Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 25.706
Filtrar
1.
Expert Opin Pharmacother ; 21(3): 353-363, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31893957

RESUMO

Introduction: Scientific evidence on subjects treated with statin or other lipid-lowering treatments has established that treatments aiming to lower low-density lipoprotein cholesterol (LDL-C) can reduce atherosclerosis. PCSK9 inhibitors (PCSK9-i), thanks to their efficacy in reducing LDL-C constitute a further step in the treatment of dyslipidemia and cardiovascular (CV) diseases.Areas covered: The purpose of this narrative review is to summarize the current knowledge of PCSK9-i, with particular regard to pharmacodynamic, pharmacokinetic, and clinical data on evolocumab and alirocumab.Expert opinion: PCSK9-I are effective in reducing atherosclerotic events through their significant LDL-C-lowering action similarly to statins. Furthermore, these drugs can be considered safe and well-tolerated. However, some controversies remain with regard to their efficacy in reducing mortality and the paucity of data on both pleiotropic effects and long-term safety of these drugs. However, future studies will focus on understanding the effects of very low cholesterol levels on health. At present, we know that the genetic model of PCSK9 deficiency is characterized by very low LDL-C levels without particular health problems. Yet, we do not know the effect of prolonged PCSK9 inhibition induced by antibody action during the lifetime of normal subjects.


Assuntos
Hipercolesterolemia/tratamento farmacológico , Pró-Proteína Convertase 9/antagonistas & inibidores , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticolesterolemiantes/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , LDL-Colesterol/sangue , Dislipidemias/tratamento farmacológico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipídeos/sangue
2.
Herz ; 45(1): 24-29, 2020 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-31970461

RESUMO

Cardiovascular diseases are among the leading causes of death worldwide. Apart from a few exceptions heart attack, stroke and peripheral arterial occlusive disease first occur in later adulthood. The cornerstone for these diseases, however, is already laid by accelerated vascular aging in childhood. Apart from pediatric medical preventive check-ups, the medical care of the parents should also be a reason for taking action. A detailed family history enables many conclusions to be drawn about the cardiovascular risk of the next generation This requires targeted diagnostics and appropriate interventions in childhood ranging from lifestyle measures up to pharmaceutical therapy. In this context the current guidelines on the diagnostics and treatment of hypercholesterolemia and arterial hypertension in children and adolescents are also presented.


Assuntos
Doenças Cardiovasculares , Hipercolesterolemia , Hipertensão , Estilo de Vida , Infarto do Miocárdio , Adolescente , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Criança , Humanos , Hipercolesterolemia/complicações , Hipercolesterolemia/tratamento farmacológico , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/prevenção & controle , Fatores de Risco
3.
Arch Oral Biol ; 109: 104553, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31563004

RESUMO

This study evaluated the effects of replacing a saturated fat diet by n-3 polyunsaturated fatty acids (n-3PUFA), on alveolar bone loss in hypercholesterolemic rats with experimental periodontitis (PD). METHODS: Eight week old Wistar rats were assigned according to dietary intake. Control group (C, n = 15) fed a commercial diet throughout the experiment. Atherogenic group (AT, n = 30) fed AT diet for 3 weeks; thereafter, AT was randomized to receive either a n-3PUFA (n = 15) or to continue with AT (n = 15) diet. Subsequently, PD was induced in all groups by unilateral ligature (L) of the first molar (M1) of the left mandible, non-ligated contralateral molars served as controls. After every week of PD induction, 5 rats per group were euthanized. Serum was collected for lipids assays and hemi-mandibles were subjected to histomorphometric (% upper and lower interradicular bone volume and periodontal ligament height, hPDL) and radiographic analyses (periodontal bone support, PBS, in ligated teeth, between M1-M2). RESULTS: Rats fed n-3PUFA diet rapidly induced a significant reduction in the serum lipids (p < 0.001). In all rats the ligated teeth showed a greater bone loss as compared with the unligated molars. At the end of the experiment the AT + L was the worst in % lower bone volume (p < 0.01), hPDL and PBS (p < 0.05). In contrast, rats fed n-3PUFA + L was similar to those rats fed C diet (p > 0.05). CONCLUSION: Alveolar bone and dyslipidemia improved by substituting saturated fat intake for a n-3PUFA rich diet, in hypercholesterolemic rats with PD.


Assuntos
Perda do Osso Alveolar/terapia , Dieta , Ácidos Graxos Ômega-3/administração & dosagem , Óleos de Peixe/administração & dosagem , Hipercolesterolemia/fisiopatologia , Periodontite/fisiopatologia , Animais , Dislipidemias/terapia , Distribuição Aleatória , Ratos , Ratos Wistar
4.
Medicine (Baltimore) ; 98(51): e18354, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31860991

RESUMO

Many cancer patients develop diabetes, which may result in reduction of chemotherapy effectiveness and increased infection risk and cardiovascular mortality. Diabetes may also increase the risks of chemotherapy-related toxicity and post-operative mortality, or represent an obstacle to optimal cancer treatment. However, the clinical predictors of diabetes in cancer patients remain largely unknown. Therefore, the aim of our study was to evaluate the risk factors for developing diabetes and construct a nomogram to predict diabetes in cancer patients.We investigated patients from a national sample cohort obtained from the Korea National Health Insurance Service (KNHIS), which included 2% of the Korean population. Patients who had undergone routine medical evaluation by the KNHIS between 2004 and 2008 and been hospitalized due to cancer (ICD-10 codes C00-97) during the past 3 years were included. After excluding patients with type 2 diabetes and missing data, 10,899 patients were enrolled and followed-up until 2013. A total of 7630 (70%) patients were assigned as the training cohort and used to construct the nomogram which was based on a multivariable logistic regression model. The remaining patients (n = 3269) were used as the validation cohort.The incidence rate of diabetes was 12.1 per 1000 person-years over a mean follow-up of 6.6 ±â€Š1.8 years. Significant risk factors for developing diabetes were age, sex, obesity, fasting plasma glucose, hypertension, and hypercholesterolmia. A nomogram was constructed using these variables and internally validated. The area under the curve was 0.70 (95% confidence interval, .666-.730, P < .0001) and the calibration plot showed agreement between the actual and nomogram-predicted diabetes probabilities.The nomogram developed in this study is easy to use and convenient for identifying cancer patients at high-risk for type 2 diabetes, enabling early type 2 diabetes screening and management.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Neoplasias/epidemiologia , Medição de Risco , Fatores Etários , Idoso , Glicemia/análise , Estudos de Coortes , Feminino , Seguimentos , Humanos , Hipercolesterolemia/epidemiologia , Hipertensão/epidemiologia , Incidência , Masculino , Nomogramas , Obesidade/epidemiologia , República da Coreia/epidemiologia , Fatores de Risco , Distribuição por Sexo , Fatores Sexuais
5.
Clín. investig. arterioscler. (Ed. impr.) ; 31(6): 251-260, nov.-dic. 2019. tab, graf
Artigo em Inglês | IBECS | ID: ibc-185150

RESUMO

Introduction: High Density Lipoproteins (HDL) are dysfunctional in hypercholesterolemia patients. The hypothesis was tested that nicotinamide (NAM) administration will influence HDL metabolism and reverse cholesterol transport from macrophages to the liver and feces in vivo (m-RCT) in a murine model of hypercholesterolemia. Methods: Apolipoprotein E-deficient (KOE) mice were challenged with a high-fat diet for 4 weeks. The effect of different doses of NAM on cholesterol metabolism, and the ability of HDL to promote m-RCT was assessed. Results: The administration of NAM to KOE mice produced an increase (∼1.5-fold; P < 0.05) in the plasma levels of cholesterol, which was mainly accounted for by the non-HDL fraction. NAM produced a [3H]-cholesterol plasma accumulation (∼1.5-fold) in the m-RCT setting. As revealed by kinetic analysis, the latter was mainly explained by an impaired clearance of circulating non-HDL (∼0.8-fold). The relative content of [3H]-tracer was lowered in the livers (∼0.6-fold) and feces (> 0.5-fold) of NAM-treated mice. This finding was accompanied by a significant (or trend close to significance) up-regulation of the relative gene expression of Abcg5 and Abcg8 in the liver (Abcg5: 2.9-fold; P < 0.05; Abcg8: 2.4-fold; P = 0.06) and small intestine (Abcg5: 2.1-fold; P = 0.15; Abcg8: 1.9-fold; P < 0.05) of high-dose, NAM-treated mice. Conclusion: The data from this study show that the administration of NAM to KOE mice impaired m-RCT in vivo. This finding was partly due to a defective hepatic clearance of plasma non-HDL


No dispnible


Assuntos
Animais , Camundongos , Apolipoproteínas E/deficiência , Niacinamida/administração & dosagem , Colesterol/análise , Hipercolesterolemia/diagnóstico , Hipercolesterolemia/tratamento farmacológico , Apolipoproteínas E/administração & dosagem , Niacinamida/metabolismo , Colesterol/metabolismo , Gorduras na Dieta , Expressão Gênica , HDL-Colesterol
6.
Clín. investig. arterioscler. (Ed. impr.) ; 31(6): 271-277, nov.-dic. 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-185153

RESUMO

Se presenta la cuarta actualización de las tablas de planificación terapéutica. Esta tabla es una sencilla herramienta de sobremesa que permite determinar la terapia hipocolesterolemiante oral más apropiada para su paciente, bien con monoterapia, bien con terapia combinada (estatinas más ezetimiba), teniendo en cuenta su colesterol ligado a lipoproteínas de baja densidad (c-LDL) de partida y el objetivo terapéutico a alcanzar. Estas indicaciones terapéuticas se basan en 2 principios fundamentales: la causalidad del c-LDL y que el efecto de protección cardiovascular depende del descenso del c-LDL. Se han diseñado como un código de colores que señala los fármacos que tienen la potencia necesaria para llevar a su paciente a objetivos terapéuticos. Se establecen unas recomendaciones sobre la estrategia a seguir para implementar el tratamiento más eficaz. También se muestra hasta qué niveles podemos esperar un descenso de c-LDL al añadir un inhibidor de PCSK9


This is the fourth update of the therapeutic planning tables. These tables are a simple desktop tool, to help in determining the most appropriate oral cholesterol-lowering therapy for patient. This can either be with monotherapy or combination therapy (statins plus ezetimibe), taking into account the patient LDL cholesterol (LDL-C) and the therapeutic objective to be achieved. These therapeutic indications are based on 2 fundamental principles: the causality of LDL-C, and that the effect of cardiovascular protection depends on the decrease in LDL-C. It is based on a colour code that indicates the drugs that have the necessary power to meet the therapeutic objectives of the patient. We provide some recommendations on the strategy to follow to implement the most effective treatment. It is assessed up to what levels a decrease in LDL-C can be expected by adding a PCSK9 inhibitor


Assuntos
Humanos , Anticolesterolemiantes/administração & dosagem , Hipercolesterolemia/tratamento farmacológico , Equivalência Terapêutica , Padrões de Referência , Anticolesterolemiantes/metabolismo , Anticolesterolemiantes/farmacologia , Valores de Referência
7.
Clín. investig. arterioscler. (Ed. impr.) ; 31(6): 278-281, nov.-dic. 2019. graf
Artigo em Espanhol | IBECS | ID: ibc-185154

RESUMO

Las estatinas están contraindicadas en pacientes con miopatías. Hasta hace unos años, la alternativa en pacientes con hipercolesterolemia familiar que tenían distrofias musculares y no conseguían niveles adecuados de colesterol era la lipoaféresis. Cuando surgieron los inhibidores de PCSK9, se consiguió suspender la lipoaféresis en algunos de estos pacientes y mantenerlos con concentraciones plasmáticas de colesterol adecuadas. Presentamos el caso de un varón, diagnosticado en la infancia de distrofia muscular congénita. A los 27 años se remitió a la unidad de lípidos por hipercolesterolemia, donde tras estudio genético se confirmó una hipercolesterolemia familiar heterocigota. A pesar del tratamiento con dieta y ezetimiba continuó con cifras elevadas de cLDL por lo que se incluyó en programa de lipoaféresis. Con esto se alcanzaron niveles de cLDL de 70 mg/dl. Al disponer de los iPCSK9, se suspendió la lipoaféresis y se inició tratamiento con alirocumab 150 mg quincenal, con buena respuesta y manteniendo valores de cLDL en torno a 75 mg/dl


Statins are contraindicated in patients with myopathies. Until a few years ago, in those patients with Familial Hypercholesterolemia who also presented muscular dystrophies and didńt reach adequate cholesterol plasmatic levels, the next therapeutic ladder was lipoapheresis. When iPCSK9 first appeared, lipoapheresis could be suspended in some of these patients, sustaining nevertheless proper levels of cholesterol. We present the case of a 27 year-old male, diagnosed with Congenital Muscular Dystrophy in the early childhood. He was referred to the Unit of Lipidology presenting hypercholesterolemia which, after genetic test, was assessed as Heterozygous Familial Hypercholesterolemia. Despite of treatment with diet and ezetimibe, cLDL blood levels abide high, being consequently included in lipoapheresis programme, therewith obtained levels of cLDL of 70 mg/dl. In providing iPCSK9, lipoapheresis was withdrawn and treatment with alirocumab 150 mg fortnightly introduced, unveiling a positive response, and sustaining cLDL levels around 75 mg/dl


Assuntos
Humanos , Masculino , Adulto , Pró-Proteína Convertase 9/administração & dosagem , Hipercolesterolemia/tratamento farmacológico , Distrofias Musculares/diagnóstico , Contraindicações de Medicamentos , Distrofias Musculares/complicações , Distrofias Musculares/congênito , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hipotonia Muscular/complicações
8.
J Agric Food Chem ; 67(48): 13307-13317, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31679333

RESUMO

Epidemiological studies have demonstrated that hypercholesterolemia is associated with an elevated risk of atherosclerosis and cardiovascular diseases. In addition to the available cholesterol-lowering drugs, nutritionally balanced diets containing functional foods have attracted much interest as potential candidates to improve hypercholesterolemia. In the study, we demonstrated that dietary succinoglycan riclin effectively alleviated diet-induced hypercholesterolemia. Compared with the high-cholesterol-diet (HCD) group, the high-riclin group significantly decreased levels of the serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), and hepatic cholesterol (34, 40, and 51%, respectively), consequently improving hepatic steatosis and reducing proinflammatory cytokine expressions. 1H nuclear magnetic resonance (NMR)-based lipidomics and metabolomics analyses revealed that the riclin group partially reversed metabolic profile changes induced by the HCD, approaching that of the normal diet (ND) group. Riclin has no direct effects on cholesterol metabolism-related gene expression among the three HCD model groups. Basically, riclin increased the solution viscosity and interfered in the process of bile acid-cholesterol emulsification, decreasing cholesterol digestion and promoting cholesterol and bile acid excretion in the feces. These results suggested potential therapeutic utility of succinoglycan riclin as a food additive for people suffering from hypercholesterolemia and related diseases.


Assuntos
Anticolesterolemiantes/metabolismo , Hipercolesterolemia/dietoterapia , Polissacarídeos Bacterianos/metabolismo , Animais , Ácidos e Sais Biliares/metabolismo , LDL-Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Humanos , Hipercolesterolemia/etiologia , Hipercolesterolemia/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL
9.
Zhonghua Nei Ke Za Zhi ; 58(11): 823-825, 2019 Nov 01.
Artigo em Chinês | MEDLINE | ID: mdl-31665858

RESUMO

This study was aimed to investigate the association between dyslipidemia and thyroid associated ophthalmopathy (TAO). We evaluated the relationship between dyslipidemia and TAO in 218 patients with Graves' disease (GD) and found that the serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) in the GD subjects with TAO (n=110) were significantly increased [(5.32±1.39) mmol/L vs. (3.18±2.12) mmol/L, (2.98±0.75) mmol/L vs. (1.25±0.98) mmol/L] than those in the GD subjects without TAO (n=108). TC and LDL-C were positively correlated with the Clinical disease activity score (CAS) [TC (r=0.7, P=0.03),LDL-C (r=0.82, P=0.03)], and the levels of TC (OR=2.56, P=0.02) and LDL-C(OR=2.01, P=0.015) were positively associated with TAO. These suggested that high serum cholesterol level is a novel risk factor for TAO, and management of blood lipids should be included in the treatment of TAO.


Assuntos
Colesterol/sangue , Oftalmopatia de Graves/diagnóstico , Hipercolesterolemia/diagnóstico , LDL-Colesterol , Oftalmopatia de Graves/sangue , Humanos , Hipercolesterolemia/sangue , Fatores de Risco
10.
Methodist Debakey Cardiovasc J ; 15(3): 192-199, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31687098

RESUMO

The extract of red yeast rice (RYR) is the most effective cholesterol-lowering nutraceutical on the market. In particular, its effectiveness is directly related to the amount of monacolin K within the extract (up to 10 mg/day). Consuming monacolin K on a daily basis reduces low-density lipoprotein (LDL) cholesterol plasma levels between 15% and 25% within 6 to 8 weeks. Certainly, the decrease in LDL-cholesterol is accompanied by a similar reduction in total cholesterol, non-high-density lipoprotein cholesterol, plasma apolipoprotein B, matrix metalloproteinases 2 and 9, and high-sensitivity C-reactive protein. Furthermore, the RYR lipid-lowering effect is associated with significant improvements in pulse wave velocity and endothelial function, which are validated and reliable biomarker tools able to detect vascular aging. Although it has a mechanism of action similar to statins, a daily consumption of between 3 and 10 mg monacolin K has only minimal associated risks, and mild myalgias are seen only in the frailest patients (those who also cannot tolerate minimal dosages of statin). The monacolin K found in RYR is a safe and effective supplement for managing mild to moderate hypercholesterolemia in people with no additional cardiovascular risk factors.


Assuntos
Produtos Biológicos/uso terapêutico , Colesterol/sangue , Suplementos Nutricionais , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Lovastatina/uso terapêutico , Animais , Produtos Biológicos/efeitos adversos , Biomarcadores/sangue , Suplementos Nutricionais/efeitos adversos , Regulação para Baixo , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hipercolesterolemia/sangue , Hipercolesterolemia/diagnóstico , Lovastatina/efeitos adversos , Resultado do Tratamento
11.
Expert Opin Drug Metab Toxicol ; 15(11): 897-911, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31648563

RESUMO

Introduction: Statins are prescribed widely for cholesterol-lowering therapy, but it is known that their efficacy and safety profiles vary, despite the shared pharmacophore and pharmacological target. The immense body of related clinical and preclinical data offers a unique opportunity to explore the possible factors underlying inter-statin and inter-individual variabilities.Area covered: Clinical and preclinical data from various statins were compiled with regard to the efficacy (cholesterol-lowering effect) and safety (muscle toxicity). Based on the compiled data, dose- and exposure-response relationships were explored to obtain mechanistic and quantitative insights into the variations in the efficacy and safety profiles of statins.Expert opinion: Our analyses indicated that the inter-statin variability in the cholesterol-lowering effect may be mainly attributable to variations in potency of inhibition of the pharmacological target, rather than variations in drug exposure at the site of drug action. However, the drug exposure at the sites of drug action (i.e., the liver for efficacy and the muscle for safety) may contribute to the differences in the efficacy and safety observed in individual patients.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hipercolesterolemia/tratamento farmacológico , Doenças Musculares/induzido quimicamente , Animais , Anticolesterolemiantes/administração & dosagem , Anticolesterolemiantes/efeitos adversos , Relação Dose-Resposta a Droga , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Doenças Musculares/epidemiologia
12.
Rev Bras Epidemiol ; 22Suppl 02(Suppl 02): E190005.SUPL.2, 2019.
Artigo em Português, Inglês | MEDLINE | ID: mdl-31596376

RESUMO

OBJECTIVE: To analyze the prevalence of altered total cholesterol and fractions levels in the Brazilian population, according to biochemical data from the National Health Survey. METHODS: A descriptive study, using data from the National Health Survey, collected between 2014 and 2015. Total cholesterol and fractions were analyzed and population prevalences of altered values according to socio-demographic variables were calculated. The cutoff points considered were: total cholesterol ≥ 200mg/dl; low-density lipoprotein LDL ≥ 130mg/dL and high-density lipoprotein HDL < 40mg/dL. RESULTS: The prevalence of total cholesterol ≥200mg/dL in the population was 32.7%, and higher in women (35.1%). The prevalence of altered HDL was 31.8%, 22.0% in females and 42.8% in males. LDL ≥ 130mg/dL was found in 18.6% and was higher in women (19.9%). The population aged 45 years old and older and those with low levels of education presented a higher prevalence of altered cholesterol. CONCLUSION: Altered values of total cholesterol and fractions were frequent in the Brazilian population, especially among women, the elderly and people with low levels of education. These results may guide control and preventative actions such as healthy eating, physical activity and treatment, all of which aim to prevent coronary diseases.


Assuntos
HDL-Colesterol/sangue , LDL-Colesterol/sangue , Colesterol/sangue , Inquéritos Epidemiológicos/métodos , Hipercolesterolemia/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Fatores Etários , Brasil/epidemiologia , Estudos Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Valores de Referência , Distribuição por Sexo , Fatores Sexuais , Fatores Socioeconômicos , Adulto Jovem
15.
J Sports Med Phys Fitness ; 59(9): 1577-1583, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31610641

RESUMO

BACKGROUND: Cardiometabolic disease (CMD) risk factors have reached epidemic proportions, with many people at risk of premature disability and death. There is insufficient data regarding the prevalence of CMD risk factors among firefighters in the Western Cape Province of South Africa. The purpose of this study was to examine the prevalence of CMD risk factors among South African firefighters in the Western Cape Province. Additional outcomes were to determine the relationship between BMI and CMD risk factors among firefighters. METHODS: A total of 219 healthy male firefighters with mean age 37.8±9.80 years volunteered to participate in the study. Anthropometric (ISAK protocol compliant) and physiological variables (ACSM protocol compliant) were assessed. Descriptive statistics, such as mean, standard deviation and percentages were used to examine the CMD risk factors prevalence among the participants. RESULTS: Based on the BMI categorization, majority (42.5%) of the participants were obese, 17.4% were overweight, 39.7% had a normal BMI, while 0.5% were underweight. The participants with systolic prehypertension were 45.7%, while 14.2% were hypertensive. Furthermore, 39.3% were prediabetic, 18.3% were diabetic, while 1.4% had blood sugar below normal level (hypoglycemic). In terms of total blood cholesterol levels, 45.7% were normal, 38.8% were borderline high, while 15.5% were high in hypercholesterolemia. The majority (51.1%) of the participants reported non-participation in regular physical activity. Between BMI and the typical risk factors, there is a significant correlation with abdominal obesity (r=0.71; P<0.001), systolic blood pressure (r=0.33; P<0.001), diastolic blood pressure (r=0.31; P<0.001), fasting blood glucose (r=0.22; P<0.01) and total cholesterol (r=0.15; P<0.05). CONCLUSIONS: There was a high prevalence of cardiometabolic disease risk factors among firefighters. Furthermore, urgent intervention focusing on the lifestyle modification and weight management is a necessity.


Assuntos
Doenças Cardiovasculares/etiologia , Bombeiros/estatística & dados numéricos , Síndrome Metabólica/etiologia , Adulto , Índice de Massa Corporal , Estudos Transversais , Humanos , Hipercolesterolemia/epidemiologia , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Prevalência , Fatores de Risco , Comportamento Sedentário , África do Sul/epidemiologia
16.
J Agric Food Chem ; 67(43): 11922-11930, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31576748

RESUMO

We investigated the regulatory effects of citrus pectin oligosaccharides (POS) from an innovative, chemically controllable degradation process on cholesterol metabolism and the gut microbial composition. The modulatory role of the intestinal flora was explored. Four-week-old male C57BL/6 mice were fed either a standard diet; a high-fat (HF) diet; or a HF diet with 0.15, 0.45, and 0.9 g/kg body weight POS for 30 days. POS reduced serum total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) in a dose-dependent manner. The relative abundances of specific bacterial groups in the feces and the concentrations of their metabolites were higher in the POS groups. There were significant correlations among Bifidobacterium, Lactobacillus, and Bacteroides and short-chain fatty acids, as well as among serum TC, LDL-C, fecal bile acids, and liver cholesterol 7-α-hydroxylase and 3-hydroxy-3-methylglutaryl-coenzyme A reductase. These findings indicate that the prepared POS exhibited hypocholesterolemic effects and that the potential regulatory mechanisms of citrus POS on cholesterol metabolism are modulated by specific bacterial groups together with their metabolites.


Assuntos
Anticolesterolemiantes/administração & dosagem , Colesterol/metabolismo , Citrus/química , Microbioma Gastrointestinal , Hipercolesterolemia/tratamento farmacológico , Oligossacarídeos/administração & dosagem , Pectinas/administração & dosagem , Extratos Vegetais/administração & dosagem , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , LDL-Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos Voláteis/metabolismo , Fezes/microbiologia , Humanos , Hipercolesterolemia/metabolismo , Hipercolesterolemia/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
18.
N Engl J Med ; 381(12): 1114-1123, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31532959

RESUMO

BACKGROUND: Persons with low socioeconomic status and nonwhite persons in the United States have high rates of cardiovascular disease. The use of combination pills (also called "polypills") containing low doses of medications with proven benefits for the prevention of cardiovascular disease may be beneficial in such persons. However, few data are available regarding the use of polypill therapy in underserved communities in the United States, in which adherence to guideline-based care is generally low. METHODS: We conducted a randomized, controlled trial involving adults without cardiovascular disease. Participants were assigned to the polypill group or the usual-care group at a federally qualified community health center in Alabama. Components of the polypill were atorvastatin (at a dose of 10 mg), amlodipine (2.5 mg), losartan (25 mg), and hydrochlorothiazide (12.5 mg). The two primary outcomes were the changes from baseline in systolic blood pressure and low-density lipoprotein (LDL) cholesterol level at 12 months. RESULTS: The trial enrolled 303 adults, of whom 96% were black. Three quarters of the participants had an annual income below $15,000. The mean estimated 10-year cardiovascular risk was 12.7%, the baseline blood pressure was 140/83 mm Hg, and the baseline LDL cholesterol level was 113 mg per deciliter. The monthly cost of the polypill was $26. At 12 months, adherence to the polypill regimen, as assessed on the basis of pill counts, was 86%. The mean systolic blood pressure decreased by 9 mm Hg in the polypill group, as compared with 2 mm Hg in the usual-care group (difference, -7 mm Hg; 95% confidence interval [CI], -12 to -2; P = 0.003). The mean LDL cholesterol level decreased by 15 mg per deciliter in the polypill group, as compared with 4 mg per deciliter in the usual-care group (difference, -11 mg per deciliter; 95% CI, -18 to -5; P<0.001). CONCLUSIONS: A polypill-based strategy led to greater reductions in systolic blood pressure and LDL cholesterol level than were observed with usual care in a socioeconomically vulnerable minority population. (Funded by the American Heart Association Strategically Focused Prevention Research Network and the National Institutes of Health; ClinicalTrials.gov number, NCT02278471.).


Assuntos
Anti-Hipertensivos/administração & dosagem , Combinação de Medicamentos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hipercolesterolemia/tratamento farmacológico , Hipertensão/tratamento farmacológico , Área Carente de Assistência Médica , Adesão à Medicação/estatística & dados numéricos , Adulto , Alabama , Anlodipino/administração & dosagem , Atorvastatina/administração & dosagem , LDL-Colesterol/sangue , Centros Comunitários de Saúde , Feminino , Humanos , Hidroclorotiazida/administração & dosagem , Hipercolesterolemia/sangue , Hipercolesterolemia/complicações , Hipertensão/complicações , Losartan/administração & dosagem , Masculino , Pessoa de Meia-Idade
19.
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
20.
World Neurosurg ; 132: e99-e108, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31518751

RESUMO

BACKGROUND: High cholesterol has been correlated with a greater risk of cerebrovascular diseases. Whether pre-existing high cholesterol exacerbates traumatic brain injury (TBI), and whether treatment with the cholesterol-lowering agent simvastatin has neuroprotective effects, especially anti-neuroinflammatory effects, after TBI are not well investigated. METHODS: Five-week-old male Sprague-Dawley rats were fed a high-fat diet for 8 weeks to induce hypercholesterolemia. Anesthetized male Sprague-Dawley rats were divided into 5 groups, including the sham-operated control, TBI control, and TBI with simvastatin treatment (4 mg/kg, 10 mg/kg, or 20 mg/kg) groups. Simvastatin was intraperitoneally injected at 0, 24, and 48 hours after TBI. Motor function was measured using an inclined plane. Neuronal apoptosis (maker Neu-N, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling), tumor necrosis factor-α expression in microglia (marker OX42) and astrocytes (marker glial fibrillary acidic protein), and Tumor necrosis factor-alpha receptor (TNFR) 1 and TNFR2 expression in neurons in the ischemic cortex were investigated using an immunofluorescence assay. All of the parameters were measured on the third day after TBI. RESULTS: TBI significantly increased the serum levels of cholesterol. The TBI-induced motor deficit was significantly attenuated by 4, 10, and 20 mg/kg simvastatin therapy on the third day after TBI. TBI-induced neuronal TNFR1 activation and apoptosis, as well as tumor necrosis factor-α expression in astrocytes in the ischemic cortex, were significantly attenuated by simvastatin, particularly when 20 mg/kg was administered. Simultaneously, the serum cholesterol remained high despite simvastatin treatment. CONCLUSIONS: The neuroprotection effects of simvastatin on the pre-existing hypercholesterolemia during TBI in rats may be related to its anti-neuroinflammatory effects but not to its cholesterol-lowing effects.


Assuntos
Anticolesterolemiantes/uso terapêutico , Lesões Encefálicas Traumáticas/complicações , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/etiologia , Fármacos Neuroprotetores/uso terapêutico , Sinvastatina/uso terapêutico , Animais , Lesões Encefálicas Traumáticas/psicologia , Colesterol/sangue , Ativação de Macrófagos/efeitos dos fármacos , Masculino , Desempenho Psicomotor/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptores do Fator de Necrose Tumoral/biossíntese , Fator de Necrose Tumoral alfa/sangue
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA