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1.
Rev Med Suisse ; 16(684): 438-443, 2020 Mar 04.
Artigo em Francês | MEDLINE | ID: mdl-32134222

RESUMO

Experts' guidelines for the management of dyslipidemias differ from country to country, with important differences between medical societies of Europe and the United States. Recently, new American and European guidelines have been established. These guidelines mainly differ for cardiovascular risk stratification in secondary prevention, and for LDL-cholesterol (LDL-c) goals to achieve. Similitudes between guidelines include the global strategy to initiate lipid-lowering drugs, which is based first on the global cardiovascular risk, then on the LDL-c level. We are here presenting a comparison and an interpretation of these guidelines.


Assuntos
LDL-Colesterol/sangue , Dislipidemias/sangue , Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipolipemiantes/uso terapêutico , Guias de Prática Clínica como Assunto , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Dislipidemias/complicações , Europa (Continente) , Humanos , Fatores de Risco , Estados Unidos
2.
N Engl J Med ; 382(3): 244-255, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31893580

RESUMO

BACKGROUND: Lipoprotein(a) levels are genetically determined and, when elevated, are a risk factor for cardiovascular disease and aortic stenosis. There are no approved pharmacologic therapies to lower lipoprotein(a) levels. METHODS: We conducted a randomized, double-blind, placebo-controlled, dose-ranging trial involving 286 patients with established cardiovascular disease and screening lipoprotein(a) levels of at least 60 mg per deciliter (150 nmol per liter). Patients received the hepatocyte-directed antisense oligonucleotide AKCEA-APO(a)-LRx, referred to here as APO(a)-LRx (20, 40, or 60 mg every 4 weeks; 20 mg every 2 weeks; or 20 mg every week), or saline placebo subcutaneously for 6 to 12 months. The lipoprotein(a) level was measured with an isoform-independent assay. The primary end point was the percent change in lipoprotein(a) level from baseline to month 6 of exposure (week 25 in the groups that received monthly doses and week 27 in the groups that received more frequent doses). RESULTS: The median baseline lipoprotein(a) levels in the six groups ranged from 204.5 to 246.6 nmol per liter. Administration of APO(a)-LRx resulted in dose-dependent decreases in lipoprotein(a) levels, with mean percent decreases of 35% at a dose of 20 mg every 4 weeks, 56% at 40 mg every 4 weeks, 58% at 20 mg every 2 weeks, 72% at 60 mg every 4 weeks, and 80% at 20 mg every week, as compared with 6% with placebo (P values for the comparison with placebo ranged from 0.003 to <0.001). There were no significant differences between any APO(a)-LRx dose and placebo with respect to platelet counts, liver and renal measures, or influenza-like symptoms. The most common adverse events were injection-site reactions. CONCLUSIONS: APO(a)-LRx reduced lipoprotein(a) levels in a dose-dependent manner in patients who had elevated lipoprotein(a) levels and established cardiovascular disease. (Funded by Akcea Therapeutics; ClinicalTrials.gov number, NCT03070782.).


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Hipolipemiantes/administração & dosagem , Lipoproteína(a)/sangue , Oligonucleotídeos/administração & dosagem , Adulto , Idoso , Doenças Cardiovasculares/sangue , Colesterol/sangue , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipolipemiantes/efeitos adversos , Hipolipemiantes/uso terapêutico , Análise dos Mínimos Quadrados , Masculino , Pessoa de Meia-Idade , Oligonucleotídeos/efeitos adversos , Fatores de Risco
3.
J Ethnopharmacol ; 247: 112273, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31586692

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Luohanguo (LHG), a traditional Chinese medicine, could clear heat, moisten the lung, soothe the throat, restore the voice, and lubricate intestine and open the bowels. LHG has been utilized for the treatment of sore throats and hyperglycemia in folk medicine as a homology of medicine and food. The hypoglycemic pharmacology of LHG has attracted considerable attention, and mogrosides have been considered to be active ingredients against diabetes mellitus. We have found that these mogrosides could be metabolized into their secondary glycosides containing 1-3 glucose residues in type 2 diabetes mellitus (T2DM) rats in previous studies. These metabolites may be the antidiabetic components of LHG in vivo. Thus far, no reports have been found on reducing blood glucose of mogrosides containing 1-3 glucose residues. AIMS OF THE STUDY: The aim of this study was to confirm that mogrosides containing 1-3 glucose residues were the active components of LHG for antidiabetic effects and to understand their potential mechanisms of action. MATERIALS AND METHODS: First, the special fraction of mogrosides containing 1-3 glucose residues was separated from a 50% ethanol extract of LHG, and the chemical components were identified by ultra-performance liquid chromatography (UPLC) and named low-polar Siraitia grosvenorii glycosides (L-SGgly). Second, the antidiabetic effects of L-SGgly were evaluated by HFD/STZ-induced (high-fat diet and streptozocin) obese T2DM rats by indexing fasting blood glucose (FBG), fasting insulin (FINS), and insulin resistance, and then compared with other fractions in the separation process. The changes in serum lipid levels were also detected. Finally, possible mechanisms of antidiabetic activity of L-SGgly were identified as increasing GLP-1 levels and activating liver AMPK in T2DM rats. RESULTS: The chemical analysis of L-SGgly showed that they contain 11-oxomogroside V, mogroside V, mogroside III, mogroside IIE, mogroside IIIA1, mogroside IIA1, and mogroside IA1, respectively. The total content of the mogrosides in L-SGgly was 54.4%, including 15.7% mogroside IIA1 and 12.6% mogroside IA1. L-SGgly showed excellent effects on obese T2DM rats compared with the other fractions of LHG extract, including significantly reducing the levels of FBG (p < 0.001) and modifying insulin resistance (p < 0.05). Meanwhile, they could significantly decrease the content of triglyceride (p < 0.01), total cholesterol (p < 0.01), low-density lipoprotein cholesterol (p < 0.01) and free fatty acid (p < 0.001) and increase the content of high-density lipoprotein cholesterol (p < 0.001) in serum of T2DM rats. Moreover, L-SGgly can significantly increase (p < 0.01) GLP-1 levels and decrease (p < 0.01) IL-6 levels in T2DM rat serum. AMPK-activating activity in T2DM rats was also upregulated by L-SGgly, but no statistical significance was shown. CONCLUSION: L-SGgly, fractions separated from LHG extract, were verified to have obvious anti-hyperglycemic and anti-hyperlipidemic effects on T2DM rats. Furthermore, L-SGgly regulated insulin secretion in T2DM rats by increasing GLP-1 levels. These findings provide an explanation for the antidiabetic role of LHG.


Assuntos
Cucurbitaceae/química , Diabetes Mellitus Tipo 2/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Glicosídeos/farmacologia , Hipoglicemiantes/farmacologia , Hipolipemiantes/farmacologia , Obesidade/tratamento farmacológico , Triterpenos/farmacologia , Administração Oral , Animais , Glicemia/análise , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Fracionamento Químico , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etiologia , Dieta Hiperlipídica/efeitos adversos , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/uso terapêutico , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Glicosídeos/análise , Glicosídeos/isolamento & purificação , Glicosídeos/uso terapêutico , Humanos , Hipoglicemiantes/análise , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/uso terapêutico , Hipolipemiantes/análise , Hipolipemiantes/isolamento & purificação , Hipolipemiantes/uso terapêutico , Insulina/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Obesidade/sangue , Obesidade/etiologia , Ratos , Estreptozocina/toxicidade , Triterpenos/análise , Triterpenos/isolamento & purificação , Triterpenos/uso terapêutico
4.
Life Sci ; 242: 117182, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31863770

RESUMO

AIMS: The present study was designed to compare the effects of a low-fat diet (LF), calorie restriction (CR), quercetin (Que) and exercise (Ex) on hepatic steatosis in a high-fat (HF) diet-induced obesity prone (OP) model in the perspective of microRNA (miR)-dependent thyroid hormone (TH) synthesis and action. MAIN METHODS: Male C57BL/6J mice were administered a HF diet for 10 weeks to induce OP phenotype and then divided into 5 groups, HF diet (OP-HF), LF diet (OP-LF), 70% CR (OP-CR), 0.05% Que (OP-Que) and a treadmill exercise regimen (OP-Ex); one additional group fed LF diet served as control (LF). 7 weeks later, serum indexes, metabolic alterations, redox status and histological appearance in the thyroid and liver, and TH related miRs with their targets expressions were determined. KEY FINDINGS: No significance on T3 levels was observed among the six groups. LF, CR, Que and Ex significantly ameliorated HF-induced hepatic steatosis to varying degrees, inhibited T4 production via differentially elevating miR-339, miR-383 and miR-146b to decrease NIS expression and regulating miR-200a/Nrf2 to maintain redox status in the thyroid. Furthermore, these four interventions differentially and significantly decreased miR-383 and miR-146b to elevate TRb and DIO1 expression, and subsequent TH responsive lipid metabolism genes regulation. Among them, the effects of CR on hepatic steatosis were the most prominent. SIGNIFICANCE: Our data indicated that amelioration of hepatic steatosis by LF, CR, Que and Ex resulted in many shared, but also many differential changes in the miR-dependent TH production and action.


Assuntos
Dieta com Restrição de Gorduras , Fígado Gorduroso/terapia , MicroRNAs/fisiologia , Obesidade/complicações , Condicionamento Físico Animal , Hormônios Tireóideos/metabolismo , Animais , Restrição Calórica , Fígado Gorduroso/dietoterapia , Fígado Gorduroso/etiologia , Hipolipemiantes/uso terapêutico , Lipídeos/análise , Fígado/química , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Estresse Oxidativo , Quercetina/uso terapêutico
5.
Rev Port Cardiol ; 38(8): 559-569, 2019 08.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31706732

RESUMO

INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in Portugal. Hypercholesterolemia has a causal role in atherosclerotic CVD. Guidelines recommend that cardiovascular (CV) risk reduction should be individualized and treatment goals identified. Low-density lipoprotein cholesterol (LDL-C) is the primary treatment target. METHODS: DISGEN-LIPID was a cross-sectional observational study conducted in 24 centers in Portugal in dyslipidemic patients aged ≥40 years, on lipid-lowering therapy (LLT) for at least three months and with an available lipid profile in the previous six months. RESULTS: A total of 368 patients were analyzed: 48.9% men and 51.1% women (93.9% postmenopausal), of whom 73% had a SCORE of high or very high CV risk. One quarter had a family history of premature CVD; 31% had diabetes; 26% coronary heart disease; 9.5% cerebrovascular disease; and 4.1% peripheral arterial disease. Mean baseline lipid values were total cholesterol (TC) 189 mg/dl, LDL-C 116 mg/dl, high-density lipoprotein cholesterol (HDL-C) 53.5 mg/dl, and triglycerides (TG) 135 mg/dl. Women had higher TC (p<0.001), LDL-C (non-significant) and HDL-C (p<0.001), and lower TG (p=0.002); 57% of men and 63% of women had LDL-C>100 mg/dl (p=0.28), and 58% of men and 47% of women had LDL-C>70 mg/dl (p=0.933). CONCLUSION: These observational data show that, despite their high-risk profile, more than half of patients under LLT, both men and women, did not achieve the recommended target levels for LDL-C, and a large proportion also had abnormal HDL-C and/or TG. This is a renewed opportunity to improve clinical practice in CV prevention.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dislipidemias/sangue , Hipolipemiantes/uso terapêutico , Lipídeos/sangue , Sistema de Registros , Adulto , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Estudos Transversais , Dislipidemias/complicações , Dislipidemias/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Portugal/epidemiologia , Estudos Retrospectivos , Taxa de Sobrevida/tendências
6.
J Interv Cardiol ; 2019: 2017958, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772516

RESUMO

Background: There is a paucity of information about the gender differences in clinical outcomes of successful percutaneous coronary intervention (PCI) compared with medical therapy (MT) in patients with coronary chronic total occlusions (CTOs). Objectives: We aimed to investigate the impact of gender on long-term clinical outcomes associated with successful CTO-PCI versus MT in patients with CTOs. Methods: Between January 2007 and December 2016, a total of 1702 patients with ≥1 CTO were enrolled. After exclusion, 1294 patients with 1520 CTOs were analyzed and were divided into the female group (n = 304, 23.5%) and the male group (n = 990, 76.5%). The patients in the female or male group were assigned to a MT group or successful CTO-PCI group according to the treatment strategy. In the female group, they were divided into two groups: 177 patients in the MT group and 127 patients in the successful CTO-PCI group. In the male group, they were divided into two groups: 623 patients in the MT group and 367 patients in the successful CTO-PCI group. The primary outcome was cardiac death. The secondary outcome was major adverse cardiac event (MACE). Results: The median overall follow-up duration was 3.6 (IQR, 2.1-5.0) years, there were no significant differences between the MT and successful CTO-PCI groups with respect to the prevalence of cardiac death (MT vs. successful PCI: 6.8% vs. 3.9%, p=0.287) and MACE (20.9% vs. 21.3%, p=0.810) in female patients. In the male group, the occurrence of cardiac death (MT vs. successful PCI: 6.6% vs. 3.8%, p=0.066) was similar between the two groups. The MACE rate (30.0% vs. 18.5%, p < 0.001) was significantly higher in the MT group. Heart failure (hazard ratio 3.40, 95% confidence interval 1.23-9.40, p=0.018) was an independent predictor of cardiac death in female patients. Conclusions: Successful CTO-PCI was not associated with reduced risk of cardiac death compared with medical therapy alone in both female and male patients. However, men have a significant reduction in MACE rate after successful CTO-PCI. Aggressive CTO-PCI should be considered carefully among female patients.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Oclusão Coronária/terapia , Hipolipemiantes/uso terapêutico , Nitratos/uso terapêutico , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/uso terapêutico , Fatores Etários , Idoso , China/epidemiologia , Feminino , Seguimentos , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais , Calcificação Vascular/mortalidade
7.
Prog Cardiovasc Dis ; 62(5): 406-413, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31672610

RESUMO

In our increasingly cost-conscious health system, patients, clinicians, hospitals, and payers all agree about the urgent need to rein in runaway healthcare costs. High pharmaceutical costs make drugs unaffordable to many patients who may benefit from them, including some insured patients who face prohibitive out-of-pocket costs. Health systems and payers can use the systematic framework of cost-effectiveness analysis and estimated budgetary impact to prioritize the adoption of new therapies and technologies. In this review article, we discuss basic principles of cost-effectiveness research for practicing clinicians, the concept of cost-effectiveness versus affordability, other considerations relevant to resource allocation, and limitations of cost-effectiveness research. We use the example of lipid lowering therapies to discuss application of cost-effectiveness research in informing health care policy, its use for health care systems and in the development of clinical practice guidelines, and its implications for clinicians and patients. As clinicians and patients become more cognizant of the cost-implications of new therapies, professional societies can help improve the quality of decision-making by incorporating unbiased value statements into their expert guidelines.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/economia , Custos de Medicamentos , Dislipidemias/tratamento farmacológico , Dislipidemias/economia , Hipolipemiantes/economia , Hipolipemiantes/uso terapêutico , Formulação de Políticas , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Análise Custo-Benefício , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Humanos , Guias de Prática Clínica como Assunto , Prevenção Primária/economia , Prevenção Primária/legislação & jurisprudência , Prevenção Secundária/economia , Prevenção Secundária/legislação & jurisprudência , Resultado do Tratamento
8.
Nutr Metab Cardiovasc Dis ; 29(11): 1168-1175, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31582198

RESUMO

BACKGROUND AND AIM: Although some earlier studies have indicated the effect of phytosterol (PS) supplementation on serum lipoprotein(a) (Lp(a)) and free fatty acid (FFA) concentration, findings are still conflicting. We aimed to assess the impact of PS supplementation on serum Lp(a) and FFA concentration through a systematic review and meta-analysis of available RCTs. METHODS AND RESULTS: We performed a systematic search of all available RCTs conducted up to 21 February 2019 in the following databases: PubMed, Scopus, and Cochrane. The choice of fixed- or random-effect model for analysis was determined according to the I2 statistic. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI). Pooling of 12 effect sizes from seven articles revealed a significant reduction of Lp(a) levels following PS supplementation (MD: -0.025 mg/dl, 95% CI: -0.045, -0.004, p = 0.017) without significant heterogeneity among the studies (I2 = 0.0%, p = 0.599). Also, PS supplementation significantly lowered FFA (MD: -0.138 mg/dl, 95% CI: -0.195, -0.081, p = 0.000) without significant heterogeneity among the studies (I2 = 0.0%, p = 0.911). The results for meta-regression and sensitivity analysis were not significant. CONCLUSION: The meta-analysis suggests that oral PS supplementation could cause a significant reduction in serum Lp(a) and FFA.


Assuntos
Suplementos Nutricionais , Dislipidemias/tratamento farmacológico , Ácidos Graxos não Esterificados/sangue , Hipolipemiantes/uso terapêutico , Lipoproteína(a)/sangue , Fitosteróis/uso terapêutico , Adulto , Biomarcadores/sangue , Suplementos Nutricionais/efeitos adversos , Regulação para Baixo , Dislipidemias/sangue , Dislipidemias/diagnóstico , Feminino , Humanos , Hipolipemiantes/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fitosteróis/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
9.
Rev. clín. med. fam ; 12(3): 132-139, oct. 2019. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-186803

RESUMO

En los últimos años las guías de práctica clínica para la prevención de eventos cardiovasculares redujeron el umbral para la indicación de hipolipemiantes (estatinas), aumentando la población susceptible de recibir estos fármacos. A su vez, estas mismas guías promueven que los médicos discutan junto al paciente los riesgos y beneficios del tratamiento farmacológico, a menudo mediante el modelo de toma de decisiones compartida (TDC). Sin embargo, la aplicación de este modelo se enfrenta con algunos desafíos. En el siguiente artículo nos propusimos discutir las dificultades para implementar este modelo en nuestro medio a la hora de realizar la prevención primaria de eventos cardiovasculares, tomando como punto de partida un caso clínico donde ilustramos la aplicación de la TDC, usando la herramienta desarrollada por la Clínica Mayo para asistir este proceso


In recent years, clinical practice guidelines for the prevention of cardiovascular events have lowered the threshold for the prescription of lipid-lowering agents (statins), increasing the population that could receive these medications. Likewise, these guidelines also encourage that doctors and patients discuss together the risks and benefits of the drug treatment, often using the shared decision making (SDM) model. However, the application of this model faces some challenges. The aim of this article was to discuss the difficulties in implementing this model in our setting as regards the primary prevention of cardiovascular events. We used a clinical case as a starting point to illustrate the application of SDM using the tool developed by the Mayo Clinic to aid this process


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Doenças Cardiovasculares/prevenção & controle , Hipolipemiantes/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Prevenção Primária/organização & administração , Fatores de Risco , Tomada de Decisões , Padrões de Prática Médica
10.
Rev Port Cardiol ; 38(7): 485-493, 2019 07.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31530423

RESUMO

INTRODUCTION AND OBJECTIVE: Lipoprotein(a) [Lp(a)] is an independent cardiovascular risk factor but is closely associated with other similar risk factors that are manageable with appropriate treatment and guidance. We aimed to study the impact of using combined therapy for managing Lp(a) levels in patients at high cardiovascular risk but without major adverse cardiovascular events, in primary prevention. METHODS: We conducted a retrospective observational study in 516 patients randomly selected from a group of 1677 patients who attended cardiovascular risk and metabolism consultations between 1995 and 2015. The disorders observed and therapies used were classified into nosological and pharmacological groups, respectively. Cardiovascular risk was calculated based on the Framingham risk score, the European Society of Cardiology's SCORE and the American College of Cardiology's ASCVD Risk Estimator, and changes in patients' lifestyle were assessed. RESULTS: Significant differences (p<0.001) were found in almost all metabolic variables, except fasting insulin and C-peptide. Lp(a) levels were also significantly reduced (p<0.001). Carotid intima-media thickness improved, decreasing from 2.90 mm to 1.40 mm; however, there was no reduction in the number of cases of vascular stenosis. Of patients with hepatic steatosis (85.5%), 40.7% presented hepatomegaly, but liver function was only altered in a few patients (14.5%). Lipid-lowering therapy, especially statins, significantly decreased Lp(a), benefiting from synergy with other treatments. CONCLUSIONS: Lp(a) is a key overall indicator of vascular risk and should be considered a therapeutic target. Besides a healthy lifestyle, primary prevention should include combined drug therapies to address all cardiovascular risk factors and to delay the atherosclerotic process.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Hipolipemiantes/uso terapêutico , Lipoproteína(a)/sangue , Prevenção Primária/métodos , Adulto , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
11.
Nutr Metab Cardiovasc Dis ; 29(11): 1151-1167, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31561944

RESUMO

BACKGROUND AND AIM: l-carnitine has an important role in fatty acid metabolism and could therefore act as an adjuvant agent in the improvement of dyslipidemia. The purpose of present systematic review and meta-analysis was to critically assess the efficacy of l-carnitine supplementation on lipid profiles. METHODS AND RESULTS: We performed a systematic search of all available randomized controlled trials (RCTs) in the following databases: Scopus, PubMed, ISI Web of Science, The Cochrane Library. Mean difference (MD) of any effect was calculated using a random-effects model. In total, there were 55 eligible RCTs included with 58 arms, and meta-analysis revealed that l-carnitine supplementation significantly reduced total cholesterol (TC) (56 arms-MD: -8.53 mg/dl, 95% CI: -13.46, -3.6, I2: 93%), low-density lipoprotein-cholesterol (LDL-C) (47 arms-MD: -5.48 mg/dl, 95% CI: -8.49, -2.47, I2: 94.5) and triglyceride (TG) (56 arms-MD: -9.44 mg/dl, 95% CI: -16.02, -2.87, I2: 91.8). It also increased high density lipoprotein-cholesterol (HDL-C) (51 arms-MD:1.64 mg/dl, 95% CI:0.54, 2.75, I2: 92.2). l-carnitine supplementation reduced TC in non-linear fashion based on dosage (r = 21.11). Meta-regression analysis indicated a linear relationship between dose of l-carnitine and absolute change in TC (p = 0.029) and LDL-C (p = 0.013). Subgroup analyses showed that l-carnitine supplementation did not change TC, LDL-C and TG in patients under hemodialysis treatment. Intravenous l-carnitine and lower doses (>2 g/day) had no effect on TC, LDL-C and triglycerides. CONCLUSION: l-carnitine supplementation at doses above 2 g/d has favorable effects on patients' lipid profiles, but is modulated on participant health and route of administration.


Assuntos
Carnitina/uso terapêutico , Suplementos Nutricionais , Dislipidemias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Lipídeos/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Carnitina/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Dislipidemias/sangue , Dislipidemias/diagnóstico , Feminino , Humanos , Hipolipemiantes/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Adulto Jovem
12.
BMJ ; 366: l5125, 2019 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-31562117

RESUMO

OBJECTIVE: To investigate whether fenofibrate as add-on to statin treatment reduce persistent cardiovascular risk in adults with metabolic syndrome in a real world setting. DESIGN: Propensity matched cohort study. SETTING: Population based cohort in Korea. PARTICIPANTS: 29 771 adults with metabolic syndrome (≥40 years) receiving statin treatment. 2156 participants receiving combined treatment (statin plus fenofibrate) were weighted based on propensity score in a 1:5 ratio with 8549 participants using statin only treatment. MAIN OUTCOME MEASURE: Primary outcome was composite cardiovascular events including incident coronary heart disease, ischaemic stroke, and death from cardiovascular causes. RESULTS: The incidence rate per 1000 person years of composite cardiovascular events was 17.7 (95% confidence interval 14.4 to 21.8) in the combined treatment group and 22.0 (20.1 to 24.1) in the statin group. The risk of composite cardiovascular events was significantly reduced in the combined treatment group compared with statin group (adjusted hazard ratio 0.74, 95% confidence interval 0.58 to 0.93; P=0.01). The significance was maintained in the on-treatment analysis (hazard ratio 0.63, 95% confidence interval 0.44 to 0.92; P=0.02). The risk of incident coronary heart disease, ischaemic stroke, and cardiovascular death was lower in the combined treatment group than statin group but was not significant. Participant characteristics did not appear to be associated with the low risk of composite cardiovascular events with combined treatment. CONCLUSION: In this propensity weighted cohort study of adults with metabolic syndrome, the risk of major cardiovascular events was significantly lower with fenofibrate as add-on to statin treatment than with statin treatment alone.


Assuntos
Doenças Cardiovasculares , Fenofibrato/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Síndrome Metabólica/tratamento farmacológico , Adulto , Idoso , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Causas de Morte , Estudos de Coortes , Quimioterapia Combinada/métodos , Quimioterapia Combinada/estatística & dados numéricos , Feminino , Humanos , Hipolipemiantes/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Pontuação de Propensão , República da Coreia/epidemiologia , Fatores de Risco
13.
Prog Cardiovasc Dis ; 62(4): 334-341, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31442512

RESUMO

Hyperlipidemia plays a crucial role in the underlying pathogenesis of multiple cardiovascular diseases (CVD), including coronary artery disease, peripheral arterial disease, carotid stenosis, and heart failure. The risk of developing such diseases in the diabetic population is relatively high. Diabetes mellitus (DM) is an independent risk factor for premature atherosclerosis. The hallmark of DM dyslipidemia is a demonstrably high level of atherogenic triglyceride rich lipids including very low-density lipoprotein, chylomicrons, and small dense low-density lipoprotein (LDL). Moderate to high intensity statins, targeting LDL cholesterol reduction, remain the cornerstone in the management of this unique disorder. Many 'non-statin' drugs have recently been studied in the DM patients who were either on a 'maximally tolerated statin' or 'statin intolerant'. Ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are particularly important and were incorporated in the recent guidelines by the European Society of Cardiology, American College of Cardiology, American Heart Association, and American Diabetes Association. Icosapent Ethyl has garnered huge interest this year following publication of the REDUCE-IT trial. There are several newer hypolipidemic drugs, including Bempedoic acid, Inclisiran and RVX-208, that are in different phases of clinical trials. In this article, we review the underlying pathophysiology of DM dyslipidemia, existing guidelines related to its management, and the potential of newer hypolipidemic and anti-inflammatory drugs being incorporated in the management of DM.


Assuntos
Anticolesterolemiantes/uso terapêutico , Doença da Artéria Coronariana/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Idoso , Anticolesterolemiantes/farmacologia , Aterosclerose/prevenção & controle , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Dislipidemias/tratamento farmacológico , Dislipidemias/epidemiologia , Dislipidemias/fisiopatologia , Feminino , Humanos , Hiperlipidemias/epidemiologia , Hiperlipidemias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
15.
J Ethnopharmacol ; 245: 112170, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31434002

RESUMO

ETHNOBOTANICAL RELEVANCE: The interest on herbal health supplements for obesity is increasing globally. Our previous ethnobotanical survey in Tiruvallur district, Tamil Nadu, India indicated the use of Spermacoce hispida L. seeds for the treatment of obesity. AIM OF THE STUDY: This study was aimed to validate the traditional claim and to identify the antihyperlipidemic principle in the seeds of Spermacoce hispida using bioassay guided fractionation method. METHODS: Bioassay monitored fractionation of the aqueous extract from Spermacoce hispida seeds was carried out using triton WR 1339 induced hyperlipidemic animals. It yielded deacetylasperulosidic acid (DAA) as the active ingredient. Pharmacokinetic properties of DAA were predicted using DataWarrior and SwissADME tools. In vitro antiobesity and antihyperlipidemic effects of DAA were evaluated in 3T3L1 preadipocytes and HepG2 cells, respectively. The chronic antihyperlipidemic efficacy of DAA was evaluated in high fat diet fed rats. RESULTS: DAA did not show any mutagenic and tumorigenic properties. It bound with PPARα with comparable ligand efficiency as fenofibrate. The treatment with DAA significantly lowered the proliferation of matured adipocytes, but not preadipocytes. The treatment of steatotic HepG2 cells with DAA significantly decreased the LDH leakage by 43.03% (P < 0.05) at 50 µM concentration. In triton WR 1339 induced hyperlipidemic animals, the treatment with 50 mg/kg dose significantly lowered the TC, TG and LDL-c levels by 40.27, 46.00 and 63.65% respectively. In HFD fed animals, the treatment at 10 mg/kg decreased BMI and AC/TC ratio without altering SRBG. It also improved serum lipid, transaminases and phosphatases levels of HFD fed animals. The treatment lowered adipocyte hypertrophy and steatosis of hepatocytes. CONCLUSION: This preliminary report supported the traditional use of Spermacoce hispida for the treatment of obesity. Further detailed investigations on the long term safety, efficacy and molecular mode of action of Spermacoce hispida and DAA will throw more light on their usefulness for the management of obesity.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Glicosídeos Iridoides/uso terapêutico , Rubiaceae , Células 3T3-L1 , Animais , Fármacos Antiobesidade/farmacocinética , Fármacos Antiobesidade/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Hep G2 , Humanos , Hipolipemiantes/farmacocinética , Hipolipemiantes/farmacologia , Índia , Glicosídeos Iridoides/farmacocinética , Glicosídeos Iridoides/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Medicina Tradicional , Camundongos , Ratos Wistar , Sementes
16.
Rev Port Cardiol ; 38(8): 531-542, 2019 08.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31447268

RESUMO

INTRODUCTION AND AIMS: Atherogenic dyslipidemia is an important contributor to residual cardiovascular (CV) risk, but it is underdiagnosed and undertreated. This study aimed to assess the opinion of Portuguese experts to generate a consensus concerning the diagnosis and treatment of atherogenic dyslipidemia, as well as to contribute toward standardization of clinical practice in this disorder. METHODS: The study consisted in the application of a questionnaire to an expert panel, following a modified Delphi methodology. RESULTS: The majority (88.4%) of the proposed items were found to be consensual. The expert panel recognized the importance of the atherogenic dyslipidemia phenotype, the role played by low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol as risk markers and therapeutic targets, the choice of statins as first-line lipid-lowering drugs, and the value of associating statins with fenofibrate as a means to reduce residual CV risk. However, the role played by triglycerides in CV risk and the therapeutic value of fibrates lacked consensus. Taking into consideration the state of the art and the opinions expressed in this study, the scientific committee developed a treatment algorithm aimed to improve the perception and treatment of atherogenic dyslipidemia. CONCLUSIONS: The experts involved in this study were shown to be familiar with the concept and the importance of atherogenic dyslipidemia. The few situations in which a consensus could not be found were mainly related to the interpretation and/or relevance of the available evidence.


Assuntos
Aterosclerose/tratamento farmacológico , LDL-Colesterol/sangue , Consenso , Gerenciamento Clínico , Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipolipemiantes/uso terapêutico , Aterosclerose/sangue , Aterosclerose/etiologia , Biomarcadores/sangue , Dislipidemias/sangue , Dislipidemias/complicações , Humanos , Portugal , Fatores de Risco
17.
Asia Pac J Clin Nutr ; 28(3): 476-485, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31464394

RESUMO

BACKGROUND AND OBJECTIVES: Obesity and diet contribute to the development of hypercholesterolemia; therefore, controlling blood lipid concentration through diet is essential. To understand the role of diet in controlling blood lipid concentration, we evaluated the food and nutrient intakes, anthropometry, and blood lipid concentrations of adults with dyslipidemia with or without lipid-lowering drug use. METHODS AND STUDY DESIGN: For this crosssectional study, three-year data were obtained from the 6th-7th Korean National Health and Nutrition Examination Survey (2015-2017). Patients with dyslipidemia were categorized as users (1,734) or nonusers (856) of lipidlowering drugs. RESULTS: Age, education level, marital status, self-reported health status, hypertension, diabetes, and alcohol intake were significantly different between users and nonusers (p<0.05). Multiple logistic regression analysis revealed a significant association between hypertension and diabetes and blood cholesterol status among users. Total cholesterol, triglycerides, and low-density lipoprotein cholesterol were significantly lower in users than in nonusers. During the study period, intake of saturated fatty acids increased significantly among users and nonusers, and intakes of vitamins A and C decreased significantly with potential detrimental health effects. However, intakes of n-3 fatty acids and dietary fiber significantly increased in users and nonusers with potential health benefits. Intakes of vegetables and fish significantly increased in users. No associations were observed between intakes of nuts, fruits, or vegetables and blood cholesterol status. CONCLUSIONS: Changes in personal behaviors of dyslipidemic patients need reinforcement for effective blood lipid management, particularly for optimal food intake patterns, whether lipid-lowering drug users or nonusers.


Assuntos
Dislipidemias/dietoterapia , Dislipidemias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Inquéritos Nutricionais , Adulto , Idoso , Estudos Transversais , Dislipidemias/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Adulto Jovem
18.
Phytother Res ; 33(11): 2862-2869, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31423665

RESUMO

The aims of this study were to evaluate the efficacy of corn silk decoction on lipid profile in patients with angina pectoris. PubMed, Cochrane, Embase, Google Scholar, Chongqing VIP Chinese Science and Technology Periodical Database, China National Knowledge Infrastructure, and Wanfang database were searched up to January 2019 for randomized controlled trials that assessed the impact of corn silk decoction on total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in patients with angina pectoris. Study evaluation and synthesis methods were in accordance with the Cochrane Handbook, and data were analyzed using Review Manager (version 5.3) software. Random effects model was applied in this systematic review and meta-analysis to compensate for potential heterogeneity among the included studies. A total of four randomized controlled trials were eligible for meta-analysis. Pooled results of these studies indicated that corn silk decoction might improve high-density lipoprotein cholesterol and reduce total cholesterol, triglycerides, and low-density lipoprotein cholesterol in patients with angina pectoris. Subgroup analyses showed that corn silk decoction or modified corn silk decoction plus conventional pharmaceutical treatment could have favorable effects on blood lipids. However, the lack of blinding in most studies may have led to overestimation of these effects. Further studies with better design are needed to confirm these findings.


Assuntos
Angina Pectoris/tratamento farmacológico , Flores/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Extratos Vegetais/uso terapêutico , Zea mays/química , Angina Pectoris/sangue , China/epidemiologia , HDL-Colesterol/sangue , HDL-Colesterol/efeitos dos fármacos , LDL-Colesterol/sangue , LDL-Colesterol/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Hipolipemiantes/uso terapêutico , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Triglicerídeos/sangue
19.
Nutrients ; 11(8)2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31405073

RESUMO

Lipid-lowering therapy (LLT) should be accompanied by dietary guidance for cardiovascular risk reduction; however, current evidence suggests sub-optimal dietary behaviors in those on LLT. We examined the associations between the dietary intake of key food groups (vegetables, fruit, cereal, protein, and dairy) and LLT use in Australian adults using quantile regression. We used data from the Australian Diabetes, Obesity and Lifestyle Study (AusDiab), a prospective population-based study of adults aged ≥25 years, conducted over 5 years (1999-2005). Measurements included a 121-item food frequency questionnaire and LLT use. LLT use was categorized as: LLT users (n = 446), commenced LLT (n = 565), ceased LLT (n = 71), and non-users (n = 4813). Less than 1% of the cohort met recommended intakes of all food groups at the baseline and follow up. The median daily dietary intake at the follow up among LLT users was 2.2 serves of vegetables, 1.4 serves of fruit, 2.8 serves of cereal, 2.0 serves of protein, and 1.4 serves of dairy. Adjusted analysis showed no differences across the quantiles of intake of key food groups in LLT users and commenced LLT compared to non-users. The LLT medication status is not associated with any difference in meeting recommended intakes of key foods.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Gorduras na Dieta/administração & dosagem , Dislipidemias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Comportamento de Redução do Risco , Adulto , Idoso , Austrália/epidemiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Comorbidade , Diabetes Mellitus/epidemiologia , Gorduras na Dieta/efeitos adversos , Gorduras na Dieta/sangue , Dislipidemias/sangue , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Feminino , Humanos , Hipolipemiantes/efeitos adversos , Masculino , Pessoa de Meia-Idade , Valor Nutritivo , Obesidade/epidemiologia , Estudos Prospectivos , Recomendações Nutricionais , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
20.
Life Sci ; 234: 116753, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31419445

RESUMO

AIMS: Hypertension is a global disease that has been combating the world health for ages. Peristrophe roxburghiana (PR) is used in traditional medicine to treat hypertension and other ailments. The present study examined phytochemical constituents, antioxidant activities and GC-MS analysis of extracts of PR leaf and also evaluated their anti-hypertensive and anti-lipidemic effects in NG-nitro-L-arginine methyl ester (L-NAME) hypertensive rats. METHODS: Wistar rats were grouped into two groups: control and hypertensive. Hypertension was induced in the hypertensive group by oral gavage of 60 mg/kg b.w of L-NAME for 3 weeks. After induction, the hypertensive group was randomly sub-grouped into hypertensive, hypertensive treated and hypertensive untreated groups. These were orally gavaged respectively with 60 mg/kg b.w of L-NAME, 60 mg/kg b.w/day of L-NAME +200 mg/kg b.w of different extracts of PR (aqueous, ethanolic and methanolic extracts) and 60 mg/kg b.w of L-NAME +20 mg/kg b.w ramipril for 3 weeks. The blood pressure was measured by tail-cuff method at the third and sixth weeks. KEY FINDINGS: The results showed that the extracts of PR significantly decrease blood pressure, pro-atherogenic lipids and atherogenic ratios in L-NAME hypertensive rats. White blood cells count, neutrophil count and creatinine level were also effectively decreased by the extracts. Furthermore, the extracts increase serum nitric oxide (NO) level, anti-atherogenic lipid, glutathione level, lymphocyte and platelet count in the rats. SIGNIFICANCE: Extracts of PR leaf decrease blood pressure and increase NO level in L-NAME hypertensive rats and also corrected the hyperlipidemia and inflammatory response arising from the reduction in NO bioavailability.


Assuntos
Acanthaceae/química , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Extratos Vegetais/uso terapêutico , Animais , Anti-Hipertensivos/química , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/sangue , Hipertensão/induzido quimicamente , Hipertensão/fisiopatologia , Hipolipemiantes/química , Lipídeos/sangue , Masculino , NG-Nitroarginina Metil Éster , Óxido Nítrico/sangue , Extratos Vegetais/química , Folhas de Planta/química , Ratos Wistar
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