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.

Looking for a definition of aortic dilatation in overweight and obese individuals: body surface area-indexed values versus height-indexed diameters / En búsqueda de la definición de dilatación aórtica en individuos con sobrepeso y obesidad: rol de la indexación por altura. Análisis del Registro MATEAR

Abstract Introduction: Patient's body size is a significant determinant of aortic dimensions. Overweight and obesity underestimate aortic dilatation when indexing diameters by body surface area (BSA). We compared the indexation of aortic dimensions by height and BSA in subjects with and without overweight to determine the upper normal limit (UNL). Methods: The MATEAR study was a prospective, observational, and multicenter study (53 echocardiography laboratories in Argentina). We included 879 healthy adult individuals (mean age: 39.7 ± 11.4 years, 399 men) without hypertension, bicuspid aortic valve, aortic aneurysm, or genetic aortopathies. Echocardiograms were acquired and proximal aorta measured at the sinus of Valsalva (SV), sinotubular junction (STJ), and ascending aorta (AA) levels (EACVI/ASE guidelines). We compared absolute and indexed aortic diameters by height and BSA between groups (men with body mass index [BMI] < 25 and BMI ≥ 25, women with BMI < 25 and BMI ≥ 25). Results: Indexing of aortic diameters by BSA showed significantly lower values in overweight and obese subjects compared to normal weight in their respective gender (for women: SV 1.75 cm/m2 in BMI < 25 vs. 1.52 cm/m2 in BMI between 25 and 29.9 vs. 1.41 cm/m2 in BMI ≥ 30; at the STJ: 1.53 cm/m2 vs. 1.37 cm/m2 vs. 1.25 cm/m2; and at the AA: 1.63 cm/m2 vs. 1.50 cm/m2 vs. 1.37 cm/m2; all p < 0.0001 and for men, all p < 0.0001). These differences disappeared when indexing by height in both gender groups (all p = NS). Conclusion: While indexing aortic diameters by BSA in obese and overweight subjects underestimate aortic dilation, the use of aortic height index (AHI) yields a similar UNL for individuals with normal weight, overweight, and obesity. Therefore, AHI could be used regardless of their weight.

Resumen Introducción: El tamaño corporal es un determinante significativo de las dimensiones aórticas. El sobrepeso lleva a subestimar la dilatación aórtica. La altura (A) permanece estable durante la adultez, por lo que sería útil para indexar diámetros aórticos en pacientes obesos, aunque desconocemos los valores normales. Comparamos la indexación de diámetros aórticos por (IA) y superficie corporal (SC) en sujetos con y sin sobrepeso para determinar el límite superior normal (LSN, P97.5). Método: Se realizó un registro nacional, prospectivo, en 53 centros de Argentina. Se realizaron ecocardiogramas a 528 sujetos con índice de masa corporal (IMC) > 25 y 351 sujetos con IMC ≤ 25 seleccionados al azar. La población se subdividió en cuatro grupos según sexo e IMC y se compararon diámetros aórticos absolutos e indexados. Resultados: Se incluyeron 879 individuos (39.7 ± 11.4 años, 399 hombres). La indexación de los diámetros aórticos por SC mostró valores significativamente más bajos en sujetos con sobrepeso y obesidad en comparación con los de peso normal en cada sexo. Estas diferencias desaparecieron al indexar por altura en ambos géneros (todos p = NS). El LSN de los diámetros IA fue de 2.20 cm/m para senos, 1.99 cm/m para unión sino-tubular (UST) y 2.09 cm/m para aorta ascendente. Conclusiones: La indexación de los diámetros aórticos por SC en individuos con sobrepeso y obesidad subestima la dilatación aórtica. El IA permite establecer un LSN sin tener en cuenta el aumento espurio de la SC determinado por la grasa corporal. Podría ser utilizado en ambos sexos y de manera independiente del peso.

Looking for a definition of aortic dilatation in overweight and obese individuals: body surface area-indexed values versus height-indexed diameters.

INTRODUCTION: Patient's body size is a significant determinant of aortic dimensions. Overweight and obesity underestimate aortic dilatation when indexing diameters by body surface area (BSA). We compared the indexation of aortic dimensions by height and BSA in subjects with and without overweight to determine the upper normal limit (UNL). METHODS: The MATEAR study was a prospective, observational, and multicenter study (53 echocardiography laboratories in Argentina). We included 879 healthy adult individuals (mean age: 39.7 ± 11.4 years, 399 men) without hypertension, bicuspid aortic valve, aortic aneurysm, or genetic aortopathies. Echocardiograms were acquired and proximal aorta measured at the sinus of Valsalva (SV), sinotubular junction (STJ), and ascending aorta (AA) levels (EACVI/ASE guidelines). We compared absolute and indexed aortic diameters by height and BSA between groups (men with body mass index [BMI] < 25 and BMI ≥ 25, women with BMI < 25 and BMI ≥ 25). RESULTS: Indexing of aortic diameters by BSA showed significantly lower values in overweight and obese subjects compared to normal weight in their respective gender (for women: SV 1.75 cm/m2 in BMI < 25 vs. 1.52 cm/m2 in BMI between 25 and 29.9 vs. 1.41 cm/m2 in BMI ≥ 30; at the STJ: 1.53 cm/m2 vs. 1.37 cm/m2 vs. 1.25 cm/m2; and at the AA: 1.63 cm/m2 vs. 1.50 cm/m2 vs. 1.37 cm/m2; all p < 0.0001 and for men, all p < 0.0001). These differences disappeared when indexing by height in both gender groups (all p = NS). CONCLUSION: While indexing aortic diameters by BSA in obese and overweight subjects underestimate aortic dilation, the use of aortic height index (AHI) yields a similar UNL for individuals with normal weight, overweight, and obesity. Therefore, AHI could be used regardless of their weight.

INTRODUCCIÓN: El tamaño corporal es un determinante significativo de las dimensiones aórticas. El sobrepeso lleva a subestimar la dilatación aórtica. La altura (A) permanece estable durante la adultez, por lo que sería útil para indexar diámetros aórticos en pacientes obesos, aunque desconocemos los valores normales. Comparamos la indexación de diámetros aórticos por (IA) y superficie corporal (SC) en sujetos con y sin sobrepeso para determinar el límite superior normal (LSN, P97.5). MÉTODO: Se realizó un registro nacional, prospectivo, en 53 centros de Argentina. Se realizaron ecocardiogramas a 528 sujetos con índice de masa corporal (IMC) > 25 y 351 sujetos con IMC ≤ 25 seleccionados al azar. La población se subdividió en cuatro grupos según sexo e IMC y se compararon diámetros aórticos absolutos e indexados. RESULTADOS: Se incluyeron 879 individuos (39.7 ± 11.4 años, 399 hombres). La indexación de los diámetros aórticos por SC mostró valores significativamente más bajos en sujetos con sobrepeso y obesidad en comparación con los de peso normal en cada sexo. Estas diferencias desaparecieron al indexar por altura en ambos géneros (todos p = NS). El LSN de los diámetros IA fue de 2.20 cm/m para senos, 1.99 cm/m para unión sino-tubular (UST) y 2.09 cm/m para aorta ascendente. CONCLUSIONES: La indexación de los diámetros aórticos por SC en individuos con sobrepeso y obesidad subestima la dilatación aórtica. El IA permite establecer un LSN sin tener en cuenta el aumento espurio de la SC determinado por la grasa corporal. Podría ser utilizado en ambos sexos y de manera independiente del peso.

Limited periauricular facelift how to deal with short scar: a technical contribution / Lifting facial periauricular limitado: cómo tratar una cicatriz corta: una contribución técnica

El lifting facial, en la actualidad, es uno de los procedimientos estéticos más demandados y considerado como la Cirugía de Rejuvenecimiento Facial por excelencia. El propósito de la presente técnica es ofrecer un procedimiento quirúrgico alternativo de cicatrices reducidas, limitadas a la zona peri-auricular, fácilmente reproducible, sin incisiones extendidas mucho más allá del surco retro-auricular ni necesidad de colgajos para la región temporal. . Nuestra técnica se basa en una reposición en bloque de la zona preauricular, movilización de colgajos cervicales y rotación de un colgajo retroauricular, evitando colgajos e incisiones en la región temporal y occipital; por lo tanto, minimizando las cicatrices visibles (cicatriz prepilosa occipital), socavación de tejidos anchos, y además reduciendo el riesgo de dañar las estructuras nerviosas con menor tiempo de recuperación para nuestros pacientes, logrando resultados naturales y duraderos.

Facelift, currently, is one of the most demanded aesthetic procedures and considered as the Ultimate Facial Rejuvenation Surgery. The purpose of this present technique is to offer an alternative surgical procedure of reduced scars, limited to the peri-auricular area, easily reproducible, without the need of extended incisions far beyond the retro-auricular sulcus neither the need of flaps for the temporal region. Our technique is based on a block reposition of the pre auricular area, cervical flaps movilization and rotation of a retro auricular flap, avoiding flaps and incisions in the temporal and occipital region; therefore, minimizing visible scars (occipital pre-pilose scar), wide-tissue undermining, and in addition reducing the risk of damaging nerve structures with less recovery time for our patients, achieving natural and long lasting results.

[Statins and influenza mortality: systematic review and meta-analysis]. / Estatinas y mortalidad por influenza: revisión sistemática y meta-análisis.

BACKGROUND: Due to their anti-inflammatory properties, it has been suggested that the use of statins could influence the evolution of influenza virus infection. AIM: To evaluate the effect of statin therapy on mortality from influenza. METHODS: A meta-analysis that included studies evaluating the use of statins in patients with influenza and reporting data on mortality, after searching the PubMed/MEDLINE, Embase, and Cochrane Controlled Trials databases, was performed. A random effects model was applied. The risk of bias was analyzed and a sensitivity analysis was performed. RESULTS: Eight studies (10 independent cohorts), which included a total of 2,390,730 patients, were identified and eligible for analysis. A total of 1,146,995 subjects analyzed received statins, while 1,243,735 subjects were part of the control group. Statin therapy was associated with lower mortality (OR: 0.66; 95% CI: 0.51-0.85). The sensitivity analysis showed that the results were robust. CONCLUSION: Our data suggest that, in a population with influenza, the use of statins was associated with a significant reduction in mortality. These results must be confirmed in future clinical trials.

Compromiso cardiovascular en pacientes recuperados de COVID-19: ¿realidad o fantasía? / Cardiovascular Involvement in Patients Recovered from COVID-19: Reality or Fantasy?

RESUMEN Introducción: Se ha descrito que la infección por COVID-19 se asocia a complicaciones cardiovasculares en pacientes hospitalizados en 7-28%de los casos, con diagnóstico basado en elevación de biomarcadores. La afección cardiaca subclínica post COVID-19 en pacientes ambulatorios representa una preocupación creciente, así como las secuelas cardiovasculares a mediano y largo plazo. El objetivo del presente trabajo fue determinar la utilidad de la detección de compromiso cardiovascular en pacientes post COVID-19 ambulatorios, y su asociación con síntomas y factores de riesgo. Material y métodos: Se incluyeron 668 pacientes de manera prospectiva, >18 años entre septiembre de 2020 y marzo de 2021. Debían tener polimerasa de transcriptasa inversa (PCR) positiva en una muestra del tracto respiratorio positiva para COVID-19, y se les realizó evaluación con examen físico, electrocardiograma (ECG) y eco Doppler cardíaco. A quienes presentaban síntomas de riesgo o anomalías en el ECG o el eco Doppler, se les solicitó resonancia cardíaca (RMC) con contraste endovenoso. Resultados: La edad media fue de 42,9 ± 14,9 años; el 56,9% fueron mujeres. El 12,9% eran hipertensos, el 4,3% diabéticos y el 6,9% obesos. El 57,6% no tenía factores de riesgo cardiovascular y solo el 4,2% contaba con antecedentes cardiovasculares. El 73,2% presentó enfermedad leve, un 16,3% requirió internación y el 1,05% asistencia ventilatoria mecánica. Solo 5 pacientes tuvieron diagnóstico por RMC de miocarditis, y tanto el derrame pericárdico como la presencia de trastornos de la repolarización se asociaron significativamente con la misma (p <0,0001). Conclusiones: La presencia de alteraciones en el ECG o el eco Doppler cardíaco en nuestra cohorte fue infrecuente. Se diagnosticaron 5 casos de miocarditis viral con clínica compatible y confirmación por RMC.

ABSTRACT Introduction: COVID-19 infection has been associated with cardiovascular complications in 7-28% of hospitalized patients, with the diagnosis based on biomarkers elevation. Subclinical cardiac involvement in outpatients recovered from COVID-19 represents a growing concern, as well as mid- or long-term cardiovascular effects. Objective: The aim of the present study was to determine the usefulness of detecting cardiovascular involvement in outpatients recovered from COVID-19, and its association with symptoms and risk factors. Methods: Between September 2020 and March 2021, 668 patients >18 years were prospectively included. All the patients had to have COVID-19 confirmed diagnosis by a positive reverse transcription-polymerase chain reaction (RT-PCR) test in a respiratory tract sample COVID-19. They were evaluated with physical examination, electrocardiogram (ECG) and Doppler echocardiography. Patients with symptoms suggestive of risk or abnormal findings on ECG or echocardiogram underwent cardiac magnetic resonance imaging (CMRI) with gadolinium-based contrast agent. Results: Mean age was 42.9 ± 14.9 years and 56.9% were women; 12.9% were hypertensive, 4.3% were diabetic and 6.9% obese. Overall, 57.6% had no cardiovascular risk factors and only 4.2% had a history of cardiovascular disease. The disease was mild in 73.2%; 16.3% required hospitalization and 1.05% needed mechanical ventilation. Only 5 patients had myocarditis diagnosed by CMRI, and both pericardial effusion and abnormal repolarization were significantly associated with myocarditis (p < 0.0001). Conclusions: Abnormal ECG or echocardiographic findings were uncommon in our cohort. The diagnosis of viral myocarditis was made in 5 cases with clinical signs and symptoms, and was confirmed by CMRI.

Estatinas y mortalidad por influenza: revisión sistemática y meta-análisis / Statins and influenza mortality: systematic review and meta-analysis

INTRODUCCIÓN: Debido a sus propiedades antiinflamatorias, se ha planteado que el uso de las estatinas podría influir en la evolución de la infección por el virus de influenza. OBJETIVO: Evaluar el efecto de la terapia con estatinas sobre la mortalidad por influenza. MATERIAL y MÉTODOS: Se realizó un meta-análisis que incluyó estudios que evaluaron el uso de estatinas en pacientes con influenza e informaron los datos sobre mortalidad, después de buscar en las bases de datos PubMed/MEDLINE, Embase y Cochrane Controlled Trials. Se aplicó un modelo de efectos aleatorios. Se analizó el riesgo de sesgos y se desarrolló un análisis de sensibilidad. RESULTADOS: Se identificaron y se consideraron elegibles para el análisis ocho estudios (diez cohortes independientes), que incluyeron un total de 2.390.730 de pacientes. Un total de 1.146.995 de sujetos analizados recibieron estatinas mientras que 1.243.735 de sujetos formaron parte del grupo control. La terapia con estatinas se asoció con una menor mortalidad (OR: 0,66; IC 95%: 0,51-0,85). El análisis de sensibilidad mostró que los resultados fueron robustos. CONCLUSIONES: Nuestros datos sugieren que, en una población con influenza, el uso de estatinas se asoció con una reducción significativa de la mortalidad. Estos resultados deben confirmarse en futuros ensayos clínicos.

BACKGROUND: Due to their anti-inflammatory properties, it has been suggested that the use of statins could influence the evolution of influenza virus infection. AIM: To evaluate the effect of statin therapy on mortality from influenza. METHODS: A meta-analysis that included studies evaluating the use of statins in patients with influenza and reporting data on mortality, after searching the PubMed/MEDLINE, Embase, and Cochrane Controlled Trials databases, was performed. A random effects model was applied. The risk of bias was analyzed and a sensitivity analysis was performed. RESULTS: Eight studies (10 independent cohorts), which included a total of 2,390,730 patients, were identified and eligible for analysis. A total of 1,146,995 subjects analyzed received statins, while 1,243,735 subjects were part of the control group. Statin therapy was associated with lower mortality (OR: 0.66; 95% CI: 0.51-0.85). The sensitivity analysis showed that the results were robust. CONCLUSION: Our data suggest that, in a population with influenza, the use of statins was associated with a significant reduction in mortality. These results must be confirmed in future clinical trials.

Low-doses aspirin in the primary prevention of cardiovascular disease in patients with diabetes: Meta-analysis stratified by baseline cardiovascular risk.

BACKGROUND AND AIM: The aim of this meta-analysis was to analyze the risks and benefits of low-dose aspirin in patients with T2D without cardiovascular conditions according to the baseline cardiovascular risk. METHODS: We performed a meta-analysis including randomized clinical trials that evaluated the use of low-dose aspirin (75-100 mg/day) versus placebo/usual care in patients with T2D. Studies were classified as low, moderate and high risk based on the number of events in the placebo/control arms or by cardiovascular risk score when reported. The incidence of MACE, cardiovascular mortality and bleeding were evaluated. RESULTS: Ten eligible trials (34069 patients) were considered eligible for the analyses. According to the stratified analysis, low-dose aspirin use was associated with reduced risk for MACE in the moderate/high-risk group (OR: 0.88; 95% CI, 0.80-0.97; I2 = 0%) but not in the low-risk group (OR: 0.89; 95% CI, 0.77-1.01; I2 = 0%). Likewise, low-dose aspirin use was associated with more bleeding in the low-risk group, showing a non-significant trend in the moderate/high-risk group. There was no reduction in cardiovascular mortality in either group. Beyond the different findings in each stratum, the differences between the subgroups were not statistically significant. CONCLUSION: This study showed that low-dose aspirin in patients with T2D reduces MACE and increases bleeding. Based on the within-subgroups results, the baseline cardiovascular risk does not modify the effect of aspirin therapy. However, few studies were included and the comparison between subgroups showed a trend in favor to the highest risk group, these results should be confirmed in future studies.

Glucagon-like Peptide-1 Receptor Agonists and Cardioprotective Benefit in Patients with Type 2 Diabetes Without Baseline Metformin: A Systematic Review and Update Meta-analysis.

INTRODUCTION: Sodium Glucose Co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1RAs) were associated with a reduction in cardiovascular disease events in cardiovascular outcomes trials (CVOTs) in type 2 diabetes. Most of the patients included in these trials received metformin as background therapy. AIM: To evaluate the effect of glucagon-like peptide 1 receptor agonists on major cardiovascular events (MACE) and mortality in metformin-naïve patients with type 2 diabetes. METHODS: A systematic review and meta-analysis of randomized controlled clinical trials of GLP-1RAs on type 2 diabetes population was performed, after searching the PubMed/MEDLINE, Embase, Scielo, Google Scholar and Cochrane Controlled Trials databases. The primary endpoint was MACE. The secondary endpoints were cardiovascular death and all-cause mortality. A meta-analysis of time-to-event outcomes was performed. This meta-analysis was registered in PROSPERO (CRD42021260040) RESULTS: Seven trials, including 11510 patients, were identified and considered eligible for the analyses. GLP-1RAs were associated with a significant reduction in MACE incidence (HR: 0.86, 95% confidence interval: 0.79-0.94; I2: 0%). The secondary endpoints analysis showed a non-significant reduction in all-cause mortality (HR: 0.86, 95% confidence interval: 0.73-1.00 I2: 0%) and cardiovascular mortality (HR: 0.81, 95% confidence interval: 0.63-1.05; I2: 0%). CONCLUSIONS: In this meta-analysis, GLP-1RAs reduced the incidence of MACE in patients with type 2 diabetes without metformin at baseline, without significant reduction in all-cause mortality and cardiovascular mortality. These results support the fact that when a GLP-1RAs is administered, the benefit on cardiovascular outcomes is independent of the use of metformin.

Statin use in patients with elevated serum hepatic transaminases at baseline: A meta-analysis.

AIMS: Clinical trials showed that statin therapy decreased cardiovascular events without significantly raising the level of transaminases. However, the information in subjects with altered liver test at baseline is more limited. The objectives of this meta-analysis were to analyze the liver safety and cardiovascular benefit when using a statin-based lipid-lowering treatment compared to a less intensive treatment or placebo, in subjects with abnormal liver tests at baseline. DATA SYNTHESIS: We performed a meta-analysis including randomized trials of statin-based lipid-lowering therapy versus less intensive lipid-lowering therapy or placebo, reporting worsening hepatic test (>3 ULN) and cardiovascular events in patients with abnormal liver tests at baseline. The random-effects model was performed. This meta-analysis was performed according to PRISMA guidelines. Five eligible trials, including 2548 patients were identified and considered eligible for the analyses. A more intensive statin-based lipid-lowering therapy were associated with a similar occurrence of serious alteration of liver tests (OR: 0.90, 95% confidence interval: 0.21-3.99; I2: 64%) compared to less intensive or placebo treatments. Likewise, more intensive lipid-lowering strategies were associated with a significant reduction in major cardiovascular events (OR: 0.34, 95% confidence interval: 0.17-0.70; I2: 66%). CONCLUSIONS: In this study, a more intensive statin-based lipid-lowering treatment, compared with less intensive treatment or placebo, showed a similar incidence of worsening transaminases levels in patients with abnormal liver tests at baseline. Also, a reduction in cardiovascular events was observed when a more intensive lipid-lowering therapy was used.

Novel antidiabetic drugs and risk of cardiovascular events in patients without baseline metformin use: a meta-analysis.

AIMS: To evaluate the effect of sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs) on major cardiovascular events (MACE) in metformin-naïve patients with type 2 diabetes (T2D). METHODS AND RESULTS: A meta-analysis was performed of randomized controlled clinical trials of GLP-1RAs and SGLT-2 inhibitors on T2D populations, after searching the PubMed/MEDLINE, Embase, and Cochrane Controlled Trials databases. The primary endpoint was MACE. The secondary endpoint, explored in the subgroup of SGLT-2 inhibitors studies, was cardiovascular death or hospitalization for heart failure. A random-effects meta-analysis model was applied. Six eligible trials (three studies of SGLT-2 inhibitors and three trials of GLP-1RAs), including 13 049 patients, were identified and considered eligible for the analyses. The new antidiabetic drugs were associated with a significant reduction in MACE [odds ratio (OR): 0.80, 95% confidence interval: 0.70-0.93; I2: 53%]. The subgroup analysis showed the following findings: GLP-1RAs group, OR: 0.77 (95% confidence interval 0.67-0.88); SGLT-2 inhibitors, OR: 0.85 (95% confidence interval 0.63-1.15). SGLT-2 inhibitors were associated with a significant reduction in hospitalization for heart failure or cardiovascular mortality incidence (OR: 0.67, 95% confidence interval: 0.47-0.95; I2: 78%). CONCLUSION: In this meta-analysis, new antidiabetic drugs reduced the incidence of MACE in metformin-naïve T2D patients. The beneficial effect was especially observed in the GLP-1RAs subgroup. The use of SGLT-2 inhibitors was associated with a reduction in cardiovascular death or hospitalization for heart failure. These results support the fact that metformin would not be indispensable to obtain positive cardiovascular effects when new antidiabetic drugs are administered.

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.

Atrial size and sports. A great training for a greater left atrium: how much is too much?

Athlete's heart results from physiological adaptations to the increased demands of exercise, and left atrial (LA) enlargement (LAE) is a fundamental component. However, LAE occurs in certain pathological conditions and it might represent a diagnostic challenge in athletes. LA volume index (LAVi) by echo is a convenient diagnostic tool for LAE identification. We hypothesized that accumulated lifetime training thousand hours (LTH) would have a main role in LAE. Therefore, our aim was to assess the association between LTH, LAVi and LAE in athletes. Young and middle-aged males with different training levels were included and grouped as recreational (REa, n = 30), competitive (COa, n = 169) and elite (ELa, n = 80) athletes for LTH calculation and echo assessment. LA dimensions resulted greater in ELa when compared to other groups (p < 0.001). LAVi correlated stronger with LTH than with age (p < 0.001). Polynomial regression analysis showed a non-linear, almost triphasic, effect of cumulative training on LA size (p < 0.02). Multivariate logistic regression, including LTH, age, body surface area, systolic blood pressure and other explanatory variables to predict LAE, showed LTH as the sole significant factor [OR 1.45 (CI 1.1-1.92), p < 0.008]. ROC analysis found an optimal cut off point of 3.6 LTH for LAE identification (AUC = 0.84, p < 0.001. RR = 5.65, p < 0.001). We conclude that LAE associates with LTH more than with other clinical parameters, and with less impact at higher amounts of LTH. Lifetime training greater than 3600 hours increases the probability of finding LAE in athletes. Future research should provide more insights and implications of these findings.

Aspirin in primary prevention. Meta-analysis stratified by baseline cardiovascular risk.

Introducción: La utilidad de la aspirina en la prevención primaria es todavía objeto de controversia. Los avances médicos y la variabilidad del riesgo cardiovascular podrían explicar la heterogeneidad de los estudios publicados, y las poblaciones de alto riesgo tendrían mayor beneficio. Objetivo: Analizar los efectos de la aspirina en pacientes sin antecedentes cardiovasculares y evaluar los resultados de acuerdo con el riesgo cardiovascular de las poblaciones. Métodos: Se incluyeron estudios que evaluaron el uso de la aspirina en comparación con placebo en la prevención primaria. Se analizó la combinación de muerte cardiovascular, infarto agudo de miocardio (IAM) y accidente cerebrovascular (ACV) isquémico. El punto final de seguridad fue la combinación de ACV hemorrágico y sangrado mayor. Se clasificaron los estudios en riesgo bajo y moderado/ alto, de acuerdo con el número de episodios en la rama de placebo. Resultados: Se evaluaron 13 estudios (n = 164,225), ocho de riesgo cardiovascular bajo (n = 118,455) y cinco de moderado/alto (n = 45,770). Se observó una reducción del punto final combinado en el grupo de aspirina (OR 0.90; IC 95%, 0.85-0.94), sin diferencias en mortalidad cardiovascular (OR 0.94; IC 95%, 0.86-1.04). No se identificaron diferencias entre los subgrupos de riesgo. Se reconocieron mayores complicaciones hemorrágicas en el grupo de aspirina (OR 1.45; IC 95%, 1.32-1.60), sin diferencias entre los subgrupos de riesgo. Conclusión: La aspirina se relacionó con una leve disminución de IAM y ACV isquémico en términos absolutos, sin diferencias en la mortalidad cardiovascular. Esto, junto con el aumento de las complicaciones hemorrágicas, se traduce en una ausencia de beneficio clínico neto. El riesgo cardiovascular basal de la población no modificó los resultados. Background: The usefulness of aspirin in primary prevention continues to be the subject of debate. Medical advances and the variability of cardiovascular risk could explain the heterogeneity of the published studies. High risk populations would have greater benefit. Objective: Analyzing the effects of aspirin in patients without cardiovascular disease and evaluating the results according to the cardiovascular risk of the populations. Methods: Studies evaluating aspirin versus placebo in primary prevention were included. The primary endpoint was the combined cardiovascular death, acute myocardial infarction (AMI) and ischemic stroke. The final safety point was the combination of hemorrhagic stroke and major bleeding. The studies were classified into low and moderate/high risk, according to the number of events in the placebo arm. Results: Thirteen studies were evaluated (n = 164,225), eight of low cardiovascular risk (n = 118,455) and five of moderate/high risk (n = 45,770). There was a reduction of the combined endpoint in the aspirin group (odds ratio [OR] 0.90; 95% confidence interval [CI], 0.85-0.94), without differences in cardiovascular mortality (OR 0.94; 95% CI, 0.86-1.04). No differences were observed when comparing the risk subgroups. Greater hemorrhagic complications were observed in the aspirin group (OR 1.45; 95% CI, 1.32-1.60), without differences between the risk subgroups. Conclusion: Aspirin was associated with a slight decrease in AMI and ischemic stroke in absolute terms, with no differences in cardiovascular mortality. This accompanied by the increase in hemorrhagic complications, results in an absence of net clinical benefit. The baseline cardiovascular risk of the population did not affect the results.

Aspirina en la prevención primaria. Metaanálisis estratificado por riesgo cardiovascular basal / Aspirin in primary prevention. Meta-analysis stratified by baseline cardiovascular risk

Resumen Introducción: La utilidad de la aspirina en la prevención primaria es todavía objeto de controversia. Los avances médicos y la variabilidad del riesgo cardiovascular podrían explicar la heterogeneidad de los estudios publicados, y las poblaciones de alto riesgo tendrían mayor beneficio. Objetivo: Analizar los efectos de la aspirina en pacientes sin antecedentes cardiovasculares y evaluar los resultados de acuerdo con el riesgo cardiovascular de las poblaciones. Métodos: Se incluyeron estudios que evaluaron el uso de la aspirina en comparación con placebo en la prevención primaria. Se analizó la combinación de muerte cardiovascular, infarto agudo de miocardio (IAM) y accidente cerebrovascular (ACV) isquémico. El punto final de seguridad fue la combinación de ACV hemorrágico y sangrado mayor. Se clasificaron los estudios en riesgo bajo y moderado/ alto, de acuerdo con el número de episodios en la rama de placebo. Resultados: Se evaluaron 13 estudios (n = 164,225), ocho de riesgo cardiovascular bajo (n = 118,455) y cinco de moderado/alto (n = 45,770). Se observó una reducción del punto final combinado en el grupo de aspirina (OR 0.90; IC 95%, 0.85-0.94), sin diferencias en mortalidad cardiovascular (OR 0.94; IC 95%, 0.86-1.04). No se identificaron diferencias entre los subgrupos de riesgo. Se reconocieron mayores complicaciones hemorrágicas en el grupo de aspirina (OR 1.45; IC 95%, 1.32-1.60), sin diferencias entre los subgrupos de riesgo. Conclusión: La aspirina se relacionó con una leve disminución de IAM y ACV isquémico en términos absolutos, sin diferencias en la mortalidad cardiovascular. Esto, junto con el aumento de las complicaciones hemorrágicas, se traduce en una ausencia de beneficio clínico neto. El riesgo cardiovascular basal de la población no modificó los resultados.

Abstract Background: The usefulness of aspirin in primary prevention continues to be the subject of debate. Medical advances and the variability of cardiovascular risk could explain the heterogeneity of the published studies. High risk populations would have greater benefit. Objective: Analyzing the effects of aspirin in patients without cardiovascular disease and evaluating the results according to the cardiovascular risk of the populations. Methods: Studies evaluating aspirin versus placebo in primary prevention were included. The primary endpoint was the combined cardiovascular death, acute myocardial infarction (AMI) and ischemic stroke. The final safety point was the combination of hemorrhagic stroke and major bleeding. The studies were classified into low and moderate/high risk, according to the number of events in the placebo arm. Results: Thirteen studies were evaluated (n = 164,225), eight of low cardiovascular risk (n = 118,455) and five of moderate/high risk (n = 45,770). There was a reduction of the combined endpoint in the aspirin group (odds ratio [OR] 0.90; 95% confidence interval [CI], 0.85-0.94), without differences in cardiovascular mortality (OR 0.94; 95% CI, 0.86-1.04). No differences were observed when comparing the risk subgroups. Greater hemorrhagic complications were observed in the aspirin group (OR 1.45; 95% CI, 1.32-1.60), without differences between the risk subgroups. Conclusion: Aspirin was associated with a slight decrease in AMI and ischemic stroke in absolute terms, with no differences in cardiovascular mortality. This accompanied by the increase in hemorrhagic complications, results in an absence of net clinical benefit. The baseline cardiovascular risk of the population did not affect the results.

Effect of bempedoic acid on new onset or worsening diabetes: A meta-analysis.

INTRODUCTION: Bempedoic acid is a new agent that reduces low-density lipoprotein cholesterol. Since inhibits cholesterol synthesis through a different mechanism than statins, the adverse effects related to it may also be different. Therefore, the objective of the present meta-analysis was to evaluate the effect of bempedoic acid on new onset or worsening diabetes. METHODS: We performed a meta-analysis including randomized trials of bempedoic acid therapy, reporting new onset or worsening diabetes with a minimum of 4 weeks of follow-up. The fixed-effects model was performed. This meta-analysis was performed according to PRISMA guidelines. RESULTS: Five eligible trials of bempedoic acid, including 3629 patients, were identified and considered eligible for the analyses. A total of 2419 subjects were allocated to receive bempedoic acid while 1210 subjects were allocated to the respective control arms. Bempedoic acid therapy is associated with a significant reduction in new onset or worsening diabetes [Odds Ratio: 0.66, 95% confidence interval: 0.48-0.90; I2: 0%]. CONCLUSION: This data suggests that the use of bempedoic acid significantly reduces the new onset or worsening diabetes risk. This finding should be confirmed with future studies.

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).

Role of Colchicine in Stroke Prevention: An Updated Meta-Analysis.

BACKGROUND: Colchicine is a microtubule inhibitor with anti-inflammatory properties. As the body and quality of evidence regarding the efficacy of colchicine for cardiovascular prevention is controversial, the aims of this study was to evaluate the effect of colchicine therapy on vascular events. METHODS: A meta-analysis was performed of randomized controlled clinical trials of colchicine on high cardiovascular risk populations, reporting data from stroke, myocardial infarction, cardiovascular mortality and all-cause mortality, after searching the PubMed/MEDLINE, Embase and Cochrane Controlled Trials databases. A random-effects meta-analysis model was then applied. RESULTS: Nine eligible trials of colchicine therapy, involving a total of 6630 patients, were considered eligible for analysis (3359 subjects were allocated to receive colchicine while 3271 subjects were allocated to the respective control arms). The stroke incidence was lower in the colchicine group compared with placebo arm (OR, .33; 95%CI, .15-.70; 6 studies evaluated). We did not find a significant reduction in the incidence of myocardial infarction, cardiovascular mortality or all-cause mortality. CONCLUSIONS: Our data suggest that in a population with high cardiovascular risk, the use of colchicine results in significant reduction on stroke risk. Colchicine is an accessible drug that could be successfully utilized for the prevention of atherosclerotic cerebrovascular disease. The tolerability and benefits should be confirmed in ongoing clinical trials.

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.