotid atherosclerotic plaque (CAP), coronary artery calcium (CAC) score and lipoprotein(a) [Lp(a)]. Objectives : The aims of this study were: 1) to determine the prevalence of risk modulators mentioned in a primary prevention population; 2) determine the concordance between the 2 methods of detecting subclinical atherosclerosis; and 3) establish which proportion of patients should receive statins according to the initial risk stratification and after being recategorized by screening for risk modulators. Methods : Individuals aged 18 to 79 years who consulted for cardiovascular risk assessment and who were not receiving lipid-lowering treatment were included. The risk score was calculated in each patient using ASCVD Risk Estimator. The presence of CAP, CAC score and Lp(a) level were evaluated. Results : The cohort was made up of 348 patients; mean age was 55.6 ± 12.2 years and 45.4% were men. In the total population, 29.8%, 36.8%, and 53.2% of patients showed Lp(a) value ≥50 mg/dL, CAP, or a CAC score >0, respectively. The prevalence of CAP and CAC score was progressively higher according to the cardiovascular risk category; however, the proportion of low-risk subjects who had risk modulators was considerable (Lp(a) ≥50 mg/dl: 25.7%; CAP: 22%; CAC score >0: 33%). In the 60 subjects <45 years, the prevalence of CAC score >0 and CAP was 18.3% and 10%, respectively. The agreement between the two methods for quantifying subclinical atheromatosis was fair (kappa= 0.33). The indication for statin treatment increased by 31.6% after evaluating the presence of modulators. Conclusion : The presence of risk modulators was common in this population in primary prevention, even in low-risk subjects or < 45 years. Detection of risk modulators could improve initial stratification and lead to reconsideration of statin treatment.

The Relationship between Basal Serum Lipoprotein(a) Levels and the Pulmonary Artery to Ascending Aorta Ratio in COVID-19 Survivors

Abstract Background: Coronavirus disease (COVID-19) can cause permanent damage to vascular structures by directly or indirectly affecting the cardiopulmonary system. Lipoprotein(a) [Lp(a)] is an important identified risk factor for vascular endothelial cell dysfunction. Objective: The aim of this study was to reveal the relationship between Lp(a) levels measured at the time of COVID-19 diagnosis and the pulmonary artery (PA) to the ascending aorta (Ao) ratio (PA:Ao ratio) in survivors evaluated by transthoracic echocardiography (TTE). Methods: The study sample consisted of 100 patients who recovered from COVID-19 in the past 3 to 6 months. The relationship between the change in the PA:Ao ratio (ΔPA:Ao) and the Lp(a) levels measured at the time of diagnosis was evaluated. Diameter measurements at baseline and follow-up were evaluated with TTE. Results: A significant increase was found in PA, Ao, and epicardial adipose tissue (EAT) thickness in TTE (p< 0.001 for all). There was a weak correlation between D-dimer and high-sensitivity cardiac troponin measured at the time of diagnosis and ΔPA:Ao and ΔEAT in survivors. However, a positive and strong correlation was observed between Lp(a) levels and ΔPa:Ao (r = 0.628, p< 0.001) and ΔEAT (r = 0.633, p< 0.001). Conclusion: There may be dysfunction in vascular structures due to COVID-19. For the first time in the literature, a strong correlation was shown between the Lp(a) levels measured at the time of diagnosis and ΔPA:Ao and ΔEAT values in patients with COVID-19.

Analysis of lipoprotein(a) level and related factors in healthy Tajik and Kazak adults in Xinjiang / 中华检验医学杂志

Objective:To investigate the distribution and related factors of lipoprotein(a) [Lp(a)] level in healthy Tajik and Kazak adults in China.Methods:A cross-sectional study was conducted from May to October 2021 and March to June 2022, and blood samples were collected from 2, 637 healthy Tajik adults [1 010 men, average age: (40.08±14.74) years; 1 627 women, average age: (38.27±12.90) years] in Tashkurgan Tajik Autonomous County and 1 911 healthy Kazak adults [720 men, average age: (42.10±12.26) years; 1 191 women, average age: (38.27±12.90) years] in Fuyun County of Xinjiang. Fasting blood glucose (FBG), creatinine (Cr), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and Lp(a) were measured. The distribution of Lp(a) levels in different sex and age groups was compared. The Lp(a) level of Tajik and Kazakh ethnic groups was compared by Mann-Whitney U test, and correlation factors of Lp(a) level were analyzed by multiple logistic regression. Results:The distribution of Lp(a) level in Tajik and Kazak population was skewed. Lp(a) levels of Tajik and Kazak ranged from the lowest 0.40 mg/L and 0.62 mg/L to the highest 1 229.40 mg/L and 2 108.58 mg/L, respectively, and the median Lp(a) level was 78.90 (38.60, 190.20) mg/L and 103.30 (49.57, 234.27) mg/L, respectively. Median Lp(a) level of Kazak was significantly higher than that of Tjik ( P<0.001). The median Lp(a) levels of Tajik males and females were similar: 77.45 (39.80, 187.10) mg/L and 79.90 (38.60, 192.30) mg/L ( P=0.948). The median Lp(a) levels of Kazakh males and females were also similar: 109.42 (50.49, 230.38) mg/L and 99.01 (49.11, 237.25) mg/L, respectively ( P=0.578). After pooling the data of Tajik and Kazak and adjusting for age, sex, BMI, smoking, drinking, blood pressure, blood glucose and other factors, Lp(a) level was correlated with ethnic (standard partial regression coefficient 0.066, P=0.008) and LDL-C level (standard partial regression coefficient 0.136, P<0.001). Conclusions:Lp(a) level in healthy Tajik and Kazak adults varied greatly among individuals, and Kazak residents had a higher Lp(a) level than Tajik residents. There was no significant sex difference in Lp(a) level among Tajik and Kazakh, and LDL-C and ethnicity are independent factors related to Lp(a) level.

Niveles elevados de lipoproteína (a) y riesgo de eventos clínicos relacionados con la estenosis valvular aórtica: una revisión sistemática / High Lipoprotein(a) Levels and Risk of Aortic Valve Stenosis Related Clinical Events: A Systematic Review

RESUMEN Introducción: Varios estudios han evaluado la asociación entre los niveles plasmáticos de lipoproteína (a) [Lp(a)] y la aparición de eventos relacionados con la estenosis valvular aórtica, aunque los resultados fueron contradictorios. Objetivo: El objetivo de esta revisión fue analizar la capacidad predictiva de los niveles elevados de Lp(a) sobre los eventos clínicos relacionados con la estenosis valvular aórtica. Material y métodos: Esta revisión sistemática se realizó de acuerdo con las recomendaciones PRISMA y STROBE. Se realizó una búsqueda en diferentes bases de datos con el objetivo de identificar estudios de cohorte que evaluaran la asociación entre los niveles de Lp(a) y los eventos de interés. El punto final primario fue la incidencia de eventos clínicos relacionados con la estenosis aórtica (reemplazo valvular aórtico, muerte u hospitalización). Esta revisión fue registrada en PROSPERO. Resultados: Se consideraron elegibles para el análisis siete estudios observacionales con un total de 58 783 pacientes. Los valores elevados de Lp(a) se asociaron con un mayor riesgo de eventos relacionados con la estenosis valvular aórtica en la mayoría de los estudios evaluados (entre un 70% y aproximadamente 3 veces más riesgo), a pesar de ajustar por otros factores de riesgo. Conclusión: Esta revisión sugiere que los niveles elevados de Lp(a) se asocian con una mayor incidencia de eventos clínicos relacionados con la estenosis valvular aórtica. Sin embargo, y considerando las limitaciones de este estudio, la utilidad clínica de la Lp(a) como marcador pronóstico en la enfermedad valvular aórtica deberá confirmarse en futuras investigaciones.

ABSTRACT Background: Several studies have evaluated the association between lipoprotein(a) plasma levels [Lp(a)] and the occurrence of aortic valve stenosis related events, with contradictory results. Objective: The main objective of this systematic review was to analyze the predictive capacity of elevated Lp(a) levels on major clinical events associated with aortic valve stenosis. Methods: This systematic review was conducted in accordance with PRISMA and STROBE recommendations. A search was carried out in order to identify studies with a cohort design evaluating the association between Lp(a) levels and the events of interest. The primary endpoint was the incidence of clinical events related with aortic valve stenosis (aortic valve replacement, death or hospitalization). This review was registered in PROSPERO. Results: Seven observational studies with a total of 58 783 patients were eligible for analysis. Our findings showed that the presence of elevated Lp(a) levels was associated with an increased risk of events related with aortic valve stenosis in most of the studies evaluated (between 70% and approximately 3-fold higher risk), despite adjusting for other risk factors. Conclusion: This review suggests that elevated Lp(a) levels are associated with a higher incidence of aortic valve stenosis related clinical events. However, considering the limitations of this study, the clinical usefulness of Lp(a) as a prognostic marker in aortic valve disease should be confirmed in future investigations.

Infarto agudo de miocardio en paciente con bajo riesgo cardiovascular y lipoproteína (a) elevada. Reporte de caso / Acute myocardial infarction in a patient with low cardiovascular risk and elevated lipoprotein (a). Case report

RESUMEN La lipoproteína (a) (Lp (a)) es un complejo proteico lipídico plasmático, que representa un factor de riesgo de enfermedad cardiovascular (ECV). Sin embargo, no se incluye la medición de Lp (a) en el perfil lipídico convencional y tampoco existen terapias específicas aprobadas para reducir sustancialmente las concentraciones de Lp (a). Se reporta el caso de un varón de 49 años con una estimación de bajo riesgo cardiovascular quien desarrolló infarto agudo de miocardio (IAM) con elevación de ST probablemente debido a elevación de Lp (a). Se presenta el caso para destacar la importancia de la detección y análisis de la Lp (a) en la evaluación del riesgo cardiovascular. Además, se describen terapias actuales y emergentes en pacientes con Lp (a) elevada.

SUMMARY Lipoprotein(a) (Lp (a)) is a plasmatic lipid protein complex, which represents a risk factor for atherosclerotic cardiovascular disease (ASCVD). However, conventional lipid assays are unable to measure or estimate Lp (a) and there are no specific therapies approved to substantially reduce Lp (a) concentrations. We report the case of a 49-year-old man with low cardiovascular risk who developed an acute myocardial infarction with ST elevation probably due to elevation of Lp (a) is reported. The purpose of this case report is to highlight the detection and analysis of Lp (a) in the assessment of cardiovascular risk. In addition, current and emerging therapies are described in patients with elevated Lp (a).

Síndrome metabólico, lipoproteína(a) y aterosclerosis subclínica en población mexicana / Metabolic syndrome, lipoprotein(a) and subclinical atherosclerosis in Mexican population

Resumen Objetivo: Investigar la asociación del síndrome metabólico y la lipoproteína(a) [Lp(a)] con el riesgo de aterosclerosis subclínica en adultos mexicanos. Método: En 953 mujeres y hombres se evaluaron datos clínicos, bioquímicos y tomográficos de grasa abdominal visceral, subcutánea, hepática y calcio arterial coronario. La Lp(a) se determinó mediante nefelometría y el síndrome metabólico se diagnosticó con los criterios del Adult Treatment Panel III. La asociación independiente de estas variables con el calcio arterial coronario se obtuvo con análisis de regresión logística multivariada. Resultados: La edad, el peso, el índice de masa corporal, la presión arterial sistólica y diastólica, los volúmenes de grasa abdominal, los lípidos, la glucosa, la insulina y el índice de resistencia a insulina fueron significativamente mayores en los sujetos con síndrome metabólico, mientras que la mediana de Lp(a) fue más baja en comparación con los sujetos sin el síndrome (3.7 [rango intercuartílico (RIC): 2.3-9.2 vs. 5.9 [RIC: 2.5-13.1) mg/dl; p < 0.01). El número de componentes y el síndrome metabólico se asociaron inversamente con la Lp(a) elevada (> 30 mg/dl). La presencia de síndrome metabólico se asoció con un riesgo de calcio arterial coronario > 0 (odds ratio [OR]: 2.19; intervalo de confianza del 95% [IC95%]: 1.64-2.94; p < 0.001), independientemente de la Lp(a) elevada. La glucemia > 100 mg/dl (OR: 2.42; IC95%: 1.7-3.4; p < 0.0001) y la presión arterial elevada (OR: 2.14; IC95%: 1.5-3.1; p > 0.0001) se asociaron con calcio arterial coronario > 0. Conclusiones: En población mexicana existe una asociación inversa entre la concentración de Lp(a) y el síndrome metabólico. Este y sus componentes se asociaron positivamente con aterosclerosis subclínica. La elevada prevalencia de obesidad, diabetes, hipertensión arterial, triglicéridos elevados y concentración de colesterol unido a lipoproteínas de alta densidad que caracterizan a la población mexicana pudieran explicar las diferencias con otras poblaciones.

Abstract Objective: To assess the relationship of metabolic syndrome (MetS) and Lp(a) with subclinical atherosclerosis (CAC) in Mexican adults. Method: Clinical, biochemical and tomographic data of visceral, subcutaneous, hepatic abdominal fat and CAC were evaluated in 953 women and men. Lp(a) was determined by nephelometry and MetS was diagnosed according to ATP III criteria. Multivariate logistic regression analysis was performed to determine the independent association of these variables with CAC. Results: Age, weight, body mass index, systolic and diastolic blood pressure, volumes of visceral, subcutaneous and hepatic abdominal fat, lipids, glucose, insulin and HOMA-RI were significantly higher in subjects with MetS. The median Lp(a) was lower in subjects with MetS compared to subjects without MetS (3.7 [IR: 2.3-9.2 vs. 5.9 [IR: 2.5-13.1) mg/dL; p < 0.01). The number of components and the MetS were inversely associated with the elevated Lp(a) (> 30 mg / dL). The presence of MetS was associated with a CAC risk >0 (OR: 2.19, [95% CI (1.64-2.94)]; p < 0.001), independently of elevated Lp(a). The components of MetS that were independently associated with the presence of CAC > 0 UA were glycaemia > 100 mg/dL (OR 2.42, [95% CI (1.7-3.4)]; p < 0.0001) and high blood pressure (OR 2.14 [95% CI (1.5-3.1)]; p < 0.0001). Conclusions: In Mexican population there is an inverse association between Lp(a) levels and MetS. The MetS and its components were associated with subclinical atherosclerosis. The high prevalence of obesity, diabetes, high blood pressure high triglycerides and low HDL-C, characteristics of Mexican population could explain the differences with other populations.

Comparison of the difference between serum lipoprotein(a) particle concentration and mass concentration in patients with chronic kidney disease / 中华检验医学杂志

Objective:To compare the difference between serum lipoprotein(a) [Lp(a)] particle concentration and mass concentration in chronic kidney disease (CKD) patients and healthy controls, and to analyze the concentration distribution of the deviations between the two measurement methods.Methods:Serum Lp(a) particle concentration and mass concentration were respectively detected in 196 patients with CKD and 97 healthy controls from Eastern Theater General Hospital during June 2018 to December 2019. The upper limit of reference value for Lp(a) particle concentration was set as 75 nmol/L and the upper limit of reference value for mass concentration was set as 300 mg/L, the difference on the positive rates of Lp(a) particle concentration and mass concentration in each group were compared. According to the quartile of Lp(a) concentration in patients with CKD, the patients were divided into 4 groups, and the results derived from the two methods were compared among groups.Results:Serum Lp(a) particle concentration (25.7 [10.5, 75.4] nmol/L vs 19.2[8.1-50.2] nmol/L, P=0.021) and mass concentration (157[64, 432] mg/L vs 127[50-274] mg/L, P=0.023) were significantly higher in patients with CKD than those in healthy controls. The positive rate of Lp(a) particle concentration was significantly lower than that of mass concentration (25.0%[48/196] vs 37.2%[73/196], P=0.009) in CKD patients. The positive rate of Lp(a) particle concentration and mass concentration was similar in healthy controls (18.6%[18/97] vs 22.7%[22/97], P=0.478). The overestimation rate of Lp(a) mass concentration in CKD patients was significantly higher than that in healthy controls (12.8%[25/196] vs 4.1%[4/97], P=0.020). Lp(a) mass concentration of group Ⅲ in CKD patients was between 157.00-432.25 mg/L, the positive rate of Lp(a) particle concentration was significantly lower than that of mass concentration (4.1%[2/49] vs 49%[24/49], P<0.001), and the overestimation rate (44.9%[22/49]) of Lp(a) mass concentration in this group was also the highest (all P<0.001). According to the conversion factor provided by the reagent manual of Lp(a) particle concentration, the test results were converted into mass concentration. The actual mass concentration of Lp(a) in CKD patients grouped by quartile was significantly higher than that after Lp(a) particle concentration conversion (all P<0.05). Conclusions:The positive rate of serum Lp(a) particle concentration is significantly lower than that of mass concentration in CKD patients and the obvious overestimation deviation of Lp(a) mass concentration is observed in this analysis.

Correlation between fibrinogen and lipoprotein (a) and early neurological deterioration in acute ischemic stroke patients with diabetes / 国际脑血管病杂志

Objective:To investigate the correlation between fibrinogen and lipoprotein (a) and early neurological deterioration (END) in acute ischemic stroke patients with diabetes.Methods:From January 2017 to December 2020, patients with acute ischemic stroke admitted to the Department of Neurology, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University within 48 h of onset were enrolled retrospectively. END was defined as the National Institutes of Health Stroke Scale (NIHSS) score within 7 d after onset increased by ≥2 or motor function score increased by ≥1 compared with the baseline. Demographic and baseline clinical data were collected. Multivariate logistic regression analysis was used to identify the independent risk factors for END in general and diabetic patients with acute ischemic stroke. Results:A total of 1 504 patients with acute ischemic stroke were enrolled. Two hundred and fifty-two (16.76%) patients had END. The age, baseline NIHSS score, random blood glucose, fibrinogen, lipoprotein (a) levels, and the proportion of patients with diabetes in the END group were higher than those in the non-END group. There were also significant differences in various stroke etiologic subtypes between the END group and the non-END group (all P<0.05). Multivariate logistic regression analysis showed that fibrinogen and lipoprotein (a) levels were not the independent risk factors for END in patients with acute ischemic stroke. Three hundred and thirty-seven patients also had diabetes mellitus, of which 85 had END (25.22%). The levels of fibrinogen and lipoprotein (a) in the END group were significantly higher than those in the non-END group ( P<0.05). Multivariate logistic regression analysis showed that fibrinogen (odds ratio 2.23, 95% confidence interval 1.75-4.54; P=0.002) and lipoprotein (a) (odds ratio 1.98, 95% confidence interval 1.57-3.65; P=0.003) were the independent risk factors for END in acute ischemic stroke patients with diabetes. Conclusion:Higher fibrinogen and lipoprotein (a) levels are associated with END in acute ischemic stroke patients with diabetes.

Dietary and Blood Lipids in Cardiovascular Disease

Blood lipids are essential for life; at the same time, elevated or reduced levels of some of the components of lipid are related to risk of atherosclerotic cardiovascular disease (ASCVD).This article provides a review on dietary and blood lipids with their impact on cardiovascular health. The role of apolipoprotein B (ApoB), Lipoprotein(a) ((Lp(a))and other lipoprotein particles in the development of ASCVD has been reviewed. There are newevidences that ApoB the structural protein of most of the lipoprotein particles (carrier of blood lipids), in addition to low density lipoprotein-cholesterol (LDL-C), plays a central role in the pathogenesis of atherosclerosis with increased risk for ASCVD. Elevated levels of Lp(a) concentrations are associated with an increased risk of ASCVD, but it appears to be a weaker risk factor than ApoB or LDL-C

Is macular lymphocytic arteritis limited to the skin? Long-term follow-up of seven patients

Abstract Background: Macular lymphocytic arteritis most commonly presents as hyperpigmented macules on the lower limbs. The pathogenesis of this disease is still unclear and there is an ongoing debate regarding whether it represents a new form of cutaneous vasculitis or an indolent form of cutaneous polyarteritis nodosa. Objective: To describe clinical, histopathological, and laboratory findings of patients with the diagnosis of macular lymphocytic arteritis. Methods: A retrospective search was conducted by reviewing cases followed at the Vasculitis Clinic of the Dermatology Department, School of Medicine, University of São Paulo, between 2005 and 2017. Seven patients were included. Results: All cases were female, aged 9-46 years, and had hyperpigmented macules mainly on the legs. Three patients reported symptoms. Skin biopsies evidencing a predominantly lymphocytic infiltrate affecting arterioles at the dermal subcutaneous junction were found, as well as a typical luminal fibrin ring. None of the patients developed necrotic ulcers, neurological damage, or systemic manifestations. The follow-up ranged from 18 to 151 months, with a mean duration of 79 months. Study limitations: This study is subject to a number of limitations: small sample of patients, besides having a retrospective and uncontrolled study design. Conclusions: To the best of the authors' knowledge, this series presents the longest duration of follow-up reported to date. During this period, none of the patients showed resolution of the lesions despite treatment, nor did any progress to systemic vasculitis. Similarities between clinical and skin biopsy findings support the hypothesis that macular lymphocytic arteritis is a benign, incomplete, and less aggressive form of cutaneous polyarteritis nodosa.

Armonizacion del estudio de lipidos en el laboratorio clinico / Harmonization of the study of lipids in the clinical laboratory

Los profesionales que ejercen la bioquimica clinica son conscientes de la falta de resultados comparables entre laboratorios, independientemente de donde y cuando se realicen. Durante muchos anos el centro de la gestion de la calidad estuvo en la estandarizacion de los procedimientos de medida, la armonizacion va mas alla del metodo y los resultados analiticos e incluye todos los aspectos que hay que tener en cuenta durante el proceso total de la prueba. Los laboratorios de bioquimica clinica han logrado en las ultimas decadas importantes mejoras en la calidad de los procesos analiticos, pero es necesario un esfuerzo mayor dedicado a la vulnerabilidad de los procedimientos extra analiticos para asegurar la comparacion y la concordancia de los resultados obtenidos por diferentes laboratorios clinicos. Las iniciativas destinadas a mejorar la armonizacion de los resultados de laboratorio tienen una dimension etica y de gran importancia en el diagnostico de las dislipemias asociadas al desarrollo de aterosclerosis y la evaluacion del riesgo cardiovascular. Los estudios poblacionales aun muestran dificultades en la identificacion del mejor biomarcador que pueda evidenciar adecuadamente el riesgo cardiovascular en un individuo. La correlacion, discordancia y concordancia muestran que es necesario el diseno de un perfil de pruebas de laboratorio personalizado, con marcadores estandarizados y armonizados, que permita la prediccion del riesgo.

The health professionals who practice clinical biochemistry are aware of the lack of comparable results between laboratories, regardless of where and when they are performed. For many years, the objective of the quality management was the standardization of measurement procedures. The harmonization is beyond the methods and the analytical results, and it includes all the aspects to be taken into account during the whole process of the test. The clinical biochemistry laboratories have achieved important improvements in the quality of the analytical processes in the last decades, but greater effort is necessary for the vulnerability of the extra analytical procedures to ensure the comparison and the agreement of the results obtained by different clinical laboratories. The initiatives aimed to improve the harmonization of laboratory results have an ethical dimension and importance in the diagnosis of dyslipidemia associated with the development of atherosclerosis and the assessment of cardiovascular risk. The population studies still show difficulties in the identification of the best biomarker that can adequately show the cardiovascular risk in an individual. The correlation, discordance and concordance between biomarkers show that it is necessary to design a personalized laboratory test profile, and with standardized and harmonized markers that allow the prediction of risk.

Os profissionais que exercem a bioquímica clínica Clinical estão cientes da falta de resultados comparáveis entre laboratórios, independentemente de onde e quando forem realizados. Por muitos anos, o centro de gestão da qualidade esteve na padronização dos procedimentos de medição, a harmonização vai além do método analítico e dos resultados analíticos e inclui todos os aspectos a considerar durante o processo do teste. Laboratórios bioquímica clínica têm alcançado, nas últimas décadas grandes melhorias na qualidade dos processos analíticos, mas precisa de um esforço maior dedicado à vulnerabilidade dos procedimentos extra-analíticos, para garantir a comparação e concordancia dos resultados obtidos pelos diferentes laboratórios clínicos. Iniciativas para melhorar a harmonização dos resultados laboratoriais têm uma dimensão ética e de grande importȃncia no diagnóstico de dislipidemias associadas ao desenvolvimento de aterosclerose e à avaliação do risco cardiovascular. As pesquisas populacionais mostram ainda dificuldades em identificar o melhor biomarcador que possa demonstrar em forma adecuada o risco cardiovascular em um individuo, a correlação, discordância e concordância mostram que é necessário o desenho de um perfil de testes personalizado, com marcadores padronizados e harmonizada, que permite a previsão de risco.

¿Qué debe saber el cardiólogo clínico sobre la lipoproteína (a)? / What the clinical cardiologist should know about lipoprotein (a)? / O que o cardiologista clínico deve saber sobre a lipoproteína (a)?

Resumen: La lipoproteína (a) (Lp(a)) elevada es un factor de riesgo vascular no tradicional, independiente, de enfermedad cardiovascular y estenosis valvular aórtica calcificada. Se trata de una de las principales dislipemias hereditarias en pacientes con enfermedad coronaria precoz. Su estructura es similar al colesterol LDL, siendo la principal diferencia estructural entre ambas que la Lp(a) tiene una segunda proteína llamada apolipoproteína (a). Se analizan en el presente trabajo las propiedades protrombóticas y proaterogénicas de la Lp(a) que por distintos mecanismos fisiopatológicos tienen influencia directa en el desarrollo, progresión y evolución de las enfermedades cardiovasculares. Se reseñan las principales evidencias científicas surgidas de estudios poblacionales y genéticos sobre la Lp(a) que demuestran su papel como factor causal del desarrollo de enfermedad cardiovascular. Se consideran, por otra parte, recomendaciones prácticas para el manejo de la Lp(a) en el consultorio, con especial énfasis en la selección de los grupos de pacientes que se benefician de su determinación y en las razones por las cuales la identificación de Lp(a) elevada implica un cambio en el manejo de la prevención primaria o secundaria de estos pacientes. Finalmente se abordan las medidas terapéuticas disponibles y en investigación. Se jerarquiza el concepto de disminución del riesgo cardiovascular global y el rol de la Lp(a) elevada en la reclasificación de éste y en la intensificación de las medidas preventivas en cada nivel de riesgo vascular.

Summary: Elevated lipoprotein (a) (Lp(a)) is a non-traditional, independent vascular risk factor for cardiovascular disease and calcified aortic valve stenosis. It is one of the main inherited dyslipidemia in patients with early coronary heart disease. Its structure is similar to LDL cholesterol, with the main structural difference between them being that Lp(a) has a second protein called apolipoprotein (a). In this work, we analyze the prothrombotic and proatherogenic properties of Lp(a), which by different pathophysiological mechanisms have a direct influence on the development, progression and evolution of cardiovascular diseases. We review the main scientific evidence emerged from population and genetic studies on Lp(a) that demonstrate its role as a causal factor in the development of cardiovascular disease. Practical recommendations for the management of Lp(a) are considered, with special emphasis made on patient groups that benefit from its determination and on the reasons why the identification of high Lp(a) implies a change in the management of primary or secondary prevention of these patients. Finally, we address the available therapeutic measures and those currently under review. We highlight the concept of reducing global cardiovascular risk and the role of elevated Lp(a) in its reclassification, and in the intensification of preventive measures at each level of vascular risk.

Resumo: A lipoproteína (a) ( Lp(a)) elevada é um fator de risco vascular independente e não tradicional para doença cardiovascular e estenose valvar aórtica calcificada. É uma das principais dislipidemias hereditárias em pacientes com doença coronariana precoce. Sua estrutura é semelhante ao colesterol LDL, a principal diferença estrutural entre os dois é que Lp(a) tem uma segunda proteína chamada apolipoproteína (a). No presente trabalho, são analisadas as propriedades protrombóticas e proatrogênicas de Lp(a), as quais, por diferentes mecanismos fisiopatológicos, têm influência direta no desenvolvimento, progressão e evolução das doenças cardiovasculares. As principais evidências científicas surgiram de estudos populacionais e genéticos sobre Lp(a) que demonstram seu papel como fator causal no desenvolvimento de doenças cardiovasculares. Por outro lado, são consideradas recomendações práticas para o manejo da Lp(a) no consultório, com ênfase especial na seleção de grupos de pacientes que se beneficiam de sua determinação e nas razões pelas quais a identificação de Lp(a) ) alta implica uma mudança no manejo da prevenção primária ou secundária desses pacientes. Finalmente, as medidas terapêuticas disponíveis e aquelas sob investigação. O conceito de reduzir o risco cardiovascular global e o papel da Lp (a) elevada na reclassificação da mesma e na intensificação de medidas preventivas em cada nível de risco vascular são classificados.

Lipoprotein(a): An underrecognized genetic risk factor for malignant coronary artery disease in young Indians

Malignant coronary artery disease (CAD) refers to a severe and extensive atherosclerotic process involving multiple coronary arteries in young individuals (aged <45 years in men and <50 years in women) with a low or no burden of established risk factors. Indians, in general, develop acute myocardial infarction (AMI) about 10 years earlier; AMI rates are threefold to fivefold higher in young Indians than in other populations. Although established CAD risk factors have a predictive value, they do not fully account for the excessive burden of CAD in young Indians. Lipoprotein(a) (Lp(a)) is increasingly recognized as the strongest known genetic risk factor for premature CAD, with high levels observed in Indians with malignant CAD. High Lp(a) levels confer a twofold to threefold risk of CAD—a risk similar to that of established risk factors, including diabetes. South Asians have the second highest Lp(a) levels and the highest risk of AMI from the elevated levels, more than double the risk observed in people of European descent. Approximately 25% of Indians and other South Asians have elevated Lp(a) levels (≥50 mg/dl), rendering Lp(a) a risk factor of great importance, similar to or surpassing diabetes. Lp(a) measurement is ready for clinical use and should be an essential part of all CAD research in Indians.

Lipoprotein(a): An independent, genetic, and causal factor for cardiovascular disease and acute myocardial infarction

Lipoprotein(a) [Lp(a)] is a circulating lipoprotein, and its level is largely determined by variation in the Lp(a) gene (LPA) locus encoding apo(a). Genetic variation in the LPA gene that increases Lp(a) level also increases coronary artery disease (CAD) risk, suggesting that Lp(a) is a causal factor for CAD risk. Lp(a) is the preferential lipoprotein carrier for oxidized phospholipids (OxPL), a proatherogenic and proinflammatory biomarker. Lp(a) adversely affects endothelial function, inflammation, oxidative stress, fibrinolysis, and plaque stability, leading to accelerated atherothrombosis and premature CAD. The INTER-HEART Study has established the usefulness of Lp(a) in assessing the risk of acute myocardial infarction in ethnically diverse populations with South Asians having the highest risk and population attributable risk. The 2018 Cholesterol Clinical Practice Guideline have recognized elevated Lp(a) as an atherosclerotic cardiovascular disease risk enhancer for initiating or intensifying statin therapy.

Focus on residual cardiovascular disease risk, re-recognizing non-traditional risk factors / 中华检验医学杂志

The residual cardiovascular disease (CVD) risk is the term applied to the cardiovascular events remain prevalent among individuals with low or normal LDL-C, normal blood pressure and glucose. Therefore, while controlling traditional risk factors, the CVD residual risk is constantly being discovered, which is crucial for further reducing CVD events. Lipoprotein (a), TRLs and their residues, HDL-C, hypersensitive CRP and homocysteine have been found to be CVD residual risk factors. Whether gene-related factors and some new non-traditional factors can predict residual CVD risk have also become the current research hotspots. Focusing on the residual risk factors of cardiovascular disease can provide new ideas for further reducing CVD events.

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.

Role of lipoprotein (a) in ischemic stroke / 中国脑血管病杂志

Lipoprotein (a) (Lp [a]) is an low density lipoprotein-like particle with constant individual concentration through life determined mainly by LPA gene variations and racial difference. Previous studies had proved the causal relationship between Lp (a) and cardiovascular disease due to potential pathogenic mechanisms including proatherogenic and prothrombotic effect. Lp (a) had been reported to be associated with ischemic stroke by many studies, especially among young people, but the conclusions remain controversial. Traditional lipid-lowering therapies, such as statins or fibrates do not effectively reduce Lp (a) levels. Possible treatment options consist of proprotein convertase subtilisin/kexin type 9 inhibitors,cholesteryl ester transfer protein,antisense oligonucleotide and apheresis.but their clinical benefits need to be confirmed by further trials. In this review,aspects of Lp (a) including the structure properties,correlation with ischemic stroke,probable pathophysiological mechanisms and recent advances in lowering Lp (a) are summarized.

Effect of Lp(a) on in-stent restenosis and non-target coronary lesions in CAD patients with drug-eluting stents / 解放军医学杂志

Objective To explore the effect of lipoprotein(a) [Lp(a)] on in-stent restenosis and non-target coronary lesions in coronary artery disease (CAD) patients implanted with drug-eluting stents. Methods One hundred and seventy-four patients, diagnosed as CAD and underwent percutaneous coronary intervention (PCI) with the implantation of drug-eluting stents (DES), were enrolled in present study; all of them were performed another elective PCI or revascularization within 1-4 years after their previous procedures. Thirty-one of enrolled patients were discovered to have in-stent restenosis. The relationship between Lp(a) and in-stent restenosis and the development of non-target coronary lesions were analyzed in groups stratified by the presence of in-stent stenosis or Lp(a) levels, and the independent risk factors of both in-stent restenosis and non-target lesions were also analyzed by multivariate logistic regression analysis. Results In CAD patients with DES, Lp(a) level in patients with in-stent restenosis showed a significant increase than those with the Lp(a) level non-restenosis [(437.57±391.60) mg vs. (279.46±288.06) mg, P=0.04]. In following analysis comparing lipid profiles and coronary angiography results between low and high Lp(a) groups, the percentage of triple-vessel disease and left main plus triple-vessel disease appeared to be statistically higher in high Lp(a) group than those in low Lp(a) group (P=0.022). Multivariate logistic regression analysis revealed that high level of Lp(a) and much number of stents implanted were the independent risk factors for in-stent restenosis of DES. In comparing the characteristics of coronary angiography and results of quantitative coronary angiography, number of cases with non-target lesions, presence of in-stent restenosis, minimal lumen diameter and in-stent late lumen loss were all significantly higher in high Lp(a) group than those in low Lp(a) group (P<0.05), and high level of Lp(a) was again proved to be an independent risk factor for non-target lesions in patients with DES (P=0.001). Conclusion Elevated Lp(a) level is an independent risk factor for both in-stent restenosis and the development of non-target coronary lesions, and is closely related to the relapse and aggravation of coronary artery disease.

PCSK9 monoclonal antibody reduces serum level of lipoprotein(a): Recent study advances / 中华老年医学杂志

Lipoprotein(a)[Lp(a)]is the independent risk factors for arteriosclerotic cardiovascular disease(ASCVD). Lp(a)combined with traditional risk factors can increase accurate prediction of the risk for ASCVD.The serum Lp(a)level is correlated with multiple-vessel disease, coronary artery plaque load, vulnerable plaque and in-stent restenosis.Lp(a)is related with coronary artery calcification, calcified aortic stenosis and heart failure.Therefore, Lp(a)level is an independent risk factor for cardiovascular events in ASCVD patients.The proprotein convertase subtilisin/kexin type 9(PCSK9)monoclonal antibody can decrease the levels of low-density lipoprotein cholesterol and Lp(a), and further reduce the residual risk of major adverse cardiovascular events in ASCAD patients on the basis of statin therapy.