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1.
BMC Musculoskelet Disord ; 22(1): 759, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488720

RESUMO

BACKGROUND: Osteoporosis and cardiovascular diseases (CVDs) are 2 major public health problems. Osteoporosis and CVDs may be linked but the association between lipid profile and osteoporosis is still controversial. The purpose of this study was to examine the associations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) with osteoporosis. METHODS: Using inpatients' and outpatients' electronic medical records (EMR) and dual X-ray absorptiometry (DXA) database stored at The Second Hospital of Jilin University, we included 481 individuals with complete and valid lipid and bone mineral density (BMD) data in 2017. Serum samples were used to measure TC, LDL-C, HDL-C and TG. Femoral neck and total hip BMD were measured by DXA; osteoporosis was defined as femoral neck or total hip T-score ≤ -2.5. Multivariable logistic regression models were used to test the associations of TC, LDL-C, HDL-C and TG with osteoporosis. RESULTS: The mean age for included individuals was 62.7 years (SD = 8.6 years); 60.1 % of them were female. Each standard deviation (SD) increase in TC (Odds Ratio [OR]: 1.48; 95 % Confidence Interval [CI]: 1.06-2.07) and TG (OR: 1.67; 95 % CI: 1.16-2.39) were associated with increased risk of osteoporosis; LDL-C and HDL-C levels were not associated with osteoporosis. Age, sex and body mass index (BMI) did not interact with the relationships of TC and TG with osteoporosis (all P > 0.10). CONCLUSIONS: Higher TC and TG levels were associated with greater risk of osteoporosis in this cross-sectional study.


Assuntos
Lipídeos/sangue , Osteoporose , Idoso , Biomarcadores/sangue , HDL-Colesterol/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/diagnóstico por imagem , Osteoporose/epidemiologia , Triglicerídeos/sangue
2.
Science ; 373(6553)2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34437091

RESUMO

The biogenesis of high-density lipoprotein (HDL) requires apoA1 and the cholesterol transporter ABCA1. Although the liver generates most of the HDL in the blood, HDL synthesis also occurs in the small intestine. Here, we show that intestine-derived HDL traverses the portal vein in the HDL3 subspecies form, in complex with lipopolysaccharide (LPS)-binding protein (LBP). HDL3, but not HDL2 or low-density lipoprotein, prevented LPS binding to and inflammatory activation of liver macrophages and instead supported extracellular inactivation of LPS. In mouse models involving surgical, dietary, or alcoholic intestinal insult, loss of intestine-derived HDL worsened liver injury, whereas outcomes were improved by therapeutics that elevated and depended upon raising intestinal HDL. Thus, protection of the liver from injury in response to gut-derived LPS is a major function of intestinally synthesized HDL.


Assuntos
Intestino Delgado/metabolismo , Lipoproteínas HDL3/metabolismo , Hepatopatias/prevenção & controle , Fígado/metabolismo , Veia Porta/metabolismo , Proteínas de Fase Aguda/metabolismo , Adulto , Animais , Proteínas de Transporte/metabolismo , HDL-Colesterol/sangue , HDL-Colesterol/metabolismo , Enterócitos/metabolismo , Humanos , Intestino Delgado/cirurgia , Macrófagos do Fígado/imunologia , Macrófagos do Fígado/metabolismo , Receptores de Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/metabolismo , Lipoproteínas HDL3/sangue , Fígado/patologia , Cirrose Hepática/patologia , Cirrose Hepática/prevenção & controle , Hepatopatias/patologia , Receptores X do Fígado/metabolismo , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Ligação Proteica , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo
3.
Braz J Med Biol Res ; 54(10): e11035, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34378675

RESUMO

In this eight-year retrospective study, we evaluated the associations between climatic variations and the biological rhythms in plasma lipids and lipoproteins in a large population of Campinas, São Paulo state, Brazil, as well as temporal changes of outcomes of cardiovascular hospitalizations. Climatic variables were obtained at the Center for Meteorological and Climatic Research Applied to Agriculture (University of Campinas - Unicamp, Brazil). The plasma lipid databases surveyed were from 27,543 individuals who had their lipid profiles assessed at the state university referral hospital in Campinas (Unicamp). The frequency of hospitalizations was obtained from the Brazilian Public Health database (DATASUS). Temporal statistical analyses were performed using the methods Cosinor or Friedman (ARIMA) and the temporal series were compared by cross-correlation functions. In normolipidemic cases (n=11,892), significantly different rhythmicity was observed in low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol (C) both higher in winter and lower in summer. Dyslipidemia (n=15,651) increased the number and amplitude of lipid rhythms: LDL-C and HDL-C were higher in winter and lower in summer, and the opposite occurred with triglycerides. The number of hospitalizations showed maximum and minimum frequencies in winter and in summer, respectively. A coincident rhythmicity was observed of lower temperature and humidity rates with higher plasma LDL-C, and their temporal series were inversely cross-correlated. This study shows for the first time that variations of temperature, humidity, and daylight length were strongly associated with LDL-C and HDL-C seasonality, but moderately to lowly associated with rhythmicity of atherosclerotic outcomes. It also indicates unfavorable cardiovascular-related changes during wintertime.


Assuntos
Doenças Cardiovasculares/epidemiologia , Clima , Lipídeos , Lipoproteínas , Brasil/epidemiologia , HDL-Colesterol/sangue , Humanos , Lipídeos/sangue , Lipoproteínas/sangue , Periodicidade , Estudos Retrospectivos , Estações do Ano , Triglicerídeos/sangue
4.
Nutrients ; 13(8)2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34444691

RESUMO

The aim of the report was to evaluate the impact of soy protein containing isoflavones and soy isoflavones extract on lipid profile in postmenopausal women, as compared with placebo or protein of milk, casein or isolated soy protein with or without trace isoflavone content. We used the following databases: MEDLINE (PubMed), EMBASE and the Cochrane Library. Quantitative data synthesis was performed by applying a random-effects model. Subgroup analysis and meta-regression were performed to assess the modifiers of treatment response. In total, in the analysis studies, 2305 postmenopausal women took part. Changes in the lipid profile showed statistically significant decreases of total cholesterol by -0.12 (95% CI: -0.21, -0.03) mmol/L, -4.64 (95% CI: -8.12, -1.16) mg/dL, p = 0.01 and increased HDL-cholesterol by 0.03 (95% CI: 0.00, 0.06) mmol/L, 1.15 (95% CI: 0.00, 1.93) mg/dL, p = 0.05, as well as in LDL-cholesterol -0.05 (95% CI: -0.11, 0.01) mmol/L, -1.93 (95% CI: -4.25, 0.39) mg/dL, p = 0.08 and triacylglycerols -0.07 (95% CI: -0.14, 0.00) mmol/L, -6.123 (95% CI: -12.25, 0.00) mg/dL, p = 0.06. Our results suggests that soy and its isoflavones can be effective in correction changes in lipid metabolism in postmenopausal women and may favorably influence in preventing cardiovascular events.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Lipídeos/sangue , Extratos Vegetais/administração & dosagem , Pós-Menopausa/sangue , Proteínas de Soja/administração & dosagem , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Isoflavonas/administração & dosagem , Metabolismo dos Lipídeos/efeitos dos fármacos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Triglicerídeos/sangue
5.
Am J Clin Dermatol ; 22(5): 693-707, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34406619

RESUMO

BACKGROUND: Pivotal phase III studies demonstrated that abrocitinib, an oral, once-daily, JAK1-selective inhibitor, is effective treatment for moderate-to-severe atopic dermatitis (AD) as monotherapy and in combination with topical therapy. OBJECTIVE: The aim of this study was to evaluate the long-term safety of abrocitinib 200 mg and 100 mg in an integrated analysis of a phase IIb study, four phase III studies, and one long-term extension study. METHODS: Two cohorts were analyzed: a placebo-controlled cohort from 12- to 16-week studies and an all-abrocitinib cohort including patients who received one or more abrocitinib doses. Adverse events (AEs) of interest and laboratory data are reported. RESULTS: Total exposure in the all-abrocitinib cohort (n = 2856) was 1614 patient-years (PY); exposure was ≥ 24 weeks in 1248 patients and ≥ 48 weeks in 606 (maximum 108 weeks). In the placebo-controlled cohort (n = 1540), dose-related AEs (200 mg, 100 mg, placebo) were nausea (14.6%, 6.1%, 2.0%), headache (7.8%, 5.9%, 3.5%), and acne (4.7%, 1.6%, 0%). Platelet count was reduced transiently in a dose-dependent manner; 2/2718 patients (200-mg group) had confirmed platelet counts of < 50 × 103/mm3 at week 4. Incidence rates (IRs) were 2.33/100PY and 2.65/100 PY for serious infection, 4.34/100PY and 2.04/100PY for herpes zoster, and 11.83/100PY and 8.73/100PY for herpes simplex in the 200-mg and 100-mg groups, respectively. IRs for nonmelanoma skin cancer, other malignancies, and major adverse cardiovascular events were < 0.5/100PY for both doses. Five venous thromboembolism events occurred (IR 0.30/100PY), all in the 200-mg group. There were three deaths due to gastric carcinoma (diagnosed at day 43), sudden death, and COVID-19. CONCLUSION: Abrocitinib, with proper patient and dose selection, has a manageable tolerability and longer-term safety profile appropriate for long-term use in patients with moderate-to-severe AD. TRIAL REGISTRIES: ClinicalTrials.gov: NCT02780167, NCT03349060, NCT03575871, NCT03720470, NCT03627767, NCT03422822.


Assuntos
Dermatite Atópica/tratamento farmacológico , Infecções/epidemiologia , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/efeitos adversos , Neoplasias Cutâneas/epidemiologia , Sulfonamidas/efeitos adversos , Acne Vulgar/induzido quimicamente , Adolescente , Adulto , Idoso , Doenças Cardiovasculares/epidemiologia , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Cefaleia/induzido quimicamente , Herpes Simples/epidemiologia , Herpes Zoster/epidemiologia , Humanos , Incidência , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Contagem de Plaquetas , Inibidores de Proteínas Quinases/administração & dosagem , Pirimidinas/administração & dosagem , Fatores de Risco , Sulfonamidas/administração & dosagem , Fatores de Tempo , Tromboembolia Venosa/epidemiologia , Adulto Jovem
6.
Molecules ; 26(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34361788

RESUMO

This research investigated a UPLC-QTOF/ESI-MS-based phytochemical profiling of Combretum indicum leaf extract (CILEx), and explored its in vitro antioxidant and in vivo antidiabetic effects in a Long-Evans rat model. After a one-week intervention, the animals' blood glucose, lipid profile, and pancreatic architectures were evaluated. UPLC-QTOF/ESI-MS fragmentation of CILEx and its eight docking-guided compounds were further dissected to evaluate their roles using bioinformatics-based network pharmacological tools. Results showed a very promising antioxidative effect of CILEx. Both doses of CILEx were found to significantly (p < 0.05) reduce blood glucose, low-density lipoprotein (LDL), and total cholesterol (TC), and increase high-density lipoprotein (HDL). Pancreatic tissue architectures were much improved compared to the diabetic control group. A computational approach revealed that schizonepetoside E, melianol, leucodelphinidin, and arbutin were highly suitable for further therapeutic assessment. Arbutin, in a Gene Ontology and PPI network study, evolved as the most prospective constituent for 203 target proteins of 48 KEGG pathways regulating immune modulation and insulin secretion to control diabetes. The fragmentation mechanisms of the compounds are consistent with the obtained effects for CILEx. Results show that the natural compounds from CILEx could exert potential antidiabetic effects through in vivo and computational study.


Assuntos
Antioxidantes/farmacologia , Combretum/química , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Arbutina/química , Arbutina/isolamento & purificação , Sítios de Ligação , Glicemia/efeitos dos fármacos , HDL-Colesterol/agonistas , HDL-Colesterol/sangue , LDL-Colesterol/antagonistas & inibidores , LDL-Colesterol/sangue , Biologia Computacional/métodos , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Flavonoides/química , Flavonoides/isolamento & purificação , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Insulina/agonistas , Insulina/metabolismo , Masculino , Modelos Moleculares , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Pâncreas/patologia , Extratos Vegetais/química , Folhas de Planta/química , Ligação Proteica , Conformação Proteica , Ratos , Ratos Long-Evans , Triterpenos/química , Triterpenos/isolamento & purificação
7.
Nutrients ; 13(8)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34444711

RESUMO

Cardiovascular disease (CVD) is a major contributor to the global burden of disease. Berberine, a long-standing, widely used, traditional Chinese medicine, is thought to have beneficial effects on CVD risk factors and in women with polycystic ovary syndrome. The mechanisms and effects, specifically in men, possibly via testosterone, have not been examined previously. To assess the effect of berberine on CVD risk factors and any potential pathway via testosterone in men, we conducted a randomized, double-blind, placebo-controlled, parallel trial in Hong Kong. In total, 84 eligible Chinese men with hyperlipidemia were randomized to berberine (500 mg orally, twice a day) or placebo for 12 weeks. CVD risk factors (lipids, thromboxane A2, blood pressure, body mass index and waist-hip ratio) and testosterone were assessed at baseline, and 8 and 12 weeks after intervention. We compared changes in CVD risk factors and testosterone after 12 weeks of intervention using analysis of variance, and after 8 and 12 weeks using generalized estimating equations (GEE). Of the 84 men randomized, 80 men completed the trial. Men randomized to berberine had larger reductions in total cholesterol (-0.39 mmol/L, 95% confidence interval (CI) -0.70 to -0.08) and high-density lipoprotein cholesterol (-0.07 mmol/L, 95% CI -0.13 to -0.01) after 12 weeks. Considering changes after 8 and 12 weeks together, berberine lowered total cholesterol and possibly low-density lipoprotein-cholesterol (LDL-c), and possibly increased testosterone. Changes in triglycerides, thromboxane A2, blood pressure, body mass index and waist-hip ratio after the intervention did not differ between the berberine and placebo groups. No serious adverse event was reported. Berberine is a promising treatment for lowering cholesterol. Berberine did not lower testosterone but instead may increase testosterone in men, suggesting sex-specific effects of berberine. Exploring other pathways and assessing sex differences would be worthwhile, with relevance to drug repositioning and healthcare.


Assuntos
Berberina/uso terapêutico , Colesterol/sangue , Fatores de Risco de Doenças Cardíacas , Adulto , Anticolesterolemiantes/administração & dosagem , Anticolesterolemiantes/efeitos adversos , Anticolesterolemiantes/uso terapêutico , Berberina/administração & dosagem , Berberina/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Índice de Massa Corporal , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Método Duplo-Cego , Humanos , Hiperlipidemias/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Testosterona/sangue , Tromboxano A2/sangue , Triglicerídeos/sangue , Relação Cintura-Quadril
8.
Lancet HIV ; 8(8): e463-e473, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34358497

RESUMO

BACKGROUND: Simplified antiretroviral therapy (ART) regimens are desirable for people with HIV. We investigated the efficacy and safety of switching from triple ART to dual dolutegravir plus lamivudine therapy. METHODS: DOLAM is a phase 4, randomised, open-label, non-inferiority trial, done at six HIV clinics in Catalonia, Spain. Adults with HIV-1 receiving a triple ART regimen, aged 18 years or older, with virological suppression, a CD4 nadir of at least 200 cells per µL, who were HBsAg-negative, and without previous viral failure or resistance mutations to study drugs were eligible. Participants underwent computer-generated randomisation, stratified by the class of the third drug, and were assigned (1:1) to switch to oral dolutegravir 50 mg and lamivudine 300 mg once daily or to continue triple ART for 48 weeks. The primary endpoint was the proportion of people with an HIV RNA value of at least 50 copies per mL at week 48 (US Food and Drug Administration snapshot algorithm, 8% non-inferiority margin). Both the primary and safety outcomes were evaluated in the intention-to-treat exposed population. The study is completed and was registered with EudraCT 201500027435. FINDINGS: Between July 7, 2015, and Oct 31, 2018, 265 participants were randomly assigned to switch to dolutegravir plus lamivudine (n=131) or to maintain triple ART (n=134) and all received at least one dose. Nine (7%) participants in the dual therapy group and ten (7%) in the triple therapy group were excluded before 48 weeks, mostly due to treatment discontinuations or virological failure. Participants were predominantly male (116 [87%] of 134 in the triple ART group and 111 [85%] of 131 in the dolutegravir plus lamivudine group). The difference in the proportion of participants with HIV RNA values of at least 50 copies per mL at 48 weeks between the dual therapy group (three [2%] of 131) and triple therapy group (two [1%] of 134) was 0·8 percentage points (95% CI -3·3 to 5·2), showing non-inferiority of dolutegravir plus lamivudine dual therapy compared with triple ART. 73 (56%) of 131 participants allocated to dual therapy had 150 adverse effects, compared with 78 (58%) of 134 participants allocated to triple therapy who also had 150 adverse events (p=0·68). Drug discontinuation due to adverse effects occurred in four people in the triple therapy group and three people in the dual therapy group. INTERPRETATION: Our findings show the efficacy and safety of dolutegravir plus lamivudine as a simplified therapy switch option for selected people with HIV with virological suppression on triple ART. FUNDING: Instituto de Salud Carlos III, Red de Investigación en Sida, and ViiV Healthcare.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Lamivudina/administração & dosagem , Oxazinas/administração & dosagem , Piperazinas/administração & dosagem , Piridonas/administração & dosagem , Adulto , Fármacos Anti-HIV/efeitos adversos , HDL-Colesterol/sangue , Quimioterapia Combinada , Feminino , Infecções por HIV/virologia , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Lamivudina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Oxazinas/efeitos adversos , Piperazinas/efeitos adversos , Piridonas/efeitos adversos
9.
Nutrients ; 13(7)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209930

RESUMO

High-density lipoproteins (HDL) maintain cholesterol homeostasis through the role they play in regulating reverse cholesterol transport (RCT), a process by which excess cholesterol is transported back to the liver for elimination. However, RCT can be altered in the presence of cardiovascular risk factors, such as aging, which contributes to the increase in the incidence of cardiovascular diseases (CVD). The present study was aimed at investigating the effect of extra virgin olive oil (EVOO) intake on the cholesterol efflux capacity (CEC) of HDL, and to elucidate on the mechanisms by which EVOO intake improves the anti-atherogenic activity of HDL. A total of 84 healthy women and men were enrolled and were distributed, according to age, into two groups: 27 young (31.81 ± 6.79 years) and 57 elderly (70.72 ± 5.6 years) subjects. The subjects in both groups were given 25 mL/d of extra virgin olive oil (EVOO) for 12 weeks. CEC was measured using J774 macrophages radiolabeled with tritiated cholesterol ((3H) cholesterol). HDL subclass distributions were analyzed using the Quantimetrix Lipoprint® system. The HDL from the elderly subjects exhibited a lower level of CEC, at 11.12% (p < 0.0001), than the HDL from the young subjects. The CEC of the elderly subjects returned to normal levels following 12 weeks of EVOO intake. An analysis of the distribution of HDL subclasses showed that HDL from the elderly subjects were composed of lower levels of large HDL (L-HDL) (p < 0.03) and higher levels of small HDL (S-HDL) (p < 0.002) compared to HDL from the young subjects. A multiple linear regression analysis revealed a positive correlation between CEC and L-HDL levels (r = 0.35 and p < 0.001) as well as an inverse correlation between CEC and S-HDL levels (r = -0.27 and p < 0.01). This correlation remained significant even when several variables, including age, sex, and BMI as well as low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and glucose levels (ß = 0.28, p < 0.002, and ß = 0.24, p = 0.01) were accounted for. Consuming EVOO for 12 weeks modulated the age-related difference in the distribution of HDL subclasses by reducing the level of S-HDL and increasing the level of intermediate-HDL/large-HDL (I-HDL/L-HDL) in the elderly subjects. The age-related alteration of the CEC of HDL was due, in part, to an alteration in the distribution of HDL subclasses. A diet enriched in EVOO improved the functionality of HDL through an increase in I-HDL/L-HDL and a decrease in S-HDL.


Assuntos
Envelhecimento/sangue , Aterosclerose/prevenção & controle , Doenças Cardiovasculares/prevenção & controle , Lipoproteínas HDL/sangue , Azeite de Oliva/administração & dosagem , Adulto , Idoso , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Voluntários Saudáveis , Humanos , Masculino
10.
Nutrients ; 13(7)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202690

RESUMO

We aimed to investigate if a home meal replacement (HMR), designed with a low ω-6/ω-3 fatty acid ratio, improves cardiometabolic parameters, including metabolic syndrome (MetS) in obese individuals. We conducted a monocentric, controlled, randomized crossover trial. The HMR contains higher protein and fat content, lower carbohydrate content, and a lower ω6FA/ω3FA ratio than the regular diet. Sixty-four participants were randomized into two groups and switched to the other group following a 4-week intervention. While subjects in the HMR group were provided three HMRs daily, those in the control group were requested to maintain their regular dietary pattern. We conducted paired t-tests, repeated measures analysis of variance, and McNemar tests before and after the intervention. Body mass index (BMI) and weight were lower in the HMR group after adjusting for age, sex, and total energy intake and significantly changed in the between-group differences. The waist circumference, systolic blood pressure, triglycerides, triglyceride-glucose index, and triglyceride to high-density lipoprotein cholesterol ratio were reduced in the HMR group (all p < 0.05). The percentage of subjects with MetS significantly decreased from 39.1% at baseline to 28.1% post-intervention (p = 0.035). Using the HMR for 4 weeks reduced the BMI, weight, and MetS prevalence in individuals with obesity. This trial was registered at clinicaltrials.gov (NCT04552574).


Assuntos
Dieta Rica em Proteínas e Pobre em Carboidratos/métodos , Síndrome Metabólica/dietoterapia , Obesidade/dietoterapia , Adulto , Glicemia/análise , Pressão Sanguínea , Índice de Massa Corporal , Peso Corporal , Fatores de Risco Cardiometabólico , HDL-Colesterol/sangue , Estudos Cross-Over , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-6/administração & dosagem , Feminino , Humanos , Masculino , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/etiologia , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/fisiopatologia , Prevalência , Resultado do Tratamento , Triglicerídeos/sangue , Circunferência da Cintura
11.
Nutrients ; 13(7)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202823

RESUMO

Little is known about which currently available a priori dietary indexes provide best guidance for reducing cardiometabolic risk factors (CMRF) among hyperlipidemic patients. This study was designed to compare the associations between four a priori dietary indexes, including Diet Balance Index (DBI-16), Chinese Healthy Eating Index (CHEI), Mediterranean Diet Score (MDS) and Dietary Approaches to Stop Hypertension (DASH) and CMRF among hyperlipidemic patients. A total of 269 participants were enrolled into the cross-sectional study. DBI-16, CHEI, MDS, and DASH scores were calculated using established methods. CMRF was measured using standard methods. DBI-total scores (DBI-TS) were inversely associated with triglyceride concentrations and TC:HDL-C ratio, and positively associated with HDL-C and ApoA1 concentrations (all p < 0.05), while the results for DBI-low bound scores (DBI-LBS) were opposite. DBI-high bound scores (DBI-HBS) and DASH scores were positively and inversely associated with glucose concentrations, respectively (both p < 0.05). Higher diet quality distance (DQD) was positively associated with higher TC, LDL-C and ApoB concentrations, and TC:HDL-C and LDL-C:HDL-C ratios, and lower HDL-C and ApoA1 concentrations and ApoA1:ApoB ratio (all p < 0.05). CHEI scores were inversely associated with triglyceride concentrations (p = 0.036). None of the dietary indexes was associated with blood pressures. DBI-16 provided most comprehensive evaluations of the overall diet quality and balance for optimizing cardiometabolic health among hyperlipidemic individuals.


Assuntos
Dieta Saudável/métodos , Hiperlipidemias/dietoterapia , Avaliação Nutricional , Apolipoproteína A-I/sangue , Fatores de Risco Cardiometabólico , HDL-Colesterol/sangue , Estudos Transversais , Dieta Mediterrânea/estatística & dados numéricos , Abordagens Dietéticas para Conter a Hipertensão/estatística & dados numéricos , Método Duplo-Cego , Feminino , Humanos , Hiperlipidemias/sangue , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes , Triglicerídeos/sangue
12.
Front Endocrinol (Lausanne) ; 12: 611526, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34248834

RESUMO

Background: It has been reported that dyslipidemia is related to coronavirus-related diseases. Critical patients with coronavirus disease 2019 (COVID-19) who suffered from multiple organ dysfunctions were treated in the intensive care unit (ICU) in Wuhan, China. Whether the lipids profile was associated with the prognosis of COVID-19 in critical patients remained unclear. Methods: A retrospective study was performed in critical patients (N=48) with coronavirus disease 2019 in Leishenshan hospital between February and April 2020 in Wuhan. The parameters including lipid profiles, liver function, and renal function were collected on admission day, 2-3days after the admission, and the day before the achievement of clinical outcome. Results: Albumin value and creatine kinase (ck) value were statistically decreased at 2-3 days after admission compared with those on admission day (P<0.05). Low density lipoprotein (LDL-c), high density lipoprotein (HDL-c), apolipoprotein A (ApoA), and apolipoprotein A (Apo B) levels were statistically decreased after admission (P<0.05). Logistic regression showed that HDL-c level both on admission day and the day before the achievement of clinical outcome were negatively associated with mortality in critical patients with COVID-19. Total cholesterol (TC) level at 2-3days after admission was related to mortality in critical patients with COVID-19. Conclusions: There were lipid metabolic disorders in the critical patients with COVID-19. Lower levels of HDL-c and TC were related to the progression of critical COVID-19.


Assuntos
COVID-19/mortalidade , Dislipidemias/epidemiologia , Mortalidade Hospitalar , Insuficiência de Múltiplos Órgãos/mortalidade , Idoso , Idoso de 80 Anos ou mais , Apolipoproteínas A/sangue , Apolipoproteínas B/sangue , COVID-19/sangue , COVID-19/epidemiologia , China/epidemiologia , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estado Terminal , Dislipidemias/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/epidemiologia , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença
13.
Arterioscler Thromb Vasc Biol ; 41(9): 2494-2508, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34233476

RESUMO

Objective: Low HDL-C (high-density lipoprotein cholesterol) is the most frequent dyslipidemia in Mexicans, but few studies have examined the underlying genetic basis. Our purpose was to identify genetic variants associated with HDL-C levels and cardiovascular risk in the Mexican population. Approach and Results: A genome-wide association studies for HDL-C levels in 2335 Mexicans, identified four loci associated with genome-wide significance: CETP, ABCA1, LIPC, and SIDT2. The SIDT2 missense Val636Ile variant was associated with HDL-C levels and was replicated in 3 independent cohorts (P=5.9×10−18 in the conjoint analysis). The SIDT2/Val636Ile variant is more frequent in Native American and derived populations than in other ethnic groups. This variant was also associated with increased ApoA1 and glycerophospholipid serum levels, decreased LDL-C (low-density lipoprotein cholesterol) and ApoB levels, and a lower risk of premature CAD. Because SIDT2 was previously identified as a protein involved in sterol transport, we tested whether the SIDT2/Ile636 protein affected this function using an in vitro site-directed mutagenesis approach. The SIDT2/Ile636 protein showed increased uptake of the cholesterol analog dehydroergosterol, suggesting this variant affects function. Finally, liver transcriptome data from humans and the Hybrid Mouse Diversity Panel are consistent with the involvement of SIDT2 in lipid and lipoprotein metabolism. Conclusions: This is the first genome-wide association study for HDL-C levels seeking associations with coronary artery disease in the Mexican population. Our findings provide new insight into the genetic architecture of HDL-C and highlight SIDT2 as a new player in cholesterol and lipoprotein metabolism in humans.


Assuntos
HDL-Colesterol/sangue , Doença da Artéria Coronariana/genética , Hiperlipoproteinemia Tipo II/genética , Proteínas de Transporte de Nucleotídeos/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idade de Início , Animais , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Modelos Animais de Doenças , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Células HEK293 , Fatores de Risco de Doenças Cardíacas , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiologia , Masculino , Análise da Randomização Mendeliana , México/epidemiologia , Camundongos , Pessoa de Meia-Idade , Proteínas de Transporte de Nucleotídeos/metabolismo , Fenótipo , Medição de Risco
14.
Clin Nutr ESPEN ; 44: 437-444, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34330502

RESUMO

BACKGROUND & AIMS: Coronavirus disease 2019 (COVID-19) patients with severe complications have shown comorbidities with cardiovascular-disease, hypertension and type 2 diabetes mellitus; clinical disorders that share the common metabolic alterations of insulin resistance and dyslipidaemia. A high triglyceride to high density lipoprotein cholesterol (Tg/HDL c) ratio has been associated with reduced insulin sensitivity, metabolic syndrome and adverse cardiovascular events. Our aim in this study was to determine the association between different components of the lipid profile and particularly the Tg/HDL c ratio with severe complications like the requirement of invasive mechanical ventilation in COVID-19 patients. METHODS: We collected demographic, clinical and biochemical data to conduct a cohort study in 43 adult patients with confirmed COVID-19 diagnosis by quantitative polymerase chain reaction (qPCR) at baseline and in the subsequent 15 days. Patients were subjected to a very similar treatment scheme with the JAK1/2 inhibitor ruxolitinib. Descriptive statistics, variable association and logistic regression were applied to identify predictors of disease severity among elements and calculations from the lipid profile. RESULTS: Patients were aged 57 ± 14 years; 55.8% were male from which 75% required hospitalization and 44.2% were female who 58% were hospitalized. The most common comorbidities were type 2 diabetes mellitus (58%) and hypertension (40%). Hospitalized and critical care patients showed lower HDL c blood levels and increased Tg/HDL c ratio than those with outpatient management and mild/asymptomatic COVID-19. Tg/HDL c ratio correlated with variables of disease severity such as lactate dehydrogenase (LDH) levels (r = 0.356; p < 0.05); National Early Warning Score 2 (NEWS 2) (r = 0.495; p < 0.01); quick sequential organ failure assessment (qSOFA) (r = 0.538; p < 0.001); increased need of oxygen support (r = 0.447; p < 0.01) and requirement of mechanical ventilation (r = 0.378; p < 0.05). Tg/HDL c ratio had a negative correlation with partial oxygen saturation/fraction of inspired oxygen (SaO 2/FiO2) ratio (r = -0.332;p < 0.05). Linear regression analysis showed that Tg/HDL c ratio can predict increases in inflammatory factors like LDH (p < 0.01); ferritin (p < 0.01) and D-dimer (p < 0.001). Logistic regression model indicated that ≥7.45 Tg/HDL c ratio predicts requirement of invasive mechanical ventilation (OR 11.815, CI 1.832-76.186, p < 0.01). CONCLUSIONS: The Tg/HDLc ratio can be used as an early biochemical marker of COVID-19 severe prognosis with requirement of invasive mechanical ventilation.


Assuntos
COVID-19/sangue , COVID-19/patologia , HDL-Colesterol/sangue , Triglicerídeos/sangue , Biomarcadores/sangue , Estudos de Coortes , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Valor Preditivo dos Testes , SARS-CoV-2 , Índice de Gravidade de Doença
15.
Nutrients ; 13(7)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203181

RESUMO

BACKGROUND: Observationally plasma apolipoprotein E (apoE) is positively associated with ischemic heart disease (IHD). A Mendelian randomization (MR) study suggesting apoE is unrelated to cardiovascular mortality did not consider specific isoforms. We used MR to obtain estimates of plasma apoE2, apoE3 and apoE4 on IHD, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, triglycerides and apolipoprotein B (apoB). METHODS: We obtained independent genetic instruments from proteome genome-wide association studies (GWAS) and applied them to large outcome GWAS. We used univariable MR to assess the role of each isoform and multivariable MR to assess direct effects. RESULTS: In univariable MR, apoE4 was positively associated with IHD (odds ratio (OR) 1.05, 95% confidence interval (CI) 1.01 to 1.09), but apoE2 and apoE3 were less clearly associated. Using multivariable MR an association of apoE2 with IHD (OR 1.16, 95% CI 0.98 to 1.38) could not be excluded, and associations of apoE3 and apoE4 with IHD were not obvious. In univariable MR, apoE2 and apoE4 were positively associated with apoB, and a positive association of apoE2 with LDL cholesterol could not be excluded. Using multivariable MR apoE2 was positively associated with LDL cholesterol, and associations with apoB could not be excluded. After adjusting for apoB, no direct effects of apoE isoforms on IHD were evident. CONCLUSIONS: Plasma apoE2 and apoE4 may play a role in lipid modulation and IHD. Whether apoE could be a potential therapeutic target requires further clarification when larger genetic studies of apoE isoforms are available.


Assuntos
Apolipoproteínas E/sangue , Isquemia Miocárdica/sangue , Adulto , Apolipoproteína E2/sangue , Apolipoproteína E2/genética , Apolipoproteína E3/sangue , Apolipoproteína E3/genética , Apolipoproteína E4/sangue , Apolipoproteína E4/genética , Apolipoproteínas B/sangue , Apolipoproteínas B/genética , Apolipoproteínas E/genética , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Estudo de Associação Genômica Ampla , Humanos , Lipídeos/sangue , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Isoformas de Proteínas , Triglicerídeos
16.
J Clin Lab Anal ; 35(8): e23911, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34260764

RESUMO

BACKGROUND: Dyslipidemia has been observed in patients with coronavirus disease 2019 (COVID-19). This study aimed to investigate blood lipid profiles in patients with COVID-19 and to explore their predictive values for COVID-19 severity. METHODS: A total of 142 consecutive patients with COVID-19 were included in this single-center retrospective study. Blood lipid profile characteristics were investigated in patients with COVID-19 in comparison with 77 age- and gender-matched healthy subjects, their predictive values for COVID-19 severity were analyzed by using multivariable logistic regression analysis, and their prediction efficiencies were evaluated by using receiver operator characteristic (ROC) curves. RESULTS: There were 125 and 17 cases in the non-severe and severe groups, respectively. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein A1 (ApoA1) gradually decreased across the groups in the following order: healthy controls, non-severe group, and severe group. ApoA1 was identified as an independent risk factor for COVID-19 severity (adjusted odds ratio [OR]: 0.865, 95% confidence interval [CI]: 0.800-0.935, p < 0.001), along with interleukin-6 (IL-6) (adjusted OR: 1.097, 95% CI: 1.034-1.165, p = 0.002). ApoA1 exhibited the highest area under the ROC curve (AUC) among all single markers (AUC: 0.896, 95% CI: 0.834-0.941); moreover, the risk model established using ApoA1 and IL-6 enhanced prediction efficiency (AUC: 0.977, 95% CI: 0.932-0.995). CONCLUSION: Blood lipid profiles in patients with COVID-19 are quite abnormal compared with those in healthy subjects, especially in severe cases. Serum ApoA1 may represent a good indicator for predicting the severity of COVID-19.


Assuntos
Apolipoproteína A-I/sangue , COVID-19/etiologia , Adulto , Idoso , Área Sob a Curva , Biomarcadores/sangue , COVID-19/sangue , COVID-19/epidemiologia , Estudos de Casos e Controles , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Comorbidade , Feminino , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença
17.
Clin Biochem ; 95: 60-65, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34097878

RESUMO

OBJECTIVE: Coronary artery disease (CAD) as an important cause of morbidity and mortality globally. The scavenger receptor class B type 1 (SCARB1) plays an essential role in the reverse cholesterol transport. We have explored the association between a genetic variant, rs5888, in the SCARB1 gene with CAD and serum HDL-C levels. METHODS: Patients were categorized into two groups' angiogram positive (>50% coronary stenosis) and angiogram negative (<50% coronary stenosis). Genotyping was carried out using polymerase chain reaction-amplification refractory mutation system. The association between the SNP rs5888 and serum HDL-C was analyzed using a logistic regression model. RESULTS: The results showed that the subjects carrying a T allele was associated with a decreased serum HDL-C levels compared to the C allele in total population (p < 0.001). The risk of angiogram positivity in subjects carrying a T allele was 3.1-fold higher than for the control group (p < 0.001). CONCLUSION: CVD patients carrying the T allele of rs5888 variant in the SCARB1 gene was associated with decreased serum level of HDL.


Assuntos
Uso do Códon/genética , Doença da Artéria Coronariana/genética , Receptores Depuradores Classe B/genética , Adulto , Idoso , Estudos de Casos e Controles , HDL-Colesterol/sangue , Doença da Artéria Coronariana/sangue , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Receptores Depuradores Classe B/química
18.
Artigo em Inglês | MEDLINE | ID: mdl-34065252

RESUMO

The protective role of high high-density lipoprotein cholesterol (HDL-C) against cardiovascular risk has been questioned recently. Due to the increasing trend of cardiovascular diseases (CVD) in Tunisia, this study aimed to determine the prevalence of high HDL-C and its associated factors in Tunisian women of childbearing age. A cross-sectional survey was conducted among a subsample of 1689 women, aged 20 to 49 years, in the Great Tunis region. Data on socio-demographic and lifestyle factors were collected by a questionnaire. Overall adiposity was assessed by body mass index (BMI). All biological variables were assayed in blood samples coated with anticoagulant ethylene diamine tetra acetic acid (EDTA) by enzymatic methods. Stata software (2015) was used for data management and statistical analysis. High HDL-C values were recorded in 26.6% of selected women. After adjustment for all socio-demographic and lifestyle factors, age, hypertension, and smoking were negatively associated with high HDL-C levels, while family history of cancer was positively associated with high HDL-C in women. An additional investigation on the relationship between high HDL-C and cancer risk should be performed due to controversial results.


Assuntos
Doenças Cardiovasculares , HDL-Colesterol/sangue , Hiperlipidemias/epidemiologia , Adulto , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Tunísia/epidemiologia , Adulto Jovem
19.
J Clin Hypertens (Greenwich) ; 23(7): 1399-1404, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34092020

RESUMO

Dyslipidemia is an emerging disease in China, especially in the presence of hypertension and diabetes mellitus. We investigated the association of dyslipidemia with the use of antihypertensive and antidiabetic agents. The study participants (n = 2423) were hypertensive and diabetic patients enrolled in a China nationwide registry. Serum mean ± (SD, except for serum triglycerides, median [interquatile range]) concentrations were 1.38 (0.97-2.02) mmol/L, 4.85 ± 1.12 mmol/L, 1.30 ± 0.36 mmol/L, and 2.89 ± 0.92 mmol/L for triglycerides and total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol, respectively. The prevalence of dyslipidemia was 18.9%, 13.5%, 16.6%, and 37.7% for hypertriglyceridemia (serum triglycerides ≥2.3 mmol/L), hypercholesterolemia (total cholesterol ≥6.2 mmol/L or LDL cholesterol ≥4.1 mmol/L), low HDL cholesterol (HDL cholesterol <1.0 mmol/L), and any of the three lipid disorders, respectively. Treated (n = 1647), compared with untreated hypertensive patients (n = 303), had a significantly (P ≤ .0006) lower serum total, LDL, and HDL cholesterol, but similar serum triglycerides (P = .20). Treated (n = 1325), compared with untreated diabetic patients (n = 238), had a significantly (P ≤ .004) lower serum triglycerides, and total and LDL cholesterol, but similar serum HDL cholesterol (P = .81). After adjustment, the odds ratios (OR) were significant for hypercholesterolemia (OR 0.76, 95% confidence interval [CI] 0.58-0.997, P = .048) and low HDL cholesterol (OR 1.56, CI 1.19-2.03, P = .001) in treated versus untreated hypertension, and for low HDL cholesterol (OR 1.50, CI 1.18-1.89, P = .0008) in treated versus untreated diabetes. In conclusion, the prevalence of dyslipidemia differed between treated and untreated hypertension and diabetes.


Assuntos
Anti-Hipertensivos/uso terapêutico , Diabetes Mellitus , Dislipidemias , Hipertensão , Hipoglicemiantes/uso terapêutico , China/epidemiologia , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Dislipidemias/tratamento farmacológico , Dislipidemias/epidemiologia , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Triglicerídeos/sangue
20.
Pan Afr Med J ; 38: 292, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34178211

RESUMO

Introduction: there is an association between hypogonadism and obesity, chronic hyperglycaemia, and ageing in men with type 2 diabetes mellitus (T2DM). T2DM is known to be associated with low testosterone. There is a paucity of data on the risk factors of hypogonadism in Nigerian men with T2DM. The objective of this study was to determine the clinical and biochemical correlates of hypogonadism and clinical predictors of low total testosterone levels in men with T2DM. Methods: this was a cross-sectional study consisting of 358 men with T2DM and 179 non-diabetic men (controls). Structured Androgen Deficiency in the Ageing Male questionnaire was administered. Clinical and biochemical parameters were measured. Free testosterone was calculated from albumin, SHBG and total testosterone using Vermeulen´s method. Hypogonadism was defined as fasting TT as < 8 nmol/L with or without symptoms or TT of 8-12 nmol/L with symptoms of androgen deficiency. Low testosterone was defined as serum total testosterone levels ≤ 12 nmol/L. Results: the mean (±SD) total testosterone of men with T2DM and controls were 8.79±3.35 nmol/L and 15.41±3.79 nmol/L respectively (p < 0.001). The risk of hypogonadism was associated with central obesity (Odds ratio [OR] 2.24, 95% confidence interval [CI] 0.38-13.07), systolic hypertension (OR 3.93, 95% CI 0.67-23.10), hyperglycaemia (OR 2.48, 95% CI 0.37-16.46) and hypercholesterolaemia (OR 2.50, 95% CI 0.43-14.61). In a multivariable regression analysis, there was a significant negative correlation between total testosterone and triglycerides (r -1.85, 95% CI -3.58 - 0.12, P = 0.04) and HDL cholesterol (r -1.25, 95% CI -5.95-3.45, P = 0.02). Conclusion: this study shows that in men with T2DM, triglycerides and HDL cholesterol are independent correlates of hypogonadism but not central adiposity, systolic blood pressure and glycaemia. Further large prospective studies are recommended.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Hipogonadismo/etiologia , Obesidade/complicações , Testosterona/sangue , Adulto , Envelhecimento , Glicemia/metabolismo , HDL-Colesterol/sangue , Estudos Transversais , Humanos , Hipogonadismo/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários , Triglicerídeos/sangue
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