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1.
Rev Fac Cien Med Univ Nac Cordoba ; 76(3): 159-163, 2019 08 29.
Artigo em Espanhol | MEDLINE | ID: mdl-31465183

RESUMO

Background: Excess weight (EW) and alterations in lipid metabolism constitute risk factors for cardiovascular disease in adults and children. Prevalence of dyslipidemia in schoolchildren from Jujuy with EW is analyzed in this study. Methods: Cross-sectional descriptive study of 891 schoolchildren 10-14 years old (367 girls; 524 boys) from the province of Jujuy (Northwestern Argentina). Prevalence of dyslipidemia for Overweight (OW) and Obesity (OB) were calculated, according to the International Obesity Task Force cut-off points. Prevalence of lipid alterations were analyzed and 7 dyslipidemic profiles were established. Comparisons and associations between variables were analyzed by Chi-square test. Crude and adjusted odds ratio were estimated from a logistic regressions. Results: Regardless of sex and nutritional status, 13.7%, 21.8%, and 16.5% of schoolchildren showed high values of total cholesterol, triglycerides, and LDL cholesterol, respectively, and 20.3% had low HDL cholesterol. Significantly higher values of HDL cholesterol were found in OW, and of triglycerides in OB. A significant association was recorded between OB and high triglycerides. Schoolchildren with OB have a 54% more chances of showing at least one lipid alteration. Conclusion: EW, and especially OB, constitutes an important risk factor in the development of dyslipidemia in schoolchildren from Jujuy.


Assuntos
Dislipidemias/sangue , Dislipidemias/etiologia , Sobrepeso/complicações , Adolescente , Argentina/epidemiologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Criança , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos Transversais , Dislipidemias/epidemiologia , Feminino , Humanos , Masculino , Obesidade/complicações , Sobrepeso/epidemiologia , Prevalência , Instituições Acadêmicas , Triglicerídeos/sangue
2.
High Blood Press Cardiovasc Prev ; 26(4): 263-272, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31313082

RESUMO

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


Assuntos
Doenças Cardiovasculares/prevenção & controle , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dislipidemias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Causas de Morte , Dislipidemias/sangue , Dislipidemias/diagnóstico , Dislipidemias/mortalidade , Feminino , Humanos , Masculino , Fatores de Proteção , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
3.
Isr Med Assoc J ; 21(6): 369-375, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31280503

RESUMO

BACKGROUND: In Israel, coronary heart disease mortality rates are significantly higher among the Arab population than the Jewish population. Dyslipidemia prevention should begin in childhood. OBJECTIVES: To identify sociodemographic disparities in the preventive health measurement of lipid profile testing and lipoprotein levels among Israeli children and adolescents. METHODS: A cross-sectional analysis of 1.2 million children and adolescents insured by Clalit Health Services between 2007 and 2011 was conducted using sociodemographic data and serum lipid concentrations. RESULTS: Overall, 10.1% individuals had undergone lipid testing. Those with male sex (odds ratio [OR] = 0.813, 95% confidence interval [95%CI] 0.809-0.816), Arab ethnicity (OR = 0.952, 95%CI 0.941-0.963), and low socioeconomic status (SES) (OR = 0.740, 95%CI 0.728-0.752) were less likely to be tested. By 2010, differences among economic sectors narrowed and Arab children were more likely to be tested (OR = 1.039, 95%CI 1.035-1.044). Girls had higher total cholesterol, triglyceride, low-density lipoprotein-cholesterol, and non-high-density lipoprotein-cholesterol levels compared to boys (P < 0.001). Jewish children had higher cholesterol and low-density and high-density lipoprotein-cholesterol, as well as lower triglyceride levels than Arabs (P < 0.001). Children with low SES had lower cholesterol, low-density and high-density lipoprotein-cholesterol, and non-high-density lipoprotein-cholesterol levels (P < 0.001). CONCLUSIONS: We found that boys, Arab children, and those with low SES were less likely to be tested. Over time there was a gradual reduction in these disparities. Publicly sponsored healthcare services can diminish disparities in the provision of preventive health among diverse socioeconomic groups that comprise the national population.


Assuntos
Árabes/estatística & dados numéricos , Dislipidemias/diagnóstico , Disparidades em Assistência à Saúde , Judeus/estatística & dados numéricos , Programas Nacionais de Saúde , Classe Social , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Dislipidemias/sangue , Feminino , Humanos , Israel , Lipídeos/sangue , Masculino , Pediatria/métodos , Fatores Sexuais
4.
High Blood Press Cardiovasc Prev ; 26(3): 199-207, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31236902

RESUMO

Proprotein convertase subtilisin/kexin type 9 (PCSK9)-related discoveries of the turn of the century have translated into substantial novelty in dyslipidemia treatment in the last 5 years. With chronic preventable atherosclerotic cardiovascular diseases (ASCVD) representing an epidemic of morbidity and mortality worldwide, low-density lipoprotein cholesterol (LDL-c) reduction represents a public health priority. By overcoming two major statin-related issues, namely intolerance and ineffectiveness, PCSK9 inhibitors have offered a safe and effective option in selected clinical settings where LDL-c reduction is required. Herein, we recapitulate recent findings, clinical applications, and ASCVD prevention potential of PCSK9 inhibition, with focus on anti-PCSK9 monoclonal antibodies, evolocumab and alirocumab.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticolesterolemiantes/uso terapêutico , Aterosclerose/prevenção & controle , LDL-Colesterol/sangue , Dislipidemias/tratamento farmacológico , Pró-Proteína Convertase 9/antagonistas & inibidores , Inibidores de Serino Proteinase/uso terapêutico , Animais , Anticorpos Monoclonais/efeitos adversos , Anticolesterolemiantes/efeitos adversos , Aterosclerose/sangue , Aterosclerose/enzimologia , Aterosclerose/epidemiologia , Biomarcadores/sangue , Dislipidemias/sangue , Dislipidemias/enzimologia , Dislipidemias/epidemiologia , Humanos , Guias de Prática Clínica como Assunto , Pró-Proteína Convertase 9/metabolismo , Fatores de Risco , Inibidores de Serino Proteinase/efeitos adversos , Resultado do Tratamento
5.
Pestic Biochem Physiol ; 157: 138-142, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31153461

RESUMO

The evidence shows that organophosphate compounds (OPCs), as toxic agents that stimulate the cholinergic system, can increase the incidence of metabolic disorders such as dyslipidemia. In the present study, we focused on the role of tumor necrosis factor alpha (TNF-α) and serum leptin and ghrelin in Diazinon (DZN)-induced dyslipidemia. The rats were randomly divided into five groups comprising eight animals, and all were treated via oral gavage for 28 consecutive days as follows: group one received only corn oil daily, while groups two through five received different doses of DZN dissolved in corn oil equal to 1/40, 1/20, 1/10 and 1/5 of the LD50 daily, respectively. The alteration of the serum lipid profile, such as triglycerides, high-density lipoprotein (HDL) and very-low-density lipoprotein (VLDL), was confirmed the occurrence of dyslipidemia in the range of doses 1/20-1/5 LD50 of DZN. Although no changes were found in the serum leptin levels, a significant increase was observed in the size of adipocytes, as well as in the TNF-α and ghrelin serum levels, and in the accumulation of epididymal fat, especially at a dose of 1/5 LD50 of DZN. It seems that interactions among the inflammatory reaction, cholinergic pathways and ghrelin secretion may be effective causes of DZN-induced dyslipidemia.


Assuntos
Diazinon/farmacologia , Dislipidemias/sangue , Dislipidemias/induzido quimicamente , Grelina/sangue , Fator de Necrose Tumoral alfa/sangue , Animais , Antioxidantes , Butirilcolinesterase/sangue , Leptina/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Masculino , Compostos Organofosforados/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ratos
6.
Vasc Health Risk Manag ; 15: 123-135, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190850

RESUMO

Purpose: Disturbed metabolism of cholesterol and triacylglycerols (TGs) carries increased risk for coronary artery calcification (CAC). However, the exact relationship between individual lipid species and CAC remains unclear. The aim of this study was to identify disturbances in lipid profiles involved in the calcification process, in an attempt to propose potential biomarker candidates. Patients and methods: We studied 70 patients at intermediate risk for coronary artery disease who had undergone coronary calcification assessment using computed tomography and Agatston coronary artery calcium score (CACS). Patients were divided into three groups: with no coronary calcification (NCC; CACS: 0; n=26), mild coronary calcification (MCC; CACS: 1-250; n=27), or severe coronary calcification (SCC; CACS: >250; n=17). Patients' serum samples were analyzed using liquid chromatography-mass spectrometry in an untargeted lipidomics approach. Results: We identified 103 lipids within the glycerolipid, glycerophospholipid, sphingolipid, and sterol lipid classes. After false discovery rate correction, phosphatidylcholine (PC)(16:0/20:4) in higher levels and PC(18:2/18:2), PC(36:3), and phosphatidylethanolamine(20:0/18:2) in lower levels were identified as correlates with SCC compared to NCC. There were no significant differences in the levels of individual TGs between the three groups; however, clustering the lipid profiles showed a trend for higher levels of saturated and monounsaturated TGs in SCC compared to NCC. There was also a trend for lower TG(49:2), TG(51:1), TG(54:5), and TG(56:8) levels in SCC compared to MCC. Conclusion: In this study we investigated the lipidome of patients with coronary calcification. Our results suggest that the calcification process may be associated with dysfunction in autophagy. The lipidomic biomarkers revealed in this study may aid in better assessment of patients with subclinical coronary artery disease.


Assuntos
Doença da Artéria Coronariana/sangue , Dislipidemias/sangue , Metabolômica/métodos , Fosfolipídeos/sangue , Calcificação Vascular/sangue , Idoso , Doenças Assintomáticas , Autofagia , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão , Angiografia por Tomografia Computadorizada , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/patologia , Dislipidemias/diagnóstico , Dislipidemias/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Espectrometria de Massas por Ionização por Electrospray , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/patologia
7.
Vasc Health Risk Manag ; 15: 149-157, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31239693

RESUMO

Introduction: Diabetes is often accompanied by undiagnosed dyslipidemia. The aim of the study is to investigate the clinical relevance of lipid profiles and lipid ratios as predictive biochemical models for glycemic control in patients with type 2 diabetes mellitus (T2DM). Methods: This is a retrospective study recruiting 140 patients with T2DM during a one-year period, 2018-2019, at the Diabetic Center Sanglah General Hospital and Internal Medicine Polyclinic Puri Raharja General Hospital. Demographic characteristics, glycosylated hemoglobin (HBA1c) , and lipid profile were recorded and analyzed using SPSS version 25.0 for Windows. The sample is then classified into good (HBA1c≤7) and poor (HBA1c>7) glycemic control. Risk analysis model, receiver operator characteristics (ROC) analysis, and correlation test were used to evaluate the association of HBA1c level with lipid profile and lipid ratio parameters. Result: Lipid profile findings such as total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) , triglycerides (TG), and lipid ratio parameter (LDL-C to high-density lipoprotein cholesterol (HDL-C) ratio) were higher in patients in the poor glycemic control group (p<0.05) and HDL-C was significantly lower in patients with poor glycemic control (p=0.001). There is a significant positive correlation between LDL, total cholesterol, LDL-C, TG, and TC to HDL-C ratio, triglycerides, and TC/HDL-C ratio with HBA1c level. Meanwhile, a negative correlation was observed on HDL-C with the HBA1c level. Only TC/HDL-C ratio and LDL-C/HDL-C ratio parameters may be used as predictive models (AUC>0.7), with cutoff point, sensitivity, and specificity of 4.68 (77%; 52%) and 3.06 (98%; 56%) respectively. A risk analysis model shows that the LDL-C/HDL-C ratio parameter is the most influential risk factor in the occurrence of poor glycemic control (adjusted OR =38.76; 95% CI: 27.32-56.64; p<0.001). Conclusion: Lipid profiles (LDL-C) and lipid ratios (LDL-C/HDL-C and TC/HDL-C ratio) show potential markers that can be used in predicting glycemic control in patients with T2DM.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Dislipidemias/sangue , Hemoglobina A Glicada/metabolismo , Lipídeos/sangue , Biomarcadores/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Dislipidemias/diagnóstico , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Triglicerídeos/sangue
8.
High Blood Press Cardiovasc Prev ; 26(3): 191-197, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31041682

RESUMO

The atherosclerotic alterations that are the basis of cardiovascular diseases can start already in childhood. For this reason the prevention of cardiovascular diseases should be undertaken very early both in the general population and, in a targeted manner, in subjects at cardiovascular risk. Preventive strategies should include measures to encourage physical activity and correct eating habits and to reduce exposure to pollutants. The main actors responsible for carrying out these preventive interventions are the local and national political authorities. Moreover, particular attention should be paid to the first thousand days of life starting from conception, to prevent unfavorable epigenetic modifications. In addition to initiatives aimed at the general population, interventions should be planned by the medical community to assess the individual risk profile. The current obesity epidemic has in fact made it relatively frequent even among children and adolescents to find some cardiovascular risk factors known in adults such as arterial hypertension, dyslipidemia, glucose metabolism disorders and increased of uric acid values. The purpose of this review is to indicate lines of intervention for cardiovascular prevention in children and adolescents.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Síndrome Metabólica/terapia , Serviços Preventivos de Saúde/métodos , Adolescente , Idade de Início , Pressão Arterial , Biomarcadores/sangue , Glicemia/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Criança , Comorbidade , Dislipidemias/sangue , Dislipidemias/epidemiologia , Dislipidemias/terapia , Transtornos do Metabolismo de Glucose/sangue , Transtornos do Metabolismo de Glucose/epidemiologia , Transtornos do Metabolismo de Glucose/terapia , Nível de Saúde , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Hipertensão/terapia , Hiperuricemia/sangue , Hiperuricemia/epidemiologia , Hiperuricemia/terapia , Lipídeos/sangue , Síndrome Metabólica/sangue , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/fisiopatologia , Obesidade Pediátrica/epidemiologia , Obesidade Pediátrica/fisiopatologia , Obesidade Pediátrica/terapia , Fatores de Proteção , Fatores de Risco , Ácido Úrico/sangue , Ganho de Peso
9.
Int J Mol Sci ; 20(9)2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31075962

RESUMO

This study focuses on the effect of honokiol (HON) on glucose homeostasis, insulin resistance, dyslipidemia, hepatic steatosis, and inflammation in type 2 diabetic db/db mice. Male C57BL/KsJ-db/db mice were fed a normal diet with or without HON (0.02%, w/w) or pioglitazone (PIO, anti-diabetic agent, 0.01%, w/w) for 5 weeks. Blood biomarker, tissue morphology and enzymatic and genetic parameters were determined. PIO significantly decreased food intake, fasting blood glucose, and glycosylated hemoglobin (HbA1c) levels, but markedly increased body weight, adipose tissue weight, and plasma leptin levels. HON did not significantly affect food intake, body weight, or levels of plasma leptin and blood glucose. However, HON led to significant decreases in adipose tissue weight, plasma insulin, blood HbA1c and HOMA-IR levels and improved glucose tolerance. The anti-diabetic and anti-adiposity effects of HON were partially related to the inhibition of gluconeogenic enzymes and their mRNA expression in the liver; and the inhibition of lipogenic enzymes in adipose tissue, respectively. Unlike PIO, HON did not affect dyslipidemia, but ameliorated hepatic steatosis by inhibiting hepatic lipogenic enzymes activity. Moreover, HON exhibited anti-inflammatory effects similar to PIO. These results suggest that HON can protect against type 2 diabetes by improving insulin resistance, glucose and lipid metabolism, and inflammation.


Assuntos
Compostos de Bifenilo/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fígado Gorduroso/tratamento farmacológico , Inflamação/tratamento farmacológico , Resistência à Insulina , Lignanas/uso terapêutico , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/patologia , Animais , Compostos de Bifenilo/farmacologia , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Dislipidemias/sangue , Dislipidemias/complicações , Fígado Gorduroso/sangue , Fígado Gorduroso/complicações , Fígado Gorduroso/patologia , Comportamento Alimentar/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Inflamação/sangue , Inflamação/complicações , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Leptina/sangue , Lignanas/farmacologia , Lipídeos/sangue , Masculino , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos
10.
Methodist Debakey Cardiovasc J ; 15(1): 16-22, 2019 Jan-Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31049145

RESUMO

Although lipid guidelines provide updated, practical, and clinically relevant information that may be used in patient care, the continuing publication of new evidence and the inevitable treatment gaps present in all guidelines reinforce the importance of clinical judgment in shared decision making. This article explores the development of the 2013 American College of Cardiology/American Heart Association Blood Cholesterol Guidelines and the evidence base for managing patients with severe hypercholesterolemia, provides more recent high-quality evidence, and identifies existing treatment gaps that should be considered when caring for such patients. Although it was submitted prior to publication of the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol, this review also includes key takeaway messages from the updated guideline.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dislipidemias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Lipídeos/sangue , Guias de Prática Clínica como Assunto/normas , Padrões de Prática Médica/normas , Adulto , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Tomada de Decisão Clínica , Dislipidemias/sangue , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Medicina Baseada em Evidências/normas , Feminino , Fidelidade a Diretrizes/normas , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento
11.
Methodist Debakey Cardiovasc J ; 15(1): 23-31, 2019 Jan-Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31049146

RESUMO

The discovery of statins (3-hydroxy-3-methylglutaryl CoA reductase inhibitors) is a consequence of the highly targeted, arduous search for naturally occurring compounds that inhibit cholesterol biosynthesis. An enormous amount of basic scientific, genetic, and clinical research substantiated the role of lipoprotein-derived cholesterol in atherogenesis. Quantifying the impact of lipid lowering on cardiovascular event rates became an issue of utmost urgency. Although a variety of nonstatin drugs had been tested in clinical trials, they found limited utility in the clinical setting due to lack of mortality reduction or tolerability issues. As multiple prospective randomized statin trials began publishing their results, it became clear that reducing atherogenic lipoprotein burden with these drugs was highly efficacious, safe, and generally well tolerated. Statins have been shown to reduce risk for nonfatal MI, ischemic stroke, need for revascularization, and cardiovascular and all-cause mortality. They have also been shown to stabilize and even regress established atherosclerotic plaque. For the first 2 decades of their use, statin dosing was largely determined by risk-stratified low-density lipoprotein cholesterol (LDL-C) goals. More recently, there has been a transition away from LDL-C goal attainment with a focus more on cardiovascular risk and percent LDL-C reduction. Unfortunately, long-term adherence rates with statin therapy remain low and, even when used, they tend to be underdosed.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , LDL-Colesterol/sangue , Cálculos da Dosagem de Medicamento , Dislipidemias/sangue , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
12.
Methodist Debakey Cardiovasc J ; 15(1): 32-38, 2019 Jan-Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31049147

RESUMO

Low-density lipoprotein cholesterol (LDL-C) is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD). Statins remain the first-line therapy for patients with elevated LDL-C and increased risk. However, many at-risk patients do not achieve adequate LDL-C lowering with statin monotherapy or do not tolerate statins because of side effects. Recent cardiovascular outcome trials involving ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have demonstrated efficacy of nonstatin therapies in further reducing LDL-C levels and ASCVD risk. This review highlights the available nonstatin therapeutic options and explores important novel therapeutic approaches currently under development.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inibidores de Serino Proteinase/uso terapêutico , Animais , Anticorpos Monoclonais/uso terapêutico , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , LDL-Colesterol/sangue , Ácidos Dicarboxílicos/uso terapêutico , Quimioterapia Combinada , Dislipidemias/sangue , Dislipidemias/epidemiologia , Dislipidemias/genética , Ezetimiba/uso terapêutico , Ácidos Graxos/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Pró-Proteína Convertase 9/antagonistas & inibidores , RNA Interferente Pequeno/uso terapêutico , Terapêutica com RNAi , Fatores de Risco , Inibidores de Serino Proteinase/efeitos adversos , Resultado do Tratamento
13.
Methodist Debakey Cardiovasc J ; 15(1): 39-46, 2019 Jan-Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31049148

RESUMO

High-density lipoprotein (HDL) is a protein-lipid nanoparticle that has predominately been characterized by its cholesterol concentration (HDL-C). Recent studies have challenged the presumed inverse association between HDL-C and cardiovascular events, suggesting a more U-shaped association. This has opened new opportunities to evaluate more novel measures of HDL metabolism, such as HDL particle number (HDL-P) and one of HDL's key functions, cholesterol efflux. Both HDL-P and cholesterol efflux are inversely associated with incident cardiovascular events and may perhaps be better targets for intervention. This review includes recent research on the emerging U-shaped association between HDL-C and cardiovascular events, recent observational studies related to HDL-P, and the effects of established and novel interventions on cholesterol efflux.


Assuntos
Anticolesterolemiantes/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Proteínas de Transferência de Ésteres de Colesterol/antagonistas & inibidores , HDL-Colesterol/sangue , Dislipidemias/tratamento farmacológico , Animais , Anticolesterolemiantes/efeitos adversos , Transporte Biológico , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Proteínas de Transferência de Ésteres de Colesterol/sangue , Dislipidemias/sangue , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Exercício , Dieta Saudável , Humanos , Comportamento de Redução do Risco , Resultado do Tratamento
14.
Methodist Debakey Cardiovasc J ; 15(1): 47-54, 2019 Jan-Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31049149

RESUMO

Dysregulated free cholesterol (FC) metabolism has been implicated in nearly all stages of atherosclerosis, the underlying cause of most cardiovascular disease. According to a widely cited model, the burden of macrophage FC in the arterial wall is relieved by transhepatic reverse cholesterol transport (RCT), which comprises three successive steps: (1) macrophage FC efflux to high-density lipoprotein (HDL) and/or its major protein, apolipoprotein AI; (2) FC esterification by lecithin:cholesterol acyltransferase (LCAT); and (3) HDL-cholesteryl ester (CE) uptake via the hepatic HDL-receptor, scavenger receptor class B type 1 (SR-B1). Recent studies have challenged the validity of this model, most notably the role of LCAT, which appears to be of minor importance. In mice, most macrophage-derived FC is rapidly cleared from plasma (t1/2 < 5 min) without esterification by hepatic uptake; the remainder is taken up by multiple tissue and cell types, especially erythrocytes. Further, some FC is cleared by the nonhepatic transintestinal pathway. Lastly, FC movement among lipid surfaces is reversible, so that a higher-than-normal level of HDL-FC bioavailability-defined by high plasma HDL levels concurrent with a high mol% HDL-FC-leads to the transfer of excess FC to cells in vivo. SR-B1-/- mice provide an animal model to study the mechanistic consequences of high HDL-FC bioavailability that provokes atherosclerosis and other metabolic abnormalities. Future efforts should aim to reduce HDL-FC bioavailability, thereby reducing FC accretion by tissues and the attendant atherosclerosis.


Assuntos
Doenças Cardiovasculares/sangue , HDL-Colesterol/sangue , Dislipidemias/sangue , Macrófagos/metabolismo , Animais , Anticolesterolemiantes/uso terapêutico , Apolipoproteína A-I/sangue , Disponibilidade Biológica , Transporte Biológico , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Dislipidemias/diagnóstico , Dislipidemias/tratamento farmacológico , Dislipidemias/epidemiologia , Humanos , Fígado/metabolismo , Macrófagos/efeitos dos fármacos , Fosfatidilcolina-Esterol O-Aciltransferase/metabolismo , Receptores Depuradores Classe B/metabolismo
15.
Methodist Debakey Cardiovasc J ; 15(1): 62-69, 2019 Jan-Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31049151

RESUMO

Cardiovascular disease is the leading cause of death worldwide, and elevated lipid levels is a major contributor. Gene delivery, which involves controlled transfer of nucleic acids into cells and tissues, has been widely used in research to study lipid metabolism and physiology. Several technologies have been developed to somatically overexpress, silence, or disrupt genes in animal models and have greatly advanced our knowledge of metabolism. This is particularly true with regard to the liver, which plays a central role in lipoprotein metabolism and is amenable to many delivery approaches. In addition to basic science applications, many of these delivery technologies have potential as gene therapies for both common and rare lipid disorders. This review discusses three major gene delivery technologies used in lipid research-including adeno-associated viral vector overexpression, antisense oligonucleotides and small interfering RNAs, and the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 genome editing system-and examines their potential therapeutic applications.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dislipidemias/terapia , Terapia Genética/métodos , Metabolismo dos Lipídeos/genética , Lipídeos/sangue , Animais , Sistemas CRISPR-Cas , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Dependovirus/genética , Dislipidemias/sangue , Dislipidemias/epidemiologia , Dislipidemias/genética , Edição de Genes/métodos , Terapia Genética/efeitos adversos , Vetores Genéticos , Humanos , Oligonucleotídeos Antissenso/genética , RNA Interferente Pequeno/genética , Terapêutica com RNAi/métodos , Resultado do Tratamento
16.
Methodist Debakey Cardiovasc J ; 15(1): 70-76, 2019 Jan-Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31049152

RESUMO

Besides the well-known hepatobiliary pathway of cholesterol excretion into the feces, transintestinal cholesterol excretion (TICE) is a second major pathway through which cholesterol is disposed from the body. In the process of TICE, cholesterol is taken up from lipoprotein particles at the basolateral side of the enterocyte and translocates towards the apical side of the enterocyte. At the apical side, the ATP-binding cassette transporters G5 and G8 form a heterodimer that transports cholesterol into the intestinal lumen. A substantial amount of the secreted cholesterol is likely reabsorbed by the cholesterol influx transporter Niemann-Pick C1-Like 1 (NPC1L1) since recent data indicate that inhibition of NPC1L1 increases the efficacy of TICE for disposal of cholesterol via the feces. The pathways and proteins involved in intracellular cholesterol trafficking in the enterocyte have not yet been identified. Therefore, in addition to discussing known mediators of TICE, this review will also examine potential candidates involved in cholesterol translocation in the enterocyte. Both the cholesterol reuptake and efflux pathways can be influenced by pharmaceutical means; thus, the TICE pathway is a very attractive target to increase cholesterol excretion from the body and prevent or mitigate atherosclerotic cardiovascular disease.


Assuntos
Anticolesterolemiantes/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Colesterol/sangue , Dislipidemias/tratamento farmacológico , Enterócitos/efeitos dos fármacos , Eliminação Intestinal/efeitos dos fármacos , Proteínas de Membrana Transportadoras/efeitos dos fármacos , Animais , Anticolesterolemiantes/efeitos adversos , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Regulação para Baixo , Dislipidemias/sangue , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Enterócitos/metabolismo , Fezes/química , Humanos , Proteínas de Membrana Transportadoras/metabolismo
17.
Mar Drugs ; 17(5)2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31067674

RESUMO

Low-fat diets, lipid-modifying nutraceuticals and a higher level of physical activity are often recommended to reduce dyslipidemia. A double-blind, randomized, crossover, controlled trial was designed to evaluate the independent and synergistic effects of Arthrospira (Spirulina) maxima supplementation (4.5 g·day-1) with or without performing a physical exercise program (PEP: aerobic exercise (3 days·week-1) + high-intensity interval training (2 days·week-1)) on blood lipids and BMI of 52 sedentary men with excess body weight. During six weeks, all participants were assigned to four intervention treatments (Spirulina maxima with PEP (SE), placebo with PEP (Ex), Spirulina maxima without PEP (Sm), placebo without PEP (C; control)) and plasma lipids were evaluated spectrophotometrically pre- vs. post intervention in stratified subgroups (overweight, obese and dyslipidemic subjects). Pre/post comparisons showed significant reductions in all plasma lipids in the SE group, particularly in those with dyslipidemia (p ≤ 0.043). Comparing the final vs. the initial values, BMI, total cholesterol, triglycerides and low-density lipoprotein cholesterol were decreased. High-density lipoprotein cholesterol increased in all treatment groups compared to C. Changes were observed mostly in SE interventions, particularly in dyslipidemic subjects (p < 0.05). Spirulina maxima supplementation enhances the hypolipidemic effect of a systematic PEP in men with excess body weight and dyslipidemia.


Assuntos
Dislipidemias/tratamento farmacológico , Exercício , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Spirulina , Adulto , Índice de Massa Corporal , Peso Corporal/efeitos dos fármacos , Colesterol/sangue , Colesterol/metabolismo , HDL-Colesterol/sangue , HDL-Colesterol/metabolismo , LDL-Colesterol/sangue , LDL-Colesterol/metabolismo , Estudos Cross-Over , Dieta , Suplementos Nutricionais , Método Duplo-Cego , Dislipidemias/sangue , Humanos , Lipídeos/sangue , Masculino , Obesidade/sangue , Sobrepeso/sangue , Triglicerídeos/sangue , Triglicerídeos/metabolismo
18.
Nat Commun ; 10(1): 1981, 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-31040273

RESUMO

Cardiovascular and metabolic disease (CMD) remains a main cause of premature death worldwide. Berberine (BBR), a lipid-lowering botanic compound with diversified potency against metabolic disorders, is a promising candidate for ameliorating CMD. The liver is the target of BBR so that liver-site accumulation could be important for fulfilling its therapeutic effect. In this study a rational designed micelle (CTA-Mic) consisting of α-tocopheryl hydrophobic core and on-site detachable polyethylene glycol-thiol shell is developed for effective liver deposition of BBR. The bio-distribution analysis proves that the accumulation of BBR in liver is increased by 248.8% assisted by micelles. Up-regulation of a range of energy-related genes is detectable in the HepG2 cells and in vivo. In the high fat diet-fed mice, BBR-CTA-Mic intervention remarkably improves metabolic profiles and reduces the formation of aortic arch plaque. Our results provide proof-of-concept for a liver-targeting strategy to ameliorate CMD using natural medicines facilitated by Nano-technology.


Assuntos
Berberina/farmacologia , Hipoglicemiantes/uso terapêutico , Nanotecnologia/métodos , Animais , Células CACO-2 , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/tratamento farmacológico , Dislipidemias/sangue , Dislipidemias/tratamento farmacológico , Células Hep G2 , Humanos , Hipoglicemiantes/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Doenças Metabólicas/sangue , Doenças Metabólicas/tratamento farmacológico , Camundongos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
19.
Methodist Debakey Cardiovasc J ; 15(1): 55-61, 2019 Jan-Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31049150

RESUMO

Plasma cholesterol levels of high-density lipoproteins (HDL) have been associated with cardioprotection for decades. However, there is an evolving appreciation that this lipoprotein class is highly heterogeneous with regard to composition and functionality. With the advent of advanced lipid-testing techniques and methods that allow both the quantitation and recovery of individual particle populations, we are beginning to connect the functionality of HDL subspecies with chronic metabolic diseases. In this review, we examine type 2 diabetes (T2D) and explore our current understanding of how obesity, insulin resistance, and hyperglycemia affect, and may be affected by, HDL subspeciation. We discuss mechanistic aspects of how insulin resistance may alter lipoprotein profiles and how this may impact the ability of HDL to mitigate both atherosclerotic disease and diabetes itself. Finally, we call for more detailed studies examining the impact of T2D on specific HDL subspecies and their functions. If these particles can be isolated and their compositions and functions fully elucidated, it may become possible to manipulate the levels of these specific particles or target the protective functions to reduce the incidence of coronary heart disease.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Dislipidemias/sangue , Lipoproteínas HDL/sangue , Biomarcadores/sangue , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Dislipidemias/diagnóstico , Dislipidemias/tratamento farmacológico , Dislipidemias/epidemiologia , Humanos , Hipolipemiantes/uso terapêutico , Insulina/sangue , Resistência à Insulina , Obesidade/sangue , Obesidade/epidemiologia
20.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1118-1119: 137-147, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31035135

RESUMO

Progress toward better diagnosis and treatment of lipid metabolism-related diseases requires high throughput approaches for multiplexed quantitative analysis of structurally diverse lipids, including phospholipids (PLs). This work demonstrates a simplified "one-pot" phospholipid extraction protocol, as an alternative to conventional liquid-liquid extraction. Performed in a 96-well format, the extraction was coupled with high throughput UPLC and multiplexed tandem mass spectrometry (MS/MS) detection, allowing non-targeted quantification of phosphatidylcholines (PC), sphingomyelins (SM), lysophosphatidylcholines (LPC), phosphatidylethanolamines (PE), and phosphatidylinositols (PI). Using 50 µL aliquots of serum samples from 110 individuals, lipoproteins were fractionated by size, and analyzed for phospholipids and non-polar lipids including free cholesterol (FC), cholesteryl esters (CEs) and triglycerides (TGs). Analysis of serum samples with wide range of Total-TG levels showed significant differences in PL composition. The correlations of molar ratios in lipoprotein size fractions, SM/PL with FC/PL, PE/PL with TG/CE, and PE/PL with PI/PL, demonstrate the applicability of the method for quantitative composition analysis of high, low and very-low density lipoproteins (HDL, LDL and VLDL), and characterization of lipid metabolism related disease states.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Dislipidemias/sangue , Dislipidemias/diagnóstico , Fosfolipídeos/sangue , Espectrometria de Massas em Tandem/métodos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Fosfolipídeos/isolamento & purificação , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
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