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1.
Nutr Metab Cardiovasc Dis ; 31(10): 2766-2778, 2021 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-34353704

RESUMO

AIMS: The DASH diet was designed for helping control of blood pressure but, fortunately, it can also be prescribed for many other chronic conditions. The current study intended to assess the potential effects of DASH diet on metabolic risk factors in patients with chronic disease. DATA SYNTHESIS: We carried out a systematic literature search for RCTs from inception until July 2020. A total of 54 clinical trials were included in the final analysis. Compared to control groups, a significant lower effect of the DASH diet was noted for body weight (-1.59 kg; p < 0.001), BMI (-0.64 kg/m2; p < 0.001), and WC (-1.93 cm; p < 0.001) as well as for SBP (-3.94 mmHg; p < 0.001) and DBP (-2.44 mmHg; P < 0.001). The DASH diet significantly decreased TC (-5.12 mg/dl; p = 0.008) and LDL-C levels (-3.53 mg/dl; p = 0.041), but not HDL-C (0.30 mg/dl; p = 0.510), TG (-4.22 mg/dl; p = 0.067), and VLDL-C (-2.16 mg/dl; p = 0.062). No significant effect of the DASH diet was noted for blood glucose (-0.38 mg/dl; p = 0.216), insulin (-0.03 µIU/mL; p = 0.817), HOMA-IR (-0.15; p = 0.132), and CRP (-0.33 mg/l; p = 0.173). CONCLUSIONS: The DASH diet is a feasible approach to weight loss and to control blood pressure and hypercholesterolemia.


Assuntos
Abordagens Dietéticas para Conter a Hipertensão , Hipercolesterolemia/dietoterapia , Hipertensão/dietoterapia , Obesidade/dietoterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Pressão Sanguínea , Fatores de Risco Cardiometabólico , Colesterol/sangue , Feminino , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/diagnóstico , Hipercolesterolemia/epidemiologia , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/epidemiologia , Obesidade/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Resultado do Tratamento , Perda de Peso , Adulto Jovem
2.
Nutr Metab Cardiovasc Dis ; 31(9): 2669-2677, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34362638

RESUMO

BACKGROUND AND AIMS: High-density lipoprotein cholesterol (HDL-C) concentration and variability are both important factors of cardiovascular disease (CVD) and mortality. We aimed to explore the associations of HDL-C and longitudinal change in HDL-C with risk of mortality. METHODS AND RESULTS: We recruited a total of 69,163 participants aged ≥40 years and had medical examination records of HDL-C during 2010-2014 from the Yinzhou District, Ningbo, China. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. We observed a non-linear association of HDL-C with risks of non-accidental and CVD mortality. Compared with the moderate concentration group (1.4-1.6 mmol/L), HDL-C <1 mmol/L was associated with a higher risk of non-accidental mortality (HR: 1.13 (95% CI: 1.01-1.27)) and both HDL-C <1 mmol/L and ≥2 mmol/L were associated with a higher risk of CVD mortality (HRs: 1.23 (95% CI: 1.01-1.50) and 1.37 (95% CI: 1.03-1.82), respectively). Compared with the stable group ([-0.1, +0.1 mmol/L]), a large decrease ([-0.5, -0.3 mmol/L]) and very large decrease (<-0.5 mmol/L) in HDL-C were associated with a higher risk of non-accidental mortality (HRs: 1.40 (95% CI: 1.21-1.63) and 1.78 (95% CI: 1.44-2.20), respectively). Similar results were observed for CVD mortality and cancer mortality. CONCLUSION: Extremely low or high HDL-C and a large decrease or very large decrease in HDL-C were associated with a higher risk of cause-specific mortality. Monitoring of HDL-C may have utility in identifying individuals at higher risk of mortality.


Assuntos
HDL-Colesterol/sangue , Dislipidemias/mortalidade , Hipercolesterolemia/mortalidade , Adulto , Idoso , Biomarcadores/sangue , China/epidemiologia , Dislipidemias/sangue , Dislipidemias/diagnóstico , Feminino , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/diagnóstico , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo
3.
Molecules ; 26(12)2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34205604

RESUMO

Rutin (R) and quercetin (Q) are two widespread dietary flavonoids. Previous studies regarding the plasma cholesterol-lowering activity of R and Q generated inconsistent results. The present study was therefore carried out to investigate the effects of R and Q on cholesterol metabolism in both HepG2 cells and hypercholesterolemia hamsters. Results from HepG2 cell experiments demonstrate that both R and Q decreased cholesterol at doses of 5 and 10 µM. R and Q up-regulated both the mRNA and protein expression of sterol regulatory element binding protein 2 (SREBP2), low-density lipoprotein receptor (LDLR), and liver X receptor alpha (LXRα). The immunofluorescence study revealed that R and Q increased the LDLR expression, while only Q improved LDL-C uptake in HepG2 cells. Results from hypercholesterolemia hamsters fed diets containing R (5.5 g/kg diet) and Q (2.5 g/kg diet) for 8 weeks demonstrate that both R and Q had no effect on plasma total cholesterol. In the liver, only Q reduced cholesterol significantly. The discrepancy between the in vitro and in vivo studies was probably due to a poor bioavailability of flavonoids in the intestine. It was therefore concluded that R and Q were effective in reducing cholesterol in HepG2 cells in vitro, whereas in vivo, the oral administration of the two flavonoids had little effect on plasma cholesterol in hamsters.


Assuntos
Colesterol/sangue , Colesterol/metabolismo , Quercetina/farmacologia , Rutina/farmacologia , Administração Oral , Animais , Linhagem Celular Tumoral , Cricetinae , Flavonoides/farmacologia , Células Hep G2 , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Receptores X do Fígado/metabolismo , Masculino , RNA Mensageiro/metabolismo , Receptores de LDL/sangue , Receptores de LDL/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Triglicerídeos/sangue , Triglicerídeos/metabolismo , Regulação para Cima/efeitos dos fármacos
4.
Biomed Pharmacother ; 139: 111668, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243630

RESUMO

Metabolic Syndrome (MetS) is a complex and multifactorial condition often characterised by obesity, hypertension, hyperlipidaemia, insulin resistance, glucose intolerance and fasting hyperglycaemia. Collectively, MetS can increase the risk of atherosclerotic-cardiovascular disease, which is the leading cause of death worldwide. However, no animal model currently exists to study MetS in the context of atherosclerosis. In this study we developed a pre-clinical mouse model that recapitulates the spectrum of MetS features while developing atherosclerosis. When BPHx mice were placed on a western type diet for 16 weeks, all the classical characteristics of MetS were observed. Comprehensive metabolic analyses and atherosclerotic imaging revealed BPHx mice to be obese and hypertensive, with elevated total plasma cholesterol and triglyceride levels, that accelerated atherosclerosis. Altogether, we demonstrate that the BPHx mouse has all the major components of MetS, and accelerates the development of atherosclerosis.


Assuntos
Aterosclerose/patologia , Dieta/efeitos adversos , Hipertensão/patologia , Síndrome Metabólica/patologia , Animais , Aterosclerose/sangue , Aterosclerose/metabolismo , Glicemia/metabolismo , Colesterol/sangue , Modelos Animais de Doenças , Feminino , Intolerância à Glucose/sangue , Intolerância à Glucose/metabolismo , Intolerância à Glucose/patologia , Hipercolesterolemia/sangue , Hipercolesterolemia/metabolismo , Hipercolesterolemia/patologia , Hiperglicemia/sangue , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Hiperlipidemias/sangue , Hiperlipidemias/metabolismo , Hiperlipidemias/patologia , Hipertensão/sangue , Hipertensão/metabolismo , Resistência à Insulina/fisiologia , Síndrome Metabólica/sangue , Síndrome Metabólica/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/sangue , Obesidade/metabolismo , Obesidade/patologia , Triglicerídeos/sangue
5.
Life Sci ; 280: 119731, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34144054

RESUMO

AIMS: Canagliflozin is an antidiabetic agent which lowers blood glucose levels by inhibiting the glucose reabsorption machinery in the proximal tubules. There have not been conducted any study on its direct impact on hypercholesterolemia and associated vascular disorders independently of blood glucose lowering activity. MATERIALS AND METHODS: Rabbits were arranged in 3 groups: Group 1 (Control): regular rabbit chow; Group 2 (HCD): 1% cholesterol-enriched chow was given to rabbits for 4 weeks; Group 3 (HCD-CANA): 1% cholesterol-enriched chow was fed to rabbits concurrently with canagliflozin (10 mg/kg/day, orally) for 4 weeks. At the end of experiment, blood and tissue samples were obtained for biochemical, histological, immunohistochemical, and vascular reactivity assessment. KEY FINDINGS: When statistically compared to Control (P < 0.05), HCD showed a significant increase in the serum triglycerides, low-density lipoprotein, total cholesterol, C-reactive protein, alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase. Furthermore, a significant decrease was seen in both liver and aortic levels of glutathione peroxidase and superoxide dismutase concurrently with a significant elevation in malondialdehyde levels. Aortic levels of nitrate/nitrite ratio were significantly elevated. Acetylcholine-induced relaxation was impaired as the Emax decreased significantly in aortae. Moreover, a significant increase was seen in the level of aortic intima/media ratio. Canagliflozin treatment significantly improved vascular function, lipid profile and inflammation and reduced liver injury. SIGNIFICANCE: Our data suggest that SGLT-2 inhibition via canagliflozin not only possesses an antihyperglycemic activity, but also improves hypercholesterolemia, vascular and liver function in dietary-induced hypercholesterolemia in the rabbit.


Assuntos
Aorta/efeitos dos fármacos , Canagliflozina/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Fígado/efeitos dos fármacos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Animais , Aorta/fisiopatologia , Colesterol na Dieta/efeitos adversos , Hipercolesterolemia/sangue , Hipercolesterolemia/etiologia , Hipercolesterolemia/fisiopatologia , Lipídeos/sangue , Fígado/fisiopatologia , Masculino , Coelhos
6.
Diabetes ; 70(8): 1807-1815, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33980690

RESUMO

After an ischemic stroke with evidence of atherosclerosis, lipid-lowering treatment with a target LDL cholesterol of <70 mg/dL compared with 100 ± 10 mg/dL reduced the risk of subsequent cardiovascular events. In this analysis, we explored the effect in the subgroup of patients with diabetes compared with the subgroup without, as well as in those with newly diagnosed diabetes. Patients with ischemic stroke in the previous 3 months or transient ischemic attack within the previous 15 days and evidence of cerebrovascular or coronary artery atherosclerosis were randomly assigned at a 1:1 ratio to a target LDL cholesterol of <70 mg/dL or 100 ± 10 mg/dL using statin or ezetimibe. The primary outcome was the composite of ischemic stroke, myocardial infarction, new symptoms requiring urgent coronary or carotid revascularization, and death resulting from vascular disease. We performed a prespecified analysis to evaluate the effect in patients with diabetes. Of 2,860 patients enrolled, 643 had diabetes at baseline, with a mean age of 66.2 years and baseline LDL cholesterol of 127 mg/dL, and were followed for a median of 3 years. The primary composite end point occurred in 27 (8.2%) of 328 patients in the lower-target group and in 44 (14.0%) of 315 patients in the higher-target group (adjusted hazard ratio [HR] 0.56; 95% CI 0.34-0.89; P = 0.016). In patients without diabetes, the HR was 0.87 (95% CI 0.66-1.14; P = 0.31; interaction P = 0.15). In those with diabetes, there were three intracranial hemorrhages in both randomization groups (0.9% vs. 1.0%, respectively). Newly diagnosed diabetes occurred in 98 (9.2%) of 1,070 and in 80 (7.4%) of 1,085 patients in the lower- and higher-target groups, respectively (HR 1.27; 95% CI 0.94-1.71; P = 0.11), and baseline higher HbA1c was the unique multivariable predictor. In conclusion, after an ischemic stroke with evidence of atherosclerosis, targeting an LDL cholesterol of <70 mg/dL compared with 100 ± 10 mg/dL consistently reduced the risk of subsequent stroke and other major vascular events in patients with and without diabetes, but the higher risk in those with diabetes yielded a higher absolute risk reduction, with number needed to treat of 17.


Assuntos
LDL-Colesterol/sangue , AVC Isquêmico/complicações , Infarto do Miocárdio/etiologia , Idoso , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Ezetimiba/uso terapêutico , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/sangue , Hipercolesterolemia/complicações , Hipercolesterolemia/tratamento farmacológico , AVC Isquêmico/sangue , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Resultado do Tratamento
7.
Aging (Albany NY) ; 13(9): 12833-12848, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33946042

RESUMO

We constructed a radiomics-clinical model to predict intraventricular hemorrhage (IVH) growth after spontaneous intracerebral hematoma. The model was developed using a training cohort (N=626) and validated with an independent testing cohort (N=270). Radiomics features and clinical predictors were selected using the least absolute shrinkage and selection operator (LASSO) method and multivariate analysis. The radiomics score (Rad-score) was calculated through linear combination of selected features multiplied by their respective LASSO coefficients. The support vector machine (SVM) method was used to construct the model. IVH growth was experienced by 13.4% and 13.7% of patients in the training and testing cohorts, respectively. The Rad-score was associated with severe IVH and poor outcome. Independent predictors of IVH growth included hypercholesterolemia (odds ratio [OR], 0.12 [95%CI, 0.02-0.90]; p=0.039), baseline Graeb score (OR, 1.26 [95%CI, 1.16-1.36]; p<0.001), time to initial CT (OR, 0.70 [95%CI, 0.58-0.86]; p<0.001), international normalized ratio (OR, 4.27 [95%CI, 1.40, 13.0]; p=0.011), and Rad-score (OR, 2.3 [95%CI, 1.6-3.3]; p<0.001). In the training cohort, the model achieved an AUC of 0.78, sensitivity of 0.83, and specificity of 0.66. In the testing cohort, AUC, sensitivity, and specificity were 0.71, 0.81, and 0.64, respectively. This radiomics-clinical model thus has the potential to predict IVH growth.


Assuntos
Hemorragia Cerebral Intraventricular/mortalidade , Ventrículos Cerebrais/diagnóstico por imagem , Hidrocefalia/diagnóstico , Hipercolesterolemia/epidemiologia , Processamento de Imagem Assistida por Computador/métodos , Idoso , Hemorragia Cerebral Intraventricular/sangue , Hemorragia Cerebral Intraventricular/complicações , Hemorragia Cerebral Intraventricular/diagnóstico , Estudos de Viabilidade , Feminino , Humanos , Hidrocefalia/sangue , Hidrocefalia/etiologia , Hidrocefalia/mortalidade , Hipercolesterolemia/sangue , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Índice de Gravidade de Doença , Máquina de Vetores de Suporte , Tomografia Computadorizada por Raios X
8.
Nutrients ; 13(4)2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33917704

RESUMO

Impaired triglyceride-rich lipoprotein plasma catabolism is considered the most important factor for hypertriglyceridemia development. The aim of this study was to evaluate the impact of hypercholesterolemia and hypertriglyceridemia on the efficiency of lipoprotein lipase (LPL)-mediated very-low-density lipoprotein (VLDL)-triglyceride lipolysis and the role of high-density lipoprotein (HDL) in this process. Subjects with no history of cardiovascular disease (CVD) and untreated with lipid-lowering agents were recruited into the study and divided into normolipidemic, hypercholesterolemic, and hyperlipidemic groups. VLDL was isolated from serum and incubated with LPL in the absence or presence of HDL. For the hypercholesterolemic and hyperlipidemic groups, a significantly lower percentage of hydrolyzed VLDL-triglyceride was achieved compared to the normolipidemic group (p < 0.01). HDL enhanced the lipolysis efficiency in the hypercholesterolemic and hyperlipidemic groups on average by ~7% (p < 0.001). The lowest electrophoretic mobility of the VLDL remnants indicating the most effective lipolysis was obtained in the normolipidemic group (p < 0.05). HDL presence significantly reduced the electrophoretic mobility of the VLDL remnants for the hypercholesterolemic and hyperlipidemic groups (p < 0.05). The results of our study indicate that VLDL obtained from hypercholesterolemic and hyperlipidemic subjects are more resistant to lipolysis and are additional evidence of the need for early implementation of hypocholesterolemic treatment, already in asymptomatic CVD subjects.


Assuntos
Hipercolesterolemia/metabolismo , Hipertrigliceridemia/metabolismo , Lipólise , Lipoproteínas HDL/metabolismo , Lipoproteínas VLDL/metabolismo , Adulto , Apolipoproteínas E/sangue , Feminino , Humanos , Hipercolesterolemia/sangue , Hipertrigliceridemia/sangue , Lipoproteínas HDL/sangue , Lipoproteínas VLDL/sangue , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangue , Adulto Jovem
9.
Nutrients ; 13(4)2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33917503

RESUMO

BACKGROUND: Dietary supplements have been proposed to help manage blood cholesterol, including red yeast rice (RYR) extracts, plant sterols and stanols, beta-glucans, and some probiotics. This study was conducted to evaluate the efficacy of RYR (containing 10 mg of monacolin K) combined with 109 CFU of three Lactoplantibacillus plantarum strains (CECT7527, CECT7528, and CECT7529). METHODS: A 12-week randomized, double-blinded, placebo-controlled clinical trial was conducted. In total, 39 adult patients were enrolled, having total cholesterol (TC) ≥200 mg/dL, and being statin-naïve or having recently stopped statin treatment because of intolerance. Active product or placebo were taken once daily, and subjects were evaluated at baseline, 6, and 12 weeks. RESULTS: Study groups were comparable at baseline, except for history of recent hypercholesterolemia treatment (81% in active vs. 22% in placebo). Changes in LDL cholesterol and TC became significant compared to placebo (mean difference between groups and standard error of the mean = 23.6 ± 1.5 mg/dL, p = 0.023 and 31.4 ± 1.9 mg/dL, p = 0.011, respectively) upon adjusting for the baseline imbalance in hypercholesterolemia treatment. No adverse effects were noted during the study. CONCLUSION: This combination of 10 mg of monacolin K and L. plantarum strains was well tolerated and achieved a statistically significant greater reduction in LDL-C and TC in the intervention group compared to the placebo, once adjusting for recent history of hypercholesterolemia treatment.


Assuntos
LDL-Colesterol/sangue , Suplementos Nutricionais , Hipercolesterolemia/dietoterapia , Lactobacillaceae , Lovastatina/administração & dosagem , Probióticos/administração & dosagem , Adulto , Método Duplo-Cego , Feminino , Humanos , Hipercolesterolemia/sangue , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Resultado do Tratamento
10.
Nat Commun ; 12(1): 2368, 2021 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-33888696

RESUMO

Endothelial cells play a key role in the regulation of disease. Defective regulation of endothelial cell homeostasis may cause mesenchymal activation of other endothelial cells or neighboring cell types, and in both cases contributes to organ fibrosis. Regulatory control of endothelial cell homeostasis is not well studied. Diabetes accelerates renal fibrosis in mice lacking the endothelial glucocorticoid receptor (GR), compared to control mice. Hypercholesterolemia further enhances severe renal fibrosis. The fibrogenic phenotype in the kidneys of diabetic mice lacking endothelial GR is associated with aberrant cytokine and chemokine reprogramming, augmented Wnt signaling and suppression of fatty acid oxidation. Both neutralization of IL-6 and Wnt inhibition improve kidney fibrosis by mitigating mesenchymal transition. Conditioned media from endothelial cells from diabetic mice lacking endothelial GR stimulate Wnt signaling-dependent epithelial-to-mesenchymal transition in tubular epithelial cells from diabetic controls. These data demonstrate that endothelial GR is an essential antifibrotic molecule in diabetes.


Assuntos
Nefropatias Diabéticas/patologia , Endotélio/patologia , Hipercolesterolemia/complicações , Túbulos Renais/patologia , Receptores de Glucocorticoides/deficiência , Adrenalectomia , Animais , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/etiologia , Células Endoteliais/patologia , Endotélio/citologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Ácidos Graxos/metabolismo , Fibrose , Glucocorticoides/metabolismo , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/etiologia , Hipercolesterolemia/patologia , Interleucina-6/antagonistas & inibidores , Interleucina-6/metabolismo , Túbulos Renais/citologia , Masculino , Camundongos , Camundongos Knockout para ApoE , Oxirredução , Receptores de Glucocorticoides/genética , Estreptozocina/administração & dosagem , Estreptozocina/toxicidade , Via de Sinalização Wnt/efeitos dos fármacos , Via de Sinalização Wnt/genética
11.
Nutrients ; 13(3)2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33802219

RESUMO

Dietary supplementation with sugar cane derivates may modulate low-density lipoprotein cholesterol (LDL-C) and proprotein convertase subtilisin/kexin type 9 (PCSK9) levels. The purpose of this study was to determine if dietary supplement (DS), containing Octacosanol (20 mg) and vitamin K2 (45 µg), could restore the disrupted physiologic relation between LDL-C and serum PCSK9. Double-blind, randomized, placebo-controlled, single-center study including 87 patients on chronic atorvastatin therapy was conducted. Eighty-seven patients were randomized to receive DS (n = 42) or placebo (n = 45), and followed for 13 weeks. Serum PCSK9 levels, lipid parameters and their relationship were the main efficacy endpoints. The absolute levels of PCSK9 and LDL-C were not significantly different from baseline to 13 weeks. However, physiologic correlation between % change of PCSK9 and % change of LDL-C levels was normalized only in the group of patients treated with DS (r = 0.409, p = 0.012). This study shows that DS can restore statin disrupted physiologic positive correlation between PCSK9 and LDL-C. Elevated PCSK9 level is an independent risk factor so controlling its rise by statins may be important in prevention of cardiovascular events.


Assuntos
LDL-Colesterol/sangue , Suplementos Nutricionais , Álcoois Graxos/administração & dosagem , Pró-Proteína Convertase 9/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticolesterolemiantes/uso terapêutico , Atorvastatina/uso terapêutico , Método Duplo-Cego , Dislipidemias/tratamento farmacológico , Feminino , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Vitamina K 2/administração & dosagem , Vitaminas/administração & dosagem
12.
J Am Coll Cardiol ; 77(11): 1439-1450, 2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33736827

RESUMO

BACKGROUND: In cholesterol guidelines, low-density lipoprotein (LDL) cholesterol remains the primary target while apolipoprotein B (apoB) and non-high-density lipoprotein (non-HDL) cholesterol are secondary targets. OBJECTIVES: This study sought to determine if elevated apoB and/or non-HDL cholesterol are superior to elevated LDL cholesterol in identifying statin-treated patients at residual risk of all-cause mortality and myocardial infarction. METHODS: In total, 13,015 statin-treated patients from the Copenhagen General Population Study were included with 8 years median follow-up. Cox regressions among apoB, non-HDL cholesterol, and LDL cholesterol, respectively, and all-cause mortality or myocardial infarction were examined on continuous scales by restricted cubic splines and by categories of concordant and discordant values defined by medians. RESULTS: High apoB and non-HDL cholesterol were associated with increased risk of all-cause mortality and myocardial infarction, whereas no such associations were found for high LDL cholesterol. Compared with concordant values below medians, discordant apoB above the median with LDL cholesterol below yielded hazard ratios of 1.21 (95% confidence interval [CI]: 1.07 to 1.36) for all-cause mortality and 1.49 (95% CI: 1.15 to 1.92) for myocardial infarction. Corresponding values for high non-HDL cholesterol with low LDL cholesterol were 1.18 (95% CI: 1.02 to 1.36) and 1.78 (95% CI: 1.35 to 2.34). In contrast, discordant high LDL cholesterol with low apoB or non-HDL cholesterol was not associated with increased risk of all-cause mortality or myocardial infarction. Also, discordant high apoB with low non-HDL cholesterol yielded hazard ratios of 1.21 (95% CI: 1.03 to 1.41) for all-cause mortality and of 0.93 (95% CI: 0.62 to 1.40) for myocardial infarction. Furthermore, dual discordant apoB and non-HDL cholesterol above the medians with LDL cholesterol below presented hazard ratios of 1.23 (95% CI: 1.07 to 1.43) for all-cause mortality and 1.82 (95% CI: 1.37 to 2.42) for myocardial infarction. CONCLUSIONS: In statin-treated patients, elevated apoB and non-HDL cholesterol, but not LDL cholesterol, are associated with residual risk of all-cause mortality and myocardial infarction. Discordance analysis demonstrates that apoB is a more accurate marker of all-cause mortality risk in statin-treated patients than LDL cholesterol or non-HDL cholesterol, and apoB in addition is a more accurate marker of risk of myocardial infarction than LDL cholesterol.


Assuntos
Apolipoproteínas B/sangue , LDL-Colesterol/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia , Infarto do Miocárdio , Idoso , Biomarcadores/sangue , Causalidade , Dinamarca/epidemiologia , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/epidemiologia , Masculino , Mortalidade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/epidemiologia , Sistema de Registros/estatística & dados numéricos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos
13.
Biochem Biophys Res Commun ; 553: 1-8, 2021 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-33752091

RESUMO

BACKGROUND AND AIMS: Hypercholesterolemia is characterized by the elevation of plasma total cholesterol level, especially low-density lipoprotein (LDL) cholesterol. This disease is usually caused by a mutation in genes such as LDL receptor, apolipoprotein B, or proprotein convertase subtilisin/kexin type 9. However, a considerable number of patients with hypercholesterolemia do not have any mutation in these candidate genes. In this study, we examined the difference in the metabolic level between patients with hypercholesterolemia and healthy subjects, and screened the potential biomarkers for this disease. METHODS: Analysis of plasma metabolomics in hypercholesterolemia patients and healthy controls was performed by gas chromatography-mass spectrometry and metabolic correlation networks were constructed using Gephi-0.9.2. RESULTS: First, metabolic profile analysis confirmed the distinct metabolic footprints between the patients and the healthy ones. The potential biomarkers screened by orthogonal partial least-squares discrimination analysis included l-lactic acid, cholesterol, phosphoric acid, d-glucose, urea, and d-allose (Variable importance in the projection > 1). Second, arginine and methionine metabolism were significantly perturbed in hypercholesterolemia patients. Finally, we identified that l-lactic acid, l-lysine, l-glutamine, and l-cysteine had high scores of centrality parameters in the metabolic correlation network. CONCLUSION: Plasma l-lactic acid could be used as a sensitive biomarker for hypercholesterolemia. In addition, arginine biosynthesis and cysteine and methionine metabolism were profoundly altered in patients with hypercholesterolemia.


Assuntos
Biomarcadores/sangue , Biomarcadores/metabolismo , Hipercolesterolemia/sangue , Hipercolesterolemia/metabolismo , Metabolômica , Adolescente , Adulto , Arginina/metabolismo , Estudos de Casos e Controles , Colesterol/metabolismo , Cisteína/metabolismo , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Glucose/metabolismo , Glutamina/metabolismo , Humanos , Ácido Láctico/sangue , Ácido Láctico/metabolismo , Lisina/metabolismo , Masculino , Metionina/metabolismo , Pessoa de Meia-Idade , Ácidos Fosfóricos/metabolismo , Ureia/metabolismo , Adulto Jovem
14.
Theranostics ; 11(9): 4363-4380, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33754066

RESUMO

Rationale: An improved understanding of thyroid hormone (TH) action on cholesterol metabolism will facilitate the identification of novel therapeutic targets for hypercholesterolemia. TH-regulated microRNAs (miRNAs) have been implicated in TH-controlled biological processes; however, whether and how TH-regulated miRNAs mediate the cholesterol-lowering effect of TH remains unclear. Our aim was to identify TH-regulated microRNAs that have cholesterol-lowering effects and explore the underlying mechanism. Method: Microarray and RNA-seq were performed to identify TH-regulated microRNAs and the genes regulated by mmu-miR-378-3p (miR-378) in the liver of mice, respectively. Recombinant adenoviruses encoding miR-378, Mafg, and shRNA for Mafg, antagomiR-378, liver-specific miR-378 transgenic mice, and miR-378 knockout mice were employed to investigate the roles of hepatic miR-378 and MAFG in cholesterol and bile acid homeostasis. The levels of bile salt species were determined by using UFLC-Triple-time of flight/MS. Results: Here, we show that hepatic miR-378 is positively regulated by TH. Transient overexpression of miR-378 in the liver of mice reduces serum cholesterol levels, accompanied with an increase in the expression of key enzymes in primary bile acid synthetic pathways and corresponding increases in biliary and fecal bile acid levels. Consistently, liver-specific miR-378 transgenic mice with moderate overexpression of hepatic miR-378 display decreased serum cholesterol levels and resistance to diet-induced hypercholesterolemia, while mice lacking miR-378 exhibit defects in bile acid and cholesterol homeostasis. Mechanistically, hepatic miR-378 regulates the expression of key enzymes in both classic and alternative bile acid synthetic pathways through MAFG, a transcriptional repressor, thereby modulating bile acid and cholesterol metabolism. Conclusions: TH-responsive hepatic miR-378 is capable of modulating serum cholesterol levels by regulating both the classic and alternative BA synthetic pathways. Our study not only identifies a previously undescribed role of hepatic miR-378 but also provides new cholesterol-lowering approaches.


Assuntos
Ácidos e Sais Biliares/metabolismo , Colesterol/sangue , Fígado/metabolismo , MicroRNAs/metabolismo , Animais , Linhagem Celular , Células HEK293 , Homeostase/genética , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/genética , Metabolismo dos Lipídeos/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos
15.
Nutr Metab Cardiovasc Dis ; 31(5): 1325-1338, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33762150

RESUMO

AIMS: To systematically evaluate the evidence regarding the effects of foods on LDL cholesterol levels and to compare the findings with current guidelines. DATA SYNTHESIS: From inception through June 2019, we searched PubMed, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials for guidelines, systematic reviews, and RCTs (for coffee intake only) of at least 13 days duration. Additionally, we searched Trip database for guidelines from 2009 through Oct 2019. Language was restricted to English. The strength of evidence was evaluated using The Grading of Recommendations Assessment, Development, and Evaluation (GRADE). A total of 37 guidelines, 108 systematic reviews, and 20 RCTs were included. With high evidence, foods high in unsaturated and low in saturated and trans fatty acids (e.g. rapeseed/canola oil), with added plant sterols/stanols, and high in soluble fiber (e.g. oats, barley, and psyllium) caused at least moderate (i.e. 0.20-0.40 mmol/L) reductions in LDL cholesterol. Unfiltered coffee caused a moderate to large increase. Soy protein, tomatoes, flaxseeds, and almonds caused small reductions. With moderate evidence, avocados and turmeric caused moderate to large reductions. Pulses, hazelnuts, walnuts, high-fiber/wholegrain foods, and green tea caused small to moderate reductions, whereas sugar caused a small increase. Other identified foods were either neutral or had low or very low evidence regarding their effects. CONCLUSIONS: Several foods distinctly modify LDL cholesterol levels. The results may aid future guidelines and dietary advice for hypercholesterolemia.


Assuntos
LDL-Colesterol/sangue , Dieta Saudável , Hipercolesterolemia/dietoterapia , Comportamento de Redução do Risco , Adulto , Biomarcadores/sangue , Dieta/efeitos adversos , Regulação para Baixo , Feminino , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/diagnóstico , Masculino , Pessoa de Meia-Idade , Valor Nutritivo , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
16.
Mol Cells ; 44(2): 116-125, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33658436

RESUMO

Cardiovascular diseases (CVDs) are the most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD) and dyslipidemia is considered at least partially responsible for the increased CVD risk in NAFLD patients. The aim of the present study is to understand how hepatic de novo lipogenesis influences hepatic cholesterol content as well as its effects on the plasma lipid levels. Hepatic lipogenesis was induced in mice by feeding a fat-free/high-sucrose (FF/HS) diet and the metabolic pathways associated with cholesterol were then analyzed. Both liver triglyceride and cholesterol contents were significantly increased in mice fed an FF/HS diet. Activation of fatty acid synthesis driven by the activation of sterol regulatory element binding protein (SREBP)-1c resulted in the increased liver triglycerides. The augmented cholesterol content in the liver could not be explained by an increased cholesterol synthesis, which was decreased by the FF/HS diet. HMGCoA reductase protein level was decreased in mice fed an FF/HS diet. We found that the liver retained more cholesterol through a reduced excretion of bile acids, a reduced fecal cholesterol excretion, and an increased cholesterol uptake from plasma lipoproteins. Very low-density lipoproteintriglyceride and -cholesterol secretion were increased in mice fed an FF/HS diet, which led to hypertriglyceridemia and hypercholesterolemia in Ldlr-/- mice, a model that exhibits a more human like lipoprotein profile. These findings suggest that dietary cholesterol intake and cholesterol synthesis rates cannot only explain the hypercholesterolemia associated with NAFLD, and that the control of fatty acid synthesis should be considered for the management of dyslipidemia.


Assuntos
Colesterol/metabolismo , Lipogênese , Fígado/metabolismo , Animais , Células Cultivadas , Ésteres do Colesterol/metabolismo , Dieta , Sacarose na Dieta , Ácidos Graxos/metabolismo , Fígado Gorduroso/sangue , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Comportamento Alimentar , Hepatócitos/metabolismo , Hipercolesterolemia/sangue , Hipercolesterolemia/metabolismo , Gotículas Lipídicas/metabolismo , Lipoproteínas/sangue , Masculino , Camundongos Endogâmicos C57BL , Receptores de LDL/metabolismo , Triglicerídeos/metabolismo
17.
Nutrients ; 13(2)2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33525601

RESUMO

BACKGROUND: Oxysterol relationship with cardiovascular (CV) risk factors is poorly explored, especially in moderately hypercholesterolaemic subjects. Moreover, the impact of nutraceuticals controlling hypercholesterolaemia on plasma levels of 24-, 25- and 27-hydroxycholesterol (24-OHC, 25-OHC, 27-OHC) is unknown. METHODS: Subjects (n = 33; 18-70 years) with moderate hypercholesterolaemia (low-density lipoprotein cholesterol (LDL-C:): 130-200 mg/dL), in primary CV prevention as well as low CV risk were studied cross-sectionally. Moreover, they were evaluated after treatment with a nutraceutical combination (Bifidobacterium longum BB536, red yeast rice extract (10 mg/dose monacolin K)), following a double-blind, randomized, placebo-controlled design. We evaluated 24-OHC, 25-OHC and 27-OHC levels by gas chromatography/mass spectrometry analysis. RESULTS: 24-OHC and 25-OHC were significantly correlated, 24-OHC was correlated with apoB. 27-OHC and 27-OHC/total cholesterol (TC) were higher in men (median 209 ng/mL and 77 ng/mg, respectively) vs. women (median 168 ng/mL and 56 ng/mg, respectively); 27-OHC/TC was significantly correlated with abdominal circumference, visceral fat and, negatively, with high-density lipoprotein cholesterol (HDL-C). Triglycerides were significantly correlated with 24-OHC, 25-OHC and 27-OHC and with 24-OHC/TC and 25-OHC/TC. After intervention, 27-OHC levels were significantly reduced by 10.4% in the nutraceutical group Levels of 24-OHC, 24-OHC/TC, 25-OHC, 25-OHC/TC and 27-OHC/TC were unchanged. CONCLUSIONS: In this study, conducted in moderate hypercholesterolemic subjects, we observed novel relationships between 24-OHC, 25-OHC and 27-OHC and CV risk biomarkers. In addition, no adverse changes of OHC levels upon nutraceutical treatment were found.


Assuntos
Aterosclerose/metabolismo , Bifidobacterium longum/fisiologia , Produtos Biológicos/uso terapêutico , Biomarcadores/metabolismo , Suplementos Nutricionais , Hipercolesterolemia/tratamento farmacológico , Oxisteróis/metabolismo , Idoso , Aterosclerose/sangue , Colesterol/sangue , Feminino , Humanos , Hipercolesterolemia/sangue , Masculino , Pessoa de Meia-Idade , Oxisteróis/sangue , Placebos
18.
J Am Coll Cardiol ; 77(5): 620-628, 2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33538260

RESUMO

The extracts of red yeast rice (RYR) are currently the most effective cholesterol-lowering nutraceuticals. This activity is mainly due to monacolin K, a weak reversible inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, whose daily consumption causes a reduction in low-density lipoprotein (LDL)-cholesterol plasma levels up to 15% to 25% within 6 to 8 weeks. The decrease in LDL-cholesterol is accompanied by a proportional decrease in total and non-high-density lipoprotein cholesterol, plasma apolipoprotein B, and high-sensitivity C-reactive protein. Some trials suggest that RYR use is associated with improvement in endothelial function and arterial stiffness, whereas a long-term study supports its role in the prevention of cardiovascular events. Despite the statin-like mechanism of action, the risk related to 3 to 10 mg monacolin K taken per day is minimal (mild myalgia in previously severely statin-intolerant subjects). RYR could represent a therapeutic tool to support lifestyle improvement in managing mild to moderate hypercholesterolemia in low-risk patients, including those who cannot be treated with statins or other LDL-cholesterol-lowering therapies.


Assuntos
Produtos Biológicos/farmacologia , LDL-Colesterol/sangue , Colesterol/sangue , Hipercolesterolemia/tratamento farmacológico , Anticolesterolemiantes/uso terapêutico , Biomarcadores/sangue , Suplementos Nutricionais , Humanos , Hipercolesterolemia/sangue
19.
PLoS One ; 16(2): e0247105, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33596242

RESUMO

OBJECTIVE: Cardiovascular disease (CVD) remains the number one cause of death in the US and Nevada is ranked 11th highest for CVD mortality. The study sought to examine the association between self-reported risk factors and CVD presence among adult Nevadans, between years 2011 and 2017. METHODS: This is a cross-sectional, population-based study that utilized the 2011 and 2017 Nevada Behavioral Risk Factor Surveillance System data. Data were analyzed between 2019 and 2020. RESULTS: A total of 5,493 and 3,764 subjects in 2011 and 2017, respectively were included. BMI (overweight/obesity) remained the most prevalent CVD risk factor. The second most common CVD risk factor was high cholesterol, followed by hypertension. Compared to females, males were 1.64 times more likely to have reported CVD in 2011, which increased to 1.92 in 2017. Compared to non-smokers, everyday smokers were 1.96 times more likely in 2011 and 3.62 times more likely in 2017. Individuals with high cholesterol status were 2.67 times more likely to have reported CVD compared to those with normal levels in 2011. In 2011, individuals with hypertension were 3.74 times more likely to have reported CVD compared to those who did not have hypertension. This relationship increased its magnitude of risk to 6.18 times more likely in 2017. In 2011, individuals with diabetes were 2.90 times more likely to have reported CVD compared to those without the condition. CONCLUSIONS: Public health and healthcare providers need to target preventable cardiovascular risk factors and develop recommendations and strategies locally, nationally, and globally.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sistema de Vigilância de Fator de Risco Comportamental , Índice de Massa Corporal , Doenças Cardiovasculares/etiologia , Colesterol/sangue , Estudos Transversais , Diabetes Mellitus/sangue , Feminino , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/complicações , Hipertensão/sangue , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Nevada/epidemiologia , Obesidade/sangue , Obesidade/complicações , Sobrepeso/sangue , Sobrepeso/complicações , Fatores de Risco , Fumar/efeitos adversos , Adulto Jovem
20.
Ann Clin Biochem ; 58(4): 289-296, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33478240

RESUMO

BACKGROUND: Hypercholesterolemia (plasma cholesterol concentration ≥5.2 mmol/L) is a risk factor for cardiovascular disease and stroke. Many different cholesterol self-tests are readily available at general stores, pharmacies and web shops. However, there is limited information on their analytical and diagnostic performance. METHODS: We included 62 adult patients who required a lipid panel measurement (cholesterol, high-density lipoprotein (HDL), triglycerides and LDLcalc) for routine care. The performance of five different cholesterol self-tests, three quantitative meters (Roche Accutrend Plus, Mission 3-in-1 and Qucare) and two semi-quantitative strip tests (Veroval and Mylan MyTest), was assessed according to the manufacturers' protocol. RESULTS: The average plasma cholesterol concentration was 5.2 ± 1.2 mmol/L. The mean absolute relative difference (MARD) of the five cholesterol self-tests ranged from 6 ± 5% (Accutrend Plus) to 20 ± 12% (Mylan Mytest). The Accutrend Plus cholesterol meter showed the best diagnostic performance with a 92% sensitivity and 89% specificity. The Qucare and Mission 3-in-1 are able to measure HDL concentrations and can thus provide a cholesterol:HDL ratio. The Passing-Bablok regression analyses for the ratio showed poor performance in both self-tests (Mission 3-in-1: y = 1.62x-1.20; Qucare: y = 0.61x + 1.75). The Accutrend Plus is unable to measure the plasma high-density lipoprotein concentration.Conclusions/interpretation: The Accutrend Plus cholesterol meter (Roche) had excellent diagnostic and analytic performance. However, several of the commercially-available self-tests had considerably poor accuracy and diagnostic performance and therefore do not meet the required qualifications, potentially leading to erroneous results. Better regulation, standardization and harmonization of cholesterol self-tests is warranted.


Assuntos
Colesterol/sangue , Hipercolesterolemia/sangue , Análise de Regressão , Adulto , Doenças Cardiovasculares/sangue , HDL-Colesterol/sangue , Humanos , Lipídeos/sangue , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Fatores de Risco , Autoteste , Sensibilidade e Especificidade , Manejo de Espécimes , Triglicerídeos/sangue
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