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2.
Int J Clin Pharmacol Ther ; 57(12): 575-589, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31549625

RESUMO

OBJECTIVE: Bococizumab, a monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9, has been shown to reduce low-density lipoprotein cholesterol (LDL-C). Here, we describe the pharmacokinetics and pharmacodynamics of bococizumab and its effect on lipoprotein particle composition and other biomarkers, based on a double-blind, placebo-controlled, randomized, dose-ranging study. MATERIALS AND METHODS: The study consisted of two populations: Japanese subjects with uncontrolled LDL-C (LDL-C ≥ 100 mg/dL) despite treatment with atorvastatin (n = 121) and Japanese subjects naïve to lipid-lowering agents with LDL-C ≥ 130 mg/dL (n = 97). Subjects were randomized to receive either bococizumab 50, 100, or 150 mg or placebo, every 2 weeks. One arm of subjects in the ator-vastatin-treated population received ezetimibe 10 mg instead of bococizumab. RESULTS: In both populations, bococizumab exposure increased with increasing dose, and subjects with lower body weights tended to have higher exposures. Bococizumab treatment was associated with a dose-dependent reduction in LDL particles and a small increase in total high-density lipoprotein (HDL) particles. Significant reductions in lipoprotein-associated phospholipase A2 (Lp-PLA2) were observed for bococizumab-treated subjects but not for subjects treated with placebo or ezetimibe. CONCLUSION: Increased bococizumab dosage resulted in increased exposure. Levels of LDL and HDL particles and biomarkers such as Lp-PLA2 were also altered with bococizumab treatment. (ClinicalTrials.gov identifier: NCT02055976).
.


Assuntos
Anticorpos Monoclonais Humanizados/farmacocinética , Anticolesterolemiantes/farmacocinética , Hipercolesterolemia/terapia , Pró-Proteína Convertase 9/antagonistas & inibidores , Atorvastatina/uso terapêutico , Biomarcadores/sangue , Método Duplo-Cego , Humanos , Japão , Resultado do Tratamento
3.
Food Funct ; 10(9): 6098-6109, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31495848

RESUMO

Hypercholesterolemia is a major risk factor for cardiovascular disease (CVD). Probiotics are one of the most popular dietary supplements for hypercholesterolemia, but there are questions as to whether there are differences between probiotics and cholesterol-lowering drugs like atorvastatin (ATO) both in effectiveness and in the underlying mechanisms. In this study, the hypocholesterolemia effects of 4 probiotic strains were investigated and compared with ATO, focusing on their impacts on the gut microbiota. A hypercholesterolemia model was established via high-fat diet (HFD) in golden hamsters after which ATO and the 4 probiotics were orally administered individually for 8 weeks. All probiotics were effective, but less than ATO, on body weight, serum parameters (TG, TC, LDL, INS, HbA1c) and expression of inflammatory factors (INF-α, IL-1ß, CRP), with strain JQII-5 being most significant. Besides, these effects were associated with restoration of microbiota dysbiosis induced by HFD. It was worth noting that ATO and probiotics induced different shifts of the gut microbiota in both structure and key phylotypes. Most interestingly, Allobaculum, a HFD-suppressed genus, reported to be involved in alleviating oxidative stress, was enriched by all tested probiotic strains, but not by ATO. Furthermore, Prevotella, also a HFD-suppressed genus, was uniquely reversed by JQII-5. Importantly, most of the alerted genera and reversed genera were found to be correlated with the inflammatory state and serum lipid level. Compared with ATO, the probiotic strains were less effective on body weight, hypercholesterolemia, and inflammation. However, probiotics exert additional favorable effects on the gut microbiota, making them excellent potential complements to cholesterol-lowering drugs like ATO.


Assuntos
Atorvastatina/uso terapêutico , Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/fisiologia , Hipercolesterolemia/terapia , Lactobacillus plantarum/fisiologia , Pediococcus/fisiologia , Animais , Anticolesterolemiantes/uso terapêutico , Bactérias/classificação , Bactérias/isolamento & purificação , Cricetinae , Citocinas/análise , Disbiose/etiologia , Disbiose/terapia , Fezes/microbiologia , Glucose/metabolismo , Hipercolesterolemia/tratamento farmacológico , Masculino , Mesocricetus , Pediococcus acidilactici/fisiologia , Pediococcus pentosaceus/fisiologia , Probióticos/uso terapêutico , Ganho de Peso/efeitos dos fármacos
4.
Med. clín (Ed. impr.) ; 153(1): 1-5, jul. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-183350

RESUMO

Antecedentes y objetivo: Varios estudios han puesto de manifiesto un cumplimiento terapéutico subóptimo en la población general, sobre todo en ancianos y en enfermos crónicos. El objetivo de este estudio es describir la adherencia al tratamiento de diabetes mellitus, dislipidemia e hipertensión arterial, e identificar los factores que la influencian. Material y métodos: Estudio observacional transversal retrospectivo sobre 16.208 pacientes mayores de 65 años de la Cohorte EpiChron, que iniciaron tratamiento en monoterapia de un antidiabético, un hipolipidemiante o un antihipertensivo en 2010. La adherencia se midió mediante el cálculo de la relación de posesión de medicación durante un año de seguimiento, considerándose adherentes los casos con posesión de medicación ≥80%. Se realizó un estudio descriptivo y un modelo de regresión logística para identificar los factores predictores de baja adherencia. Resultados: La adherencia a los antidiabéticos, antihipertensivos e hipolipidemiantes fue del 72,4; 50,7 y 44,3%, respectivamente. Se observó un aumento en la adherencia del 3-8% por cada enfermedad crónica adicional del paciente. La presencia de enfermedad mental no afectó a la adherencia, y el sexo, edad y número de fármacos prescritos no presentaron efectos consistentes. Conclusiones: Los resultados obtenidos ponen de manifiesto una adherencia al tratamiento subóptima en las enfermedades crónicas estudiadas. La adherencia aumentó con el número de enfermedades crónicas, mientras que sexo, edad y número de fármacos no presentaron un efecto consistente. Es necesario investigar si existen otros factores que puedan influir en la adherencia terapéutica, ya que su mejora puede tener mayor impacto en la salud que cualquier avance en las terapias


Background and objective: Sub-optimal adherence to treatment in the general population has been highlighted in several studies, especially in the elderly and/or chronic patients. This study aims to describe the adherence to treatment of diabetes mellitus, dyslipidaemia and hypertension, and to identify the factors that influence adherence. Material and method: Retrospective, cross-sectional observational study on 16,208 patients aged ≥65 years from the EpiChron Cohort who initiated monotherapy treatment of an antidiabetic, a lipid-lowering or an antihypertensive medication in 2010. Adherence was measured by calculating the medication possession ratio during one year, considering those cases with medication possession ratio ≥80% to be adherent. We performed a descriptive study, and a logistic regression model was used to identify the predictors of low adherence. Results: Adherence to antidiabetics, antihypertensive and lipid-lowering drugs was 72.4%, 50.7% and 44.3%, respectively. An increase in adherence of 3-8% was observed for each additional chronic disease suffered by the patient. The presence of mental illness did not affect adherence, and sex, age and number of prescribed drugs did not present consistent effects. Conclusion: The results obtained show a sub-optimal adherence to treatment for the 3chronic diseases studied. Adherence increased with the number of chronic diseases, while sex, age and number of drugs did not show a consistent effect. It is necessary to investigate if there are other factors that may influence therapeutic adherence, since improving adherence may have a greater impact on health than any progress in therapies


Assuntos
Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Cooperação e Adesão ao Tratamento , Hipertensão/terapia , Hipercolesterolemia/terapia , Diabetes Mellitus/terapia , Estudos de Coortes , Estudos Transversais , Estudos Retrospectivos , Modelos Logísticos , Doença Crônica/tratamento farmacológico , Doença Crônica/epidemiologia
5.
Appl Microbiol Biotechnol ; 103(15): 5993-6006, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31201452

RESUMO

Atherosclerosis is the major cause of cardiovascular diseases, which are considered the fatal ailment globally. Hypercholesterolaemia plays a critical role in the development of atherosclerosis and cardiovascular diseases. Many studies have been stated that probiotics could affect hypercholesterolemia via cholesterol metabolism. Probiotics are live bacteria which are good for our health when administered orally in high amounts. Recently, many studies have revealed the beneficial effects of the nutritional ingestion of probiotics which can decrease serum cholesterol levels. The aim of this review is, firstly, to explore the hypercholesterolemia effect of how it progresses into atherosclerosis and, secondly, to summarize the hypocholesterolaemia effect of probiotics on atherosclerosis and the up-to-date information on their basic mechanisms. The most important mechanisms responsible for the hypocholesterolemic effect of probiotics are the suppression of the reabsorption of bile acids and inhibition of the intestinal cholesterol absorption. Current studies indicate that numerous mechanisms within the cholesterol metabolism, e.g., ones involving the Niemann-Pick C1-Like 1 protein, 3-hydroxy-3-methylglutaryl-CoA reductase, and 7α- and 27α-hydroxylases, have been recommended where regulation may take place after oral intake of probiotics. However, these mechanisms are still poorly understood. Thus, further studies are required to examine the possible mechanisms, whereby probiotics can be utilized safely and considered for the treatment of hypercholesterolemia.


Assuntos
Aterosclerose/prevenção & controle , Aterosclerose/fisiopatologia , Hipercolesterolemia/complicações , Hipercolesterolemia/terapia , Probióticos/administração & dosagem , Probióticos/farmacologia , Animais , Colesterol/metabolismo , Humanos
6.
Biomater Sci ; 7(7): 2777-2792, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31041934

RESUMO

Cationic liposomes have shown great potential in efficient siRNA delivery, and their positive charge is crucial for tight extracellular siRNA binding, effective intracellular siRNA disassembly and physiological toxicity. Thus, the development of novel cationic lipids with a suitable positive charge is desirable for safe and efficient siRNA delivery. Herein, we fabricated a library of 21 tertiary amine-derived cationic lipids (TA) to achieve a balance between effectiveness and safe siRNA delivery. The screened TA13 liposomes, which consisted of TA13 and helper lipid DOPE at a mole ratio of 1 : 1, readily condensed siRNA to form lipoplexes (TA13 LPs), achieving stronger gene silencing in diverse cells than the commercially available vector Lipo2000. Moreover, the TA13 LPs demonstrated effective in vivo gene silencing and good safety in normal mice. The improved gene silencing efficiency of the TA13 LPs is ascribed to their capability of sequentially conquering the barriers met by in vivo siRNA delivery. Notably, the TA13 LPs delivered ApoB-siRNA and obviously decreased ApoB mRNA expression in the liver and the total cholesterol and low-density lipoprotein in the serum of hypercholesterolemia mice, indicating a potential siRNA therapeutic for hypercholesterolemia treatment. It is anticipated that these novel tertiary amine-based liposomes can provide a simple and widely-used platform for the safe and effective delivery of siRNA, and their structure-activity relationships can aid in the further development of effective cationic lipids.


Assuntos
Aminas/química , Portadores de Fármacos/química , Lipídeos/química , RNA Interferente Pequeno/química , Segurança , Animais , Portadores de Fármacos/toxicidade , Inativação Gênica , Células HeLa , Humanos , Hipercolesterolemia/genética , Hipercolesterolemia/terapia , Lipídeos/toxicidade , Células MCF-7 , Masculino , Camundongos , RNA Interferente Pequeno/genética
7.
Int J Mol Sci ; 20(9)2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31064116

RESUMO

Hypercholesterolemia may be causally related to heart failure with preserved ejection fraction (HFpEF). We aimed to establish a HFpEF model associated with hypercholesterolemia and type 2 diabetes mellitus by feeding a high-sucrose/high-fat (HSHF) diet to C57BL/6J low-density lipoprotein receptor (LDLr)-/- mice. Secondly, we evaluated whether cholesterol-lowering adeno-associated viral serotype 8 (AAV8)-mediated LDLr gene transfer prevents HFpEF. AAV8-LDLr gene transfer strongly (p < 0.001) decreased plasma cholesterol in standard chow (SC) mice (66.8 ± 2.5 mg/dl versus 213 ± 12 mg/dl) and in HSHF mice (84.6 ± 4.4 mg/dl versus 464 ± 25 mg/dl). The HSHF diet induced cardiac hypertrophy and pathological remodeling, which were potently counteracted by AAV8-LDLr gene transfer. Wet lung weight was 19.0% (p < 0.001) higher in AAV8-null HSHF mice than in AAV8-null SC mice, whereas lung weight was normal in AAV8-LDLr HSHF mice. Pressure-volume loop analysis was consistent with HFpEF in AAV8-null HSHF mice and showed a completely normal cardiac function in AAV8-LDLr HSHF mice. Treadmill exercise testing demonstrated reduced exercise capacity in AAV8-null HSHF mice but a normal capacity in AAV8-LDLr HSHF mice. Reduced oxidative stress and decreased levels of tumor necrosis factor-α may mediate the beneficial effects of cholesterol lowering. In conclusion, AAV8-LDLr gene therapy prevents HFpEF.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Cardiomiopatias Diabéticas/prevenção & controle , Terapia Genética/métodos , Insuficiência Cardíaca/prevenção & controle , Hipercolesterolemia/terapia , Receptores de LDL/genética , Animais , Colesterol/sangue , Dependovirus/genética , Diabetes Mellitus Tipo 2/etiologia , Cardiomiopatias Diabéticas/fisiopatologia , Dieta Hiperlipídica/efeitos adversos , Sacarose na Dieta/efeitos adversos , Feminino , Insuficiência Cardíaca/fisiopatologia , Hipercolesterolemia/complicações , Hipercolesterolemia/etiologia , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Receptores de LDL/metabolismo , Volume Sistólico , Fator de Necrose Tumoral alfa/sangue
8.
Benef Microbes ; 10(5): 555-567, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31090460

RESUMO

Hypercholesterolemia is a main risk factor of cardiovascular disease. Probiotics are a safe approach to reduce elevated cholesterol without any deleterious effect to human health. Saccharomyces boulardii CNCM I-745 probiotic properties are well documented in a context of intestinal dysbiosis. Recent in vitro and preclinical studies have suggested its potential effects on dyslipidemia. This is the first controlled study investigating the effects of S. boulardii CNCM I-745 on lipidemic profile and gut microbiota in a hamster hypercholesterolemic model. Daily administration (3 g/kg) of S. boulardii for 21 or 39 days in hamsters fed a 0.3% cholesterol-diet significantly reduced total plasma cholesterol (P<0.001) and increased faecal total cholesterol (P<0.05) compared to vehicle-treated animals. S. boulardii significantly modified the gut microbiota composition of the hamster fed a 0.3% cholesterol-diet. These microbial abundancy modifications of the microbiota were correlated to variations of lipidemic values or liver genes expressions. In particularly we found that abundance of g_Allobaculum, the most modified taxon after S. boulardii treatment (+236%; P<0.05), was correlated to variations in plasmatic lipoproteins level and ABCG5 hepatic gene expression. We also observed a not previously described correlation between the levels of g_Oxalobacter in the gut microbiota and total cholesterol plasma concentration. In conclusion, we confirmed the cholesterol-lowering effects of S. boulardii intake and we demonstrated for the first time the S. boulardii effect on gut microbiota in the context of hypercholesterolemia in hamsters. Our results provide new insights for a beneficial and safe approach of hypercholesterolemia treatment and could be considered for clinical development, alone or in addition to conventional treatment.


Assuntos
Disbiose/complicações , Disbiose/terapia , Hipercolesterolemia/terapia , Lipídeos/análise , Plasma/química , Probióticos/administração & dosagem , Saccharomyces boulardii/crescimento & desenvolvimento , Animais , Cricetinae , Modelos Animais de Doenças , Fezes/química , Microbioma Gastrointestinal , Resultado do Tratamento
10.
Dtsch Med Wochenschr ; 144(5): 322-328, 2019 03.
Artigo em Alemão | MEDLINE | ID: mdl-30836403

RESUMO

Atherosclerotic cardiovascular disease is the leading cause of premature mortality and morbidity worldwide. Dyslipidemia is a commonly encountered clinical condition and is an important determinant of cardiovascular disease. The causality of plasma low-density lipoprotein-cholesterol (LDL-C) in the pathophysiology of cardiovascular disease has been established beyond any reasonable doubt. In this context, individual risk estimation, the determination of target values and lipid-lowering strategies represent an essential part and a challenge in the daily clinical practice to prevent cardiovascular events. Statins are recommended as first-line therapy for patients with hypercholesterolemia in secondary prevention. Controversies remain in the context of primary prevention, however, as to which kind of subjects to treat, the magnitude of the benefit, and potential harm. This article gives a brief overview of the current evidence, guideline recommendations and strategies for lowering of LDL-C in the primary prevention of cardiovascular disease.


Assuntos
Hipercolesterolemia , Prevenção Primária , Humanos , Hipercolesterolemia/prevenção & controle , Hipercolesterolemia/terapia , Guias de Prática Clínica como Assunto
11.
J Clin Apher ; 34(4): 423-433, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30817043

RESUMO

INTRODUCTION: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition with monoclonal antibodies has complemented the armamentarium of lipid-lowering therapy (LLT) before the final step of commencing chronic lipoprotein apheresis (LA). Data are scarce on patients who, after escalation of LLT with PCSK9 antibodies, have commenced chronic LA or PCSK9 antibody treatment during ongoing long-term LA. PATIENTS AND METHODS: In this study, a cohort of 110 patients with established atherosclerotic cardiovascular disease (ASCVD) due to hypercholesterolemia or concomitant lipoprotein(a)-hyperlipoproteinemia, who received PCSK9 antibodies for the first time during routine care, were consecutively identified. RESULTS: Mean LDL-C concentration prior to initiation of LA or PCSK9 antibody treatment was 5.3 ± 2.6 mmol/L (205 ± 102 mg/dL). Due to established ASCVD, the risk-adjusted LDL-C target value was <1.8 mmol/L (<70 mg/dL) in all patients. Use of PCSK9 antibodies increased the proportion of patients attaining the LDL-C target concentration by 41.8% overall. Treatment emergent adverse events (TEAE) associated with PCSK9 antibody medication were reported in 35 patients (31.8%). Discontinuation of PCSK9 antibody therapy due to TEAEs occurred in 25 patients (22.7%). CONCLUSION: Finally, 55.5% of patients received a combination of PCSK9 antibody therapy and LA at individually optimized treatment frequencies resulting in an increase of target attainment in 54.1% of patients. About 18.1% of chronic LA patients terminated LA treatment in this real-world study. The termination of long-term LA therapy, which has hitherto prevented the progression of ASCVD, requires careful individual risk assessment and cannot be recommended by the general criteria of LDL-C reduction.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Remoção de Componentes Sanguíneos/métodos , Terapia Combinada/métodos , Lipoproteínas/isolamento & purificação , Pró-Proteína Convertase 9/antagonistas & inibidores , Aterosclerose/terapia , LDL-Colesterol/isolamento & purificação , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Hipercolesterolemia/terapia , Lipídeos/isolamento & purificação , Lipoproteína(a)/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Pró-Proteína Convertase 9/imunologia
12.
Blood Purif ; 47(4): 301-316, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30799420

RESUMO

BACKGROUND AND AIM: Elevated low-density lipoprotein cholesterol and/or lipoprotein(a) are established risk factors for cardiovascular disease (CVD). Management of hypercholesterolemia consists of drug therapies, including statins and proprotein convertase subtilisin/kexin type 9 inhibitors. In patients with familial hypercholesterolemia (FH), lipoprotein apheresis (LA) is utilized to control lipid levels. However, LA is not currently a standard therapy for non-FH. This review summarizes the literature regarding LA therapy in CVD prevention. METHODS: PubMed/MEDLINE databases were searched using the keywords "LA" and "CVD". Citations were individually reviewed for relevance. RESULTS: The efficacy of LA was clearly demonstrated, largely based on evidence from observational studies. In patients who are unresponsive to traditional lipid-lowering medications, LA effectively reduced serum lipoprotein levels and adverse cardiovascular events. CONCLUSION: It was concluded that LA is a safe and effective technique that could be considered in the management of hypercholesterolemia and future risk. Randomized control trials would further support a role for LA as a therapeutic option.


Assuntos
Doenças Cardiovasculares/terapia , Lipoproteína(a)/sangue , Plasmaferese , Aterosclerose/sangue , Aterosclerose/etiologia , Aterosclerose/prevenção & controle , Aterosclerose/terapia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol/sangue , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/complicações , Hipercolesterolemia/terapia , Plasmaferese/efeitos adversos , Plasmaferese/métodos , Fatores de Risco , Padrão de Cuidado , Resultado do Tratamento
13.
Appl Microbiol Biotechnol ; 103(7): 3181-3191, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30783721

RESUMO

Hypercholesterolemia plays a critical role in the development of atherosclerosis and cardiovascular diseases. Many works have been reported that gut microbiota could affect hypercholesterolemia through cholesterol metabolism. However, the role of gut microbiota on cholesterol transportation remains unclear. In this study, 8-week-old C57BL/6J mice were fed with high-cholesterol diet to build the hypercholesterolemic mice. Then, the hypercholesterolemic mice got the oral administration of Enterococcus faecalis ATCC19433 at a dose of 109 CFU/mL/day or PBS with high-cholesterol diet for 4 weeks. Serum was collected to detect the concentration of total cholesterol (TC). Meanwhile, pathology, histology, real-time polymerase chain reaction, Western blot, and immunofluorescence were used to evaluate the expression of ABCG5 and ABCG8 in the liver and small intestine. We also analyzed the composition of gut microbiota through high-throughput sequencing method. Oral administration of E. faecalis ATCC19433 significantly decreased the concentration of serum cholesterol in hypercholesterolemic mice. Furthermore, E. faecalis ATCC19433 reduced the concentration of liver cholesterol and improved cholesterol by increasing the expression of ABCG5 and ABCG8. Moreover, oral administration of E. faecalis ATCC19433 modulated the composition of gut microbiota and increased the counts of Lactobacillus, Bifidobacterium, and Akkermansia. Our results showed that E. faecalis ATCC19433 could exert hypocholesterolemic effect on hypercholesterolemic mice by improving transporter ABCG5 and ABCG8. E. faecalis ATCC19433 maybe contribute to the transportation of cholesterol potentially and modulate the composition of gut microbiota.


Assuntos
Colesterol/metabolismo , Enterococcus faecalis/metabolismo , Microbioma Gastrointestinal , Interações Microbianas , Membro 5 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Membro 8 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Administração Oral , Animais , Bifidobacterium/isolamento & purificação , Transporte Biológico , Colesterol/sangue , Hipercolesterolemia/terapia , Lactobacillus/isolamento & purificação , Metabolismo dos Lipídeos , Lipoproteínas/genética , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL
14.
Pathology ; 51(2): 227-232, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30611543

RESUMO

Low-density lipoprotein (LDL)-cholesterol (LDL-c) and lipoprotein(a) [Lp(a)] are independent cardiovascular risk factors. Reduction of LDL-c leads to reduction in cardiovascular events, regardless of the method of reducing LDL-c levels. Lifestyle modification and drugs are first line treatment options. However, many patients do not reach treatment goals, as defined in guidelines worldwide, through standard medication. So far, drugs are not efficient in lowering Lp(a) levels, or the reduction of plasma levels does not result in clinical benefit. In these two groups of patients lipoprotein apheresis is very efficient in decreasing LDL-c and Lp(a) levels. A single apheresis session can decrease LDL-c and Lp(a) by approximately 65%, and apheresis performed weekly or biweekly results in considerably decreased mean interval concentrations (approximately 30% reduction). Most apheresis systems (HELP, heparin induced extracorporeal LDL precipitation; DALI, direct adsorption of lipoproteins; lipoprotein apheresis with dextran sulfate; lipid filtration; immunoadsorption) decrease LDL-c and Lp(a). Lipopac is a specific form of immunapheresis and only decreases Lp(a). Lipoprotein apheresis is a well-tolerated treatment option but it is expensive and time consuming. The evidence for clinical benefit through regular apheresis comes from observational data. Adequate, randomised, controlled trials are lacking.


Assuntos
LDL-Colesterol/sangue , Hipercolesterolemia/terapia , Lipoproteína(a)/sangue , Adsorção , Remoção de Componentes Sanguíneos , Sulfato de Dextrana/uso terapêutico , Filtração , Humanos , Hipercolesterolemia/sangue
15.
J Clin Nurs ; 28(9-10): 1745-1759, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30667574

RESUMO

AIMS AND OBJECTIVES: To identify the key factors of adopting self-care behaviours in the treatment of diabetes mellitus II, hypertension and hypercholesterolaemia when the three conditions appear simultaneously. BACKGROUND: Diabetes, hypertension and hypercholesterolaemia are chronic health problems which often appear together. The correct monitoring of these pathologies when they concur simultaneously requires specific health management behaviours, to which a significant part of the population is unable of adhering, despite recommendations from professional healthcare workers. DESIGN: A qualitative study using focus groups techniques was carried out. The elements related to the content were drafted following the recommendations of the Consolidated Criteria for Reporting Qualitative Research (COREQ checklist). METHODS: Patients with simultaneous diabetes, hypertension and hypercholesterolaemia, as well as nursing professionals and family doctors who have treated patients at primary care centres, were the key sources of information. The methodology used to analyse the information was content analysis. RESULTS: There were factors which can positively or negatively determine the adoption of the self-management recommendations that healthcare professionals make to patients who simultaneously have diabetes, hypertension and hypercholesterolaemia. These factors were not only associated with the patient, but also with the health carers themselves and the healthcare system and policies in force. CONCLUSIONS: When health professionals provide recommendations for self-care to people diagnosed with diabetes, hypertension and hypercholesterolaemia simultaneously, they should bear in mind not only the determinants of behaviour associated with the patient, but also those that are related to the health professionals themselves and with the healthcare system. The PRECEDE model could be a good tool to identify and design health education programs. RELEVANCE TO CLINICAL PRACTICE: The knowledge of the determinants of health behaviour of patients with chronic diseases could improve adherence patients to health recommendations, avoid associated complications and increase their quality of life.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Hipercolesterolemia/complicações , Hipertensão/complicações , Cooperação do Paciente/psicologia , Autogestão/psicologia , Idoso , Diabetes Mellitus Tipo 2/psicologia , Diabetes Mellitus Tipo 2/terapia , Feminino , Grupos Focais , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde/normas , Humanos , Hipercolesterolemia/psicologia , Hipercolesterolemia/terapia , Hipertensão/psicologia , Hipertensão/terapia , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto/normas , Pesquisa Qualitativa , Qualidade de Vida
16.
Ir J Med Sci ; 188(1): 179-188, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29858795

RESUMO

Atherosclerosis begins in childhood. Fatty streaks, the earliest precursor of atherosclerotic lesions, have been found in the coronary arteries of children of 2 years of age. Hypercholesterolaemia is a risk factor for coronary artery disease. Hypercholesterolaemia can be either primary, when it is characteristic of the main disease, or secondary when it occurs as a result of either a disease process or drug treatment. Given the risk of vascular disease, including myocardial infarction (MI), cerebrovascular accidents (CVA, also known as strokes), peripheral vascular disease (PVD) and ruptured aortic aneurysm, which may follow atherosclerosis, it is important to prevent or slow the early development of atherosclerotic lesions. This prevention necessitates the control of key risk factors such hypercholesterolaemia, dyslipidaemia, hypertension etc. However, at what point this prevention ought to occur, and in what form, is uncertain. Using pharmacological primary prevention for hypercholesterolaemia in the paediatric population is controversial. In an adult patient, hypercholesterolaemia warrants the initiation of a statin. Statins, also known as hydroxymethylglutaryl co-enzyme A inhibitors (or HMG-CoA inhibitors) act by altering cholesterol metabolism. In the paediatric population, the clinical course of vascular disease and the effect of altering this clinical course are less certain. This article reviews the published literature on hypercholesterolaemia in children and the use of statins as a treatment for dyslipidaemia in children. The US National Cholesterol Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents 2012 guidelines (NCEP guidelines) regarding the recognition and treatment of childhood dyslipidaemia are reviewed.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipídeos/sangue , Programas de Rastreamento , Anticolesterolemiantes/uso terapêutico , Aterosclerose/complicações , Aterosclerose/terapia , Criança , Humanos , Hipercolesterolemia/terapia , Hiperlipidemias/terapia , Pediatria , Guias de Prática Clínica como Assunto , Prevenção Primária
17.
J Microbiol Biotechnol ; 29(3): 473-481, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30415528

RESUMO

Statins are a class of lipid-lowering drugs commonly used in the prevention of cardiovascular diseases. However, statin therapy presents many limitations, which have led to an increased interest in non-drug therapies, such as probiotics, to improve blood cholesterol levels. Indeed, probiotic strains such as Lactobacillus acidophilus have been found to improve blood lipid profiles, especially in reducing total cholesterol and LDL-C levels. In this study, we established a high-cholesterol rat model and studied the effect of Lactobacillus acidophilus administration alone or in conjunction with rosuvastatin. We were able to show that indeed Lactobacillus exerts a cholesterol-lowering effect. Additionally, we observed that when administered together, rosuvastin and Lactobacillus exert a combined cholesterol-lowering effect. Altogether, our data advocate for the possibility of establishing probiotics as non-drug supplements for the treatment of hypercholesterolemia.


Assuntos
Colesterol/sangue , Hipercolesterolemia/terapia , Lactobacillus acidophilus/fisiologia , Probióticos/uso terapêutico , Rosuvastatina Cálcica/farmacologia , Animais , Anticolesterolemiantes/farmacologia , Doenças Cardiovasculares/prevenção & controle , Colesterol na Dieta , LDL-Colesterol/sangue , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Quimioterapia Combinada , Fezes/microbiologia , Microbioma Gastrointestinal , Lactobacillus acidophilus/genética , Lipídeos/sangue , Modelos Animais , Probióticos/administração & dosagem , Ratos
18.
Transfus Apher Sci ; 58(1): 61-64, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30545658

RESUMO

INTRODUCTION: Different modalities of low-density lipoprotein (LDL) apheresis are used to treat patients with familial hypercholesterolemia (FH). The aim of this study was to describe the efficacy of the Double Filtration Plasmapheresis (DFPP) method for FH cases in our hands and to compare with other LDL apheresis techniques. MATERIALS AND METHODS: This retrospective study was conducted between January 2016 and January 2018 in the University of Health Sciences, Diskapi Yildirim Beyazit Training and Research Hospital, Adult Hematology Clinic and Therapeutic Apheresis Unit. The study included 5 patients with a diagnosis of homozygous FH. A total of 288 DFFP procedures were performed twice a month (every 15 days) for 2 years. RESULTS: The percentage reductions in Lipoprotein A, total cholesterol, Low Density Lipoprotein-C, High Density Lipoprotein-C and triglyceride levels were found to be 84%, 69.2%, 69.8%, 58.8% and 50.1% respectively (5 cases, n = 288). No cardiac event occurred after the initiation of LA with DFPP. CONCLUSION: DFPP is an effective and safe LA method that can be used in the treatment of homozygous FH patients who do not respond to diet and statin therapy.


Assuntos
Hipercolesterolemia/terapia , Plasmaferese/métodos , Adulto , Feminino , Homozigoto , Humanos , Hipercolesterolemia/patologia , Masculino , Estudos Retrospectivos , Adulto Jovem
19.
Exp Clin Endocrinol Diabetes ; 127(5): 276-280, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-29890549

RESUMO

INTRODUCTION/BACKGROUND: Atherosclerosis is an inflammatory disorder in which several converging immune responses modulate and induce lipid accumulation in macrophages. Activated leukocyte cell adhesion molecule (ALCAM) has been described as a structural homologue of HDL-receptor and functions as a pattern recognition receptor (PRR), while its soluble form sALCAM is involved in ALCAM-dependent and -independent immune mechanisms. The aim of this study was to investigate the effect of aggressive removal of low density lipoprotein-cholesterol (LDL-C) and lipoprotein(a) (Lp [a]) by lipoprotein-apheresis (LA) on sALCAM and blood viscosity as well as to evaluate its association with lipoproteins and serum markers of inflammation.


Assuntos
Antígenos CD/sangue , Aterosclerose/sangue , Aterosclerose/terapia , Remoção de Componentes Sanguíneos/métodos , Moléculas de Adesão Celular Neuronais/sangue , LDL-Colesterol/sangue , Proteínas Fetais/sangue , Hipercolesterolemia/sangue , Hipercolesterolemia/terapia , Inflamação/sangue , Lipoproteína(a)/sangue , Receptores de Reconhecimento de Padrão/sangue , Adulto , Idoso , Feminino , Humanos , Hipercolesterolemia/genética , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
20.
J Am Coll Cardiol ; 72(23 Pt B): 2980-2995, 2018 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-30522632

RESUMO

People who maintain ideal cardiovascular heath have a low lifetime risk of cardiovascular disease. Therefore, encouraging people to achieve ideal cardiovascular health represents an important opportunity to improve the prevention of cardiovascular disease. However, preventing cardiovascular disease by promoting ideal cardiovascular health requires shifting the focus from treating disease after it develops to preventing cardiovascular events before they happen by slowing the progression of atherosclerosis. Because atherogenic lipoproteins play a central causal role in the initiation and progression of atherosclerosis, maintaining optimal lipid levels is necessary to achieve ideal cardiovascular health. This review describes the cumulative effect of lipid-carrying lipoproteins on the risk of cardiovascular disease, estimates the magnitude of the clinical benefit that can be achieved by maintaining optimal lipid levels, identifies the most effective timing for implementing strategies designed to achieve optimal lipid levels, and provides a clinical pathway to help people achieve the lipid levels necessary for ideal cardiovascular health.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/terapia , LDL-Colesterol/sangue , Promoção da Saúde/métodos , Doenças Cardiovasculares/diagnóstico , LDL-Colesterol/antagonistas & inibidores , Promoção da Saúde/tendências , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/diagnóstico , Hipercolesterolemia/terapia , Lipídeos/antagonistas & inibidores , Lipídeos/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Fatores de Risco
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