Impacto de la optimización del tratamiento hipolipemiante en el riesgo cardiovascular residual / Impact of Optimizing Lipid-Lowering Therapy on Residual Cardiovascular Risk

RESUMEN Introducción: el modelo SMART-REACH predice el riesgo de eventos cardiovasculares recurrentes. Objetivos: los objetivos de este estudio fueron: a) evaluar el riesgo residual en una población en prevención secundaria y niveles de colesterol asociado a lipoproteínas de baja densidad (C-LDL) fuera de meta; b) mediante un modelo de simulación, determinar el impacto de optimizar las terapias hipolipemiantes en términos de reducción del riesgo residual. Material y métodos: estudio transversal, descriptivo y multicéntrico. Se incluyeron consecutivamente pacientes con antecedentes cardiovasculares y un C-LDL mayor o igual que 55 mg/dL. El riesgo de eventos recurrentes (infarto agudo de miocardio, accidente cerebrovascular o muerte vascular) a 10 años y a lo largo de la vida se estimó utilizando el modelo SMART-REACH. Mediante una simulación, se optimizó el tratamiento hipolipemiante de cada paciente (utilizando estatinas, ezetimibe o inhibidores de proproteína convertasa subtilisina kexina tipo 9 [iPCSK9]), se estimó el descenso del C-LDL, se verificó el alcance del objetivo lipídico y se calculó la reducción del riesgo cardiovascular y el número necesario a tratar (NNT) correspondiente. Resultados: se incluyeron 187 pacientes (edad media 67,9 ± 9,3 años, 72,7% hombres). Los riesgos residuales calculados a 10 años y a lo largo de la vida fueron 37,1 ± 14,7% y 60,3 ± 10,7%, respectivamente. Globalmente, se pudo optimizar una sola estrategia farmacológica con estatinas, ezetimibe o un iPCSK9 en el 38,5%, el 11,5% y el 5,5% de la población, respectivamente. La optimización basada en dos tratamientos se realizó en el 27,5% (estatinas + ezetimibe), el 7,7% (estatinas + iPCSK9) y el 1,1% (ezetimibe + iPCSK9) de los casos. En 15 pacientes se optimizó el tratamiento considerando los tres fármacos. El 53,9% y el 62,9% de las acciones para optimizar el tratamiento mostraron un NNT menor que 30 para evitar un evento a 10 años o a lo largo de la vida, respectivamente. Conclusión: en este estudio, los pacientes con antecedentes cardiovasculares que no alcanzan la meta de C-LDL mostraron un riesgo residual considerable. La simulación mostró un importante margen para optimizar el tratamiento, con un impacto notable en el riesgo residual.

ABSTRACT Background: The SMART-REACH model predicts the risk or recurrent cardiovascular events. Objectives: The objectives of this study were: a) to evaluate the residual cardiovascular risk in a secondary prevention population with LDL-C levels above the recommended goal, using a simulation model; and b) to determine the impact of optimizing lipid-lowering therapies in terms of residual cardiovascular risk reduction. Methods: We conducted a cross-sectional, descriptive and multicenter study. Patient with a history of cardiovascular disease and a LDL-C ≥55 mg/dL were consecutively included. The 10-year and lifetime risk of recurrent events (myocardial infarction, stroke, or vascular death) were estimated using the SMART-REACH model. By means of a simulation, lipid-lowering treatment was optimized for each patient [using statins, ezetimibe and/or PCSK9 (PCSK9) inhibitors], with estimation of LDL-C reduction, checking if lipid-lowering goal was achieved and calculating the reduction in cardiovascular risk and the corresponding number needed to treat (NNT). Results: The cohort was made up of 187 patients; mean age was 67.9 ± 9.3 years and 72.7% were men. The calculated 10-year and lifetime residual risks were 37.1 ± 14.7% and 60.3 ± 10.7%, respectively. Overall, treatment was optimized with a single pharmacological strategy with statins, ezetimibe or PCSK9 inhibitor in 38.5%, 11.5% and 5.5% of the population, respectively. Optimization based on two treatments was performed in 27.5% (statins + ezetimibe), 7.7% (statins + PCSK9 inhibitor) and 1.1% (ezetimibe + PCSK9 inhibitor) of the cases. In 15 patients, treatment was optimized when the three drugs (statins + ezetimibe + PCSK9 inhibitor) were considered. Overall, 53.9% and 62.9% of the actions implemented to optimize treatment showed a 10-year or lifetime NNT < 30 to prevent an event, respectively. Conclusion: In this study, patients with a history of cardiovascular disease who do not reach LDL-C goal showed significant residual cardiovascular risk. The simulation model showed a significant margin for optimizing treatment, with a marked reduction in residual cardiovascular risk.

Residual cardiovascular risk, use of standard care treatments, and achievement of treatment goals in patients with cardiovascular disease.

Background: Residual risk management in patients with previous cardiovascular disease (CVD) is a relevant issue. Objectives: 1) to assess the residual risk of patients with CVD using the new scores developed to predict recurrent CVD events (SMART score/SMART-REACH model); 2) to determine the use of therapies with cardiovascular benefit and the achievement of therapeutic goals in patients with very high residual risk. Methods: A multicenter, descriptive, cross-sectional study was performed. Individuals over 18 years of age with CVD were included consecutively. The 10-year risk of recurrent events was estimated using the SMART score and the SMART-REACH model. A value ≥ 30% was considered "very high risk". Results: In total, 296 patients (mean age 68.2 ± 9.4 years, 75.7% men) were included. Globally, 32.43% and 64.53% of the population was classified as very high risk by the SMART score and the SMART-REACH model, respectively. Among patients classified as very high risk by the SMART score, 45.7% and 33.3% were treated with high-intensity statins and reached the goal of LDL-C <55 mg/dL, respectively. The results were similar when evaluating very high patients according to the SMART-REACH model (high-intensity statins: 59.7%; LDL-C <55 mg/dL: 43.9%). Few very high-risk patients with diabetes were receiving glucose-lowering drugs with demonstrated cardiovascular benefit. Conclusion: In this secondary prevention population, the residual risk was considerable. Underutilization of standard care treatments and failure to achieve therapeutic goals were evident even in subjects with very high residual risk.

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.

Screening program for familial hyperchylomicronemia syndrome detection: Experience of a university health system

ABSTRACT Objective: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive metabolic disorder caused by mutations related to chylomicron metabolism. The objective of this study is to show the development and results of a screening program for FCS in Argentina. Materials and methods: A cross-sectional study was performed. All patients > 18 years with a triglyceride level ≥ 1,000 mg/dL in the period from January 1, 2017 to December 31, 2021 were included. The program was developed in three stages: (1) Review of electronic records and identification of suspected laboratory cases (triglyceride level ≥ 1,000 mg/dL); (2) Identification of suspected clinical cases (all suspected laboratory cases that had no relevant secondary factors) and application of the FCS score to define probable cases (score ≥ 10); (3) Perform genetic tests in probable cases. Results: Globally, 348 suspected laboratory cases (mean age of 49.9 years, 77.3% men) were included. The median triglycerides level was 1,309 mg/dL (interquartile range 1,175-1,607 mg/dL). In total, 231 patients were categorized as suspected clinical cases. After applying the FCS score, 3% of them were classified as "very likely FCS" (probable cases). Four variants of uncertain significance have been identified. No previously reported pathogenic variants were detected. Conclusion: This study shows a screening program for the detection of FCS. Although no patient was diagnosed with FCS, we believe that more programs of these characteristics should be developed in our region, given the importance of early detection of this metabolic disorder.

Screening program for familial hyperchylomicronemia syndrome detection: Experience of a university health system.

Objective: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive metabolic disorder caused by mutations related to chylomicron metabolism. The objective of this study is to show the development and results of a screening program for FCS in Argentina. Materials and methods: A cross-sectional study was performed. All patients > 18 years with a triglyceride level ≥ 1,000 mg/dL in the period from January 1, 2017 to December 31, 2021 were included. The program was developed in three stages: (1) Review of electronic records and identification of suspected laboratory cases (triglyceride level ≥ 1,000 mg/dL); (2) Identification of suspected clinical cases (all suspected laboratory cases that had no relevant secondary factors) and application of the FCS score to define probable cases (score ≥ 10); (3) Perform genetic tests in probable cases. Results: Globally, 348 suspected laboratory cases (mean age of 49.9 years, 77.3% men) were included. The median triglycerides level was 1,309 mg/dL (interquartile range 1,175-1,607 mg/dL). In total, 231 patients were categorized as suspected clinical cases. After applying the FCS score, 3% of them were classified as "very likely FCS" (probable cases). Four variants of uncertain significance have been identified. No previously reported pathogenic variants were detected. Conclusion: This study shows a screening program for the detection of FCS. Although no patient was diagnosed with FCS, we believe that more programs of these characteristics should be developed in our region, given the importance of early detection of this metabolic disorder.

Reduction of cardiovascular events with the use of lipid-lowering medication in patients with familial hypercholesterolemia or severe primary hypercholesterolemia: A systematic review.

BACKGROUND: Lipid-lowering medication is effective in reducing the risk of cardiovascular disease in several clinical scenarios. However, the evidence in patients with familial hypercholesterolemia (FH) and severe primary hypercholesterolemia is less robust. OBJECTIVES: The main objective of the present systematic review was to analyze the association between lipid-lowering medication and cardiovascular risk reduction in patients with FH or severe primary hypercholesterolemia. METHODS: This systematic review was performed according to PRISMA guidelines. A literature search was performed to detect studies that evaluated the association between lipid-lowering medication and cardiovascular events in FH patients. The diagnosis of FH varied in the studies analyzed. Genetic and clinical criteria or a combination of both were used. Likewise, we considered patients with severe primary hypercholesterolemia. RESULTS: Fourteen studies including 21059 patients were considered eligible for this research. This systematic review showed that the vast majority of the studies with statins reported a significant cardiovascular risk reduction. Statin use was associated with a lower risk of major adverse cardiovascular events (3 studies), coronary heart disease (2 studies), cardiovascular death (4 studies), all-cause mortality (4 studies) and combined endpoint of coronary heart disease and mortality (1 study). When analyzing the association between non-statin lipid-lowering medications and the incidence of cardiovascular events, the results were conflicting. CONCLUSION: Despite the low level of evidence, this systematic review showed that statins reduce cardiovascular events in patients with HeFH. Evidence for other lipid-lowering drugs is not conclusive.

LDL-C Levels Below 55 mg/dl and Risk of Hemorrhagic Stroke: A Meta-Analysis.

OBJECTIVE: To evaluate the effect of very low levels of LDL-C (< 55 mg/dl) achieved with lipid-lowering therapy on hemorrhagic stroke incidence. METHODS: We performed a meta-analysis including randomized trials that achieved LDL-C levels under 55 mg/dl in more intensive lipid-lowering arms, regardless of the lipid-lowering drug used. A fixed-effects model was used. This meta-analysis was performed according to PRISMA guidelines. RESULTS: Eight eligible trials including 122.802 patients, were identified and considered eligible for the analyses. A total of 62.526 subjects were allocated to receive more intensive lipid-lowering therapy while 60.276 subjects were allocated to the respective control arms. There were no differences in the incidence of hemorrhagic stroke between the group that received a more intensive lipid-lowering therapy (achieved LDL-C level <55 mg/dl), and the group that received a less intense scheme (OR, 1.05; 95%CI, 0.85-1.31). The statistical heterogeneity was low (I2 = 2%). The sensitivity analysis showed that the results were robust. CONCLUSIONS: The use of more intensive lipid-lowering therapy that achieved an LDL-C level lower than 55 mg/dl in patients with high cardiovascular risk, is not associated with an increased risk of hemorrhagic stroke. Considering the cardiovascular benefit and safety observed with the achievement of very low LDL-C values, the challenging lipid goals recommended by the new guidelines seem consistent.

Aplicación sistemática de un algoritmo para el manejo lipídico en pacientes de muy alto riesgo cardiovascular. Impacto en los objetivos lipídicos / Systematic Application of an Algorithm for Lipid Management in Cardiovascular High-Risk Patients. Impact on Lipid Goals

RESUMEN Objetivo: Analizar el tratamiento hipolipemiante indicado y verificar el cumplimiento de las metas lipídicas recomendadas durante la internación y en el seguimiento precoz, luego de aplicar sistemáticamente un algoritmo para el manejo lipídico basado en las recomendaciones actuales. Material y métodos: Se incluyeron en forma consecutiva pacientes internados con síndrome coronario agudo o revascularización programada. Se aplicó sistemáticamente un algoritmo para el manejo lipídico, que incluyó: 1) indicación precoz de estatinas de alta intensidad en la internación; 2) seguimiento precoz (controles a las 6 y 12 semanas). La terapia indicada se basó en los documentos de posición de la Sociedad Argentina de Cardiología. Se analizó el cumplimiento de las metas de C-LDL (<70 mg/dl) a las 6 y 12 semanas. Resultados: Se incluyeron 292 pacientes. Se indicó estatinas (95,9% de alta intensidad) a todos los pacientes al alta hospitalaria. A las 6 semanas, el 62,5% alcanzó la meta de C-LDL. Se modificó el esquema terapéutico en el 36,3% de los sujetos (aumento de la dosis de estatinas: 19,7%; agregado de ezetimibe: 67,7%). A las 12 semanas, el 69,1% del subgrupo que no había alcanzado la meta a las 6 semanas logró el objetivo lipídico. Se indicó un inhibidor de la PCSK9 (iPCSK9) a 7 pacientes. Globalmente, el 88,4% alcanzó la meta de C-LDL a las 12 semanas. Conclusión: La aplicación sistemática de un algoritmo basado en las guías determinó que muchos sujetos de alto riesgo cardiovascular alcanzaran las metas de C-LDL a las 12 semanas. La indicación de un iPCSK9 quedó reservada para un grupo reducido de pacientes.

ABSTRACT Objective: The aim of this study was to analyze the indicated lipid-lowering therapy and verify the achievement of the recommended lipid goals during hospitalization and early follow-up, after the systematic application of a lipid management algorithm based on current recommendations. Methods: Patients hospitalized for acute coronary syndrome or programmed revascularization surgery were prospectively included in the study. A lipid management algorithm, including; 1) early indication of high-intensity statins during hospitalization and 2) early follow-up (6 and 12-week controls), was systematically applied. The therapy indicated was based on position documents of the Argentine Society of Cardiology. Achievement of LDL-C goals (<70 mg/dl) at 6 and 12 weeks was analyzed. Results: A total of 292 patients were prescribed statins (high-intensity in 95.9% of cases) at hospital discharge. AT 6 weeks, 62.5% reached the LDL-C goal. The therapeutic plan was modified in 36.3% of patients (increased dose of statins in 19.7% and addition of ezetimibe in 67.7%). At 12 weeks, 69.1% of the subgroup which has not fulfilled the goal at 6 weeks, attained the lipid target. A PCSK9 inhibitor (PCSK9i) was indicated in 7 patients. Overall, 88.4% of patients achieved the LDL-C goal at 12 weeks. Conclusion: Many cardiovascular high-risk patients reached LDL-C goals at 12 weeks with the systematic application of a guideline-based algorithm. The indication of a PCSK9i was reserved for a reduced group of patients.

Role of non-statin lipid-lowering therapy in coronary atherosclerosis regression: a meta-analysis and meta-regression.

BACKGROUND: Several studies have investigated the association between non-statin lipid-lowering therapy and regression of atherosclerosis. However, these studies were mostly small and their results were not always robust. The objectives were: (1) to define if a dual lipid-lowering therapy (statin + non-statin drugs) is associated with coronary atherosclerosis regression, estimated by intravascular ultrasound (IVUS); (2) to assess the association between dual lipid-lowering-induced changes in low density lipoprotein cholesterol (LDL-C) and non-high-density-lipoprotein cholesterol (non-HDL-C) levels and atherosclerosis regression. METHODS: A meta-analysis including trials of non-statin lipid-lowering therapy, reporting LDL-C, non-HDL-C and total atheroma volume (TAV) with a minimum of 6 months of follow-up was performed. The primary endpoint was defined as the change in TAV measured from baseline to follow-up, comparing groups of subjects on statins alone versus combination of statin and non-statin drugs. The random-effects model and meta-regression were performed. RESULTS: Eight eligible trials of non-statin lipid-lowering drugs (1759 patients) were included. Overall, the dual lipid-lowering therapy was associated with a significant reduction in TAV [- 4.0 mm3 (CI 95% -5.4 to - 2.6)]; I2 = 0%]. The findings were similar in the stratified analysis according to the lipid-lowering drug class (ezetimibe or PCSK9 inhibitors). In the meta-regression, a 10% decrease in LDL-C or non-HDL-C levels, was associated, respectively, with 1.0 mm3 and 1.1 mm3 regressions in TAV. CONCLUSION: These data suggests the addition of ezetimibe or PCSK9 inhibitors to statin therapy results in a significant regression of TAV. Reduction of coronary atherosclerosis observed with non-statin lipid-lowering therapy is associated to the degree of LDL-C and non-HDL-C lowering. Therefore, it seems reasonable to achieve lipid goals according to cardiovascular risk and regardless of the lipid-lowering strategy used (statin monotherapy or dual treatment).

Impact of the 2019 European Guidelines on Diabetes in Clinical Practice: Real and Simulated Analyses of Lipid Goals.

BACKGROUND: Recent European guidelines on diabetes, prediabetes, and cardiovascular disease developed for the European Society of Cardiology (ESC) in collaboration with the European Association for the Study of Diabetes (EASD) significantly changed some concepts on risk stratification, lipid goals, and recommendations for the use of lipid-lowering drugs. The objectives of this work were to describe the lipid-lowering treatment prescribed for patients with diabetes and to determine the percentage of patients that achieved the lipid goals recommended by the 2019 ESC/EASD Guidelines on Diabetes in real and simulated scenarios. METHODS: A multicenter, cross-sectional study was performed. Subjects >18 years with type 2 diabetes were included. The recommendations of the 2019 ESC/EASD Guidelines were followed. The real and simulated (ideal setting using adequate doses of statins ± ezetimibe) scenarios were analyzed. RESULTS: Overall, 528 patients were included. In total, 62.5% of patients received statins (17.1% high intensity). Most patients were stratified as "very high risk" (54.2%) or "high risk" (43.4%). Only 13.3% achieved the double lipid goal (LDL-C and non-HDL-C goals according to the risk categories). In the simulation analysis, the proportion of subjects that did not reach the therapeutic objective decreased in all risk strata, although a considerable proportion of subjects persisted outside the target. CONCLUSION: The difficulty of achieving lipid goals in diabetic patients was considerable when applying the new guidelines. The situation would improve if we optimized treatment, but the prescription of new lipid-lowering drugs could be limited by their high cost.

Impact of Lipid-Lowering Therapy on Mortality According to the Baseline Non-HDL Cholesterol Level: A Meta-Analysis.

INTRODUCTION: Previous report showed that more intensive lipid-lowering therapy was associated with less mortality when baseline LDL-C levels were > 100 mg/dL. Non-HDL-C is a better predictor of cardiovascular risk than simpler LDL-C. AIM: The objective of this meta-analysis was to define the impact of lipid-lowering therapy on the reduction of total and cardiovascular mortality by different baseline levels of non-HDL-C. METHODS: We performed a meta-analysis including randomized, controlled clinical trials of lipid-lowering therapy, reporting mortality with a minimum of 6 months of follow-up, searching in PubMed/Medline, EMBASE and Cochrane Clinical Trials databases. The random-effects model and meta-regression were performed. RESULTS: Twenty nine trials of lipid-lowering drugs, including 233,027 patients, were considered eligible for the analyses. According to the baseline non-HDL-C level, the results on cardiovascular mortality were: (1) ≥ 190 mg/dL: OR 0.63 (95% CI 0.53-0.76); (2) 160-189 mg/dL: OR 0.82 (95% CI 0.75-0.89); (3) 130-159 mg/dL: OR 0.71 (95% CI 0.52-0.98); (4) < 130 mg/dL: OR 0.95 (95% CI 0.87-1.05). When evaluating mortality from any cause, the results were the following: (1) ≥ 190 mg/dL: OR 0.70 (95% CI 0.61-0.82); (2) 160-189 mg/dL: OR 0.91 (95% CI 0.83-0.98); (3) 130-159 mg/dL; OR 0.88 (95% CI 0.77-1.00); (4) < 130 mg/dL: OR 0.98 (95% CI 0.91-1.06). The meta-regression analysis showed a significant association between baseline non-HDL-C and mortality. CONCLUSIONS: In these meta-analyses, lipid-lowering therapy was associated with reduction in the risk of all-cause and cardiovascular mortality when baseline non-HDL-C levels were above than 130 mg/dL.

[Eligibility for the indication of PCSK9 inhibitors according to the recommendations of different scientific societies]. / Elegibilidad para la indicación de inhibidores de PCSK9 según las recomendaciones de diferentes sociedades científicas.

LDL-cholesterol (LDL-C) lowering is a primary objective in cardiovascular prevention. Recent studies demonstrated clinical benefit when proprotein convertase subtilisin/kexin-9 inhibitors (PCSK9i) were added to the treatment in patients who had not achieved the LDL-C goal despite being treated with high intensity statins and ezetimibe, however the use of these drugs is limited by their cost. The American College of Cardiology, the Argentine Society of Cardiology and the European Society of Cardiology recommend an LDL-C goal less than 70 mg/dl in secondary prevention, determining thresholds of LDL-C to start treatment with PCSK9i of 70, 100 or 140 mg/dl respectively. In order to evaluate the lipid-lowering regimen prescribed in patients hospitalized for acute coronary syndrome or coronary revascularization and analyze the proportion of eligible to be treated with PCSK9i in a real and simulated scenario, we conducted a study that included 351 patients with coronary disease collected from an electronic database of a university hospital. The 48.4% received high intensity statins, 11.4% ezetimibe and 54.7% did not achieve the LDL-C goal of less than 70 mg/dL. Using a simulation model in which all would be treated with high intensity statins and ezetimibe, the eligibility to prescribe PCSK9i was 31.1%, 12.8% and 9.1% according to the C- LDL thresholds determined by the three scientific societies. Our study demonstrated a gap between the consensus recommendations for LDL-C lowering and the current practice that should be minimized to optimize the cost/effectiveness ratio in secondary prevention.

La reducción del colesterol-LDL (C-LDL) es un objetivo primordial en prevención cardiovascular. Estudios recientes demostraron beneficio clínico al administrar inhibidores de la proprotein convertase subtilisin/kexin-9 (iPCSK9) a pacientes que no habían logrado la meta de C-LDL con estatinas de alta intensidad y ezetimibe, sin embargo el uso de estos fármacos está limitado por su costo. El American College of Cardiology, la Sociedad Argentina de Cardiología y la European Society of Cardiology recomiendan una meta de C-LDL menor a 70 mg/dl en prevención secundaria, determinando umbrales de C-LDL de 70, 100 o 140 mg/dl respectivamente, para iniciar el tratamiento con iPCSK9. Con el objetivo de evaluar el esquema hipolipemiante prescripto en internados por síndrome coronario agudo o revascularización coronaria y analizar la proporción de elegibles para ser tratados con iPCSK9 en un escenario real y simulado, realizamos un estudio que incluyó 351 pacientes con enfermedad coronaria, tomados de una base de datos electrónica de un hospital universitario. El 48.4% recibió estatinas de elevada intensidad, 11.4% ezetimibe y 54.7% no logró la meta de C-LDL menor a 70 mg/dl. Utilizando un modelo de simulación en el que todos serían medicados con estatinas de elevada intensidad y ezetimibe, la elegibilidad para prescribir iPCSK9 fue de 31.1%, 12.8% y 9.1% según los umbrales de C-LDL determinados por las tres sociedades científicas. Nuestro estudio demostró una brecha entre las recomendaciones de los consensos para reducir el colesterol y la práctica habitual que debería ser minimizada para optimizar la relación costo/efectividad en prevención secundaria.

Elegibilidad para la indicación de inhibidores de PCSK9 según las recomendaciones de diferentes sociedades científicas / Eligibility for the indication of PCSK9 inhibitors according to the recommendations of different scientific societies

La reducción del colesterol-LDL (C-LDL) es un objetivo primordial en prevención cardiovascular. Estudios recientes demostraron beneficio clínico al administrar inhibidores de la proprotein convertase subtilisin/kexin-9 (iPCSK9) a pacientes que no habían logrado la meta de C-LDL con estatinas de alta intensidad y ezetimibe, sin embargo el uso de estos fármacos está limitado por su costo. El American College of Cardiology, la Sociedad Argentina de Cardiología y la European Society of Cardiology recomiendan una meta de C-LDL menor a 70 mg/dl en prevención secundaria, determinando umbrales de C-LDL de 70, 100 o 140 mg/dl respectivamente, para iniciar el tratamiento con iPCSK9. Con el objetivo de evaluar el esquema hipolipemiante prescripto en internados por síndrome coronario agudo o revascularización coronaria y analizar la proporción de elegibles para ser tratados con iPCSK9 en un escenario real y simulado, realizamos un estudio que incluyó 351 pacientes con enfermedad coronaria, tomados de una base de datos electrónica de un hospital universitario. El 48.4% recibió estatinas de elevada intensidad, 11.4% ezetimibe y 54.7% no logró la meta de C-LDL menor a 70 mg/dl. Utilizando un modelo de simulación en el que todos serían medicados con estatinas de elevada intensidad y ezetimibe, la elegibilidad para prescribir iPCSK9 fue de 31.1%, 12.8% y 9.1% según los umbrales de C-LDL determinados por las tres sociedades científicas. Nuestro estudio demostró una brecha entre las recomendaciones de los consensos para reducir el colesterol y la práctica habitual que debería ser minimizada para optimizar la relación costo/efectividad en prevención secundaria.

LDL-cholesterol (LDL-C) lowering is a primary objective in cardiovascular prevention. Recent studies demonstrated clinical benefit when proprotein convertase subtilisin/kexin-9 inhibitors (PCSK9i) were added to the treatment in patients who had not achieved the LDL-C goal despite being treated with high intensity statins and ezetimibe, however the use of these drugs is limited by their cost. The American College of Cardiology, the Argentine Society of Cardiology and the European Society of Cardiology recommend an LDL-C goal less than 70 mg/dl in secondary prevention, determining thresholds of LDL-C to start treatment with PCSK9i of 70, 100 or 140 mg/dl respectively. In order to evaluate the lipid-lowering regimen prescribed in patients hospitalized for acute coronary syndrome or coronary revascularization and analyze the proportion of eligible to be treated with PCSK9i in a real and simulated scenario, we conducted a study that included 351 patients with coronary disease collected from an electronic database of a university hospital. The 48.4% received high intensity statins, 11.4% ezetimibe and 54.7% did not achieve the LDL-C goal of less than 70 mg/dL. Using a simulation model in which all would be treated with high intensity statins and ezetimibe, the eligibility to prescribe PCSK9i was 31.1%, 12.8% and 9.1% according to the C- LDL thresholds determined by the three scientific societies. Our study demonstrated a gap between the consensus recommendations for LDL-C lowering and the current practice that should be minimized to optimize the cost/effectiveness ratio in secondary prevention.

Hipertrigliceridemia grave. Características clínicas y manejo terapéutico / Severe hypertriglyceridemia. Clinical characteristics and therapeutic management

Introducción: El manejo terapéutico de la hipertrigliceridemia grave representa un desafío clínico. Objetivos: 1) Identificar las características clínicas de los pacientes con hipertrigliceridemia grave; 2) Analizar el tratamiento instaurado por el médico en cada caso. Métodos: Se realizó un estudio de corte transversal a partir de la historia clínica electrónica. Se incluyeron todos los pacientes > 18 años con una determinación en sangre de triglicéridos ≥ 1.000mg/dL entre el 01/01/2011 y el 31/12/2016. Se identificaron variables clínicas y de laboratorio. Se analizó la conducta de los médicos tratantes en los 6 meses posteriores al hallazgo lipídico. Resultados: Se incluyeron 420 pacientes (edad media 49,1 ± 11,4 años, varones el 78,8%). La mediana de triglicéridos fue 1.329mg/dL (rango intercuartílico 1.174-1.658). En el 34,1% de los pacientes no se encontraron causas secundarias. Las causas secundarias más frecuentes fueron la obesidad (38,6%) y la diabetes (28,1%). Se recomendó realizar actividad física y se derivó a un nutricionista en el 49,1% y el 44,2% de los pacientes respectivamente. Las causas secundarias se identificaron y se intentaron corregir en el 40,7% de los casos. Los esquemas terapéuticos más indicados fueron fenofibrato 200 mg/día (26,5%) y gemfibrozil 900 mg/día (19,3%). Pocos pacientes recibieron la indicación de ácidos grasos omega 3 o niacina. Conclusión: Nuestro trabajo mostró por primera vez en nuestro país las características de una población con hipertrigliceridemia grave. Las medidas terapéuticas instauradas por los médicos fueron insuficientes. Conocer las características en este particular escenario clínico podría mejorar el abordaje actual de estos pacientes

Introduction: The therapeutic management of severe hypertriglyceridaemia represents a clinical challenge. Objectives: The objectives of this study were 1) to identify the clinical characteristics of patients with severe hypertriglyceridaemia, and 2) to analyse the treatment established by the physicians in each case. Methods: A cross-sectional study was carried out using the computerised medical records of all patients > 18 years of age with a blood triglyceride level ≥ 1,000 mg/dL between 1 January 2011 and 31 December 2016. Clinical and laboratory variables were collected. The behaviour of the physicians in the 6 months after the lipid finding was analysed. Results: A total of 420 patients were included (mean age 49.1±11.4 years, males 78.8%). The median of triglycerides was 1,329 mg/dL (interquartile range 1,174 - 1,658). No secondary causes were found in 34.1% of the patients. The most frequent secondary causes were obesity (38.6%) and diabetes (28.1%). Physical activity was recommended and a nutritionist was referred to in 49.1% and 44.2% of the patients, respectively. Secondary causes were identified and attempts were made to correct them in 40.7% of cases. The most indicated pharmacological treatments were fenofibrate 200 mg/day (26.5%) and gemfibrozil 900 mg/day (19.3%). Few patients received the indication of omega 3 fatty acids or niacin. Conclusion: This study showed, for the first time in our country, the characteristics of a population with severe hypertriglyceridaemia. The therapeutic measures instituted by the physicians were insufficient. Knowing the characteristics in this particular clinical scenario could improve the current approach of these patients

Severe hypertriglyceridemia. Clinical characteristics and therapeutic management. / Hipertrigliceridemia grave. Características clínicas y manejo terapéutico.

INTRODUCTION: The therapeutic management of severe hypertriglyceridaemia represents a clinical challenge. OBJECTIVES: The objectives of this study were 1) to identify the clinical characteristics of patients with severe hypertriglyceridaemia, and 2) to analyse the treatment established by the physicians in each case. METHODS: A cross-sectional study was carried out using the computerised medical records of all patients>18 years of age with a blood triglyceride level≥1,000mg/dL between 1 January 2011 and 31 December 2016. Clinical and laboratory variables were collected. The behaviour of the physicians in the 6 months after the lipid finding was analysed. RESULTS: A total of 420 patients were included (mean age 49.1±11.4 years, males 78.8%). The median of triglycerides was 1,329mg/dL (interquartile range 1,174-1,658). No secondary causes were found in 34.1% of the patients. The most frequent secondary causes were obesity (38.6%) and diabetes (28.1%). Physical activity was recommended and a nutritionist was referred to in 49.1% and 44.2% of the patients, respectively. Secondary causes were identified and attempts were made to correct them in 40.7% of cases. The most indicated pharmacological treatments were fenofibrate 200mg/day (26.5%) and gemfibrozil 900mg/day (19.3%). Few patients received the indication of omega 3 fatty acids or niacin. CONCLUSION: This study showed, for the first time in our country, the characteristics of a population with severe hypertriglyceridaemia. The therapeutic measures instituted by the physicians were insufficient. Knowing the characteristics in this particular clinical scenario could improve the current approach of these patients.

Discordancia lipídica y placa carotídea en pacientes obesos en prevención primaria / Lipid discordance and carotid plaque in obese patients in primary prevention

Introducción: Los pacientes obesos con discordancia lipídica podrían tener una mayor prevalencia de aterosclerosis subclínica. Los objetivos de nuestro trabajo fueron: 1) determinar la prevalencia de discordancia lipídica en una población de pacientes obesos en prevención primaria; 2) investigar la asociación entre la discordancia lipídica y la presencia de placa aterosclerótica carotídea (PAC). Métodos: Se incluyeron sujetos mayores de 18 años obesos (índice de masa corporal ≥30kg/m2) sin enfermedad cardiovascular, diabetes, o tratamiento hipolipemiante, provenientes de 6 centros de cardiología. Se definió «discordancia lipídica» cuando, independientemente del valor de c-LDL, el valor de colesterol no HDL superaba 30mg/dL el valor de c-LDL. Se identificó la presencia de PAC por ultrasonido. Se realizaron análisis uni y multivariados explorando la asociación entre la discordancia lipídica y la presencia de PAC. Resultados: Se incluyeron 325 pacientes obesos (57,2% hombres, edad media: 52,3 años). La prevalencia de discordancia lipídica fue del 57,9%. Mostraron PAC el 38,6% de los pacientes. Esta proporción fue mayor en los sujetos con discordancia lipídica en comparación con los pacientes sin este patrón lipídico (44,4% vs. 30,7%, p=0,01). En el análisis univariado (OR: 1,80; IC95%: 1,14-2,87; p=0,01) y en el multivariado (OR: 2,07; IC95%: 1,22-3,54; p=0,007), la presencia de discordancia lipídica se asoció con una mayor probabilidad de presentar PAC. Conclusión: En pacientes obesos, la discordancia lipídica se asoció con una mayor prevalencia de PAC. Evaluar pacientes obesos con esta estrategia podría identificar a los sujetos con mayor riesgo cardiovascular residual (AU)

Introduction: Obese patients with lipid discordance (non-HDL cholesterol levels 30mg/dL above the LDL-c value) may have a greater prevalence of carotid atherosclerotic plaque (CAP). Our study objectives were: 1) To assess the prevalence of lipid discordance in a primary prevention population of obese patients; 2) To investigate the association between lipid discordance and presence of CAP. Methods: Obese subjects aged >18 years (BMI ≥30kg/m2) with no cardiovascular disease, diabetes, or lipid-lowering treatment from six cardiology centers were included. Lipid discordance was defined when, regardless of the LDL-c level, the non-HDL cholesterol value exceeded the LDL-c value by 30mg/dL. Presence of CAP was identified by ultrasonography. Univariate and multivariate analyses were performed to explore the association between lipid discordance and presence of CAP. Results: The study simple consisted of 325 obese patients (57.2% men; mean age, 52.3 years). Prevalence of lipid discordance was 57.9%. CAP was found in 38.6% of patients, but the proportion was higher in subjects with lipid discordance as compared to those without this lipid pattern (44.4% vs. 30.7%, P=.01). In both the univariate (OR: 1.80; 95% CI: 1.14-2.87; P=.01) and the multivariate analysis (OR: 2.07; 95% CI: 1.22-3.54; P=.007), presence of lipid discordance was associated to an increased probability of CAP. Conclusion: In these obese patients, lipid discordance was associated to greater prevalence of CAP. Evaluation of obese patients with this strategy could help identify subjects with higher residual cardiovascular risk (AU)

Lipid discordance and carotid plaque in obese patients in primary prevention. / Discordancia lipídica y placa carotídea en pacientes obesos en prevención primaria.

INTRODUCTION: Obese patients with lipid discordance (non-HDL cholesterol levels 30mg/dL above the LDL-c value) may have a greater prevalence of carotid atherosclerotic plaque (CAP). Our study objectives were: 1) To assess the prevalence of lipid discordance in a primary prevention population of obese patients; 2) To investigate the association between lipid discordance and presence of CAP. METHODS: Obese subjects aged >18 years (BMI ≥30kg/m2) with no cardiovascular disease, diabetes, or lipid-lowering treatment from six cardiology centers were included. Lipid discordance was defined when, regardless of the LDL-c level, the non-HDL cholesterol value exceeded the LDL-c value by 30mg/dL. Presence of CAP was identified by ultrasonography. Univariate and multivariate analyses were performed to explore the association between lipid discordance and presence of CAP. RESULTS: The study simple consisted of 325 obese patients (57.2% men; mean age, 52.3 years). Prevalence of lipid discordance was 57.9%. CAP was found in 38.6% of patients, but the proportion was higher in subjects with lipid discordance as compared to those without this lipid pattern (44.4% vs. 30.7%, P=.01). In both the univariate (OR: 1.80; 95% CI: 1.14-2.87; P=.01) and the multivariate analysis (OR: 2.07; 95% CI: 1.22-3.54; P=.007), presence of lipid discordance was associated to an increased probability of CAP. CONCLUSION: In these obese patients, lipid discordance was associated to greater prevalence of CAP. Evaluation of obese patients with this strategy could help identify subjects with higher residual cardiovascular risk.

Discordant Lipid Pattern and Carotid Atherosclerotic Plaque. Importance of Remnant Cholesterol.

BACKGROUND:: Subjects with levels of non-HDL-C 30 mg/dL above those of LDL-C (lipid discordance) or with high remnant cholesterol levels could have a greater residual cardiovascular risk. OBJECTIVES:: To determine the prevalence of lipid discordance in a primary prevention population and analyze the clinical variables associated with it; To investigate the association between lipid discordance and remnant cholesterol with the presence of carotid plaque. METHODS:: Primary prevention patients without diabetes or lipid-lowering therapy were included. Regardless of the LDL-C level, we define "lipid discordance" if the non-HDL-C value exceeded 30 mg/dL that of LDL-C. Remnant cholesterol was calculated as total cholesterol minus HDL-C minus LDL-C when triglycerides were < 4.0 mmol/L. Ultrasound was used to assess carotid plaque occurrence. Multiple regression logistic models were performed. RESULTS:: The study included 772 patients (mean age 52 ± 11 years, 66% women). The prevalence of lipid discordance was 34%. Male sex and body mass index were independently associated with discordant lipid pattern. The prevalence of carotid plaque was higher in subjects with lipid discordance (40.2% vs. 29.2, p = 0.002). The multivariate analysis showed that the discordant lipid pattern was associated with the greater probability of carotid plaque (OR 1.58, 95% CI 1.08-2.34, p = 0.02). Similarly, a significant association between calculated remnant cholesterol and carotid plaque was found. CONCLUSION:: Lipid discordance and presence of a higher level of calculated remnant cholesterol are associated with subclinical atherosclerosis. Our findings could be used to improve the residual cardiovascular risk evaluation. FUNDAMENTO:: Indivíduos com níveis de não HDL-C excedendo em 30 mg/dl aqueles de LDL-C (discordância lipídica) ou com altos níveis de colesterol remanescente poderiam ter maior risco cardiovascular residual. OBJETIVOS:: determinar a prevalência de discordância lipídica em uma população de prevenção primária e analisar as variáveis clínicas com ela associadas; investigar a associação de discordância lipídica e colesterol remanescente calculado com a presença de placa carotídea. MÉTODOS:: Pacientes de prevenção primária sem diabetes ou sem terapia hipolipemiante foram incluídos. Independentemente do nível de LDL-C, definiu-se "discordância lipídica" como um valor de não HDL-C excedendo em 30 mg/dl aquele de LDL-C. Calculou-se o colesterol remanescente como colesterol total menos HDL-C menos LDL-C na presença de triglicerídeos < 4,0 mmol/l. Usou-se ultrassom para avaliar a presença de placa carotídea. Modelos de regressão logística múltipla foram construídos. RESULTADOS:: Este estudo incluiu 772 pacientes (idade média, 52 ± 11 anos; 66% mulheres). A prevalência de discordância lipídica foi de 34%. Sexo masculino e índice de massa corporal mostraram associação independente com padrão lipídico discordante. A prevalência de placa carotídea foi maior em indivíduos com discordância lipídica (40,2% vs. 29,2; p = 0,002). A análise multivariada mostrou associação do padrão lipídico discordante com maior probabilidade de placa carotídea (OR: 1,58; IC95%: 1,08-2,34; p = 0,02). Da mesma forma, identificou-se uma significativa associação entre colesterol remanescente calculado e placa carotídea. CONCLUSÃO:: Discordância lipídica e presença de nível mais alto de colesterol remanescente calculado acham-se associados com aterosclerose subclínica. Nossos achados podem ser usados para aprimorar a avaliação de risco cardiovascular residual.

Discordant Lipid Pattern and Carotid Atherosclerotic Plaque. Importance of Remnant Cholesterol / Padrão Lipídico Discordante e Placa Aterosclerótica Carotídea. Importância do Colesterol Remanescente

Abstract Background: Subjects with levels of non-HDL-C 30 mg/dL above those of LDL-C (lipid discordance) or with high remnant cholesterol levels could have a greater residual cardiovascular risk. Objectives: To determine the prevalence of lipid discordance in a primary prevention population and analyze the clinical variables associated with it; To investigate the association between lipid discordance and remnant cholesterol with the presence of carotid plaque. Methods: Primary prevention patients without diabetes or lipid-lowering therapy were included. Regardless of the LDL-C level, we define "lipid discordance" if the non-HDL-C value exceeded 30 mg/dL that of LDL-C. Remnant cholesterol was calculated as total cholesterol minus HDL-C minus LDL-C when triglycerides were < 4.0 mmol/L. Ultrasound was used to assess carotid plaque occurrence. Multiple regression logistic models were performed. Results: The study included 772 patients (mean age 52 ± 11 years, 66% women). The prevalence of lipid discordance was 34%. Male sex and body mass index were independently associated with discordant lipid pattern. The prevalence of carotid plaque was higher in subjects with lipid discordance (40.2% vs. 29.2, p = 0.002). The multivariate analysis showed that the discordant lipid pattern was associated with the greater probability of carotid plaque (OR 1.58, 95% CI 1.08-2.34, p = 0.02). Similarly, a significant association between calculated remnant cholesterol and carotid plaque was found. Conclusion: Lipid discordance and presence of a higher level of calculated remnant cholesterol are associated with subclinical atherosclerosis. Our findings could be used to improve the residual cardiovascular risk evaluation.

Resumo Fundamento: Indivíduos com níveis de não HDL-C excedendo em 30 mg/dl aqueles de LDL-C (discordância lipídica) ou com altos níveis de colesterol remanescente poderiam ter maior risco cardiovascular residual. Objetivos: determinar a prevalência de discordância lipídica em uma população de prevenção primária e analisar as variáveis clínicas com ela associadas; investigar a associação de discordância lipídica e colesterol remanescente calculado com a presença de placa carotídea. Métodos: Pacientes de prevenção primária sem diabetes ou sem terapia hipolipemiante foram incluídos. Independentemente do nível de LDL-C, definiu-se "discordância lipídica" como um valor de não HDL-C excedendo em 30 mg/dl aquele de LDL-C. Calculou-se o colesterol remanescente como colesterol total menos HDL-C menos LDL-C na presença de triglicerídeos < 4,0 mmol/l. Usou-se ultrassom para avaliar a presença de placa carotídea. Modelos de regressão logística múltipla foram construídos. Resultados: Este estudo incluiu 772 pacientes (idade média, 52 ± 11 anos; 66% mulheres). A prevalência de discordância lipídica foi de 34%. Sexo masculino e índice de massa corporal mostraram associação independente com padrão lipídico discordante. A prevalência de placa carotídea foi maior em indivíduos com discordância lipídica (40,2% vs. 29,2; p = 0,002). A análise multivariada mostrou associação do padrão lipídico discordante com maior probabilidade de placa carotídea (OR: 1,58; IC95%: 1,08-2,34; p = 0,02). Da mesma forma, identificou-se uma significativa associação entre colesterol remanescente calculado e placa carotídea. Conclusão: Discordância lipídica e presença de nível mais alto de colesterol remanescente calculado acham-se associados com aterosclerose subclínica. Nossos achados podem ser usados para aprimorar a avaliação de risco cardiovascular residual.