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1.
JAMA ; 322(18): 1780-1788, 2019 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-31714986

RESUMO

Importance: Additional treatment options are needed for patients who do not achieve sufficient reduction in low-density lipoprotein cholesterol (LDL-C) level with available lipid-lowering therapies. Objective: To assess the efficacy of bempedoic acid vs placebo in patients at high cardiovascular risk receiving maximally tolerated lipid-lowering therapy. Design, Setting, and Participants: Phase 3, randomized, double-blind, placebo-controlled clinical trial conducted at 91 clinical sites in North America and Europe from November 2016 to September 2018, with a final date of follow-up of September 22, 2018. A total of 779 patients with atherosclerotic cardiovascular disease, heterozygous familial hypercholesterolemia, or both met randomization criteria, which included LDL-C level 70 mg/dL (1.8 mmol/L) or greater while receiving maximally tolerated lipid-lowering therapy. Interventions: Patients were randomized 2:1 to treatment with bempedoic acid (180 mg) (n = 522) or placebo (n = 257) once daily for 52 weeks. Main Outcomes and Measures: The primary end point was percent change from baseline in LDL-C level at week 12. Secondary measures included changes in levels of lipids, lipoproteins, and biomarkers. Results: Among 779 randomized patients (mean age, 64.3 years; 283 women [36.3%]), 740 (95.0%) completed the trial. At baseline, mean LDL-C level was 120.4 (SD, 37.9) mg/dL. Bempedoic acid lowered LDL-C levels significantly more than placebo at week 12 (-15.1% vs 2.4%, respectively; difference, -17.4% [95% CI, -21.0% to -13.9%]; P < .001). Significant reductions with bempedoic acid vs placebo were observed at week 12 for non-high-density lipoprotein cholesterol (-10.8% vs 2.3%; difference, -13.0% [95% CI, -16.3% to -9.8%]; P < .001), total cholesterol (-9.9% vs 1.3%; difference, -11.2% [95% CI, -13.6% to -8.8%]; P < .001), apolipoprotein B (-9.3% vs 3.7%; difference, -13.0% [95% CI, -16.1% to -9.9%]; P < .001), and high-sensitivity C-reactive protein (median, -18.7% vs -9.4%; difference, -8.7% [asymptotic confidence limits, -17.2% to -0.4%]; P = .04). Common adverse events included nasopharyngitis (5.2% vs 5.1% with bempedoic acid and placebo, respectively), urinary tract infection (5.0% vs 1.9%), and hyperuricemia (4.2% vs 1.9%). Conclusions and Relevance: Among patients at high risk for cardiovascular disease receiving maximally tolerated statins, the addition of bempedoic acid compared with placebo resulted in a significant lowering of LDL-C level over 12 weeks. Further research is needed to assess the durability and clinical effect as well as long-term safety. Trial Registration: ClinicalTrials.gov Identifier: NCT02991118.


Assuntos
Anticolesterolemiantes/uso terapêutico , Aterosclerose/tratamento farmacológico , Ácidos Dicarboxílicos/uso terapêutico , Ácidos Graxos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemia Familiar Combinada/tratamento farmacológico , Idoso , Anticolesterolemiantes/efeitos adversos , Aterosclerose/sangue , Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol/sangue , Ácidos Dicarboxílicos/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Ácidos Graxos/efeitos adversos , Feminino , Humanos , Hiperlipidemia Familiar Combinada/sangue , Masculino , Pessoa de Meia-Idade
2.
Nutrients ; 11(8)2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31357492

RESUMO

To investigate the associations between dietary fatty acids and cholesterol consumption and stomach cancer (SC), we analyzed data from a population-based case-control study with a total of 1900 SC cases and 6532 controls. Dietary data and other risk or protective factors were collected by face-to-face interviews in Jiangsu Province, China, from 2003 to 2010. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multiple unconditional logistic regression models and an energy-adjusted method. The joint associations between dietary factors and known risk factors on SC were examined. We observed positive associations between dietary saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and total cholesterol and the development of SC, comparing the highest versus lowest quarters. Increased intakes of dietary SFAs (p-trend = 0.005; aOR, 1.11; 95% CI, 1.01-1.22 with a 7 g/day increase as a continuous variable) and total cholesterol (p-trend < 0.001; aOR, 1.13; 95% CI, 1.06-1.22 with a 250 mg/day increase as a continuous variable) were monotonically associated with elevated odds of developing SC. Our results indicate that dietary SFAs, MUFAs, and total cholesterol are associated with stomach cancer, which might provide a potential dietary intervention for stomach cancer prevention.


Assuntos
Colesterol na Dieta/efeitos adversos , Dieta/efeitos adversos , Ácidos Graxos/efeitos adversos , Neoplasias Gástricas/epidemiologia , Idoso , Estudos de Casos e Controles , China/epidemiologia , Colesterol na Dieta/administração & dosagem , Ácidos Graxos/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Proteção , Recomendações Nutricionais , Medição de Risco , Fatores de Risco , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/prevenção & controle
3.
BMC Public Health ; 19(1): 818, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31238900

RESUMO

BACKGROUND: Saturated fatty acids (SFA) have been reported to promote inflammation. Nevertheless, evidence linking dietary SFA and low-grade inflammation in adolescents is scarce and inconsistent. The modulatory role of physical activity (PA) on fat metabolism and inflammation may provide a potential explanation. Thus, we assessed the association of dietary SFA with high-sensitivity C-reactive protein (hsCRP), a marker of low-grade inflammation, in 15-year-olds, and evaluated possible interactions between dietary SFA and different levels of PA. METHODS: Children participating in the 15-year follow-ups of the GINIplus and LISA German birth cohort studies were included (N = 824). SFA intake was estimated by means of a food frequency questionnaire and PA recorded by accelerometers. Average daily minutes of PA were classified into "sedentary", "light" and "moderate-to-vigorous" (MVPA), using Freedson's cut-offs. HsCRP concentrations were measured in serum and categorized into 3 sex-specific levels (below detection limit (I), above 75th percentile (III), in between (II)). Sex-stratified cross-sectional associations between SFA and hsCRP were assessed using multinomial logistic regression, adjusting for potential confounders. Interaction terms were included between SFA and the different PA levels; and if significant interactions were observed, analyses stratified by tertiles of the relevant PA levels were performed. Relative risk ratios (RRR) and 95% confidence intervals (95%CI) were presented for a 1% increase in SFA. RESULTS: An inverse association was observed between SFA intake and hsCRP (II vs. I) in males (RRR = 0.85 [95%CI = 0.76;0.96], p = 0.008), whereas no significant association was observed in females. A significant interaction was observed with "sedentary" and "light" PA but not with MVPA in both sexes (p < 0.05). Stratified analyses indicated a significant inverse association between SFA and medium hsCRP levels in males in the highest light PA tertile (hsCRP II vs. I: 0.67 [0.517;0.858], p = 0.002). CONCLUSION: Our findings do not support a detrimental role of dietary SFA in low-grade inflammation among adolescents. In males, higher dietary SFA was associated with lower hsCRP, although this should be interpreted in the context of possibly correlated nutrients. Children spending the most time in light PA drove the observed inverse association, suggesting a synergistic effect of SFA and lifestyle PA in the resultant inflammatory response.


Assuntos
Gorduras na Dieta/efeitos adversos , Exercício/fisiologia , Ácidos Graxos/efeitos adversos , Inflamação/etiologia , Acelerometria , Adolescente , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Estudos de Coortes , Estudos Transversais , Gorduras na Dieta/administração & dosagem , Ácidos Graxos/administração & dosagem , Feminino , Alemanha , Humanos , Inflamação/sangue , Masculino
5.
Nutrients ; 11(5)2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31137794

RESUMO

Fatty acids come in a variety of structures and, because of this, create a variety of functions for these lipids. Some fatty acids have a role to play in energy metabolism, some help in lipid storage, cell structure, the physical state of the lipid, and even in food stability. Fatty acid metabolism plays a particularly important role in meeting the energy demands of the heart. It is the primary source of myocardial energy in control conditions. Its role changes dramatically in disease states in the heart, but the pathologic role these fatty acids play depends upon the type of cardiovascular disease and the type of fatty acid. However, no matter how good a food is for one's health, its taste will ultimately become a deciding factor in its influence on human health. No food will provide health benefits if it is not ingested. This review discusses the taste characteristics of culinary oils that contain fatty acids and how these fatty acids affect the performance of the heart during healthy and diseased conditions. The contrasting contributions that different fatty acid molecules have in either promoting cardiac pathologies or protecting the heart from cardiovascular disease is also highlighted in this article.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Ácidos Graxos/administração & dosagem , Comportamento Alimentar , Valor Nutritivo , Óleos/administração & dosagem , Percepção Gustatória , Paladar , Animais , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/metabolismo , Metabolismo Energético , Ácidos Graxos/efeitos adversos , Ácidos Graxos/metabolismo , Humanos , Miocárdio/metabolismo , Óleos/efeitos adversos , Óleos/metabolismo , Fatores de Proteção , Fatores de Risco
6.
Nutrients ; 11(4)2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30991629

RESUMO

It remains unclear whether cholesterol intake can increase serum cholesterol. Therefore, the present study aimed to investigate the hypothesis that the risk for hypercholesterolemia was not associated with intake of dietary cholesterol after adjusting for saturated fatty acid (SFA). Based on the data from the 2012-2016 KNHANES, dietary cholesterol was positively associated with the risk for abnormalities in total cholesterol (TC) (odds ratio (OR): 1.153, 95% confidence interval (CI): 0.995-1.337; p = 0.028) and low-density lipoprotein cholesterol (LDL-C) (OR: 1.186, 95% CI: 1.019-1.382; p = 0.018) levels before adjusting for SFA; after adjusting for SFA, no significant associations were found between these variables. The mediation analysis showed that dietary cholesterol had no direct effects on the serum levels of TC and LDL-C; in contrast, SFA had significant indirect effects on the association between dietary cholesterol and serum levels of TC and LDL-C. Furthermore, processed meats, but not eggs and other meats, were positively associated with the risk for abnormalities in both TC (OR: 1.220, 95% CI: 1.083-1.374; p = 0.001) and LDL-C (OR: 1.193, 95% CI: 1.052-1.354; p = 0.004) levels. The present study suggested that higher intake of processed meats with high SFA, but not dietary cholesterol was associated with higher risk for abnormalities in TC and LDL-C levels.


Assuntos
Colesterol na Dieta/efeitos adversos , Dieta , Comportamento Alimentar , Hipercolesterolemia/etiologia , Adulto , Colesterol na Dieta/sangue , LDL-Colesterol/sangue , Ingestão de Energia , Ácidos Graxos/efeitos adversos , Feminino , Humanos , Hipercolesterolemia/sangue , Masculino , Carne , Pessoa de Meia-Idade , Inquéritos Nutricionais , Razão de Chances , República da Coreia
7.
Lipids Health Dis ; 18(1): 91, 2019 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-30954077

RESUMO

BACKGROUND: Several epidemiological studies have investigated the association between dietary fat intake and cardiovascular disease. However, dietary recommendations based on systematic review and meta-analysis might be more credible. METHODS AND RESULTS: Pubmed, Embase and Cochrane library were searched up to July 1st 2018 for cohort studies reporting associations of dietary fat intake and risk of CVDs. By comparing the highest vs. the lowest categories of fat or fatty acids intake, we found that higher dietary trans fatty acids (TFA) intake was associated with increased risk of CVDs [RR:1.14(1.08-1.21)]. However, no association was observed between total fat, monounsaturated fatty acids (MUFA), saturated fatty acids (SFA), and polyunsaturated fatty acids (PUFA), and risk of CVDs. Subgroup analysis found a cardio-protective effect of PUFA in the studies that has been followed up more than 10 years [0.95(0.91-0.99), I2 = 62.4%]. Dose-response analysis suggested that the risk of CVDs increased 16% [1.16 (1.07-1.25), Plinearity = 0.033] for an increment of 2% energy/day of TFA intake. CONCLUSIONS: This current meta-analysis of cohort studies suggested that total fat, SFA, MUFA, and PUFA intake were not associated with the risk of cardiovascular disease. However, we found that higher TFA intake is associated with greater risk of CVDs in a dose-response fashion. Furthermore, the subgroup analysis found a cardio-protective effect of PUFA in studies followed up for more than 10 years.


Assuntos
Doenças Cardiovasculares/epidemiologia , Gorduras na Dieta/efeitos adversos , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos/efeitos adversos , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Dieta , Ácidos Graxos Monoinsaturados/efeitos adversos , Humanos , Fatores de Risco , Ácidos Graxos Trans/efeitos adversos
8.
Nutrients ; 11(2)2019 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-30813339

RESUMO

Interesterified fats are being widely used by the food industry in an attempt to replace trans fatty acids. The effect of interesterified fats containing palmitic or stearic acids on lipid metabolism and inflammatory signaling pathways in adipose and hepatic tissues was evaluated. Male LDLr-KO mice were fed a high-fat diet containing polyunsaturated (PUFA), palmitic (PALM), palmitic interesterified (PALM INTER), stearic (STEAR), or stearic interesterified (STEAR INTER) fats for 16 weeks. The expression of genes and protein levels involved in lipid metabolism and inflammatory processes in liver and white adipose tissue was determined by quantitative RT-PCR and by Western blot, respectively. The infiltration of inflammatory cells in hepatic and adipose tissues was determined by eosin and hematoxylin, while liver collagen content was determined by Sirius Red staining. Both interesterified fats increased liver collagen content and JNK phosphorylation. Additionally, the STEAR INTER group developed nonalcoholic steatohepatitis (NASH) associated with higher neutrophil infiltration. PALM INTER induced adipose tissue expansion and enlargement of adipocytes. Furthermore, PALM INTER triggered increased IKK phosphorylation and TNFα protein content, conditions associated with the upstream activation of the NFkB signaling pathway. STEAR INTER induced NASH, while PALM INTER triggered hepatic fibrosis and adipocyte hypertrophy with inflammatory response in LDLr-KO mice.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Ácidos Graxos/efeitos adversos , Fígado/efeitos dos fármacos , Receptores de LDL/metabolismo , Tecido Adiposo/patologia , Animais , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/efeitos adversos , Ácidos Graxos/administração & dosagem , Ácidos Graxos/química , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/patologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Knockout , Obesidade/induzido quimicamente , Receptores de LDL/genética
9.
J Nutr Sci ; 8: e10, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30918631

RESUMO

CVD is common in older adults. Consumption of 'meat' (beef, pork, lamb, game, poultry, seafood, eggs) and dairy foods (milk, cheese, yoghurt) is encouraged in older adults as these foods provide protein and nutrients such as essential fatty acids, Ca, Fe, Zn and vitamins A, D and B12 required for healthy ageing. However, these foods also contain saturated fats considered detrimental to cardiovascular health. To determine the effect of their consumption on CVD risk we assessed associations between fat intake from 'meat' and dairy foods and serum cholesterol levels in 226 aged-care residents (mean age 85·5 years, 70 % female). Dietary intake was determined over 2 d using visual estimation of plate waste. Fat content of foods was determined using nutrition analysis software (Xyris, Australia). Fasting serum total cholesterol (TC), LDL-cholesterol and HDL-cholesterol were measured, and the TC:HDL-cholesterol ratio calculated. Associations were determined using random-effect models adjusted for CVD risk factors using STATA/IC 13.0. Total fat and saturated fat from 'meat' and dairy foods were associated with higher serum HDL-cholesterol levels, and dairy fat intake and number of servings were associated with a lower TC:HDL-cholesterol ratio. Every 10 g higher intake of fat and saturated fat from dairy products, and each additional serving was associated with a -0·375 (95 % CI -0·574, -0·175; P = 0·0002), a -0·525 (95 % CI -0·834, -0·213; P = 0·001) and a -0·245 (95 % CI -0·458, -0·033; P = 0·024) lower TC:HDL-cholesterol ratio, respectively. Provision of dairy foods and 'meat' in recommended amounts to institutionalised older adults potentially improves intakes of key nutrients with limited detriment to cardiovascular health.


Assuntos
Colesterol/efeitos adversos , Colesterol/sangue , Laticínios/efeitos adversos , Gorduras na Dieta/efeitos adversos , Carne/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Austrália , Doenças Cardiovasculares , Sistema Cardiovascular , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos Transversais , Dieta , Ácidos Graxos/efeitos adversos , Feminino , Instituição de Longa Permanência para Idosos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
10.
Andrologia ; 51(5): e13259, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30873638

RESUMO

Our objectives were to assess sperm alteration and adipose tissue (AT) genes expression related to steroid metabolism subsequent to fatty acids consumption. Twenty-nine mature male mice were divided into: fat diet (FD; n = 15) and the control group (n = 14). FD group was fed with low level of trans and saturated fatty acids source for 60 days. Sperm parameters, levels of hormones and the mRNA abundance of the target genes in AT were assessed. The sperm concentration, total and progressive motilities were lower in FD group compared to that of control (p < 0.01). Blood estradiol levels increased in FD (p < 0.001), whereas no significant difference was observed in testosterone. The mRNA levels of StAR, CYP11A1, CYP17A1, 17ßHSD7 and 17ßHSD12 in AT of FD were higher than those of the control (p < 0.05). In contrast, mRNA level of Cyp19a1 in FD was significantly (p < 0.05) lower than that of control. 17ßHSD12 and 17ßHSD7 (as oestrogenic genes) increased, while 17ßHSD5 and 17ßHSD3 (as androgenic genes) remained unchanged, indicating that dietary trans/saturated fatty acids affect AT genes expression. Probably, sperm parameters were altered by increment of expression level of genes involved in oestrogenic metabolism rather than those engaged in androgenic metabolism after fatty acids consumption.


Assuntos
Tecido Adiposo/metabolismo , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/efeitos adversos , Ácidos Graxos/efeitos adversos , Esteroides/metabolismo , Androgênios/sangue , Androgênios/metabolismo , Animais , Estrogênios/sangue , Estrogênios/metabolismo , Masculino , Camundongos , Modelos Animais , Contagem de Espermatozoides
11.
N Engl J Med ; 380(11): 1022-1032, 2019 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-30865796

RESUMO

BACKGROUND: Short-term studies have shown that bempedoic acid, an inhibitor of ATP citrate lyase, reduces levels of low-density lipoprotein (LDL) cholesterol. Data are limited regarding the safety and efficacy of bempedoic acid treatment in long-term studies involving patients with hypercholesterolemia who are receiving guideline-recommended statin therapy. METHODS: We conducted a randomized, controlled trial involving patients with atherosclerotic cardiovascular disease, heterozygous familial hypercholesterolemia, or both. Patients had to have an LDL cholesterol level of at least 70 mg per deciliter while they were receiving maximally tolerated statin therapy with or without additional lipid-lowering therapy. (Maximally tolerated statin therapy was defined as the highest intensity statin regimen that a patient was able to maintain, as determined by the investigator.) Patients were randomly assigned in a 2:1 ratio to receive bempedoic acid or placebo. The primary end point was safety, and the principal secondary end point (principal efficacy end point) was the percentage change in the LDL cholesterol level at week 12 of 52 weeks. RESULTS: The trial involved 2230 patients, of whom 1488 were assigned to receive bempedoic acid and 742 to receive placebo. The mean (±SD) LDL cholesterol level at baseline was 103.2±29.4 mg per deciliter. The incidence of adverse events (1167 of 1487 patients [78.5%] in the bempedoic acid group and 584 of 742 [78.7%] in the placebo group) and serious adverse events (216 patients [14.5%] and 104 [14.0%], respectively) did not differ substantially between the two groups during the intervention period, but the incidence of adverse events leading to discontinuation of the regimen was higher in the bempedoic acid group than in the placebo group (162 patients [10.9%] vs. 53 [7.1%]), as was the incidence of gout (18 patients [1.2%] vs. 2 [0.3%]). At week 12, bempedoic acid reduced the mean LDL cholesterol level by 19.2 mg per deciliter, representing a change of -16.5% from baseline (difference vs. placebo in change from baseline, -18.1 percentage points; 95% confidence interval, -20.0 to -16.1; P<0.001). Safety and efficacy findings were consistent, regardless of the intensity of background statin therapy. CONCLUSIONS: In this 52-week trial, bempedoic acid added to maximally tolerated statin therapy did not lead to a higher incidence of overall adverse events than placebo and led to significantly lower LDL cholesterol levels. (Funded by Esperion Therapeutics; CLEAR Harmony ClinicalTrials.gov number, NCT02666664.).


Assuntos
LDL-Colesterol/sangue , Ácidos Dicarboxílicos/uso terapêutico , Ácidos Graxos/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , ATP Citrato (pro-S)-Liase/antagonistas & inibidores , Idoso , Apolipoproteínas B/sangue , Proteína C-Reativa/análise , Colesterol/sangue , Ácidos Dicarboxílicos/efeitos adversos , Quimioterapia Combinada , Ácidos Graxos/efeitos adversos , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/sangue , Hipoglicemiantes/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Resultado do Tratamento
12.
Int J Food Sci Nutr ; 70(6): 749-758, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30764669

RESUMO

Dietary food, depending on timing, amount and composition can influence gene expression in various tissues. Here, we investigated the effect of high-fat meal diets of different compositions on the gene expression pattern of human skeletal muscle. Gene expression data of skeletal muscle samples from human volunteers prior and 4 h after the consumption of high lipid-containing meal consisting of either saturated-, monounsaturated- or polyunsaturated fatty acids were downloaded from the public repository. List of 843 differently expressed genes (DEGs) was generated. Functional analysis revealed that circadian rhythm-, inflammation- and oxidative stress-related genes are highly overrepresented among the DEGs. The magnitude of gene expression changes significantly increases with the saturation level of the dietary fatty acids and the majority of the DEGs are upregulated. We propose that, by altering circadian clock gene expression and inducing inflammation and oxidative stress, high lipid intake can contribute to muscle function decay in the long run.


Assuntos
Relógios Circadianos/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/metabolismo , Refeições , Músculo Esquelético/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Relógios Circadianos/genética , Gorduras na Dieta/efeitos adversos , Gorduras na Dieta/metabolismo , Ácidos Graxos/efeitos adversos , Perfilação da Expressão Gênica , Genoma Humano , Humanos , Inflamação/genética , Família Multigênica , Músculo Esquelético/metabolismo , Estresse Oxidativo/genética
13.
Expert Opin Pharmacother ; 20(7): 791-803, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30810432

RESUMO

INTRODUCTION: Tolerability problems in treating hypercholesterolemic patients undergoing statin treatment are of growing concern to physicians and patients, thus underlining the need for an agent with a similar mechanism but minimal side effects. A drug with a somewhat similar mechanism to statins but free of muscular side effects is ETC-1002 (bempedoic acid). It inhibits cholesterol biosynthesis at a step preceding HMG-CoA reductase, i.e. ATP citrate lyase (ACLY). A prodrug, ETC-1002 is converted to the active agent only in liver, not in skeletal muscle, and this may prevent any myotoxic activity. Area covered: The mechanism of ETC-1002 activity is described in detail, considering that ACLY inhibition markedly attenuated atherosclerosis in animal models. Clinical studies are also reported. Expert opinion: Present day LDL-C lowering treatments lead to significant reductions of cardiovascular (CV) events but, at times, the need to interrupt statin treatment appears to be dangerous due to a rapid rise in CV risk. The excellent tolerability of ETC-1002 makes it a useful alternative, either alone or as an adjunct to ezetimibe, for patients with statin intolerance needing to achieve significant CV risk reduction. ETC-1002 is also associated with a marked fall in high-sensitivity C-reactive protein.


Assuntos
Anticolesterolemiantes/uso terapêutico , Ácidos Dicarboxílicos/uso terapêutico , Ácidos Graxos/uso terapêutico , Hiperlipidemias/tratamento farmacológico , ATP Citrato (pro-S)-Liase/antagonistas & inibidores , ATP Citrato (pro-S)-Liase/genética , ATP Citrato (pro-S)-Liase/metabolismo , Animais , Anticolesterolemiantes/efeitos adversos , Aterosclerose/tratamento farmacológico , Proteína C-Reativa/metabolismo , Ensaios Clínicos como Assunto , Ácidos Dicarboxílicos/efeitos adversos , Quimioterapia Combinada , Ezetimiba/uso terapêutico , Ácidos Graxos/efeitos adversos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Fígado/metabolismo
14.
Kardiol Pol ; 77(2): 207-216, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30740643

RESUMO

BACKGROUND: Due to the myopathic adverse events of statins, safer alternatives are being studied. Bempedoic acid (ETC-1002) is a novel low-density lipoprotein cholesterol (LDL-C)-lowering agent, currently under trial in hypercholesterolaemic patients. AIM: To investigate the tolerability and efficacy of ETC-1002 in hypercholesterolaemic patients through a systematic review of published randomised controlled trials (RCTs). METHODS: Five databases were searched for RCTs that investigated the safety and efficacy of ETC-1002 in hypercholesterol-aemic patients. The retrieved search results were screened, and then data were extracted and analysed (as mean difference [MD] or odds ratio [OR]) using the RevMan software. RESULTS: Five RCTs (625 hypercholesterolaemic patients) were identified. ETC-1002 was superior to placebo in terms of percent-age changes from baseline in serum levels of LDL-C (MD -26.58, 95% confidence interval [CI] -35.50 to -17.66, p < 0.0001), non-high-density lipoprotein cholesterol (MD -21.54, 95% CI -28.48 to -14.6, p < 0.00001), and apolipoprotein-B (MD -15.97, 95% CI -19.36 to -12.57, p < 0.0001). When compared to ezetimibe, ETC-1002 was superior in reducing LDL-C (-30.1 ± 1.3 vs. -21.1 ± 1.3). Regarding safety, ETC-1002 did not increase the risk of all adverse events (OR 0.58, 95% CI 0.37-0.91, p = 0.02) and arthralgia (OR 0.32, 95% CI 0.13-0.81, p = 0.02) compared to placebo. All other adverse events including myalgia, headache, and urinary tract infections were similar between ETC-1002 and placebo groups. The evidence certainty in the assessed outcomes was moderate to high except for lipoprotein(a), free fatty acids, and very low-density lipoprotein particle number (very low certainty). CONCLUSIONS: ETC-1002 is a safe and effective lipid-lowering agent and may be a suitable alternative in statin-intolerant pa-tients. Well-designed studies are needed to explore the long-term safety and efficacy of ETC-1002 in these patients.


Assuntos
Ácidos Dicarboxílicos/uso terapêutico , Ácidos Graxos/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Idoso , LDL-Colesterol/sangue , Ácidos Dicarboxílicos/efeitos adversos , Ezetimiba/efeitos adversos , Ezetimiba/uso terapêutico , Ácidos Graxos/efeitos adversos , Feminino , Humanos , Hipercolesterolemia/sangue , Hipolipemiantes/efeitos adversos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
15.
Neurobiol Aging ; 76: 45-52, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30682676

RESUMO

Alzheimer's disease (AD) risk increases with age and lacks efficacious pharmacological options. Summaries of the existing evidence reveal an association between Mediterranean-style diet adherence and reduced AD incidence; however, no review has investigated this relationship with respect to the hallmark AD biomarkers (tau and beta-amyloid) that manifest decades before clinical symptomatology. MEDLINE, PubMed, PsycINFO, Google Scholar, and SCOPUS databases were systematically searched to identify peer-reviewed articles investigating diet and AD biomarkers in the last 2 decades. Two thousand seven hundred twenty-six records were extracted, quality assessed, and double-blind screened by 2 authors. Fifteen studies met the inclusion criteria and 13 studies found a significant relationship. Of these, 4 studies found a high-glycemic load was related to an increase in AD biomarker burden; 6 found adherence to a Mediterranean or "AD-protective" dietary pattern conferred a reduction in AD biomarker burden. Meta-analysis revealed a small but significant effect of diet on AD biomarkers (ß = 0.11 [95% CI 0.04-0.17], p = 0.002). This systematic review supports the notion that diet and nutrition display potential for nonpharmacological AD prevention.


Assuntos
Doença de Alzheimer/diagnóstico , Doença de Alzheimer/prevenção & controle , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Dieta Mediterrânea , Adulto , Idoso , Doença de Alzheimer/etiologia , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Bases de Dados Bibliográficas , Dieta Hiperlipídica/efeitos adversos , Carboidratos da Dieta/efeitos adversos , Ácidos Graxos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Proteínas tau/líquido cefalorraquidiano
16.
Adv Food Nutr Res ; 87: 43-146, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30678820

RESUMO

Dietary fatty acids are present in a wide variety of foods and appear in different forms and lengths. The different fatty acids are known to have various effects on metabolic health. The metabolic syndrome (MetS) is a constellation of risk factors of chronic diseases. The etiology of the MetS is represented by a complex interplay of genetic and environmental factors. Dietary fatty acids can be important contributors of the evolution or in prevention of the MetS; however, great interindividual variability exists in the response to fatty acids. The identification of genetic variants interacting with fatty acids might explain this heterogeneity in metabolic responses. This chapter reviews the mechanisms underlying the interactions between the different components of the MetS, dietary fatty acids and genes. Challenges surrounding the implementation of personalized nutrition are also covered.


Assuntos
Gorduras na Dieta/administração & dosagem , Ácidos Graxos/administração & dosagem , Síndrome Metabólica/dietoterapia , Gorduras na Dieta/efeitos adversos , Ácidos Graxos/efeitos adversos , Predisposição Genética para Doença , Genômica , Humanos , Síndrome Metabólica/genética , Fatores de Risco
17.
Circ Res ; 124(8): 1266-1275, 2019 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-30689516

RESUMO

RATIONALE: Dietary monounsaturated fatty acids (MUFAs) can come from both plant and animal sources with divergent nutrient profiles that may potentially obscure the associations of total MUFAs with chronic diseases. OBJECTIVE: To investigate the associations of cis-MUFA intake from plant (MUFA-P) and animal (MUFA-A) sources with total and cause-specific mortality. METHODS AND RESULTS: We followed 63 412 women from the NHS (Nurses' Health Study; 1990-2012) and 29 966 men from the HPFS (Health Professionals Follow-Up Study; 1990-2012). MUFA-Ps and MUFA-As were calculated based on data collected through validated food frequency questionnaires administered every 4 years and updated food composition databases. During 1 896 864 person-years of follow-up, 20 672 deaths occurred. Total MUFAs and MUFA-Ps were inversely associated with total mortality after adjusting for potential confounders, whereas MUFA-As were associated with higher mortality. When MUFA-Ps were modeled to isocalorically replace other macronutrients, hazard ratios (HRs, 95% CIs) of total mortality were 0.84 (0.77-0.92; P<0.001) for replacing saturated fatty acids, 5% of energy); 0.86 (0.82-0.91; P<0.001) for replacing refined carbohydrates (5% energy); 0.91 (0.85-0.97; P<0.001) for replacing trans fats (2% energy), and 0.77 (0.71-0.82; P<0.001) for replacing MUFA-As (5% energy). For isocalorically replacing MUFA-As with MUFA-Ps, HRs (95% CIs) were 0.74 (0.64-0.86; P<0.001) for cardiovascular mortality; 0.73 (0.65-0.82; P<0.001) for cancer mortality, and 0.82 (0.73-0.91; P<0.001) for mortality because of other causes. CONCLUSIONS: Higher intake of MUFA-Ps was associated with lower total mortality, and MUFA-As intake was associated with higher mortality. Significantly lower mortality risk was observed when saturated fatty acids, refined carbohydrates, or trans fats were replaced by MUFA-Ps, but not MUFA-As. These data suggest that other constituents in animal foods, such as saturated fatty acids, may confound the associations for MUFAs when they are primarily derived from animal products. More evidence is needed to elucidate the differential associations of MUFA-Ps and MUFA-As with mortality.


Assuntos
Causas de Morte , Gorduras na Dieta/efeitos adversos , Ácidos Graxos Monoinsaturados/efeitos adversos , Adulto , Idoso , Animais , Doenças Cardiovasculares/mortalidade , Inquéritos sobre Dietas , Carboidratos da Dieta/administração & dosagem , Carboidratos da Dieta/efeitos adversos , Gorduras na Dieta/administração & dosagem , Ingestão de Energia , Ácidos Graxos/administração & dosagem , Ácidos Graxos/efeitos adversos , Ácidos Graxos Monoinsaturados/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Óleos Vegetais/administração & dosagem , Óleos Vegetais/química , Plantas , Modelos de Riscos Proporcionais , Estudos Prospectivos , Estados Unidos
18.
Circ Res ; 124(5): 757-768, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30636521

RESUMO

RATIONALE: Evidence linking saturated fat intake with cardiovascular health is controversial. The associations of unsaturated fats with total and cardiovascular disease (CVD) mortality remain inconsistent, and data about non-CVD mortality are limited. OBJECTIVE: To assess dietary fat intake in relation to total and cause-specific mortality. METHODS AND RESULTS: We analyzed data of 521 120 participants aged 50 to 71 years from the National Institutes of Health-American Association of Retired Persons Diet and Health Study with 16 years of follow-up. Intakes of saturated fatty acids (SFAs), trans-fatty acids, monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) were assessed via food frequency questionnaires. Hazard ratios and 95%CIs were estimated using the Cox proportional hazards model. Overall, 129 328 deaths were documented during 7.3 million person-years of follow-up. In the replacement of carbohydrates, multivariable-adjusted hazard ratios of total mortality comparing extreme quintiles were 1.29 (95% CI, 1.25-1.33) for SFAs, 1.03 (1.00-1.05) for trans-fatty acids, 0.98 (0.94-1.02) for MUFAs, 1.09 (1.06-1.13) for animal MUFAs, 0.94 (0.91-0.97) for plant MUFAs, 0.93 (0.91-0.95) for PUFAs, 0.92 (0.90-0.94) for marine omega-3 PUFAs, 1.06 (1.03-1.09) for α-linolenic acid, 0.88 (0.86-0.91) for linoleic acid, and 1.10 (1.08-1.13) for arachidonic acid. CVD mortality was inversely associated with marine omega-3 PUFA intake ( P trend <0.0001), whereas it was positively associated with SFA, trans-fatty acid, and arachidonic acid intake. Isocalorically replacing 5% of the energy from SFAs with plant MUFAs was associated with 15%, 10%, 11%, and 30% lower total mortality, CVD, cancer, and respiratory disease mortality, respectively. Isocaloric replacement of SFA with linoleic acid (2%) was associated with lower total (8%), CVD (6%), cancer (8%), respiratory disease (11%), and diabetes mellitus (9%) mortality. CONCLUSIONS: Intakes of SFAs, trans-fatty acids, animal MUFAs, α-linolenic acid, and arachidonic acid were associated with higher mortality. Dietary intake of marine omega-3 PUFAs and replacing SFAs with plant MUFAs or linoleic acid were associated with lower total, CVD, and certain cause-specific mortality. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00340015.


Assuntos
Doenças Cardiovasculares/mortalidade , Gorduras na Dieta/efeitos adversos , Ácidos Graxos/efeitos adversos , Idoso , Ácido Araquidônico/administração & dosagem , Ácido Araquidônico/efeitos adversos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/prevenção & controle , Causas de Morte , Gorduras na Dieta/administração & dosagem , Ácidos Graxos/administração & dosagem , Ácidos Graxos Monoinsaturados/administração & dosagem , Ácidos Graxos Monoinsaturados/efeitos adversos , Ácidos Graxos Ômega-3/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Proteção , Medição de Risco , Fatores de Risco , Fatores de Tempo , Ácidos Graxos Trans/administração & dosagem , Ácidos Graxos Trans/efeitos adversos , Estados Unidos/epidemiologia , Ácido alfa-Linoleico/administração & dosagem , Ácido alfa-Linoleico/efeitos adversos
19.
Int J Cardiol ; 279: 18-26, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30482628

RESUMO

BACKGROUND: The effect of individual saturated fatty acids (SFAs) on serum cholesterol levels depends on their carbon-chain length. Whether the association with myocardial infarction (MI) also differs across individual SFAs is unclear. We examined the association between consumption of individual SFAs, differing in chain lengths ranging from 4 through 18 carbons, and risk of MI. METHODS: We used data from 22,050 and 53,375 participants from EPIC-Norfolk (UK) and EPIC-Denmark, respectively. Baseline SFA intakes were assessed through validated, country-specific food frequency questionnaires. Cox regression analysis was used to estimate associations between intakes of individual SFAs and MI risk, for each cohort separately. RESULTS: During median follow-up times of 18.8 years in EPIC-Norfolk and 13.6 years in Denmark, respectively, 1204 and 2260 MI events occurred. Mean (±SD) total SFA intake was 13.3 (±3.5) en% in EPIC-Norfolk, and 12.5 (±2.6) en% in EPIC-Denmark. After multivariable adjustment, intakes of C12:0 (lauric acid) and C14:0 (myristic acid) inversely associated with MI risk in EPIC-Denmark (HR upper versus lowest quintile: 0.80 (95%CI: 0.66, 0.96) for both SFAs). Intakes in the third and fourth quintiles of C4:0-C10:0 also associated with lower MI risk in EPIC-Denmark. Moreover, substitution of C16:0 (palmitic acid) and C18:0 (stearic acid) with plant proteins resulted in a reduction of MI risk in EPIC-Denmark (HR per 1 energy%: 0.86 (95%CI: 0.78, 0.95) and 0.87 (95%CI: 0.79, 0.96) respectively). No such associations were found in EPIC-Norfolk. CONCLUSION: The results from the present study suggest that the association between SFA and MI risk depends on the carbon chain-length of the SFA.


Assuntos
/métodos , Gorduras na Dieta/administração & dosagem , Ácidos Graxos/administração & dosagem , Infarto do Miocárdio/epidemiologia , Proteínas de Vegetais Comestíveis/administração & dosagem , Adulto , Idoso , Dinamarca/epidemiologia , Gorduras na Dieta/efeitos adversos , Ácidos Graxos/efeitos adversos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/diagnóstico , Fatores de Risco , Reino Unido/epidemiologia
20.
Br J Sports Med ; 53(22): 1393-1396, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30108061

RESUMO

US public health dietary advice was announced by the Select Committee on Nutrition and Human needs in 1977 and was followed by UK public health dietary advice issued by the National Advisory Committee on Nutritional Education in 1983. Dietary recommendations in both cases focused on reducing dietary fat intake; specifically to (i) reduce overall fat consumption to 30% of total energy intake and (ii) reduce saturated fat consumption to 10% of total energy intake. The recommendations were an attempt to address the incidence of coronary heart disease. These guidelines have been reiterated in the Dietary Guidelines for Americans since the first edition in 1980. The most recent edition has positioned the total fat guideline with the use of 'Acceptable Macronutrient Distribution Ranges'. The range given for total fat is 20%-35% and the AMDR for saturated fat is given as <10%-both as a percentage of daily calorie intake. In February 2018, the Center for Nutrition Policy and Promotion announced 'The US Departments of Agriculture and Health and Human Services currently are asking for public comments on topics and supporting scientific questions to inform our development of the 2020-2025 Dietary Guidelines for Americans'. Public comments were invited on a number of nutritional topics. The question asked about saturated fats was: 'What is the relationship between saturated fat consumption (types and amounts) during adulthood and risk of cardiovascular disease?' This article is a response to that question.


Assuntos
Doença das Coronárias/prevenção & controle , Gorduras na Dieta/administração & dosagem , Política Nutricional , Doença das Coronárias/epidemiologia , Gorduras na Dieta/efeitos adversos , Ingestão de Energia , Ácidos Graxos/administração & dosagem , Ácidos Graxos/efeitos adversos , Humanos , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisão Sistemática como Assunto , Estados Unidos
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