Debilidad muscular proximal progresiva de inicio subagudo en un paciente anciano: descripción de un caso / Progressive proximal muscle weakness with subacute onset in an elderly patient: a case report

Introducción: Las estatinas son de los medicamentos más recetados. Aunque las estatinas generalmente se toleran bien, pueden provocar efectos secundarios musculoesqueléticos. La miopatía autoinmune necrotizante inducida por estatinas (SINAM) es una afección rara y la prevalencia sólo es de 1 de cada 100.000 personas. Este trastorno se caracteriza por debilidad muscular simétrica progresiva y grave, elevación marcada de la creatincinasa y síntomas persistentes a pesar de la interrupción de la estatina. La electromiografía suele mostrar un patrón de miopatía irritable inespecífico, indistinguible de otras miopatías inflamatorias. La biopsia muscular muestra la presencia de fibras necróticas, fibras en regeneración sin células inflamatorias significativas y una regulación positiva difusa o focal de la expresión del complejo mayor de histocompatibilidad de clase I. Los anticuerpos anti-3-hidroxi-3-metilglutaril-coenzima A (anti-HMG-CoA) reductasa representan un rasgo serológico característico de la SINAM.Caso clínico: Presentamos a un paciente que desarrolló debilidad muscular progresiva después de tomar simvastatina durante los últimos siete años. En la presentación inicial, su nivel de creatincinasa fue de 2.954 U/L y los anticuerpos anti-HMG-CoA reductasa fueron positivos. La biopsia mostró rasgos miopáticos profundos con numerosas fibras necróticas, algunas fibras en regeneración e infiltrado de células inflamatorias perimisial, combinado con una sobreexpresión difusa del complejo mayor de histocompatibilidad de clase I. Se le diagnosticó SINAM, se suspendió la estatina y se inició una dosis alta de corticoides sistémicos, inmunoglobulina intravenosa y metotrexato. Después de tres meses de seguimiento, tuvo una mejora significativa en la fuerza muscular y el nivel de creatincinasa volvió a la normalidad.(AU)

Introduction: Statins are some of the most widely prescribed medications. Although statins are generally well tolerated, they can lead to musculoskeletal side effects. Statin-induced necrotizing autoimmune myositis (SINAM) is a rare condition and the prevalence is only 1 per 100,000 people. This disorder is characterized by progressive and severe symmetric muscle weakness, marked elevation of creatine kinase and persistent symptoms despite statin discontinuation. Electromyography commonly shows a nonspecific irritable myopathy pattern indistinguishable from other inflammatory myopathies. Muscle biopsy shows the presence of necrotic fibers, regenerating fibers without significant inflammatory cells and diffuse or focal upregulation of major histocompatibility complex class I expression. The anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibodies represent a characteristic serological feature of SINAM. Case report: We present a patient who developed progressive muscle weakness after taking simvastatin for the last seven years. At initial presentation, her creatine kinase level was 2,954 U/L and anti-HMGCR antibodies were positive. The biopsy showed a profound myopathic features with numerous necrotic fibers, some regenerating fibers and perimysial inflammatory cell infiltrate, combined with a diffuse overexpression of major histocompatibility complex class I products. She was diagnosed with SINAM, statin was suspended and a high dose of systemic corticosteroids, intravenous immunoglobulin therapy and methotrexate was started. At three-month follow-up, she had significant improvement in muscle strength and creatine kinase level returned to normal...(AU)

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.

Evidencia del manejo de miopatías asociadas a estatina con coenzima Q10 / Evidence for the management of myopathies associated with statin with coenzyme Q10

Introducción: La incidencia de eventos cardiovasculares fatales es muy elevada y el tratamiento con estatinas es vital para reducir este riesgo en muchos pacientes, sin embargo, sus efectos adversos sobre el músculo esquelético dificultan la adherencia o la continuación del mismo. Se ha propuesto la suplementación de coenzima Q10 para revertir mialgias asociadas a el empleo de estatinas. Los ensayos clínicos que se realizaron en los últimos 10 años obtuvieron resultados contrapuestos. El objetivo de este trabajo es revisar la evidencia sobre la eficacia del empleo de suplementos de coenzima Q10 en para mitigar las miopatías causadas por las estatinas. Metodología: Se realizó una búsqueda sistemática de la literatura publicada hasta Julio de 2020. Las bases de datos consultadas fueron MEDLINE y SCOPUS. También se consultaron instituciones como la Agencia Española del Medicamento y Productos Sanitarios (AEMPS), la European Medicines Agency (EMA) y la Food and Drug Administration (FDA). Resultados: La etiología de las mialgias asociadas a estatinas sigue siendo desconocida y la evidencia encontrada en los ensayos clínicos y metaanalisis obtuvieron conclusiones dispares. La European Medicine Agency (EMA) solo considera el empleo de suplementos en síndrome de deficiencia primaria de coenzima Q10, mientras en Reino Unido el National Institute for Health and Care Excellence (NICE) y el National Institute of Health (NIH) no recomiendan el empleo de estos suplementos para tratar mialgias asociadas al empleo de estatinas. Conclusiones: El conjunto de los estudios analizados no consiguió una evidencia unánime para poder recomendar este empleo de suplementos de coenzima Q10 de modo confiable. Se necesitan estudios mejor diseñados que aporten reproducibilidad y robustez a futuros ensayos clínicos. (AU)

Introduction: The incidence of fatal cardiovascular events is very high and statin treatment is vital to reduce this risk in many patients, however, its adverse effects on skeletal muscle make it difficult to adhere or continue it. Coenzyme Q10 supplementation has been proposed to reverse myalgia associated with the use of statins. The clinical trials carried out in the last 10 years obtained conflicting results. The aim of the present work is to review the evidence on the efficacy of the use of coenzyme Q10 supplements in mitigating myopathies caused by statins. Methodology: A systematic review of the published literature until July 2020 was undertaken. The searched databases were MEDLINE and SCOPUS. Institutions such as the Agencia Española del Medicamento y productos Sanitarios (AEMPS), European Medicines Agency (EMA) and Food and Drug Administration were also consulted. Results: The etiology of statin-associated myalgias remains unknown, and the evidence found in clinical trials and meta-analysis drew disparate conclusions. The European Medicine Agency (EMA) only considers the use of supplements in primary coenzyme Q10 deficiency syndrome, while in the United Kingdom the National Institute for Health and Care Excellence (NICE) and the National Institute of Health (NIH) do not recommend the use of these supplements to treat myalgias associated with the use of statins. Conclusions: The set of studies analyzed did not obtain unanimous evidence to be able to reliably recommend this use of coenzyme Q10 supplements. Better designed studies that provide reproducibility and robustness to future clinical trials are needed. (AU)

Estudo do efeito de estatinas e antiplaquetários na evolução do infarto agudo do miocárdio: uma abordagem metabolômica multiplataform / Effect of statins and antiplatelets in the evolution of acute myocardium infarction: a multiplatform metabolomics approach

O infarto agudo do miocárdio (IAM) é a maior causa de mortalidade no mundo. A oclusão coronária determina a necrose completa de cardiomiócitos (células musculares cardíacas) durante as primeiras horas do IAM. Porém, mesmo após a perda de massa de miocárdio viável cessar, a região infartada pode se expandir ou contrair no decorrer das primeiras semanas, afetando o prognóstico dos pacientes. Alguns tratamentos podem auxiliar na recuperação e melhoria do prognóstico desses pacientes, como o uso de estatinas e antiplaquetários, que quando utilizados em conjunto, proporcionam efeitos sinérgicos. O presente estudo investigou e comparou, através da óptica da metabolômica global multiplataforma, tratamentos concomitantes de estatinas (sinvastatina ou rosuvastatina) e antiplaquetários bloqueadores do receptor de ADP (clopidogrel ou ticagrelor), em pacientes que sofreram IAM. Foram coletadas amostras de plasma e urina de cerca 40 pacientes tratados com clopidrogrel e sinvastatina ou ticagrelor e rosuvastatina no Hospital São Paulo em diferentes períodos (basal, 1 mês e 6 meses após IAM). Amostras de plasma (basal e 1 mês) foram analisadas por RPLC-MS nos modos de ionização positivo e negativo, GC-MS e CEMS. Amostras de urina (basal, 1 mês e 6 meses) foram analisadas por RPLC-MS no modo de ionização positivo e HILIC-MS nos modos de ionização positivo e negativo. A abordagem metabolomica global multiplataforma evidenciou alterações no metabolismo de diferentes vias pelos dois tratamentos. Os dois tratamentos proporcionaram um efeito pronunciado no metabolismo de diferentes lipídios, como glicerolipídios, esfingolipídios, glicerofosfolipídios e ácidos graxos, sendo que a combinação rosuvastatina e ticagrelor resultou num efeito mais acentuado. Já o tratamento com clopidogrel e sinvastatina alterou de maneira mais pronunciada o metabolismo de aminoácidos ramificados e de acilcarnitinas de cadeia curta. Observou-se ainda a alteração de possíveis biomarcadores relatados na literatura como associados a problemas cardiovasculares, como hipoxantina, ácido 2-hidroxibutírico, algumas espécies de ceramidas, fosfatidilcolinas e acilcarnitinas de cadeia curta

cute myocardium infarction (AMI) is the main mortality cause in the world. The coronary occlusion determines the complete necrosis of cardiomyocytes (cardiac muscle cells) during the first hours of AMI. However, even after the loss of viable myocardial mass ceases, the infarcted area may still expand or contract during the first weeks after AMI, affecting the patient prognosis. Some treatments may assist patient recovery and improve prognostic, such as statins and antiplatelets which, when combined, provide synergic effects. This study investigated and compared, by untargeted multiplatform metabolomics, simultaneous treatments of statins (simvastatin or rosuvastatin) and ADP receptor antagonist antiplatelets (clopidogrel or ticagrelor) in patients that suffered AMI. Plasma and urine samples from around 40 patients treated with clopidogrel and simvastatin or ticagrelor and rosuvastatin were collected in Hospital Sao Paulo at different time points (basal, 1 month, 6 months after AMI). Plasma samples (basal and 1 month) were analyzed by RPLC-MS in positive and negative ionization modes, GC-MS and CE-MS. Urine samples (basal, 1 month, 6 months) were analyzed by RPLC-MS in positive ionization mode and by HILIC-MS in positive and negative ionization modes. The untargeted multiplatform metabolomics approach has shown that different metabolic pathways have been altered by the two treatments. Both treatments had a profound impact on the metabolism of different lipids, such as glycerolipids, sphingolipids, glycerophospholipids, and fatty acids. However, the combined treatment using rosuvastatin and ticagrelor impacted the most the lipid pathways. On the other hand, clopidogrel and simvastatin treatment affected more intensily the branched chain amino acids and short chain acylcarnitines metabolisms. Reported biomarkers in the literature related to cardiovascular diseases were also observed in this study, such as hypoxanthine, 2-hydroxybutyric acid, some species of ceramides, phosphatidylcholines and short chain acylcarnitines

Efectividad clínica y radiográfica de las estatinas en el tratamiento de la periodontitis / Clinical and radiographic effectiveness of statins in the treatment of periodontitis

Introducción: La enfermedad periodontal es un padecimiento inflamatorio, infeccioso y multifactorial crónico, caracterizado por la inflamación de los tejidos blandos periodontales. En estadios avanzados (periodontitis), produce la destrucción progresiva de los tejidos duros periodontales, lo que conduce a la posterior pérdida de dientes, si esta no es tratada. Objetivo: Determinar la efectividad clínica y radiográfica de las estatinas en el tratamiento de la periodontitis. Métodos: Se realizó una búsqueda de la literatura hasta abril del 2019, en las bases de datos biomé dicas: PubMed, Embase, SciELO, Science Direct, Scopus, Sistema de información sobre literatura gris en Europa, Literatura Latinoamericana y del Caribe en Ciencias de la Salud, Google Académico y el Registro Central de Ensayos Clínicos Cochrane. Se definieron como criterios de selección de los estudios que fueran ensayos clínicos aleatorizados, con una antigüedad máxima de cinco años y que reportaran los efectos clínicos y radiográficos (profundidad al sondaje, nivel de inserción clínica, índice de placa, índice de sangrado, índice gingival, defecto intraóseo y profundidad del defecto) de las estatinas en el tratamiento de la periodontitis. Se analizó el riesgo de sesgo de los estudios por el Manual Cochrane de revisiones sistemáticas de intervenciones. Resultados: La estrategia de búsqueda arrojó 19 artículos, de los cuales el 100 por ciento reportó que había diferencia en la profundidad al sondaje, nivel de inserción clínica, índice de placa, índice de sangrado, índice gingival, defecto intraóseo y profundidad del defecto de las estatinas en el tratamiento de la periodontitis. Conclusiones: La literatura revisada sugiere que el uso de estatinas es efectivo, clínica y radiográficamente, en el tratamiento de la periodontitis(AU)

Introduction: Periodontal disease is a chronic multifactorial infectious inflammatory condition characterized by inflammation of soft periodontal tissue. In advanced stages (periodontitis) it causes progressive destruction of hard periodontal tissue, leading to eventual tooth loss if not treated. Objective: Determine the clinical and radiographic effectiveness of statins in the treatment of periodontitis. Methods: A search was carried out in the literature published until April 2019 in the biomedical databases PubMed, Embase, SciELO, Science Direct, Scopus, System for Information on Gray Literature in Europe, Latin American and Caribbean Health Sciences Literature, Google Scholar, and Cochrane Central Register of Clinical Trials. The following selection criteria were defined for the studies: randomized clinical trials published in the last five years and reporting on clinical and radiographic effects (probing depth, clinical insertion level, plaque index, bleeding index, gingival index, intraosseous defect and defect depth) of statins in the treatment of periodontitis. Bias risk analysis was based on the Cochrane manual of systematic reviews of interventions. Results: A total 19 papers were retrieved, of which 100 percent reported differences in the probing depth, clinical insertion level, plaque index, bleeding index, gingival index, intraosseous defect and defect depth of statins in the treatment of periodontitis. Conclusions: The literature review conducted suggests that the use of statins is clinically and radiographically effective in the treatment of periodontitis(AU)

Coenzima Q10versus vitamina D en el manejo de las mialgias asociadas a estatinas / Coenzyme Q10 versus vitamin D when handling myalgias associated to statins

Introducción: Las estatinas han mostrado ser una herramienta esencial en la prevención de eventos cardiovasculares, sin embargo, sus efectos adversos sobre el músculo esquelético conocidos como SAMS (Statin-Associated Muscle Symptoms) son frecuentes y motivan la falta de adherencia al tratamiento. Es necesario superar esta barrera con nuevas estrategias, se ha sugerido en diferentes estudios que la suplementación de vitamina D o de coenzima Q10 (CoQ10) podrían revertir este inconveniente. El objetivo de este trabajo es revisar y comparar la evidencia disponible sobre CoQ10 y la vitamina D como posibles candidatos para el manejo de las SAMS. Método: Se ha realizado una búsqueda bibliográfica de la literatura, las bases de datos consultadas fueron Medline a través de PubMed y Scopus. Resultados: Los ensayos clínicos que evaluaron la suplementación de CoQ10 con este fin obtuvieron conclusiones dispares, la suplementación oral aumentó las concentraciones séricas, pero no se ha confirmado con claridad que este incremento se transfiera al tejido musculo-esquelético ya que pocos ensayos emplearon biopsias, además, cuando se emplearon arrojaron resultados contrapuestos. Respecto a la vitamina D, destacaron estudios transversales y retrospectivos en los que se evidenció que la hipovitaminosis D se asocia a exacerbación de estas miopatías asociadas, en cambio, los ensayos que valoraron la suplementación no obtuvieron una evidencia unánime. Conclusión: No se pueden recomendar suplementos de CoQ10 de modo confiable para tratar SAMS. El estatus de vitamina D al inicio de la terapia con estatinas es un buen marcador de riesgo y mejora el pronóstico de las miopatías asociadas, en cambio, se necesitan más ensayos clínicos controlados con placebo para contrastar la utilidad en suplementación.(AU)

Introduction: Statins have shown to be an essential tool in the prevention of cardiovascular events. However, their adverse effects on skeletal muscle are common and lead to lack of adherence to treatment. Different studies suggest that vitamin D or coenzyme Q10 supplementation could reverse this problem. The aimof this work is to review and compare the available evidence on coenzyme Q10and vitamin D as possible candidates for the management of statin-related myalgias. Method: A bibliographic search of literature was conducted, databases consulted were Medline through Pubmed and Scopus. Results: Clinical trials that evaluated coenzyme Q10 supplementation obtained disparate results. Oral supplementation increased coenzyme Q10 serum concentrations, but it has not been confirmed clearly that this increase is transferred to muscular-skeletal tissue, since few trials used biopsies, and when applied, opposing results were obtained. With regard to vitamin D, some cross-sectional and retrospective studies stand out. They showed hypovitaminosis D is associated with statin-related myalgias exacerbation. However, trials that assessed its supplementation did not obtain unanimous evidence. Conclusion: Coenzyme Q10 supplements cannot be recommended reliably to treat statin-related myalgias. Vitamin D status at the beginning of statin therapy is a good risk marker and improves statin-related myalgias prognosis, but more placebo-controlled clinical trials are needed to prove its supplementation usefulness.(AU)

Association between statin use and mortality risks during the acute phase of ischemic stroke in patients admitted to an intensive care unit / Associação entre o uso de estatina e risco de mortalidade durante a fase aguda do acidente vascular cerebral isquêmico em pacientes admitidos em uma unidade de terapia intensiva

Abstract Ischemic stroke is a common cause of death. The role of statins in the secondary prevention of the chronic ischemic stroke phase has been established. However, evidence regarding their efficacy in this phase is limited and contradictory. Objective: To evaluate the association between statin use and mortality risk during the acute phase of ischemic stroke in patients admitted to an intensive care unit. Methods: This was an observational and prospective study of ischemic stroke patients aged ≥18, admitted to an intensive care unit. Medications used during the first 7 days after the ictus, as well as medications used previously, were recorded. The primary outcome was all-cause mortality during the first 7 days. Results: We screened 212 patients and included 97 patients with ischemic stroke in the study period. The mortality rate among patients who used statins during the acute IS phase [14% (9/63)] was significantly lower than that among patients who did not use statins [41% (14/34); p=0.007]. This was confirmed in logistical regression with an 0.19 Odds Ratio - OR [p=0.018; 95% confidence interval - 95%CI 0.05-0.75]. Patients who died were older, had a higher incidence of acute myocardial infarction, higher scores on the NIHSS and lower systolic blood pressure. Statins and angiotensin converting enzyme inhibitors were used more frequently among survivors. These associations persisted even after adjustment for confounding variables. Conclusion: Statins and angiotensin converting enzyme inhibitors use during hospitalization were independently associated to a lower rate of all-cause mortality in the first 7 days of intensive care unit admission.

Resumo O acidente vascular cerebral (AVC) isquêmico é uma causa comum de morte. O papel das estatinas na prevenção secundária da fase crônica do AVC isquêmico foi estabelecido. No entanto, as evidências sobre a sua eficácia na fase aguda do AVC isquêmico são limitadas e contraditórias. Objetivo: Avaliar a associação entre o uso de estatinas e o risco de mortalidade durante a fase aguda do AVC isquêmico em pacientes internados em uma unidade de terapia intensiva. Métodos: Estudo observacional e prospectivo de pacientes com AVC isquêmico com idade ≥18 anos, internados em uma unidade de terapia intensiva. Os medicamentos utilizados durante os primeiros 7 dias após o ictus, bem como os medicamentos utilizados anteriormente, foram registrados. O desfecho primário foi mortalidade por todas as causas durante os primeiros 7 dias. Resultados: Foram selecionados 212 pacientes e incluídos 97 pacientes com AVC isquêmico no período do estudo. A taxa de mortalidade entre os pacientes que usaram estatinas durante a fase aguda do AVC [14% (9/63)] foi significativamente menor do que a dos pacientes que não usaram estatinas [41% (14/34); p=0,007]. Isso foi confirmado na regressão logística com Odds Ratio - OR 0,19 [p=0,018; intervalo de confiança de 95% - IC95% 0,05-0,75]. Os pacientes que morreram eram mais velhos, apresentavam maior incidência de infarto agudo do miocárdio, escores mais altos na National Institute of Health Stroke Scale (NIHSS) e menor pressão arterial sistólica. Estatinas e inibidores da enzima conversora de angiotensina foram utilizados com maior frequência entre os sobreviventes. Essas associações persistiram mesmo após o ajuste para variáveis de confundimento. Conclusão: O uso de estatinas e inibidores da enzima conversora de angiotensina durante a hospitalização foram associados de forma independente à uma menor taxa de mortalidade por todas as causas nos primeiros 7 dias de internação na unidade de terapia intensiva.

Inhibidores de la PCSK9: una nueva era en el control del riesgo cardiovascular / PCSK9 inhibitors: a new era in the control of cardiovascular risk / Inibidores da PCSK9: uma nova era no controle do risco cardiovascular

Resumen: Las estatinas constituyen aún la pieza fundamental para el manejo del riesgo cardiovascular. Utilizadas en dosis de alta intensidad logran reducciones de colesterol asociado a lipoproteínas de baja densidad (C-LDL) de 50%-60%. Sin embargo, en pacientes con hipercolesterolemia severa, las estatinas solas o asociadas a ezetimibe pueden no ser suficientes para alcanzar los objetivos de descenso de C-LDL. Tal es el caso de las dislipemias genéticas como la hipercolesterolemia familiar. Lo mismo ocurre en pacientes con intolerancia total o parcial a estatinas, en los que se requiere de alternativas farmacológicas modernas que permitan reducir el riesgo cardiovascular elevado. En este escenario, los inhibidores de la proproteína convertasa subtilisina kexina tipo 9, se han convertido en una piedra angular para lograr no solo una reducción jamás antes vista del C-LDL, sino también del riesgo cardiovascular. La nueva evidencia posiciona a estos fármacos en un lugar de privilegio, siendo eficaces y bien tolerados, con el costo como principal limitante, a pesar de su marcado descenso en los últimos años.

Summary: Statins are still the fundamental piece for cardiovascular risk management. Used in doses of high intensity achieve reductions in cholesterol associated with low density lipoproteins of 50%-60%. However, in patients with severe hypercholesterolemia, statins alone or associated with ezetimibe may not be sufficient to achieve cholesterol associated with low density lipoproteins decrease targets. Such is the case of genetic dyslipidemias as familial hypercholesterolemia. Also in patients with total or partial statin intolerance, a modern pharmacological alternative is required to reduce high cardiovascular risk. In this scenario, proprotein convertase subtilisin kexin type 9 inhibitors have become a cornerstone to achieve not only a reduction never seen before of cholesterol associated with low density lipoproteins levels, but also of cardiovascular risk. These drugs are in a privilege position due to the new evidence, being effective and well tolerated, with cost as its main limitation despite its marked decline in recent years.

Resumo: As estatinas ainda são a peça fundamental da gestão de risco cardiovascular. Utilizada em dose de alta intensidade atinge reduções associadas com colesterol da lipoproteína de baixa densidade de 50%-60%. No entanto em pacientes com hipercolesterolemia grave, estatinas, sozinhas ou associadas a ezetimiba podem não ser suficientes para alcançar os objetivos de redução de colesterol da lipoproteína de baixa densidade. Tal é o caso das dislipidemias genéticas como a hipercolesterolemia familiar. O mesmo ocorre em pacientes com intolerância total ou parcial de estatinas, que exige modernas alternativas farmacológicas que permitem reduzir o risco cardiovascular alto. Neste panorama, os inibidores da pró-proteína convertasa subtilisina kexina tipo 9, se tornaram uma pedra angular para alcançar não apenas uma redução em nunca antes visto colesterol da lipoproteína de baixa densidade, mas de risco cardiovascular. Novas provas colocam essas drogas em um lugar de privilégio, por ser eficaz e bem tolerado, com o custo como sua principal limitante a pesar do seu grande declínio nos últimos anos.

High-intensity Statin Treatments in Clinically Stable Patients on Aspirin Monotherapy 12 Months After Drug-eluting Stent Implantation: A Randomized Study.

INTRODUCTION AND OBJECTIVES: Current guidelines on the treatment of blood cholesterol recommend continuous maintenance of high-intensity statin treatment in drug-eluting stent (DES)-treated patients. However, high-intensity statin treatment is frequently underused in clinical practice after stabilization of DES-treated patients. Currently, the impact of continuous high-intensity statin treatment on the incidence of late adverse events in these patients is unknown. We investigated whether high-intensity statin treatment reduces late adverse events in clinically stable patients on aspirin monotherapy 12 months after DES implantation. METHODS: Clinically stable patients who underwent DES implantation 12 months previously and received aspirin monotherapy were randomly assigned to receive either high-intensity (40mg atorvastatin, n = 1000) or low-intensity (20mg pravastatin, n = 1000) statin treatment. The primary endpoint was adverse clinical events at 12-month follow-up (a composite of all death, myocardial infarction, revascularization, stent thrombosis, stroke, renal deterioration, intervention for peripheral artery disease, and admission for cardiac events). RESULTS: The primary endpoint at 12-month follow-up occurred in 25 patients (2.5%) receiving high-intensity statin treatment and in 40 patients (4.1%) receiving low-intensity statin treatment (HR, 0.58; 95%CI, 0.36-0.92; P = .018). This difference was mainly driven by a lower rate of cardiac death (0 vs 0.4%, P = .025) and nontarget vessel myocardial infarction (0.1 vs 0.7%, P = .033) in the high-intensity statin treatment group. CONCLUSIONS: Among clinically stable DES-treated patients on aspirin monotherapy, high-intensity statin treatment significantly reduced late adverse events compared with low-intensity statin treatment. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01557075.

[Optimal cholesterol levels in patients in real-life. A systematic review]. / Niveles óptimos de colesterol en los pacientes con dislipemia. Revisión sistemática de la evidencia.

Dyslipidaemia is one of the main risk factors for the development of atherosclerosis. Different studies have demonstrated that the lower the LDL cholesterol, the better. Current evidence shows that the LDL cholesterol targets recommended by the clinical practice guidelines are beneficial and safe. However, consistent data show that higher reductions might provide additional cardiovascular beneficial effects, without an increase in side effects. Unfortunately, the current control of dyslipidaemia is very poor. Although statins are the treatment of choice in the majority of patients with dyslipidaemia, the current therapeutic armamentarium has different alternatives that effectively reduce LDL cholesterol levels, and that alone, or in combination, help to achieve LDL cholesterol targets in the majority of patients.

Avaliação dos níveis séricos de glicose e insulina no uso de alendronato de sódio e atorvastatina cálcica na osteoporose induzida com dexametasona / Evaluation of serum levels of glucose and insulin in the use of sodium alendronate and atorvastatin calcium in dexamethasone-induced osteoporosis

Introdução: Além da indução da osteoporose, os glicocorticoides ocasionam aumento da resistência à insulina e gliconeogênese hepática, tendo como consequência a hiperglicemia. Objetivo: Avaliar comparativamente os efeitos do alendronato de sódio e da atorvastatina cálcica nos níveis séricos de glicose e insulina na osteoporose induzida com dexametasona. Métodos: A indução da osteoporose consistiu na administração de dexametasona na dose de 7,5 mg/kg de peso corporal, uma vez por semana durante 4 semanas, à exceção dos animais do grupo controle (G1). Os animais foram distribuídos nos seguintes grupos: G1 (grupo controle sem osteoporose), G2 (controle com osteoporose sem tratamento), G3 (com osteoporose tratado com alendronato de sódio 0,2 mg/kg) e G4 (com osteoporose tratado com atorvastatina cálcica 1,2 mg/kg). No período de 30 e 60 após o início do tratamento, foram coletadas amostras de sangue para as dosagens dos níveis séricos de glicose e insulina. Resultados: Os grupos G2 e G3, quando comparados com o grupo normal G1, apresentaram aumento da glicemia e insulinemia durante todo o período experimental. O grupo G4 apresentou, com 30 dias, aumento da glicemia e insulinemia e, com 60 dias, aumento da glicemia e queda da insulinemia. Conclusão: Os resultados demonstraram o quadro de hiperglicemia consequente do aumento da resistência à insulina, presentes na indução da osteoporose pela dexametasona. O alendronato de sódio não ocasionou nenhuma melhora da glicemia e insulinemia. A atorvastatina cálcica ocasionou agravamento da hiperglicemia e hiperinsulinemia, potencializando o quadro de resistência à insulina e levando a uma insuficiência relativa de insulina característica do diabetes mellitus tipo 2.

Introduction: In addition to the induction of osteoporosis, glucocorticoids cause increased insulin resistance and hepatic gluconeogenesis resulting in hyperglycemia. Objective: Evaluate the effects of sodium alendronate and atorvastatin calcium on serum glucose and insulin levels in osteoporosis induced by dexamethasone. Methods: The induction of osteoporosis consisted of the administration of dexamethasone at a dose of 7.5 mg / kg body weight, once a week for 4 weeks, except for the control animals (G1). The animals were divided into the following groups: G1 (control group without osteoporosis), G2 (control with untreated osteoporosis), G3 (with osteoporosis treated with sodium alendronate 0.2 mg / kg) and G4 (with osteoporosis treated with atorvastatin calcium 1,2 mg / kg). In the 30 and 60 period after the start of the treatment blood samples were collected for dosages of serum glucose and insulin levels. Results: The G2 and G3 groups, when compared with the normal group G1, presented increased glycemia and insulinemia throughout the experimental period. The G4 group presented a 30-day increase in glycemia and insulinemia and at 60 days increased glycemia and decreased insulinemia. Conclusion: The results demonstrated the hyperglycaemia associated with the increase in insulin resistance present in the induction of osteoporosis by dexamethasone. Sodium alendronate did not cause any improvement in glycemia and insulinemia. Atorvastatin calcium caused worsening of hyperglycemia and hyperinsulinemia enhancing insulin resistance, leading to a relative insufficiency of insulin characteristic of type 2 diabetes mellitus.

Practical recommendations for the management of cardiovascular risk associated with atherogenic dyslipidemia, with special attention to residual risk. Spanish adaptation of a European Consensus of Experts. / Recomendaciones prácticas para el manejo del riesgo cardiovascular asociado a la dislipemia aterogénica, con especial atención al riesgo residual. Adaptación española de un Consenso Europeo de Expertos.

This document has discussed clinical approaches to managing cardiovascular risk in clinical practice, with special focus on residual cardiovascular risk associated with lipid abnormalities, especially atherogenic dyslipidaemia (AD). A simplified definition of AD was proposed to enhance understanding of this condition, its prevalence and its impact on cardiovascular risk. AD can be defined by high fasting triglyceride levels (≥2.3mmol/L / ≥200mg/dL) and low high-density lipoprotein cholesterol (HDL-c) levels (≤1,0 / 40 and ≤1,3mmol/L / 50mg/dL in men and women, respectively) in statin-treated patients at high cardiovascular risk. The use of a single marker for the diagnosis and treatment of AD, such as non-HDL-c, was advocated. Interventions including lifestyle optimization and low density lipoprotein (LDL) lowering therapy with statins (±ezetimibe) are recommended by experts. Treatment of residual AD can be performed with the addition of fenofibrate, since it can improve the complete lipoprotein profile and reduce the risk of cardiovascular events in patients with AD. Others clinical condictions in which fenofibrate may be prescribed include patients with very high TGs (≥5.6mmol/L / 500mg/dL), patients who are intolerant or resistant to statins, and patients with AD and at high cardiovascular risk. The fenofibrate-statin combination was considered by the experts to benefit from a favorable benefit-risk profile. In conclusion, cardiovascular experts adopt a multifaceted approach to the prevention of atherosclerotic cardiovascular disease, with lifestyle optimization, LDL-lowering therapy and treatment of AD with fenofibrate routinely used to help reduce a patient's overall cardiovascular risk.

Combined bioactive approach over atherosclerosis risk biomarkers / Abordagem combinada de compostos bioativos sobre biomarcadores de risco para aterosclerose

Atherosclerosis, one major cause of morbidity and mortality worldwide, is a complex and multifactorial disease that involves three mainly conditions: chronic inflammation, dyslipidemia and oxidative stress. Although statins are the first-line therapy for LDL cholesterol (LDL-C) lowering, the efficacy of cardiovascular events prevention is limited to 30-40%. This residual risk brought attention to the need of new therapies and clinical targets beyond LDL-C, such as inflammation and oxidative stress. Importantly, suboptimal treatment and/or statin discontinuation due to adverse effects have also been a very challenging clinical problem. Complementary diet therapy can be an effective and safe approach to support pharmacological treatment, especially when drugs alone are insufficient to attenuate risk factors and/or the recommended dose is not well tolerated. The aim of this study was to evaluate the effects of three bioactive components, namely omega-3 fatty acids, plant sterols and polyphenols, on markers of dyslipidemia, inflammation and oxidative stress in patients treated with statins. A randomized, crossover clinical study was carried out, with the participation of 53 subjects. At each intervention period, study participants received a packaged for the functional or control treatment. Functional treatment consisted of fish oil (1.7 g of EPA+DHA/day), chocolate containing plant sterols (2.2 g/day) and green tea (two tea sachets/day). Control treatment consisted of soy oil softgels, regular chocolate and anise tea. After 6 weeks of intervention, functional treatment reduced plasma LDL-C (-13.7% ± 3.7, p=0.002) and C-reactive protein (-35.5% ± 5.9, p=0.027). Plasma triacylglycerol (-15.68% ± 5.94, p=0.02) and MDA (-40.98% ± 6.74, p=0.04) were reduced in subgroups of patients (n=23) with baseline values above the median (93 mg/dL and 2.23 umol/L, respectively). Analysis of lathosterol and campesterol in plasma suggested that intensity of LDL-C reduction was influenced by cholesterol absorption rate rather than its endogenous synthesis. After multivariate analysis, patients identified as "good responders" to supplementation (n=10) were recruited for a pilot protocol of statin dose reduction with complementary diet therapy. Responders received the functional treatment for 12 weeks: standard statin therapy was kept during the first 6 weeks and reduced by 50% from weeks 6 to 12. No difference was observed for plasma lipids and inflammation biomarkers, cholesterol efflux capacity or HDL particle number after statin dose reduction when compared to standard therapy. Although limited by the small sample size, our study demonstrates the potential for a new therapeutic approach combining lower statin dose and specific dietary compounds. This may be particularly helpful for the many patients with, and at risk for, CVD who cannot tolerate high-dose statin therapy

A aterosclerose, uma importante causa mundial de morbidade e mortalidade, é uma doença complexa e multifatorial que envolve três principais condições: inflamação crônica, dislipidemia e estresse oxidativo. Embora as estatinas sejam fármacos de primeira linha para redução de LDL colesterol (LDL-C), sua eficácia na prevenção de eventos cardiovasculares é limitadada a 30-40%. Este risco cardiovascular residual evidencia a necessidade de novas terapias e marcadores clínicos que vão além do LDL-C, como inflamação e estresse oxidativo. Não obstante, tratamento subótimo e/ou interrupção do uso de estatinas devido à ocorrencia de efeitos adversos também é um grave obstáculo na clínica médica. Neste contexto, a terapia dietética complementar representa uma abordagem efetiva e segura para o suporte do tratamento farmacológico, especialmente quando as drogas são insuficientes para atenuar fatores de risco e/ou quando a dose recomendada não é bem tolerada. O objetivo do presente estudo foi avaliar o efeito de três compostos bioativos - ácidos graxos ômega 3, fitosteróis e polifenóis - sobre marcadores de inflamação, lipemia e estresse oxidativo em indivíduos tradados com estatinas. Foi realizado um estudo clínico randomizado, de delineamento crossover, com a participação de 53 voluntários. A cada período de intervenção, os participantes receberam um tratamento funcional ou controle. O tratamento funcional foi composto por cápsulas de óleo de peixe (1.7 g/dia de EPA+DHA), chocolate contendo fitosteróis (2.2 g/dia) e chá verde (dois sachês/dia). O tratamento controle foi composto por cápsulas de óleo de soja, chocolate sem adição de fitosteróis e chá de anis. Após 6 semanas de intervenção, o tratamento funcional reduziu a concentração plasmática de LDL-C (-13.7% ± 3.7, p=0.002) e proteína C-reativa (-35.5% ± 5.9, p=0.027). Triglicerídeos (- 15.68% ± 5.94, p=0.02) e malondialdeído (-40.98% ± 6.74, p=0.04) foram reduzidas apenas em subgrupos de indivíduos que apresentavam valores basais acima da mediana (93 mg/dL e 2.23 umol/L, respectivamente). A análise de latosterol e campesterol no plasma sugeriu que a intensidade da redução de LDL-C não foi influenciada pela síntese endógena de colesterol, mas sim pela taxa de absorção. Após análise multivariada dos resultados, pacientes identificados como "good responders" à suplementação (n=10) foram recrutados para um estudo piloto de redução da dosagem da estatina, aliado à terapia dietética complementar. Estes pacientes receberam o tratamento funcional por 12 semanas: durante as 6 primeiras semanas mantevese a dosagem de estatina, que em seguida foi reduzida em 50% das semanas 6 a 12. Não foram observadas diferenças para os marcadores plasmáticos de lipídeos, inflamação, capacidade de efluxo de colesterol ou número de partículas de HDL após a redução da dose de estatina, quando comparada à terapia convencional. Embora limitado pelo reduzido número de pacientes, o estudo demonstra o potencial para uma nova abordagem terapêutica, combinando reduzida dose de estatina com específicos compostos bioativos. Esta pode ser uma importante alternativa para muitos pacientes em risco cardiovascular e que são intolerantes à terapia com altas doses de estatina.

[Consensus for pharmacologic treatment of atherogenic dyslipidemia with statin-fenofibrate combined therapy]. / Consenso sobre tratamiento farmacológico de la dislipidemia aterogénica con terapia combinada estatina-fenofibrato.

LDLc levels are associated with increase of cardiovascular risk, and statins are currently used for their control. Nevertheless, a despite of LDLc levels at goal, a residual risk is persistent, commonly associated with persistent lipids modifications (high triglycerides and low HDLc). So, it is necessary to evaluate triglycerides and HDL to assessment cardiovascular risk. Clinical data are consistent with efficacy and safety of combination therapy with statin and other lipid lowering drugs, for instance fenofibrate. Patients with hipertriglyceridemia and low HDLc are the group with most potential improve. In that patients with atherogenic dyslipidemia, the target for therapeutic objectives related with non-HDL-cholesterol is a priority, because non-HDL-cholesterol is considered as a more accuracy measure to assessment cardiovascular risk.

Use of statins and the incidence of type 2 diabetes mellitus / Uso de estatinas e a incidência de diabetes mellitus tipo 2

SummaryIntroduction:the use of statins is associated with reduced cardiovascular risk in studies of primary and secondary prevention, and the reduction is directly proportional to the reduction of LDL-cholesterol. Recent evidence suggests that statins may be associated with a higher incidence of new cases of diabetes. The aim of this review is to explore this possibility, identifying factors associated with the increase in risk and the potential diabetogenic mechanisms of statins. In addition, we evaluated if the risk of diabetes interferes with the reduction in cardiovascular risk achieved with statins.Methods:we reviewed articles published in the Scielo and Pubmed databases, which assessed or described the association between use of statins and risk of diabetes up to June 2015.Results:use of statins is associated with a small increase in the incidence of new cases of diabetes. Age, potency of statin therapy, presence of metabolic syndrome, impaired fasting blood glucose, overweight and previously altered glycated hemoglobin levels are associated with increased risk of diabetes, but there is no consensus about the possible diabetogenic mechanisms of statins. In patients candidate to hypolipemiant drug therapy, the benefit of reducing cardiovascular risk outweighs any risk increase in the incidence of diabetes.Conclusion:statins are associated with a small increase in incidence of diabetes in patients predisposed to glycemic alteration. However, since the benefit of cardiovascular risk reduction prevails even in this group, there is no evidence to date that this finding should change the recommendation of starting statin therapy.

ResumoIntrodução:o uso de estatinas está associado à redução do risco cardiovascular em estudos de prevenção primária e secundária, e essa redução ocorre de modo diretamente proporcional à redução de LDL-colesterol. Evidências recentes sugerem que estatinas podem estar associadas à maior incidência de novos casos de diabetes. O objetivo desta revisão é identificar os fatores associados ao aumento de risco e os potenciais mecanismos diabetogênicos das estatinas. Além disso, avaliou-se se o risco de diabetes interfere na redução de risco cardiovascular obtida com as estatinas.Métodos:foram revisados artigos publicados nas bases de dados Scielo e Pubmed, que avaliaram ou descreveram a associação do uso de estatinas com o risco de diabetes até junho de 2015.Resultados:o uso de estatinas está associado a um pequeno aumento na incidência de novos casos de diabetes. Idade, potência do tratamento com estatina, presença de síndrome metabólica, glicemia de jejum alterada, excesso de peso e hemoglobina glicada previamente alterada estão associados a um maior risco de diabetes, mas não há consenso sobre os possíveis mecanismos diabetogênicos das estatinas. Nos pacientes candidatos à terapêutica hipolipemiante, o benefício de redução do risco cardiovascular supera qualquer aumento de risco na incidência de diabetes.Conclusão:estatinas estão associadas a um pequeno aumento na incidência de diabetes em pacientes predispostos a alterações glicêmicas. Entretanto, como persiste, mesmo nesse grupo, o benefício da redução de risco cardiovascular, não há qualquer evidência até o momento de que esse achado deva mudar a decisão de iniciar o tratamento com estatinas.

Pityriasis lichenoides chronica associated with use of HMG-CoA reductase inhibitors / Pitiriasis liquenoide crónica asociada con el uso de inhibidores de la reductasa de HMG-CoA

Herein, we present three cases of Pityriasis lichenoides chronica (PLC) in patients who developed the rash after use of 3-hydroxy-3-methyl-glutaryl-Coenzyme A (HMG-CoA) reductase inhibitors. The patients had complete resolution after standard treatment by dermatologists and withdrawal of the offending agents. In one case, the patient had a previous episode of a similar rash that occurred with HMG-CoA reductase inhibitors use many years previously. Pityriasis lichenoides chronica is a condition of unknown aetiology. Several agents have been associated with its presentation. We postulate HMG-CoA reductase inhibition in skin presents a final common pathway for the presentation of PLC in select patients.

Se presentan tres casos de pitiriasis liquenoide crónica (PLC) en pacientes que desarrollaron una erupción tras el uso de inhibidores de la reductasa de la hidroxi-metilglutaril-coenzima A (HMG-CoA). Los pacientes tuvieron resolución completa después del tratamiento estándar dado por los dermatólogos, y la suspensión de los agentes ofensivos. En un caso, el paciente tuvo un episodio de una erupción similar anterior, que ocurrió debido al uso de inhibidores de la reductasa de HMG-CoA muchos años atrás. La pitiriasis liquenoide crónica es una condición de etiología desconocida. Varios agentes han sido asociados con su manifestación. Se postula que la inhibición de la reductasa de HMG-CoA presenta un camino final común para la manifestación de PLC en determinados pacientes.

Tratamento atual das dislipidemias / Current treatment of dyslipidemia

A dislipidemia representa um dos principais fatores de risco para o desenvolvimento da aterosclerose. A identificação da etiologia da dislipidemia consiste em uma das principais etapas do seu manejo clínico. O tratamento deve levar em consideração a estratificação de risco cardiovascular de cada paciente: quanto maior o risco, maior o benefício de um tratamento mais intensivo. As maiores evidências de benefícios são vistas com a classe das estatinas. É importante considerar que a meta primária de tratamento deve ser focada no LDL-colesterol, exceto em casos extremos de triglicérides muito elevados, em que o risco de pancreatite deve ser levado em consideração e a redução de triglicérides deve ser prioritária. A elevação do HDL-colesterol deforma “artificial” por enquanto não apresenta benefício de forma robusta, porém novas medicações estão em estudo e podem trazer novas perspectivas nesse contexto.

Dyslipidemia is one of the main risk factors for the development of atherosclerosis. The identification of the etiology of dyslipidemia is one of the main steps of clinical management. The treatment should consider the stratification of cardiovascular risk for each patient: the higher the risk, the greater the benefit of a more intensive treatment. Statins are the drugs where the benefits for the treatment of dyslipidemia were stronger. The primary goal of treatment should be focused on LDL-cholesterol, except in cases of very high triglycerides, whose risk of associated pancreatitis should be taken into consideration and reduction of triglycerides should be the priority. Artificial elevation of HDL-cholesterol does not have shown reduction of cardiovascular disease, but new drugs are under study and can bring new perspectives in this regard.

Influência do gel de sinvastatina tópico no destorque de implantes instalados em tíbias de coelhos / Influence of simvastatin gel on implant torque removal values: a rabbit tibia model

O objetivo deste estudo foi avaliar a influência do gel de sinvastatina tópico no destorque de implantes instalados em tíbias de coelhos. Foram realizadas 32 cirurgias em 16 coelhos New Zealand para instalação de dois implantes em uma de suas tíbias. Um dos alvéolos foi previamente preenchido com o gel de estatina 30 mg/ml. O torque inicial foi de 20 Ncm e o destorque foi avaliado aos 28 e 56 dias com torquímetro Tohnichi. Os alvéolos cirúrgicos foram divididos em grupo IG -28 (teste - 28 dias): oito implantes + gel - 28 dias (IG-28); grupo IG-56 (teste - 56 dias): oito implantes + estatina - 56 dias (IG-56); grupo I-28 (controle - 28 dias): oito implantes - 28 dias (I-28); grupo I-56 (controle 56 dias): oito implantes - 56 dias (I-56). Valores do grupo IG-56 foram maiores que os grupos IG-28, I-28 e I-56 (p < 0,05). O gel de estatina aumentou a força de destorque no grupo IG-56 (teste 56 dias).

The aim of this study was to evaluate the influence of topical simvastatin application on implant removal torque values using a rabbit tibia model. Thirty-two surgeries were performed on 16 New Zealand rabbits for installation of two implants. One of the alveolus was first filled with the 30 mg/ml of simvastatin gel. The initial torque was 20 Ncm and removal torque was evaluated at 28 and 56 days with a Tohnichi torque wrench. The alveoli were divided into surgical Group IG-28: eight implants + simvastatin - 28 days, group IG-56 (test 56 days): eight implants + simvastatin - 56 days, group I-28 (control - 28 days): eight implants - 28 days, group I-56 (control 56 days): eight implants - 56 days. Mean values of group IG-56 were higher than groups IG-28, I-28 and I-56 (p < 0.05). Groups IG-28, I-28 and I-56 were similar (p > 0.05). The simvastatin gel increased torque removal values in group IG-56 (test - 56 days).

Colesterol, tratamento anticolesterol e câncer / Cholesterol, anti-cholesterol treatment and cancer

Neste artigo, o autor comenta sobre a inquietante evidência da associação de baixa concentração sanguínea de colesterol e a alta frequência de câncer. Analisa alguns artigos que tentam minimizar essa associação, especialmente aqueles que usaram estatina para o tratamento da hipercolesterolemia, e chama a atenção sobre os gravesconflitos de interesses envolvidos entre pesquisadores e a indústria de medicamentos. Além disso, o autor comenta sobre as limitações do uso das estatinas na prevenção de eventos cardiovasculares.

In this paper, the author comments on the disturbing evidence of the association of low concentrations of blood cholesterol and high frequency of cancer. Some articles that attempt to minimize this association are analyzed, Including those that used statins for the treatment of hypercholesterolemia, calling attention to the serious conflicts of interest between researchers and the pharmacological industry. Furthermore, the author comments the limitations in the use of statins in preventing cardiovascular events.