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.

Comparação das Novas Equações de Martin/Hopkins e Sampson para o Cálculo do Colesterol de Lipoproteína de Baixa Densidade em Pacientes Diabéticos / Comparison of Novel Martin/Hopkins and Sampson Equations for Calculation of Low-Density Lipoprotein Cholesterol in Diabetic Patients

Resumo Fundamentos A determinação precisa do colesterol de lipoproteína de baixa densidade (LDL-C) é importante para se alcançar concentrações de LDL-C recomendadas por diretrizes e para reduzir resultados cardiovasculares adversos em pacientes diabéticos. A equação de Friedewald comumente usada (LDL-Cf) produz resultados imprecisos em pacientes diabéticos devido a dislipidemia diabética associada. Recentemente, duas novas equações - Martin/Hopkins (LDL-CMH) e Sampson (LDL-Cs) - foram desenvolvidas para melhorar a precisão da estimativa de LDL-C, mas os dados são insuficientes para sugerir a superioridade de uma equação sobre a outra. Objetivos O presente estudo comparou a precisão e a utilidade clínica das novas equações de Martin/Hopkins e Sampson em pacientes diabéticos. Método Foram incluídos no estudo quatrocentos e dois (402) pacientes com diabetes. O risco cardiovascular dos pacientes e as metas de LDL-C foram calculadas por diretrizes europeias. As concentrações de LDL-Cmh, LDL-Cs, e LDL-Cf calculadas foram comparadas à concentração de LDL-C direto (LDL-Cd) para testar a concordância entre essas equações e LDL-Cd. Um P valor <0,05 foi aceito como estatisticamente significativo. Resultados A LDL-CMH e a LDL-Cs tiveram concordância melhor com o LDL-Cd em comparação com a LDL-Cf, mas não houve diferenças estatísticas entre as novas equações para concordância com o LDL-Cd (Alfa de Cronbach de 0,955 para ambos, p=1). Da mesma forma, a LDL-CMH e a LDL-Cs tinham um grau semelhante de concordância com o LDL-Cd para determinar se o paciente estava dentro da meta de LDL-C (96,3% para LDL-Cmh e 96,0% para LDL-Cs), que eram ligeiramente melhores que a LDL-Cf (94,6%). Em pacientes com uma concentração de triglicérides >400 mg/dl, a concordância com o LDL-Cd foi ruim, independentemente do método usado. Conclusão As equações de Martin/Hopkins e Sampson mostram uma precisão similar para o cálculo de concentrações de LDL-C nos pacientes com diabetes, e ambas as equações são ligeiramente melhores que a equação de Friedewald.

Abstract Background The accurate determination of low-density lipoprotein cholesterol (LDL-C) is important to reach guideline-recommended LDL-C concentrations and to reduce adverse cardiovascular outcomes in diabetic patients. The commonly used Friedewald equation (LDL-Cf), gives inaccurate results in diabetic patients due to accompanying diabetic dyslipidemia. Recently two new equations - Martin/Hopkins (LDL-Cmh) and Sampson (LDL-Cs) - were developed to improve the accuracy of LDL-C estimation, but data are insufficient to suggest the superiority of one equation over the other one. Objective The present study compared the accuracy and clinical usefulness of novel Martin/Hopkins and Sampson equations in diabetic patients. Methods This study included 402 patients with diabetes. Patients' cardiovascular risk and LDL-C targets were calculated per European guidelines. Calculated LDL-Cmh, LDL-Cs, and LDL-Cf concentrations were compared with direct LDL-C concentration (LDL-Cd) to test agreement between these equations and LDL-Cd. A p-value <0.05 was accepted as statistically significant. Results Both LDL-Cmh and LDL-Cs had a better agreement with LDL-Cd as compared to LDL-Cf, but no statistical differences were found among novel equations for agreement with LDL-Cd (Cronbach's alpha 0.955 for both, p=1). Likewise, LDL-Cmh and LDL-Cs showed a similar degree of agreement with LDL-Cd in determining whether a patient was in a guideline-recommended LDL-C target (96.3% for LDL-Cmh and 96.0% for LDL-Cs), which were marginally better than LDL-Cf (94.6%). In patients with a triglyceride concentration >400 mg/dl, agreement with LDL-Cd was poor, regardless of the method used. Conclusion Martin/Hopkins and Sampson's equations show a similar accuracy for calculating LDL-C concentrations in patients with diabetes, and both equations were marginally better than the Friedewald equation.

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).

Efecto de la inhibición de la proteína símil angiopoyetina tipo 3 (ANGPTL3): utilidad para el tratamiento de las dislipemias graves / Angiopoietin-like type 3 (angptl) inhibition: its role in the treatment of severe dyslipidemia

Las variantes de ANGPTL3 con pérdida de función están asociadas con efectos beneficiosos sobre el metabolismo lipídico y de carbohidratos y con riesgo reducido de enfermedad coronaria. Los cambios beneficiosos en los parámetros lipídicos que se obtienen con la inhibición de ANGPTL3 junto con la reducción en aterosclerosis que se observa en modelos animales y en estudios epidemiológicos de genética humana hacen de ANGPTL3 un nuevo objetivo terapéutico para prevenir las enfermedades cardiovasculares. Dos estrategias novedosas han surgido para inhibir esta proteína: un anticuerpo monoclonal y un oligonucleótido antisentido, con capacidad para reducir tanto el colesterol como los triglicéridos plasmáticos en forma notoria. Aunque el horizonte es promisorio, todavía no sabemos si los efectos de una variante presente desde el comienzo de la vida serán reproducidos por la inhibición de esta proteína que se realiza más tarde en la vida a través de una intervención farmacológica. (AU)

Loss-of-function ANGPTL3 variants are associated with beneficial effects on carbohydrate and lipid metabolism, and reduced risk of coronary heart disease. The beneficial changes in lipid parameters obtained by ANGPTL3 inhibition together with atheroprotection observed in animal models and in epi-demiological studies of human genetics make ANGPTL3 a new therapeutic target to prevent cardiovascular diseases. Two novel strategies have emerged to inhibit this protein: a monoclonal antibody and an antisense oligonucleotide, with the ability to significantly lower plasma cholesterol and triglycerides. Although the horizon is promising, we still do not know if the effects of a variant present from the beginning of life will be reproduced by the inhibition of this protein that takes place later in life through a pharmacological intervention. (AU)

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.

Hipertrigliceridemia grave y síndrome de quilomicronemia familiar: una revisión de la literatura reciente / Severe hypertriglyceridemia and familial chylomicronemia syndrome: a review of recent literature

Resumen La hipertrigliceridemia (HTG) es un problema que se presenta con frecuencia en la práctica clínica. Su prevalencia en adultos es cercana al 10%. El espectro varía desde una predisposición que resulta en HTG solo en presencia de sobrepeso considerable o consumo excesivo de alcohol hasta mutaciones graves muy raras que pueden conducir a HTG grave en la infancia, incluso en ausencia de factores adicionales, como en el síndrome de quilomicronemia familiar (FCS, familial chylomicronemia syndrome). Este es un trastorno autosómico recesivo poco frecuente del metabolismo del quilomicrón que causa una importante elevación de los triglicéridos (>10 mmol/885 mg/dl). Esta condición está asociada con un riesgo significativo de pancreatitis aguda recurrente. La aproximación diagnóstica se logra mediante la caracterización fenotípica, y el hallazgo de la alteración genética ayuda a dar un diagnóstico más preciso. Además, se ha propuesto una puntuación clínica para el diagnóstico de FCS, pero necesita más validación. Las opciones de tratamiento disponibles para reducir los triglicéridos, como los fibratos y los ácidos grasos omega-3, no son eficaces en los pacientes con FCS. Actualmente, el único tratamiento sigue siendo una dieta de por vida muy baja en grasas, que reduce la formación de quilomicrones. Finalmente, los inhibidores de la apolipoproteína C-III están en desarrollo y podrían constituir opciones de tratamiento para estos pacientes. Considerando lo anterior, el objetivo de este artículo es realizar una revisión general sobre la HTG grave, con énfasis en el FCS, basados en la literatura disponible más reciente.

Abstract Hypertriglyceridemia (HTG) is a problem that occurs frequently in clinical practice. Its prevalence in adults is close to 10% and it varies between regions. The spectrum ranges from a disposition that results in HTG only in the presence of considerable overweight and/or excessive alcohol consumption to very rare serious mutations that can lead to severe HTG in childhood, even in the absence of additional factors such as familial chylomicronemia syndrome (FCS). This is a rare autosomal recessive disorder of chylomicron metabolism that causes a severe elevation in triglyceride levels (>10 mmol/885 mg/dL). This condition is associated with a significant risk of recurrent acute pancreatitis. Because this is a genetic condition, the optimal diagnostic strategy remains the genetic test. In addition, a clinical score for the diagnosis of FCS has been proposed but it needs further validation. Available treatment options to lower triglycerides, such as fibrates or omega-3 fatty acids, are not effective in patients with FCS. Currently, the cornerstone of treatment remains a very low-fat, lifetime diet that reduces chylomicron formation. Finally, apolipoprotein C-3 inhibitors are under development and may eventually be treatment options for these patients. The objective of this article is to carry out a general review of severe HTG, with an emphasis on FCS and based on the most recent available literature.

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.

Effectiveness of tes-tris or tris association with low density lipoprotein on in vitro longevity of refrigerated buffalo semen / Eficácia da associação TES-TRIS ou TRIS com lipoproteína de baixa densidade sobre a longevidade in vitro de sêmen refrigerado de búfalos

This study investigated in vitro the efficacy of four different extenders (TES-TRIS and TRIS with LDL low-density lipoprotein at concentrations of 10 or 5%) on the longevity of buffalo sperm in the refrigeration process at 5ºC. Sperm motility was assessed every 24 hours up to 72 hours of incubation using computer assisted sperm analysis and sperm membrane integrity was examined by the hypoosmotic test (HOST) at T1, T24, T48 and T72 hours. Eleven buffaloes (1 ejaculate per buffalo) of the Murrah breed were used, ranging in age from 4 to 5 years. Immediately after collection, each ejaculate was fractionated into 4 aliquots, and each aliquot was diluted in one of four diluents to obtain 50x106SPTZ/mL. The samples were packed in 0.5mL straws and refrigerated (-0.25°C/min) to 5°C and maintained at this temperature until evaluation. Prior to evaluation the samples were heated at 37°C for 30 seconds. The statistical package used for analysis was STATA 12.0 "Statistical Analysis Software" and means were compared by the Friedman test (P<0.05). The results of sperm kinetics and HOST indicate that the TRIS diluent with 10% LDL could be a promising alternative for semen refrigeration at 5ºC, to be used in conventional and fixed time artificial insemination.(AU)

Este estudo investigou in vitro a eficácia de quatro diferentes extensores (TES-TRIS e TRIS com lipoproteína de baixa densidade - LDL, nas concentrações de 10 ou 5%) sobre a longevidade espermática de búfalos no processo de refrigeração a 5ºC. A motilidade espermática foi avaliada a cada 24 horas até 72 horas de incubação, por sistema computadorizado "CASA", e a integridade de membrana espermática foi examinada pelo teste hiposmótico (HOST) em T1, T24, T48 e T72 horas. Foram utilizados 11 búfalos (um ejaculado por búfalo) da raça Murrah, com idade variando de quatro a cinco anos. Imediatamente após a coleta, cada ejaculado foi fracionado em quatro alíquotas, e cada alíquota foi diluída em um dos quatro diluidores para a obtenção de 50x106 SPTZ/mL. As amostras foram envasadas em palhetas de 0,5 mL, refrigeradas (-0,25oC/minuto) até 5oC e mantidas nessa temperatura até a avaliação. Previamente à avaliação, as amostras foram aquecidas a 37oC por 30 segundos. O pacote estatístico utilizado para as análises foi o STATA 12.0 "Statistical Analysis Software", e as médias foram comparadas pelo teste de Friedman (P<0,05). Os resultados de cinética e HOST até o tempo de 48 horas indicam que o diluidor TRIS com 10% LDL seria uma alternativa promissora para a refrigeração do sêmen a 5ºC, a ser utilizado na inseminação artificial e na inseminação artificial em tempo fixo.(AU)

Heparin and insulin in the management of acute hypertriglyceridemic pancreatitis / Heparina e insulina en el manejo de pancreatitis aguda asociada a hipertrigliceridemia

Abstract Hypertriglyceridemic pancreatitis (HTGP) is the third cause of acute pancreatitis in most studies, with a triglyceride (TG) risk value of more than 1000 mg/dL. The pathophysiological mechanism involves triglyceride hydrolysis by pancreatic lipase and the release of fatty acids which cause damage by producing free radicals. The reduction of TGs below 500 mg/dL is the treatment goal, based on increased lipoprotein lipase activity and chylomicron degradation. We present the case of a patient with HTGP with an adequate response to concomitant insulin and heparin therapy. (Acta Med Colomb 2020; 45. DOI: https://doi.org/10.36104/amc.2020.1491).

Resumen La pancreatitis secundaria a hipertrigliceridemia (PASHT) es la tercera causa de pancreatitis aguda en la mayoría de series, teniendo como factor de riesgo un valor de triglicéridos (TG) mayor a 1000 mg/dL. El mecanismo fisiopatológico involucra la hidrólisis de triglicéridos por la lipasa pancreática y la liberación de ácidos grasos que inducen el daño por la generación de radicales libres. La reducción de los TG a niveles menores de 500 mg/dL es el objetivo del tratamiento, basado en el aumento de la actividad de la lipoproteinlipasa y degradación de quilomicrones. Presentamos un caso de un paciente que presenta PASHT con adecuada respuesta al manejo concomitante de insulina y heparina.(Acta Med Colomb 2020; 45. DOI:https://doi.org/10.36104/amc.2020.1491).

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.

Encare clínico de las dislipemias / Clinical care of dyslipidemias / Encargo clínico de dislipidemias

Resumen: El manejo de los pacientes con dislipemias en la práctica clínica diaria implica el conocimiento de la evidencia científica relevante, la experiencia clínica, el sentido común, así como el respeto a la voluntad del paciente. La evidencia demuestra que el tratamiento hipolipemiante con estatinas reduce la morbimortalidad cardiovascular en un amplio grupo de pacientes, con un porcentaje de efectos colaterales bajo. Un punto crítico en el tratamiento es la decisión de iniciar o no dichos fármacos. Hay pacientes que tienen indicación formal de estatinas sin necesidad de hacer una evaluación del riesgo vascular. Tal es el caso de los que están en prevención secundaria, pacientes con colesterol unido a las lipoproteínas de baja densidad (C-LDL) muy alto (>190 mg/dl) y diabéticos entre 40 y 75 años. En los demás individuos la indicación de estatinas pasa en primer lugar por una evaluación formal del riesgo cardiovascular. Con este fin, las guías estadounidenses sugieren el uso de las Pooled Cohort Equations, en tanto que las guías europeas utilizan el Heartscore. Ambos scores estratifican a los pacientes en cuatro grupos según la intensidad del riesgo. El beneficio absoluto en la reducción del riesgo de eventos es tanto mayor cuanto más elevado sea el riesgo basal del paciente. Es por ello que se recomienda que tanto la intensidad del tratamiento, como el nivel de descenso objetivo de C-LDL, sean tanto mayores cuanto mayor sea el riesgo del paciente. Las recomendaciones de ambas guías no son coincidentes en algunos casos. Por lo tanto, además del riesgo cardiovascular se debe considerar el riesgo de efectos adversos potenciales y la voluntad del paciente en una discusión franca con su médico. El ezetimibe primero y los inhibidores PCSK9 después (limitados en estos momentos por costos y disponibilidad) aparecen como los grandes aliados de las estatinas, cuando no se toleran las dosis adecuadas o no se llega al C-LDL objetivo. A los efectos del abordaje del tema hemos optado por analizar cinco historias clínicas representativas de los principales escenarios clínicos que obligan al médico a tomar decisiones terapéuticas específicas.

Summary: In daily clinical practice the management of patients with dyslipidemias implies knowledge of relevant clinical scientific evidence, common sense, as respect of patient preferences. There is strong evidence that treatment of dyslipidemias mainly with statins reduces morbidity and mortality in a wide group of patients with few side effects. A critical step in management of this individuals is to make the decision of whether statin treatment is indicated or not. There are patients that have a clear indication of statin use without any further cardiovascular risk calculation. Such is the case in secondary prevention, patients with extremely high low density lipoprotein cholesterol levels (>190 mg/dl) and diabetics between 40 and 75 years-old. In all other patients, statin indication should start with a formal cardiovascular risk evaluation. American guidelines suggest using the Pooled Cohort Risk Equations and European guidelines prefer Heartscore. Both scoring systems stratify risk in four categories according to risk intensity. The absolute cardiovascular risk reduction obtained with treatment increases in parallel with the basal cardiovascular risk. This explains the recommendation that both treatment intensity and magnitude of low density lipoprotein cholesterol lowering should increase as the risk of the patient increases. Recommendations provided by American and European guidelines do not always coincide. Thus, besides basal cardiovascular risk estimation, potential adverse drug effects and patient preferences should always be considered in the context of a clinician-patient frank discussion. Ezetimibe first and PCSK9 inhibitors eventually (currently limited by costs and availability) appear as the great allies of statins, when adequate doses are not tolerated or the target is not reached. We will tackle the subject through five cases that illustrate the main clinical situations in which physicians have to adopt specific therapeutic decisions.

Resumo: O manejo de pacientes com dislipidemias na prática clínica diária envolve conhecimento de provas científicas relevantes, experiência clínica, senso comum, bem como a respeito da vontade do paciente. A evidência mostra que o tratamento hipolipemiente com estatina reduz a morbimortalidade cardiovascular em um grande grupo de pacientes com uma baixa taxa de efeitos colaterais. Um ponto crítico no tratamento desses pacientes é a decisão de iniciar ou não estas drogas. Há pacientes que têm indicação formal de estatinas sem necessidade de fazer uma avaliação de risco vascular. Tal é o caso dos pacientes que estão na prevenção secundária, pacientes com colesterol da lipoproteína de baixa densidade muito alta (>190 mg/dl) e diabéticos entre 40 e 75 anos. Em outros indivíduos a indicação de uma estatinas passa primeiro através de uma avaliação formal de risco cardiovascular. Para este fim diretrizes Americanas sugerem o uso do Pooled Cohort Equations, enquanto as directrizes europeias usam o Heartscore. Ambos scores estratificam pacientes em quatro grupos de acordo com a intensidade do risco. O benefício absoluto na redução do risco de eventos é maior quanto mais elevado seja o risco base do paciente. Por isso, recomenda-se que tanto a intensidade do tratamento e do nível de descida desejada da lipoproteína de baixa densidade, são muito maior quanto maior for o risco do paciente. As recomendações de ambas as guias em alguns casos não são coincidentes. Portanto, além do risco cardiovascular deve ser considerado o risco de efeitos adversos potenciais e a vontade do paciente em uma discussão franca entre médico e paciente. Ezetimiba primeiro e os inibidores PCSK9 depois (limitado atualmente pela disponibilidade e custo) aparecem como os grandes aliados das estatinas, quando não são toleradas doses adequadas ou não se chega ao objetivo. Para efeitos da abordagem do assunto que escolhemos para analisar cinco histórias clínicas de pacientes representativos dos principais cenários clínicos que exige do médico a tomar decisões terapêuticas específicas.