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1.
Medicine (Baltimore) ; 100(10): e25103, 2021 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-33725906

RESUMEN

BACKGROUND: With the development of the social level and the improvement of living standards, people's dietary structure changes in the direction of high blood fat, high sugar and high fever, which leads to the occurrence of many diseases.Long-term increase in blood lipids can easily cause cholesterol to invade the walls of large blood vessels, deposit and accumulate, and promote the proliferation of smooth muscle cells and fibroblasts in the arterial intima, leading to coronary heart disease and atherosclerosis (AS) and other cardiovascular and cerebrovascular diseases. METHODS: Electronic databases including Google Scholar, PubMed, Web of Science(WOS), the Cochrane Library, EMBASE and VIP Database for Chinese Technical Periodicals, China National Knowledge Infrastructure, and Wanfang. These databases will be searched to identify randomized controlled trials published January 1, 1980, and January 20, 2021. Language is limited with English and Chinese. We will use the standards provided in Cochrane Handbook 5.3.0 for quality assessment and risk assessment, and use Revman 5.3 software for meta-analysis. The primary outcomes are mainly evaluated by total cholesterol and triglyceride. CONCLUSION: The results of this study can provide a beneficial basis for the improvement of total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, and triglyceride in patients with hyperlipidemia.


Asunto(s)
Terapia por Ejercicio/métodos , Ejercicio Físico/fisiología , Hiperlipidemias/terapia , Metabolismo de los Lípidos/fisiología , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Terapia Combinada , Humanos , Hiperlipidemias/sangre , Hiperlipidemias/diagnóstico , Metaanálisis como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Revisiones Sistemáticas como Asunto , Resultado del Tratamiento , Triglicéridos/sangre
2.
J Stroke Cerebrovasc Dis ; 30(5): 105681, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33652345

RESUMEN

BACKGROUND: A third to half of recurrent stroke occur while on antiplatelet therapy, but no study has explored factors relating to prognosis of recurrent ischemic stroke. This study aimed to clarify the risk factors to determine the clinical outcome of recurrent ischemic stroke. METHODS: A total of 1,333 consecutive acute ischemic stroke patients (first n = 492, recurrent n = 841) were enrolled. We explored factors influencing the modified Rankin Scales (mRS) at discharge that included platelet aggregability, preceding medicines, and well-known risks of biochemical data using Chi-square test or Fisher's exact probability test. RESULTS: As to preceding medicines, the proportion of patients who were functionally independent (mRS 0-2) at discharge was higher in preceding P2Y12 inhibitor that suppressed ADP- and collagen-induced macro-aggregation of platelet and Xa inhibitor or warfarin in cardioembolic stroke, but lower in P2Y12 inhibitor and Xa inhibitor or warfarin in lacunar stroke compared with no medicine. Regardless of LDL-cholesterol and HA1c, the mRS at discharge ≤ 2 was increased in the third tertile of serum albumin and body mass index (BMI) in atherothrombotic stroke; serum albumin and high-density lipoprotein cholesterol (HDL-C) in lacunar stroke; and serum albumin, HDL-C and BMI in cardioembolic stroke. Logistic regression analysis identified the following independent predictors for clinical outcome: serum albumin, HDL-C, BMI, and preceding Xa inhibitor and P2Y12 inhibitor. CONCLUSION: Regardless of well-known risk factors such as diabetes and high LDL-C, preceding treatment for Xa inhibitor or P2Y12 inhibitor, serum albumin, HDL-C, and BMI were associated with prognosis in recurrent ischemic stroke.


Asunto(s)
Índice de Masa Corporal , Inhibidores del Factor Xa/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Albúmina Sérica Humana/análisis , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , HDL-Colesterol/sangre , Evaluación de la Discapacidad , Femenino , Humanos , /diagnóstico , Masculino , Persona de Mediana Edad , Limitación de la Movilidad , Pronóstico , Recurrencia , Medición de Riesgo , Factores de Riesgo
3.
Medicine (Baltimore) ; 100(12): e24884, 2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33761646

RESUMEN

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease characterized by excess accumulation of fat in hepatocytes. Because no drug has been approved for NAFLD treatment, this work analyzed the effects of agents resulting from 2 research hotspots, metabolic target agents, and natural plant drugs, on NAFLD with network meta-analysis. METHODS: Public databases were searched through August 14, 2020. Randomized controlled trials that compared obeticholic acid, elafibranor, cenicriviroc, selonsertib, curcumin, silymarin, and resveratrol to placebo were included. Liver pathology improvement, hepatic biochemical indicators, and lipid metabolism indicators were analyzed. RESULTS: Thirty-five studies were included in the meta-analysis. Obeticholic acid was found to significantly increase the frequency of liver biopsy improvement compared to placebo (OR: 2.10; 95% CI: 1.60, 2.77). The ranking results among the hepatic biochemical indicators showed that obeticholic acid (94.9%) and elafibranor (86.3%) have a relative advantage in reducing alanine aminotransferase (ALT) levels, and obeticholic acid also had an advantage (95.4%) in reducing aspartate aminotransferase (AST) levels. Considering lipid metabolic indicators, elafibranor (expSMD: 0.01; 95% CI: 0.00, 0.05; SUCRA: 100%), and obeticholic acid (expSMD: 0.48; 95% CI: 0.28,0.84; SUCRA: 75.6%) significantly reduced triglyceride (TG) levels compared with placebo; moreover, obeticholic acid, but not elafibranor, caused a serious increase in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels and a decrease in high-density lipoprotein cholesterol (HDL-C) levels. CONCLUSIONS: Novel metabolic targeted agents generally have better effects than natural plant drugs, especially obeticholic acid, and elafibranor. However, obeticholic acid showed serious adverse effects such as increasing LDL-C levels and decreasing HDL-C levels. Curcumin showed potential advantages for NAFLD but lacked statistical significance.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Preparaciones de Plantas/uso terapéutico , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Chalconas/uso terapéutico , Ácido Quenodesoxicólico/efectos adversos , Ácido Quenodesoxicólico/análogos & derivados , Ácido Quenodesoxicólico/uso terapéutico , HDL-Colesterol/sangre , HDL-Colesterol/efectos de los fármacos , LDL-Colesterol/sangre , LDL-Colesterol/efectos de los fármacos , Curcumina/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Humanos , Metaanálisis en Red , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/enzimología , Propionatos/uso terapéutico , Triglicéridos/sangre
4.
Clin Chim Acta ; 517: 66-73, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33639119

RESUMEN

BACKGROUND: We investigated the dynamic changes in lipid profiles and their correlations with disease severity and clinical outcome in patients with severe COVID-19. METHODS: We retrospectively reviewed 519 severe COVID-19 patients with confirmed outcomes (discharged or deceased), admitted to the West Court of Union Hospital in Wuhan, China, between 29 January and 8 April 2020. RESULTS: Altogether, 424 severe COVID-19 patients, including 34 non-survivors and 390 survivors, were included in the final analyses. During hospitalization, low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apoA-I) showed an increasing trend in survivors, but showed a downward trend in non-survivors. The serum concentrations of HDL-C and apoA-I were inversely correlated with C-reactive protein (CRP), length of hospital stay of survivors, and disease severity scores. For in-hospital deaths, the areas under the receiver operating characteristic curves (AUCs) of the ratios of CRP/HDL-C and CRP/apoA-I at admission were 0.84 and 0.83, respectively. Moreover, patients with high ratios of CRP/HDL-C (>77.39) or CRP/apoA-I (>72.37) had higher mortality rates during hospitalization (log-rank p < 0.001). Logistic regression analysis demonstrated that hypertension, lactate dehydrogenase, SOFA score, and High CRP/HDL-C ratio were independent predictors of in-hospital mortality. CONCLUSIONS: During severe COVID-19, HDL-C and apoA-I concentrations are dramatically decreased in non-survivors. Moreover, High CRP/HDL-C ratio is significantly associated with an increase in mortality and a poor prognosis.


Asunto(s)
Metabolismo de los Lípidos , Anciano , Apolipoproteína A-I/sangre , Proteína C-Reactiva/análisis , /mortalidad , China , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
5.
Gene ; 778: 145485, 2021 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-33581269

RESUMEN

Recent genome-wide association studies (GWAS) highlighted the importance of genetic variations on SLC22A3 and MIA3 genes in developing coronary heart disease (CHD) among different ethnicities. However, the influence of these variations is not recognized within the Iranian population. Hence, in the present study, we aim to investigate two key single nucleotide polymorphisms (SNPs) on CHD incidence in this population. For this purpose, from Tehran Cardiometabolic Genetic Study (TCGS), 453 individuals with CHD were selected as a case and 453 individuals as a control that matched their age and gender. After quality control of two selected SNPs, rs2048327 (SLC22A3) and rs17465637 (MIA3), we used genotyps resulted from chip-typing technology and conducted the logistic regression analysis adjusted for non-genetic risk factors to detect the possible association of these SNPs with the CHD development. Our findings demonstrated the rs2048327-G and rs17465637-C can significantly increase the risk of CHD development about two times in only males and females, respectively. Interestingly, in the male carriers of the risk allele (G) of rs2048327, the low high-density lipoprotein (HDL) level can significantly predispose them to develop coronary heart disease in the future. According to our results, paying more attention to gender and genetic markers can help more efficient coronary heart disease screening and diagnosis.


Asunto(s)
Translocador Nuclear del Receptor de Aril Hidrocarburo/genética , HDL-Colesterol/sangre , Enfermedad Coronaria/genética , Proteínas de Transporte de Catión Orgánico/genética , Polimorfismo de Nucleótido Simple , Anciano , Estudios de Casos y Controles , Enfermedad Coronaria/sangre , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Irán , Modelos Logísticos , Masculino , Persona de Mediana Edad
6.
Am J Cardiol ; 146: 8-14, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33535058

RESUMEN

Several studies designed to augment high density lipoprotein (HDL) levels have so far been unsuccessful in reducing rates of major adverse cardiovascular and cerebrovascular events (MACCE). In this study, we report the effect of HDL-C levels on overall survival outcomes and rates of MACCE following percutaneous coronary intervention (PCI). We reviewed patients who underwent PCI at the Cleveland Clinic from 2005 to 2017 and followed them through the end of 2018. Restricted cubic splines incorporated into Cox proportional hazard regression models were used to assess the outcomes. The HDL-C level associated with the lowest mortality was used as a reference value.15,633 patients underwent PCI during the study period, of which 70% were male, 81% were white, and 73% were on statins. The mean age at the time of procedure was 65.8 ± 11.8 years. After adjusting for demographics, co-morbidities, lipid profile, statin use, and date of procedure, our model demonstrated a U-shaped association between HDL-C and overall mortality, with HDL-C levels of 30-50 mg/dl associated with the most favorable outcomes, and HDL-C levels < 30 mg/dl or > 50 mg/dl associated with worse outcomes. A sensitivity analysis in men yielded a similar U-shaped association. In conclusion, our study shows that both low and high levels of HDL-C are associated with worse overall survival, with no effect on rates of MACCE in PCI patients. Further studies are required to understand the mechanism of this association between elevated HDL-C levels with increased overall mortality in patients with atherosclerotic cardiovascular disease (ASCVD).


Asunto(s)
Enfermedades Cardiovasculares/sangre , Trastornos Cerebrovasculares/sangre , HDL-Colesterol/sangre , Anciano , Biomarcadores/sangre , Enfermedades Cardiovasculares/mortalidad , Trastornos Cerebrovasculares/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia/tendencias , Factores de Tiempo , Estados Unidos/epidemiología
7.
Nutr Metab Cardiovasc Dis ; 31(4): 1166-1176, 2021 04 09.
Artículo en Inglés | MEDLINE | ID: mdl-33579580

RESUMEN

BACKGROUND AND AIMS: Developing laboratory assays to evaluate HDL functions and improve cardiovascular disease (CVD) risk assessment has recently emerged as a challenge. The present study was conducted to help predict the risk of coronary artery disease (CAD) by investigating new cardiometabolic risk factors based on substituting paraoxonase 1 (PON1) as a critical enzyme in the functionality of HDL for that of HDL-C. METHODS AND RESULTS: The present study recruited 274 subjects undergoing diagnostic coronary angiography, 92 without significant CAD (non-CAD), and 182 with a severe CAD. The diagnostic accuracy of the new biomarkers in non-CAD versus multi-vessel disease was obtained in descending order of AUC as 0.72 (P < 0.001) for log (TG/PON1), 0.70 (P < 0.001) for nonHDL-C/PON1, and 0.67 (P < 0.001) for LDL-C/PON1. After performing a multivariate adjustment for age, gender, BMI, statin therapy, and diabetes mellitus, the increased odds of CAD remained significant for the new cardiometabolic ratios as independent variables [adjusted OR = 1.47 (1.15-1.88), p = 0.002 for LDL-C/PON1; adjusted OR = 2.15 (1.41-3.5), p = 0.009 for nonHDL-C/PON1; adjusted OR = 5.03 (2.14-13.02), p = 0.004 for log (TG/PON1)]. CAD was diagnosed with an optimal discriminating cutoff of 1.84 for LDL-C/PON1, 2.8 for nonHDL-C/PON1, and 0.48 for log (TG/PON1). CONCLUSIONS: To improve CAD's risk assessment, the PON1 activity was proposed as an alternative to HDL-C in the commonly used atherogenic lipid ratios. Substituting the PON1 activity for the HDL-C concentration can provide an index of the HDL activity. The present study sought to exploit the lipoprotein-related risk factors of CAD from a more effective perspective.


Asunto(s)
Arildialquilfosfatasa/sangre , HDL-Colesterol/sangre , Enfermedad de la Arteria Coronaria/sangre , Adulto , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/enzimología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Medición de Riesgo , Índice de Severidad de la Enfermedad
8.
Adv Clin Exp Med ; 30(2): 153-156, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33571404

RESUMEN

BACKGROUND: The new coronavirus pneumonia (NCP, COVID-19) outbreak began in Wuhan in December 2019. The new coronavirus (2019 novel coronavirus (2019-nCoV)) can cause multiple organ damage, mainly to lung tissue, and induce inflammation in the body. OBJECTIVES: To investigate the changes of high-density lipoprotein (HDL) level in patients with COVID-19 and assess its value in the evaluation and prognosis of this disease. MATERIAL AND METHODS: This paper is a cross-sectional retrospective study. Eighty-six severe COVID-19 patients, 132 non-severe COVID-19 patients and 76 healthy individuals (control group) were recruited to measure triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) using enzyme-coupled colorimetry. RESULTS: The serum HDL-C level in COVID-19 group was 1.02 ±0.28 mmol/L which was significantly lower than in control group (1.52 ±0.55 mmol/L) (p < 0.05). In addition, the serum HDL-C level in severe COVID-19 group was 0.83 ±1.67 mmol/L, which was significantly lower than that in non-severe COVID-19 group (1.15 ±0.27 mmol/L) (p < 0.05). CONCLUSIONS: Changes in HDL levels in patients with COVID-19 can reflect the severity of the disease and have a clinical significance in establishing the prognosis.


Asunto(s)
/epidemiología , HDL-Colesterol/sangre , Lipoproteínas HDL/sangre , Adulto , Anciano , Estudios de Casos y Controles , Enfermedad Crítica , Estudios Transversales , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Triglicéridos/sangre
9.
Nutr Metab Cardiovasc Dis ; 31(3): 869-879, 2021 03 10.
Artículo en Inglés | MEDLINE | ID: mdl-33549441

RESUMEN

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) may be crucial in subjects with familial hypercholesterolemia (FH). We aimed to evaluate the effect of the inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9-i) on steatosis biomarkers such as triglyceride-glucose index (TyG) and hepatic steatosis index (HSI) and analyse the role of TG/HDL in this population before and after adding-on PCSK9-i. METHODS AND RESULTS: In this observational study, we evaluated 26 genetically confirmed FH patients with NAFLD and an LDL-C off-target despite high-intensity statins plus ezetimibe. All patients added PCSK9-i treatment and obtained biochemical analysis and TyG and HSI evaluation at baseline and after six months of PCSK9-i. No difference of steatosis biomarkers was found after adding-on PCSK9-i therapy. In a secondary analysis, we divided the study population in two groups according to TG/HDL median value: high TG/HDL group (H-TG/HDL) and low TG/HDL group (L-TG/HDL). TyG and HSI were significantly lower in the L-TG/HDL than H-TG/HDL group (for TyG 9.05 ± 0.34 vs 9.51 ± 0.32; for HSI 38.43 ± 1.35 vs 41.35 ± 1.83, p value for both < 0.05). After six months of PCSK9-i therapy, TyG and HSI were significantly reduced in the L-TG/HDL group after PCSK9-i therapy (-7.5% and -8.4% respectively, p value for both < 0.05) and these biomarkers were lower compared to H-TG/HDL group (for TyG 8.37 ± 0.14 vs 9.19 ± 0.12; for HSI 35.19 ± 1.32 vs 39.48 ± 1.33, p value for both < 0.05). CONCLUSION: In conclusion, PCSK9-i therapy significantly ameliorate steatosis biomarkers in FH patients with low TG/HDL; our results appear to be consistent with a beneficial role of PCSK9-i on steatosis biomarkers in FH subjects with NAFLD.


Asunto(s)
Anticolesterolemiantes/uso terapéutico , Hiperlipoproteinemia Tipo II/tratamiento farmacológico , Mediadores de Inflamación/sangre , Lípidos/sangre , Enfermedad del Hígado Graso no Alcohólico/etiología , Proproteína Convertasa 9/antagonistas & inhibidores , Inhibidores de Serina Proteinasa/uso terapéutico , Anciano , Anticolesterolemiantes/efectos adversos , Biomarcadores/sangre , Glucemia/metabolismo , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Quimioterapia Combinada , Ezetimiba/uso terapéutico , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hiperlipoproteinemia Tipo II/sangre , Hiperlipoproteinemia Tipo II/complicaciones , Hiperlipoproteinemia Tipo II/diagnóstico , Italia , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Estudios Prospectivos , Inhibidores de Serina Proteinasa/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Triglicéridos/sangre
10.
Neurology ; 96(10): e1391-e1401, 2021 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-33536275

RESUMEN

OBJECTIVE: To investigate the longitudinal association among high-density lipoprotein cholesterol (HDL-C) level, HDL-C variability, and the risk of developing Parkinson disease (PD). METHODS: We conducted a nationwide, population-based cohort study. We included 382,391 patients aged ≥65 years who underwent at least 3 health examinations provided by the Korean National Health Insurance System from 2008 to 2013 and followed up until 2017. Individuals with a history of PD and missing values were excluded (n = 1,987). We assessed HDL-C variability using 3 indices, including variability independent of the mean (VIM). A multivariate-adjusted Cox proportional hazards regression analysis was performed. RESULTS: Among the 380,404 participants, 2,733 individuals were newly diagnosed with PD during a median follow-up period of 5 years. The lowest quartile (Q1) group of baseline HDL-C and mean HDL-C was associated with increased PD incidence as compared with the highest quartile (Q4) group (adjusted hazard ratio [aHR], 1.20; 95% confidence interval [CI], 1.08-1.34; and aHR, 1.16; 95% CI, 1.04-1.30, respectively). The Q4 group of HDL-C variability (VIM) was associated with increased PD incidence compared to the Q1 group (aHR, 1.19; 95% CI, 1.06-1.33). The group with the Q1 of baseline HDL-C and with the Q4 of HDL-C variability had the highest risk of PD incidence (aHR, 1.6; 95% CI, 1.31-1.96). CONCLUSION: Lower HDL-C level and greater HDL-C variability were associated with a higher incidence of PD.


Asunto(s)
HDL-Colesterol/sangre , Enfermedad de Parkinson/sangre , Anciano , Estudios de Cohortes , Comorbilidad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/epidemiología , Modelos de Riesgos Proporcionales , República de Corea/epidemiología , Medición de Riesgo , Factores de Riesgo
11.
Carbohydr Polym ; 255: 117335, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33436178

RESUMEN

Nanocellulose has gained much attention because of its excellent properties. Cationic cellulose nanocrystals (cCNC) shows good adsorptivity toward negative ions and molecules. Phosphate binders are most used to treat hyperphosphatemia and it is significant to develop its alternatives with high specific and low cost in the clinic. Herein, we prepared cCNC and characterized it by FTIR, TEM, dynamic light scattering, and viscosity method. We simulated the binding process of cationic cellulose for phosphate and used it as phosphate binder for hyperphosphatemia therapy to study the phosphate binding effect and evaluate the oral toxicity. Cationic cellulose improved the conditions of mice models and efficiently decreased the level of phosphate in the serum. cCNC had a better binding effect than cationic microcrystalline cellulose both in vitro and in vivo. cCNC could be used as alternatives to phosphate binder for therapy of chronic renal failure and hyperphosphatemia.


Asunto(s)
Celulosa/farmacología , Quelantes/farmacología , Hiperfosfatemia/tratamiento farmacológico , Riñón/efectos de los fármacos , Nanopartículas/química , Fosfatos/aislamiento & purificación , Adenina/administración & dosificación , Adsorción , Animales , Biomarcadores/sangre , Celulosa/química , Celulosa/metabolismo , Quelantes/metabolismo , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Modelos Animales de Enfermedad , Heces/química , Humanos , Hiperfosfatemia/inducido químicamente , Hiperfosfatemia/metabolismo , Hiperfosfatemia/patología , Intestino Delgado/efectos de los fármacos , Intestino Delgado/metabolismo , Riñón/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Nanopartículas/administración & dosificación , Fosfatos/metabolismo , Resultado del Tratamiento , Triglicéridos/sangre
12.
Arterioscler Thromb Vasc Biol ; 41(3): 1229-1238, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33504178

RESUMEN

OBJECTIVE: The aim of this study was to comprehensively assess the association of multiple lipid measures with incident peripheral artery disease (PAD). Approach and Results: We used Cox proportional hazards models to characterize the associations of each of the fasting lipid measures (total cholesterol, LDL-C [low-density lipoprotein cholesterol], HDL-C [high-density lipoprotein cholesterol], triglycerides, RLP-C [remnant lipoprotein cholesterol], LDL-TG [LDL-triglycerides], sdLDL-C [small dense LDL-C], and Apo-E-HDL [Apo-E-containing HDL-C]) with incident PAD identified by pertinent International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) hospital discharge codes (eg, 440.2) among 8330 Black and White ARIC (Atherosclerosis Risk in Communities) participants (mean age 62.8 [SD 5.6] years) free of PAD at baseline (1996-1998) through 2015. Since lipid traits are biologically correlated to each other, we also conducted principal component analysis to identify underlying components for PAD risk. There were 246 incident PAD cases with a median follow-up of 17 years. After accounting for potential confounders, the following lipid measures were significantly associated with PAD (hazard ratio per 1-SD increment [decrement for HDL-C and Apo-E-HDL]): triglycerides, 1.21 (95% CI, 1.08-1.36); RLP-C, 1.18 (1.08-1.29); LDL-TG, 1.18 (1.05-1.33); HDL-C, 1.39 (1.16-1.67); and Apo-E-HDL, 1.27 (1.07-1.51). The principal component analysis identified 3 components (1: mainly loaded by triglycerides, RLP-C, LDL-TG, and sdLDL-C; 2: by HDL-C and Apo-E-HDL; and 3: by LDL-C and RLP-C). Components 1 and 2 showed independent associations with incident PAD. CONCLUSIONS: Triglyceride-related and HDL-related lipids were independently associated with incident PAD, which has implications on preventive strategies for PAD. However, none of the novel lipid measures outperformed conventional ones. Graphic Abstract: A graphic abstract is available for this article.


Asunto(s)
Lípidos/sangre , Enfermedad Arterial Periférica/sangre , Anciano , Anciano de 80 o más Años , Apolipoproteínas E/sangre , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Estudios de Cohortes , Dislipidemias/sangre , Dislipidemias/complicaciones , Femenino , Humanos , Lipoproteínas/sangre , Lipoproteínas HDL/sangre , Lipoproteínas LDL/sangre , Masculino , Enfermedad Arterial Periférica/etiología , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Triglicéridos/sangre
13.
Nutrients ; 13(1)2021 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-33477356

RESUMEN

Fasting is becoming an increasingly popular practice. Nevertheless, its clinical benefits and possible inconveniences remain limitedly evaluated. We observed the effects of a seven-day fast conducted in a non-medical center located in the Swiss Alps. Clinical parameters were measured on the first and last day of fasting (D1 and D7), and two months later (D60). Among the 40 participants, blood analyses were done on 25 persons with an increased metabolic risk, with the primary goal of assessing the lasting effect on low-density lipoprotein (LDL) cholesterol. By comparing D60 with D1, high-density lipoprotein cholesterol (HDL) (+0.15 mmol/L) and insulin-like growth factor-1 (IGF-1) (+2.05 mmol/L) increased (both p < 0.009), all other blood parameters (LDL, glucose, total cholesterol, triglycerides, C-reactive protein (CRP)) did not change; weight (-0.97 kg) and hearth rate (-7.31 min-1) decreased (both p < 0.006). By comparing D7 with D1, total cholesterol (+0.44 mmol/L), triglycerides (+0.37 mmol/L) and CRP (+3.37 mg/L) increased (all p < 0.02). The lack of LDL variation at D60 may be due to the low metabolic risk level of the participants. The increase of total cholesterol, triglycerides and CRP at D7 warrants studies to understand whether such fluctuations represent a stress reaction to the fasting state, which may vary in different fasting types.


Asunto(s)
Proteína C-Reactiva/análisis , LDL-Colesterol/sangre , Ayuno/sangre , Lípidos/sangre , Adulto , Composición Corporal , Colesterol/sangre , HDL-Colesterol/sangre , Femenino , Humanos , Factor I del Crecimiento Similar a la Insulina/análisis , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Suiza , Factores de Tiempo , Triglicéridos/sangre
14.
Ecotoxicol Environ Saf ; 208: 111682, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33396014

RESUMEN

Iodine is important in both thyroid function and lipid metabolism. Some studies have explored the effect of thyroid hormones (THs) and urinary iodine concentration (UIC) on serum lipid levels. However, the association between iodine intake and dyslipidemia has not been well established. This study aimed to investigate the relationship between water iodine concentration (WIC) and dyslipidemia, including hypercholesterolemia, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C) and high low-density lipoprotein cholesterol (LDL-C). A cross-sectional survey was conducted involving 409, 390 and 436 adults (≥18 years) from the iodine-deficient (median water iodine, MWI < 10 µg/L), iodine-adequate (MWI between 40 and 100 µg/L) and iodine-excess (MWI > 100 µg/L) areas, respectively. WIC, total cholesterol (TC), triglyceride (TRIG), HDL-C and LDL-C were measured. The prevalence of dyslipidemia were calculated based on the level of WIC using the chi-square method. To further explore whether prevalence was associated with WIC, simple linear regressions and multiple logistic regression models were used. Compared to those with WIC of 40-100 µg/L, a WIC of >100 µg/L was found to be protective associated with against the occurrence of hypertriglyceridemia [adjusted odds ratio (AOR) = 0.649, 95% confidence interval (CI): 0.455-0.924] and low HDL-C (AOR = 0.429, 95% CI: 0.264-0.697). The prevalence of hypertriglyceridemia, low HDL-C and high LDL-C as a function of WIC was found to be an inverted U-shaped association with a zenith at a WIC of 40-100 µg/L. Collectively, our research showed that serum lipid levels are related to WIC. The benefit effect association between WIC and dyslipidemia appears in cases of iodine excess (>100 µg/L).


Asunto(s)
Agua Potable/química , Dislipidemias/epidemiología , Yodo/análisis , Lípidos/sangre , Adulto , China , HDL-Colesterol/sangre , Estudios Transversales , Agua Potable/normas , Dislipidemias/sangre , Femenino , Humanos , Metabolismo de los Lípidos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Prevalencia , Encuestas y Cuestionarios , Triglicéridos/sangre
15.
Nutr Metab Cardiovasc Dis ; 31(2): 602-607, 2021 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-33358712

RESUMEN

BACKGROUND AND AIMS: Loss of the cholesteryl ester transfer protein (CETP) function affects HDLc levels, but its effects on major HDL protein component ApoA1 are not well understood in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: We investigated the effects of an East Asian loss-of-function variant (rs2303790; p.D442G) in CETP gene on HDLc and ApoA1 levels and its relationship with AMI. A total of 2327 AMI patients and 2615 age- and sex-matched controls from INTERHEART-China study were included. In controls, both levels of HDLc (1.24 vs. 1.04 mmol/L, P = 0.001) and ApoA1 (1.48 vs. 1.37 mmol/L, P = 0.042) were significantly higher in CETP variant G allele carriers compared to CETP wildtype D allele carriers. In AMI patients, levels of HDLc were significantly higher (1.14 vs. 1.01 mmol/L, P = 0.013) while levels of ApoA1 were not statistically difference (1.31 vs. 1.32 mmol/L, P = 0.468) in CETP variant group compared to CETP wildtype group. Moreover, CETP variant is associated with HDLc increase, but is not associated with AMI risk (P = 0.564), even after adjusting for age, sex, history of hypertension and diabetes, waist to hip ratio, smoking, total cholesterol, LDL cholesterol, triglycerides, physical activity, depression, alcohol, vegetables and fruit consumption. CONCLUSIONS: Loss of CETP function is associated with increased HDLc and ApoA1 levels in healthy subjects, and in AMI patients, it is associated with HDLc levels but not ApoA1 levels. The lack of association of CETP variant with AMI may be related to the inability to increase ApoA1 levels and warranted further studies.


Asunto(s)
Apolipoproteína A-I/sangre , Grupo de Ascendencia Continental Asiática/genética , Proteínas de Transferencia de Ésteres de Colesterol/genética , HDL-Colesterol/sangre , Mutación con Pérdida de Función , Infarto del Miocardio/genética , Anciano , Biomarcadores/sangre , China/epidemiología , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/etnología , Fenotipo , Estudios Retrospectivos , Regulación hacia Arriba
16.
Clin Drug Investig ; 41(1): 19-28, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33368025

RESUMEN

BACKGROUND AND OBJECTIVE: A limited number of trials have evaluated the efficacy of a fixed-dose combination of bempedoic acid and ezetimibe for the treatment of hypercholesterolemia. The aim of this meta-analysis of existing studies was to evaluate the efficacy and safety of fixed-dose bempedoic acid and ezetimibe combination therapy for the treatment of hypercholesterolemia. METHODS: A systematic literature search was conducted to identify randomized controlled trials (RCTs) comparing bempedoic acid and ezetimibe, versus placebo or ezetimibe alone, to 30 August 2020. A meta-analysis was conducted to investigate the efficacy of bempedoic acid and ezetimibe on lipid parameters and highly sensitive C-reactive protein (hsCRP) levels in patients with hypercholesterolemia or established atherosclerotic cardiovascular disease (ASCVD). Mean differences (MDs) or relative risk (RR) with their corresponding 95% confidence intervals (CIs), using random-effects models, were used to provide pooled estimates. RESULTS: A total of three phase II and III RCTs, comprising 388 patients, of whom 49.2% were treated with bempedoic acid and ezetimibe, and 197 controls, were identified. The duration of treatment was 12 weeks. Bempedoic acid and ezetimibe significantly reduced low-density lipoprotein cholesterol (MD - 29.14%, 95% CI - 39.52 to - 18.76; p < .001), total cholesterol (MD - 15.78%, 95% CI - 20.84 to - 10.72; p = 0.01), non-high-density lipoprotein cholesterol (MD - 18.36%, 95% CI - 24.60 to - 12.12; p = 0.01), and hsCRP levels (MD - 30.48%, 95% CI - 44.69 to - 16.28; p = 0.04). No significant effects on triglycerides (MD - 8.35%, 95% CI - 16.08 to - 0.63; p = 0.72) and improvement in high-density lipoprotein cholesterol (MD 1.63%, 95% CI - 4.03 to 7.28; p = 0.92) were observed with the fixed-dose combination therapy. Regarding safety, bempedoic acid and ezetimibe combination was associated with a non-significant increased risk of drug-related adverse events (RR 1.61, 95% CI 0.86-2.35) and overall adverse events (RR 1.16. 95% CI 0.97-1.35); however, the incidence of discontinuation of therapy (RR 0.75, 95% CI 0.35-1.49) was lower. CONCLUSION: This review found bempedoic acid and ezetimibe significantly lowered lipid parameters, attenuated hsCRP levels, and had an acceptable safety profile for the treatment of hypercholesterolemia and ASCVD.


Asunto(s)
Ácidos Dicarboxílicos/administración & dosificación , Ezetimiba/administración & dosificación , Ácidos Grasos/administración & dosificación , Hipercolesterolemia/tratamiento farmacológico , Anticolesterolemiantes/administración & dosificación , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Combinación de Medicamentos , Ezetimiba/efectos adversos , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Triglicéridos/sangre
17.
Artículo en Inglés | MEDLINE | ID: mdl-32961276

RESUMEN

We studied the mechanism of HDL denaturation with concomitant apoA-I dissociation with HDL preparations from 48 patients with a wide range of plasma HDL-C and evaluated the contribution of lipid-free apoA-I into cholesterol efflux from macrophage, in particular, mediated by cholesterol transporter ABCA1. We prepared HDL by precipitation of apoB-containing lipoproteins by polyethylene glycol and used the chaotropic agent urea to denature HDL preparations. Apo-I dissociation from urea-treated HDL was assessed by the increase of preß-band fraction with agarose gel electrophoresis followed by electro transfer and immunodetection and by the increase of ABCA1-mediated efflux of fluorescent analogue BODIPY-Cholesterol from RAW 264.7 macrophages. The HDL denaturation is governed by a single transition to fully dissociated apoA-I and the transition cooperativity decreases with increasing HDL-C. The apoA-I release depends on phospholipid concentration of HDL preparation and HDL compositional and structural heterogeneity and is well described by apolipoprotein partition between aqueous and lipid phases. Dissociated apoA-I determines the increase of ABCA1-mediated efflux of BODIPY-Cholesterol from RAW 264.7 macrophages to patient HDL. The increase in apoA-I dissociation is associated with the increase of ABCA1 gene transcript in peripheral blood mononuclear cells from patients. The low level of plasma HDL particles may be compensated by their increased potency for apoA-I release, thus suggesting apoA-I dissociation as a new HDL functional property.


Asunto(s)
Transportador 1 de Casete de Unión a ATP/metabolismo , Apolipoproteína A-I/metabolismo , HDL-Colesterol/sangre , Dislipidemias/sangre , Urea/química , Transportador 1 de Casete de Unión a ATP/genética , Adulto , Animales , Apolipoproteína A-I/genética , Transporte Biológico , Índice de Masa Corporal , Compuestos de Boro/química , LDL-Colesterol/sangre , Estudios de Cohortes , Dislipidemias/genética , Dislipidemias/patología , Colorantes Fluorescentes/química , Expresión Génica , Humanos , Masculino , Ratones , Persona de Mediana Edad , Polietilenglicoles/química , Desnaturalización Proteica/efectos de los fármacos , Células RAW 264.7 , Coloración y Etiquetado/métodos , Triglicéridos/sangre , Urea/farmacología
18.
Artículo en Inglés | MEDLINE | ID: mdl-33010452

RESUMEN

Type-1 diabetes mellitus (T1DM) is associated with metabolic changes leading to alterations in glucose and lipid handling. While T1DM-associated effects on many major plasma lipids have been characterised, such effects on plasma free fatty acids (FFA) have not been fully examined. Using gas chromatography-mass spectrometry, we measured the plasma concentrations of FFA species in individuals with T1DM (n = 44) and age/sex-matched healthy controls (n = 44). Relationships between FFA species and various parameters were evaluated. Plasma concentrations of myristate (14:0), palmitoleate (16:1), palmitate (16:0), linoleate (18:2), oleate (18:1c9), cis-vaccenate (18:1c11), eicosapentaenoate (20:5), arachidonate (20:4) and docosahexanoate (22:6) were reduced in the T1DM group (p < 0.0001 for all, except p = 0.0020 for eicosapentaenoate and p = 0.0068 for arachidonate); α-linolenate (18:3) and dihomo-γ-linolenate (20:3) concentrations were unchanged. The saturated/unsaturated FFA ratio, n-3/n-6 ratio, de novo lipogenesis index (palmitate (main lipogenesis product)/linoleate (only found in diet)) and elongase index (oleate/palmitoleate) were increased in the T1DM group (p = 0.0166, p = 0.0089, p < 0.0001 and p = 0.0008 respectively). The stearoyl-CoA desaturase 1 (SCD1) index 1 (palmitoleate/palmitate) and index 2 (oleate/stearate) were reduced in T1DM (p < 0.0001 for both). The delta-(5)-desaturase (D5D) index (arachidonate/dihomo-γ-linolenate) was unchanged. Age and sex had no effect on plasma FFA concentrations in T1DM, while SCD1 index 1 was positively correlated (p = 0.098) and elongase index negatively correlated with age (p = 0.0363). HbA1c was negatively correlated with all plasma FFA concentrations measured except α-linolenate and dihomo-γ-linolenate. Correlations were observed between plasma FFA concentrations and cholesterol and HDL concentrations, but not LDL concentration or diabetes duration. Collectively, these results aid our understanding of T1DM and its effects on lipid metabolism.


Asunto(s)
HDL-Colesterol/sangre , LDL-Colesterol/sangre , Diabetes Mellitus Tipo 1/sangre , Ácidos Grasos no Esterificados/sangre , Metabolismo de los Lípidos/genética , Triglicéridos/sangre , Adolescente , Adulto , Glucemia/metabolismo , Índice de Masa Corporal , Estudios de Casos y Controles , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/patología , Ayuno/sangre , Ácidos Grasos no Esterificados/clasificación , Femenino , Expresión Génica , Hemoglobina A Glucada/genética , Hemoglobina A Glucada/metabolismo , Humanos , Lipidómica/métodos , Masculino , Albúmina Sérica Humana/metabolismo , Estearoil-CoA Desaturasa/sangre , Estearoil-CoA Desaturasa/genética
19.
Biochim Biophys Acta Gen Subj ; 1865(3): 129811, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33309687

RESUMEN

BACKGROUND: There is growing evidence to support beneficial effects of the hypothalamic synthesised hormone, oxytocin, on metabolism. However, the biological half-life of oxytocin is short and receptor activation profile unspecific. METHODS: We have characterised peptide-based oxytocin analogues with structural modifications aimed at improving half-life and receptor specificity. Following extensive in vitro and in vivo characterisation, antidiabetic efficacy of lead peptides was examined in high fat fed (HFF) mice. RESULTS: Following assessment of stability against enzymatic degradation, insulin secretory activity, receptor activation profile and in vivo bioactivity, analogues 2 N (Ac-C ˂YIQNC >PLG-NH2) and D7R ((d-C)YIQNCYLG-NH2) were selected as lead peptides. Twice daily injection of either peptide for 22 days reduced body weight, energy intake, plasma glucose and insulin and pancreatic glucagon content in HFF mice. In addition, both peptides reduced total- and LDL-cholesterol, with concomitant elevations of HDL-cholesterol, and D7R also decreased triglyceride levels. The two oxytocin analogues improved glucose tolerance and insulin responses to intraperitoneal, and particularly oral, glucose challenge on day 22. Both oxytocin analogues enhanced insulin sensitivity, reduced HOMA-IR and increased bone mineral density. In terms of pancreatic islet histology, D7R reversed high fat feeding induced elevations of islet and beta cell areas, which was associated with reductions in beta cell apoptosis. Islet insulin secretory responsiveness was improved by 2 N, and especially D7R, treatment. CONCLUSION: Novel, enzymatically stable oxytocin analogues exert beneficial antidiabetic effects in HFF mice. GENERAL SIGNIFICANCE: These observations emphasise the, yet untapped, therapeutic potential of long-acting oxytocin-based agents for obesity and type 2 diabetes.


Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/farmacología , Islotes Pancreáticos/efectos de los fármacos , Obesidad/tratamiento farmacológico , Oligopéptidos/farmacología , Oxitocina/farmacología , Animales , Glucemia/metabolismo , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/etiología , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/etiología , Diabetes Mellitus Tipo 2/patología , Dieta Alta en Grasa/efectos adversos , Ingestión de Energía/efectos de los fármacos , Ingestión de Energía/genética , Femenino , Glucagón/sangre , Semivida , Hipoglucemiantes/síntesis química , Insulina/metabolismo , Resistencia a la Insulina , Secreción de Insulina/efectos de los fármacos , Islotes Pancreáticos/metabolismo , Islotes Pancreáticos/patología , Masculino , Ratones , Obesidad/sangre , Obesidad/etiología , Obesidad/patología , Oligopéptidos/síntesis química , Oxitocina/análogos & derivados , Oxitocina/síntesis química , Estabilidad Proteica , Triglicéridos/sangre
20.
Nutrients ; 12(12)2020 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-33322340

RESUMEN

BACKGROUND: During overeating, a low protein diet slowed the rate of weight gain and increased the energy cost of the added weight, suggesting that low protein diets reduced energy efficiency. The Protein Overfeeding (PROOF) study explored the metabolic changes to low and high protein diets, and this sub-study examined the changes in body composition and blood lipids when eating high and low protein diets during overeating. METHODS: Twenty-three healthy volunteers (M = 14; F = 9) participated in an 8-week, parallel arm study where they were overfed by ~40% with diets containing 5% (LPD = low protein diet), 15% (NPD = normal protein diet), or 25% (HPD = high protein diet) protein. Dual energy X-ray absorptiometry (DXA) and computer tomography (CT) were used to quantify whole body and abdominal fat and intrahepatic lipid, respectively. Metabolites were measured by standard methods. RESULTS: Protein intake and fat intake were inversely related since carbohydrate intake was fixed. Although overeating the LPD diet was associated with a significant increase in high density lipoprotein (HDL)-cholesterol (p < 0.001) and free fatty acids (p = 0.034), and a significant decrease in fat free mass (p < 0.0001) and liver density (p = 0.038), statistical models showed that dietary protein was the main contributor to changes in fat free mass (p = 0.0040), whereas dietary fat was the major predictor of changes in HDL-cholesterol (p = 0.014), free fatty acids (p = 0.0016), and liver fat (p = 0.0007). CONCLUSIONS: During 8 weeks of overeating, the level of dietary protein intake was positively related to the change in fat free mass, but not to the change in HDL-cholesterol, free fatty acids, and liver fat which were, in contrast, related to the intake of dietary fat.


Asunto(s)
Tejido Adiposo/efectos de los fármacos , Composición Corporal/efectos de los fármacos , Proteínas en la Dieta/farmacología , Hiperfagia/fisiopatología , Lípidos/sangre , Grasa Abdominal/diagnóstico por imagen , Grasa Abdominal/efectos de los fármacos , Absorciometría de Fotón , Tejido Adiposo/diagnóstico por imagen , Adulto , HDL-Colesterol/sangre , Ingestión de Alimentos/fisiología , Ácidos Grasos no Esterificados/sangre , Femenino , Voluntarios Sanos , Humanos , Hígado/diagnóstico por imagen , Hígado/metabolismo , Masculino , Tomografía Computarizada por Rayos X , Adulto Joven
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