RESUMEN
To investigate the influence of climate on hospitalizations of sickle cell anemia (SCA) adults and children, we analyzed the health and meteorological parameters from a metropolis (1999-2018). 1462 hospitalizations were coded for SCA patients in crisis (M:F = 715:747) and 1354 hospitalizations for SCA patients without crisis (M:F = 698:656) [age = 22.9 vs 15.2 years and duration of hospitalization (DoH) = 5.7 vs 4.4 days, respectively,]. More hospitalizations were for adults than children in crisis, and for children than adults without crisis. More children and adults were hospitalized in winter andspring than in summer and autumn Hospitalizations correlated positively with humidity (lag -5), maximum pressure (lag -2), mean pressure (lag -2), and thermal amplitude (lag -2), and negatively with maximum temperature (lag -3). DoH positively correlated with minimum temperature (lag -4). Understanding these complex associations would induce attitudinal/behavioral modifications among patients and their caregivers.
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Anemia de Células Falciformes , Clima , Niño , Adulto , Humanos , Adulto Joven , Estudios Retrospectivos , Brasil/epidemiología , Anemia de Células Falciformes/epidemiología , HospitalizaciónRESUMEN
BACKGROUND: Increased cholesterol absorption and reduced synthesis are processes that have been associated with cardiovascular disease risk in a controversial way. However, most of the studies involving markers of cholesterol synthesis and absorption include conditions, such as obesity, diabetes, dyslipidemia, which can be confounding factors. The present study aimed at investigating the relationships of plasma cholesterol synthesis and absorption markers with cardiovascular disease (CVD) risk factors, cIMT (carotid intima-media thickness), and the presence of carotid plaques in asymptomatic subjects. METHODS: A cross-sectional study was carried out in 270 asymptomatic individuals and anthropometrical parameters, fasting plasma lipids, glucometabolic profiles, high-sensitivity C-reactive protein (hs-CRP), markers of cholesterol synthesis (desmosterol and lathosterol), absorption (campesterol and sitosterol), cIMT, and the presence of atherosclerotic plaques were analyzed. RESULTS: Among the selected subjects aged between 19 and 75 years, 51% were females. Age, body mass index, systolic and diastolic blood pressure, total cholesterol, non-HDL-C, triglycerides, glucose, and lathosterol/sitosterol ratios correlated positively with cIMT (p ≤ 0.05). Atherosclerotic plaques were present in 19% of the subjects. A direct association of carotid plaques with campesterol, OR = 1.71 (95% CI = 1.04-2.82, p ≤ 0.05) and inverse associations with both ratios lathosterol/campesterol, OR = 0.29 (CI = 0.11-0.80, p ≤ 0.05) and lathosterol/sitosterol, OR = 0.45 (CI = 0.22-0.95, p ≤ 0.05) were observed in univariate logistic regression analysis. CONCLUSIONS: The findings suggested that campesterol may be associated with atherosclerotic plaques and the lathosterol/campesterol or sitosterol ratios suggested an inverse association. Furthermore, synthesis and absorption of cholesterol are inverse processes, and the absorption marker, campesterol, may reflect changes in body cholesterol homeostasis with atherogenic potential.
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Enfermedades Cardiovasculares , Fitosteroles , Placa Aterosclerótica , Adulto , Anciano , Biomarcadores/metabolismo , Proteína C-Reactiva , Grosor Intima-Media Carotídeo , Colesterol/análogos & derivados , Colesterol/metabolismo , Estudios Transversales , Desmosterol , Femenino , Glucosa , Humanos , Masculino , Persona de Mediana Edad , Sitoesteroles , Triglicéridos , Adulto JovenRESUMEN
BACKGROUND: This study aimed to evaluate the associations between Lipoprotein (a) â Lp(a) levels and carotid Intima-Media Thickness (cIMT) and with carotid plaques in healthy subjects because of previous contradictory data. METHODS: A total of 317 healthy normolipidemic subjects (20â77 years old) were selected. The cIMT and atherosclerotic plaques were determined by B-mode ultrasonography. Mann-Whitney tests were performed to compare the groups according to Lp(a) levels and to explore the associations between Lp(a), carotid plaques, and cIMT, logistic and linear regression analyses were performed. RESULTS: Studied population (51% females, median age 43 years old) presented carotid plaques and cIMT ≥ 0.9 mm in 23% and 18% of the participants, respectively. The group with Lp(a) levels > 30 mg/dL presented significantly higher age and atherosclerotic plaques. Indeed, multivariate linear regression analysis showed a significant association between Lp(a), age, and race. On the other hand, logistic regression analysis demonstrated that the subjects with Lp(a) > 30 mg/dL have a significantly high risk of carotid plaques. CONCLUSION: The data from the present study indicate that Lp(a) levels above 30 mg/dL contribute to the development of carotid plaques even in apparently healthy participants.
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Enfermedades de las Arterias Carótidas , Placa Aterosclerótica , Adulto , Anciano , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/epidemiología , Grosor Intima-Media Carotídeo , Femenino , Humanos , Lipoproteína(a) , Masculino , Persona de Mediana Edad , Placa Aterosclerótica/diagnóstico por imagen , Factores de Riesgo , Adulto JovenRESUMEN
Non-cholesterol sterols are transported in plasma lipoproteins and are consequently important in cholesterol metabolism. We investigated the distribution of non-cholesterol sterol precursors of cholesterol synthesis (NCSPCS), oxysterols, and phytosterols in lipoproteins of healthy subjects differing according to HDL-Cholesterol (HDL-C) plasma levels. Elevated NCSPCS (desmosterol, lathosterol) in the High HDL group suggests that HDL exports these sterols from cells, but not the cholesterol metabolite 24-OHC which was higher in the Low HDL group than in the High HDL group. 27-hydroxycholesterol (27OH-C) plasma levels did not differ between groups. Percentage of NCSPCS and phytosterols predominates in LDL, but did not differ between groups. Thirty percent of desmosterol and lathosterol are present in HDL, with the High HDL group carrying higher percentage of these sterols. A high percentage of campesterol and sitosterol in HDL suggests that phytosterols are absorbed by enterocytes, and that HDL could be a marker of the ABCA1/ApoA1 intestinal activity.
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Several proteins are involved in cholesterol homeostasis, as scavenger receptor class B type I and ATP-binding cassette (ABC) transporters including ABCA1, ABCG1, ABCG5, and ABCG8. This study aimed to determine the effects of single nucleotide variants (SNVs) rs2275543 (ABCA1), rs1893590 (ABCG1), rs6720173 (ABCG5), rs6544718 (ABCG8), and rs5888 (SCARB1) on plasma lipids, lipoproteins, and adiposity markers in an asymptomatic population and its sex-specific effects. Volunteers (n = 590) were selected and plasma lipids, lipoproteins, and adiposity markers (waist-to-hip and waist-to-height ratios, lipid accumulation product and body adiposity index) were measured. Genomic DNA was isolated from peripheral blood cells according to the method adapted from Gross-Bellard. SNVs were detected in the TaqMan® OpenArray® Real-Time polymerase chain reaction platform and data analyses were performed using the TaqMan® Genotyper Software. The rs2275543*C point to an increase of high-density lipoprotein size in females while in males very-low-density lipoprotein, cholesterol, and triglycerides were statistically lower (P value < 0.05). The rs1893590*C was statistically associated with lower apolipoprotein A-I levels and higher activities of paraoxonase-1 and cholesteryl ester transfer protein (P value < 0.05). The rs6720173 was statistically associated with an increase in cholesterol and low-density lipoprotein cholesterol in males; moreover, rs6544718*T reduced adiposity markers in females (P value < 0.05). Regarding the rs5888, a decreased adiposity marker in the total population and in females occurred (P value < 0.05). Multivariate analysis of variance showed that SNVs could influence components of high-density lipoprotein metabolism, mainly through ABCG1 (P value < 0.05). The ABCA1 and ABCG5 variants showed sex-specific effects on lipids and lipoproteins, while SCARB1 and ABCG8 variants might influence adiposity markers in females. Our data indicate a possible role of ABCG1 on HDL metabolism.
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Adiposidad , Lipoproteínas , Transportador 1 de Casete de Unión a ATP/genética , Transportador 1 de Casete de Unión a ATP/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 5/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 5/metabolismo , Transportador de Casete de Unión a ATP, Subfamilia G, Miembro 8/genética , Transportador de Casete de Unión a ATP, Subfamilia G, Miembro 8/metabolismo , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Adiposidad/genética , Colesterol/metabolismo , Femenino , Humanos , Lipoproteínas/genética , Lipoproteínas/metabolismo , Lipoproteínas HDL/genética , Masculino , Receptores Depuradores de Clase B/genética , Receptores Depuradores de Clase B/metabolismoRESUMEN
PURPOSE: Sodium-glucose cotransporter 2 inhibitors increase glucagon secretion by pancreatic alpha cells and the susceptibility to ketoacidosis. On the other hand, growth hormone (GH) stimulates peripheral lipolysis and provides free fatty acids (FFA) for ketogenesis; however, it remains unresolved whether GH directly impacts hepatic ketogenesis. We aimed to investigate the role of physiologic GH levels in promoting ketogenesis in prediabetic or type 2 diabetic patients under empagliflozin treatment. METHODS: Sixteen patients (11 women, 5 men) with prediabetes or type 2 diabetes mellitus, aged 55.6 ± 4.7 years and with a mean BMI of 30.7 ± 4.8 kg/m2 and HbA1c 7.1 ± 1.6% (means ± SD), participated in this study. All of them were submitted to three mixed-meal tests: they received placebo at -60 min (test 1), and empagliflozin 25 mg (test 2, 21st day) and empagliflozin 25 mg plus pegvisomant 30 mg were administered subcutaneously 36 h before (test 3, 28th day). After test 1, all patients were instructed to take empagliflozin 25 mg daily. RESULTS: The empagliflozin treatment decreased the plasma concentrations of glucose by 14% (P < 0.01), FFA by 23% (P < 0.01), and the insulin/glucagon ratio by 26% (P < 0.01), and it increased ß-hydroxybutyrate by 44% (P < 0.05). The GH receptor block by pegvisomant restored the plasma ß-hydroxybutyrate to baseline levels. CONCLUSIONS: We conclude that GH has a direct effect on promoting the ketogenesis environment in patients treated with empagliflozin.
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Diabetes Mellitus Tipo 2 , Estado Prediabético , Compuestos de Bencidrilo/farmacología , Compuestos de Bencidrilo/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Glucósidos/farmacología , Glucósidos/uso terapéutico , Hormona del Crecimiento , Humanos , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , MasculinoRESUMEN
BACKGROUND AND AIM: Obesity-related decline in high-density lipoprotein (HDL) functions such as cholesterol efflux capacity (CEC) has supported the notion that this lipoprotein dysfunction may contribute for atherogenesis among obese patients. We investigated if potentially other HDL protective actions may be affected with weight gain and these changes may occur even before the obesity range in a cross-sectional analysis. METHODS AND RESULTS: Lipid profile, body mass index (BMI), biochemical measurements, and carotid intima-media thickness (cIMT) were obtained in this cross-sectional study with 899 asymptomatic individuals. Lipoproteins were separated by ultracentrifugation and HDL physical-chemical characterization, CEC, antioxidant activity, anti-inflammatory activity, HDL-mediated platelet aggregation inhibition were measured in a randomly-selected subgroup (n = 101). Individuals with increased HDL-C had an attenuated increase in cIMT with elevation of BMI (interaction effect ß = -0.054; CI 95% -0.0815, -0.0301). CEC, HDL-C, HDL size and HDL-antioxidant activity were negatively associated with cIMT. BMI was inversely correlated with HDL-mediated inhibition of platelet aggregation (Spearman's rho -0.157, p < 0.03) and CEC (Spearman's rho -0.32, p < 0.001), but surprisingly it was directly correlated with the antioxidant activity (Spearman's rho 0.194, p = 0.052). Thus, even in non-obese, non-diabetic individuals, increased BMI is associated with a wide change in protective functions of HDL, reducing CEC and increasing antioxidant activity. In these subjects, decreased HDL concentration, size or function are related to increased atherosclerotic burden. CONCLUSION: Our findings demonstrate that in non-obese, non-diabetic individuals, the increasing values of BMI are associated with impaired protective functions of HDL and concomitant increase in atherosclerotic burden.
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HDL-Colesterol/sangre , Dislipidemias/sangre , Sobrepeso/sangre , Aumento de Peso , Adulto , Anciano , Antioxidantes/análisis , Biomarcadores/sangre , Índice de Masa Corporal , Enfermedades de las Arterias Carótidas/sangre , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/fisiopatología , Grosor Intima-Media Carotídeo , Estudios Transversales , Dislipidemias/diagnóstico , Dislipidemias/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sobrepeso/diagnóstico , Sobrepeso/fisiopatología , Agregación Plaquetaria , Medición de Riesgo , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Misclassification of patients as low cardiovascular risk (LCR) remains a major concern and challenges the efficacy of traditional risk markers. Due to its strong association with cholesterol acceptor capacity, high-density lipoprotein (HDL) size has been appointed as a potential risk marker. Hence, we investigate whether HDL size improves the predictive value of HDL-cholesterol in the identification of carotid atherosclerotic burden in individuals stratified to be at LCR. METHODS AND FINDINGS: 284 individuals (40-75 years) classified as LCR by the current US guidelines were selected in a three-step procedure from primary care centers of the cities of Campinas and Americana, SP, Brazil. Apolipoprotein B-containing lipoproteins were precipitated by polyethylene glycol and HDL size was measured by dynamic light scattering (DLS) technique. Participants were classified in tertiles of HDL size (<7.57; 7.57-8.22; >8.22 nm). Carotid intima-media thickness (cIMT) <0.90 mm (80th percentile) was determined by high resolution ultrasonography and multivariate ordinal regression models were used to assess the association between cIMT across HDL size and levels of lipid parameters. HDL-cholesterol was not associated with cIMT. In contrast, HDL size >8.22 nm was independently associated with low cIMT in either unadjusted and adjusted models for age, gender and Homeostasis Model Assessment 2 index for insulin sensitivity, ethnicity and body mass index (Odds ratio 0.23; 95% confidence interval 0.07-0.74, pâ=â0.013). CONCLUSION: The mean HDL size estimated with DLS constitutes a better predictor for subclinical carotid atherosclerosis than the conventional measurements of plasma HDL-cholesterol in individuals classified as LCR.
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Aterosclerosis/sangre , Enfermedades de las Arterias Carótidas/sangre , HDL-Colesterol/sangre , Adulto , Anciano , Enfermedades Asintomáticas , Aterosclerosis/diagnóstico , Enfermedades de las Arterias Carótidas/diagnóstico , HDL-Colesterol/química , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tamaño de la Partícula , Medición de Riesgo , Factores de RiesgoRESUMEN
Regardless of its effect on the concentrations of serum cholesterol, statins exert pleiotropic effects, including the regulation of endothelial function, reduced oxidative stress and inflammation, as well as a slight improvement in the concentrations of high density lipoprotein (HDL). However, its role on the composition of HDL is not yet established. The aim of this study was to evaluate the composition of HDL subfractions, HDLsub>2 and HDL3, after 14 days of placebo and atorvastatin (10 mg/day) use in 30 asymptomatic volunteers. The serum parameters and the HDL subfractions compositions were determined using radiometric, nephelometric and biochemical enzymatic methods. We observed significant reductions of total cholesterol, low density lipoprotein (LDL) and apolipoprotein B-100 by 28%, 40% and 38%, respectively. The analyses of chemical composition of the subfractions revealed a lower lipid protein ratio in HDL2, suggesting enrichment in proteins, and also lower in HDL3, probably by an increase in the number of particles. Several mechanisms can be suggested for the effects observed after the use of atorvastatin, such as a possible action on the reverse cholesterol transport (decreased activity of hepatic lipase and increased phospholipid transfer protein, PLTP), which would explain the enrichment of HDL. The results suggest that statin use may be relevant in the primary prevention of atherosclerosis not only by its lowering effect on LDLcholesterol and its anti-inflammatory effect but also by beneficial changes in HDL subfractions.
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Ácidos Heptanoicos/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Lipoproteínas HDL2/análisis , Lipoproteínas HDL3/análisis , Pirroles/farmacología , Adulto , Atorvastatina , Humanos , MasculinoRESUMEN
Assessment of lipid profile parameters has been considered a cornerstone in classifying individuals and populations at risk for cardiovascular disease. Recently, however, preliminary data have raised the possibility of seasonal variations in these parameters, which may cause under- or overestimation. Biological rhythms and seasonal variation of lipid profile was investigated in 227 359 consecutive individuals who underwent health checkups in primary care centers between 2008 and 2010. Plasma low-density lipoprotein cholesterol (LDL-C) >130 mg/dL was 8% more prevalent during winter than summer, with a larger difference among women and middle-aged adults (p < 0.001). High-density lipoprotein cholesterol (HDL-C) <40 mg/dL and triglycerides (TG) >150 mg/dL were respectively 9% and 5% more prevalent during the summer (p < 0.001). Variation amplitude was 3.4 ± 0.3 mg/dL for HDL-C (p = 0.005), 7 ± 2 mg/dL for LDL-C (p = 0.047), and 12 ± 9 mg/dL for TG (p = 0.058). Based on a large population sample, this study confirms the existence of biological rhythms and seasonal variation in lipid profile. This finding must be particularly accounted for in cross-sectional analyses of relative risk, prevalence, or the rate of goal achievement for lipid parameters.
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Dislipidemias/epidemiología , Periodicidad , Estaciones del Año , Adolescente , Adulto , Distribución por Edad , Factores de Edad , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Brasil/epidemiología , Niño , Preescolar , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Estudios Transversales , Dislipidemias/sangre , Dislipidemias/diagnóstico , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Dinámicas no Lineales , Prevalencia , Factores de Riesgo , Distribución por Sexo , Factores Sexuales , Factores de Tiempo , Triglicéridos/sangre , Adulto JovenRESUMEN
BACKGROUND: Cholesteryl ester transfer protein (CETP) plays a major role in lipid metabolism, but studies on the association of CETP polymorphisms with risks of cardiovascular disease are inconsistent. This study investigated whether the CETP gene I405V and Taq1B polymorphisms modified subclinical atherosclerosis in an asymptomatic Brazilian population sample. METHODS: The polymorphisms were analyzed using polymerase chain reaction in 207 adult volunteers. Serum lipid profiles, oxLDL Ab titers, C-reactive protein and tumor necrosis factor-α concentrations and CETP and phospholipid transfer protein (PLTP) activities were determined, and common carotid artery intima-media thickness (cIMT) was measured using ultrasonography. RESULTS: No differences in cIMT were observed between the presence or absence of the minor B2 and V alleles in either polymorphism. However, inverse correlations between mean cIMT and CETP activity in the presence of these polymorphisms were observed, and positive correlations of these polymorphisms with PLTP activity and oxLDL Ab titers were identified. Moreover, logistic multivariate analysis revealed that the presence of the B2 allele was associated with a 5.1-fold (CI 95%, OR: 1.26 - 21.06) increased risk for cIMT, which was equal and above the 66th percentile and positively interacted with age. However, no associations with the V allele or CETP and PLTP activities were observed. CONCLUSIONS: None of the studied parameters, including CETP activity, explained the different relationships between these polymorphisms and cIMT, suggesting that other non-determined factors were affected by the genotypes and related to carotid atherosclerotic disease.
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Enfermedades de las Arterias Carótidas/genética , Proteínas de Transferencia de Ésteres de Colesterol/genética , Polimorfismo Genético , Adulto , Anciano , Autoanticuerpos/sangre , Brasil , Proteína C-Reactiva/metabolismo , Enfermedades de las Arterias Carótidas/sangre , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/inmunología , Grosor Intima-Media Carotídeo , Proteínas de Transferencia de Ésteres de Colesterol/sangre , Femenino , Frecuencia de los Genes , Humanos , Lípidos/sangre , Lipoproteínas LDL/sangre , Lipoproteínas LDL/inmunología , Masculino , Persona de Mediana Edad , Proteínas de Transferencia de Fosfolípidos/sangre , Factor de Necrosis Tumoral alfa/sangre , Adulto JovenRESUMEN
The aim of the study was to verify whether post-menopausal hormone replacement therapy (HRT) modifies autoantibody titers against oxidized low-density lipoprotein (LDL) (anti-LDLoxi), against epitopes of oxidized apolipoprotein B100 and common carotid intima-media thickness (IMT) in these women. Sixty-eight women in pre-menopause (PMW) and 216 in post-menopause (POMW) were recruited; eighty-three had undergone HRT for at least 12 months, where 48 received conjugated estrogens alone (EHRT) and 35 received conjugated estrogen and medroxyprogesterone acetate (CHRT). ELISA was used to determine autoantibodies. Lipoprotein lipase (LPL), hepatic lipase (HL), cholesterol ester transfer protein (CETP) and phospholipid transfer protein (PLTP) activities were assayed by radiometric methods. IMT was measured using Doppler ultrasound. Anti-oxidized LDL and anti-D antibodies increased by 40% (p ≤ 0.003) and 42% (p ≤ 0.006), respectively, with menopause. There was a surprising and significant 7% reduction in anti-D2 antibody titers with HRT (p ≤ 0.050), indicating a positive effect of treatment on the immune response to oxidized LDL. Combined HRT decreased activities of HL and LPL. HRT did not change common carotid IMT, which was increased by 32% as expected after menopause (p ≤ 0.030). This study describes, for the first time, the protective effect of HRT on decreasing autoantibody titers against oxidized apolipoprotein B in LDL.
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Apolipoproteína B-100/antagonistas & inhibidores , Autoanticuerpos/análisis , Enfermedades Autoinmunes/prevención & control , Terapia de Reemplazo de Estrógeno , Lipoproteínas LDL/antagonistas & inhibidores , Menopausia/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Apolipoproteína B-100/química , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/patología , Enfermedades Cardiovasculares/prevención & control , Arteria Carótida Común/diagnóstico por imagen , Arteria Carótida Común/efectos de los fármacos , Arteria Carótida Común/inmunología , Arteria Carótida Común/patología , Grosor Intima-Media Carotídeo , Epítopos , Terapia de Reemplazo de Estrógeno/métodos , Estrógenos Conjugados (USP)/uso terapéutico , Femenino , Humanos , Lipasa/sangre , Lipoproteína Lipasa/sangre , Acetato de Medroxiprogesterona/uso terapéutico , Menopausia/inmunología , Persona de Mediana Edad , Oxidación-ReducciónRESUMEN
Lipid abnormalities in children have become more common in recent decades. This trend is related to the increase in overweight and obesity. The 2002 National Health and Nutrition Examination Survey reported that the percentage of risk for overweight and overweight in children aged > 6 years is 31%, higher than the previous surveys. Serum lipids tend to increase quickly up to 6 months of age and reach values very close to adult values by age 2. As suggested by the American Heart Association, serum lipid values for children and adolescents (2-19 years old) are considered abnormal when total cholesterol is >200 mg/dL, high-density lipoprotein is <35 mg/dL, low-density lipoprotein is >130 mg/dL, and triglycerides are >150 mg/dL. Dyslipidemia can be found in patients with malnutrition, a severe condition that needs prompt nutrition intervention. This report describes a case of malnutrition causing severe dyslipidemia in a newborn. Primary dyslipidemia was excluded by the presence of primary malnutrition, normal response to a postheparin lipoprotein lipase activity test, a favorable clinical course after nutrition intervention, and relatives' blood lipid levels close to normal that did not indicate familial dyslipidemia. The child was fed fat-free milk formula supplemented with medium-chain triglycerides and had adequate weight gain with a decrease in blood lipids. Subsequently the formula was changed to regular milk-based formula, and the child maintained adequate growth rate. Although blood lipids never returned to normal values for age and sex, they were lower than before treatment.
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Grasas de la Dieta/administración & dosificación , Dislipidemias/etiología , Lípidos/sangre , Desnutrición/complicaciones , Triglicéridos/administración & dosificación , Femenino , Humanos , Lactante , Fórmulas Infantiles , Recién Nacido , Desnutrición/sangre , Desnutrición/dietoterapia , Aumento de PesoRESUMEN
OBJECTIVE: Clinical trials of statins during myocardial infarction (MI) have differed in their therapeutic regimes and generated conflicting results. This study evaluated the role of the timing and potency of statin therapy on its potential mechanisms of benefit during MI. METHODS AND RESULTS: ST-elevation MI patients (n=125) were allocated into 5 groups: no statin; 20, 40, or 80 mg/day simvastatin starting at admission; or 80 mg/day simvastatin 48 hours after admission. After 7 days, all patients switched their treatment to 20 mg/day simvastatin for an additional 3 weeks and then underwent flow-mediated dilation in the brachial artery. As of the second day, C-reactive protein (CRP) differed between non-statin users (12.0±4.1 mg/L) and patients treated with 20 (8.5±4.0 mg/L), 40 (3.8±2.5 mg/L), and 80 mg/day (1.4±1.5 mg/L), and the daily differences remained significant until the seventh day (P<0.0001). The higher the statin dose, the lower the elevation of interleukin-2 and tumor necrosis factor-α, the greater the reduction of 8-isoprostane and low-density lipoprotein(-), and the greater the increase in nitrate/nitrite levels during the first 5 days (P<0.001). Later initiation of statin was less effective than its early introduction in relation to attenuation of CRP, interleukin-2, tumor necrosis factor-α, 8-isoprostane, and low-density lipoprotein(-), as well as in increase in nitrate/nitrite levels (P<0.0001). At the 30th day, there was no longer a difference in lipid profile or CRP between groups; the flow-mediated dilation, however, was proportional to the initial statin dose and was higher for those who started the treatment early (P=0.001). CONCLUSIONS: This study demonstrates that the timing and potency of statin treatment during MI are key elements for their main mechanisms of benefit. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00906451.
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Endotelio Vascular/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Mediadores de Inflamación/metabolismo , Infarto del Miocardio/tratamiento farmacológico , Simvastatina/administración & dosificación , Adulto , Anciano , Análisis de Varianza , Biomarcadores/sangre , Brasil , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Endotelio Vascular/inmunología , Endotelio Vascular/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/inmunología , Óxido Nítrico/metabolismo , Estrés Oxidativo/efectos de los fármacos , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento , Vasodilatación/efectos de los fármacosRESUMEN
OBJECTIVE: Low levels of high density lipoprotein-cholesterol (HDL-C) are highly prevalent in subjects presenting premature atherosclerosis. It is indeterminate as to whether high cardiovascular risk in low HDL-C subjects occurs concomitantly with elevated oxidative stress and/or with biologically dysfunctional HDL particles. METHODS AND RESULTS: Systemic oxidative stress (as plasma 8-isoprostanes) was 2.3-fold elevated (p<0.05) in normocholesterolemic, normotriglyceridemic, normoglycemic low HDL-C subjects (plasma HDL-C, <40 mg/dL; n=8) as compared to normolipidemic controls (n=15). HDL subfractions (HDL2b, 2a, 3a, 3b and 3c) isolated by density gradient ultracentrifugation from low HDL-C subjects displayed significantly lower (-21 to -43%, p<0.05) specific antioxidative activity (sAA; capacity to protect LDL from oxidation on a unit particle mass or on a particle number basis) as compared to controls. Altered chemical composition (core triglyceride enrichment, cholesteryl ester depletion) paralleled antioxidative dysfunction of HDL subfractions. Plasma 8-isoprostane levels negatively correlated with sAA of HDL subfractions and positively correlated with the total cholesterol/HDL-C ratio, which was significantly elevated in the low HDL-C phenotype. CONCLUSIONS: Low HDL-C subjects display elevated oxidative stress and possess HDL particle subspecies with attenuated intrinsic antioxidative activity which is intimately related to their altered chemical composition.
Asunto(s)
Antioxidantes/metabolismo , Aterosclerosis/metabolismo , HDL-Colesterol/metabolismo , Estrés Oxidativo/fisiología , Triglicéridos/sangre , Adulto , Ácido Araquidónico/metabolismo , Aterosclerosis/epidemiología , HDL-Colesterol/sangre , Dinoprost/análogos & derivados , Dinoprost/metabolismo , Humanos , Peróxidos Lipídicos/metabolismo , Lipoproteínas LDL/metabolismo , Masculino , Persona de Mediana Edad , Fenotipo , Factores de RiesgoRESUMEN
CONTEXT: Plasma phospholipid transfer protein mediates the transfer of phospholipids from triglyceride-rich lipoproteins, very low density lipoproteins and low density lipoproteins to high density lipoproteins, a process that is also efficient between high density lipoprotein particles. It promotes a net movement of phospholipids, thereby generating small lipid-poor apolipoprotein AI that contains particles and subfractions that are good acceptors for cell cholesterol efflux. CASE REPORT: We measured the activity of plasma phospholipid transfer protein in two cholestatic patients, assuming that changes in activity would occur in serum that was positive for lipoprotein X. Both patients presented severe hypercholesterolemia, high levels of low density lipoprotein cholesterol and, in one case, low levels of high density lipoprotein cholesterol and high levels of phospholipid serum. The phospholipid transfer activity was close to the lower limit of the reference interval. To our knowledge, this is the first time such results have been presented. We propose that phospholipid transfer protein activity becomes reduced under cholestasis conditions because of changes in the chemical composition of high density lipoproteins, such as an increase in phospholipids content. Also, lipoprotein X, which is rich in phospholipids, could compete with high density lipoproteins as a substrate for phospholipid transfer protein.
Asunto(s)
Colestasis/metabolismo , Lipoproteína X/sangre , Proteínas de Transferencia de Fosfolípidos/metabolismo , Adulto , Apolipoproteínas/sangre , Colesterol/sangre , Electroforesis en Gel de Agar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fosfolípidos/sangreRESUMEN
OBJECTIVE: Hyperalphalipoproteinemia (HALP) is characterized by elevated plasma levels of high-density lipoprotein (HDL) particles with altered composition, metabolism, and function. The impact of such modification on antioxidative activities of HDL subfractions is indeterminate. METHODS AND RESULTS: Gradient fractionation revealed that buoyant HDL2b and 2a and small dense HDL3b and 3c levels were elevated up to 2.0-fold in HALP subjects (n=9; mean plasma HDL cholesterol, 79 mg/dL) with low hepatic lipase activity. HDL2a, 3a, 3b, and 3c displayed lower specific antioxidative activity (sAA) during low-density lipoprotein (LDL) oxidation (-15% to -86%, on a unit particle mass basis) than their normolipidemic counterparts (n=13). LDL oxidation was delayed by control HDL3a, 3b, and 3c (up to -79%) but specifically by HDL3c (-54%) in HALP. Paraoxonase activity was deficient in all HALP HDL subfractions. Paraoxonase, PAF-AH, and LCAT activities together accounted for approximately 50% of variation in sAA. Abnormal chemical composition of HDL3b and 3c (cholesterol-deficient, triglyceride-enriched) in HALP was associated with impaired sAA. Systemic oxidative stress (as plasma 8-isoprostanes) tended to be elevated (1.5-fold) in HALP and negatively correlated with sAA (as TBARS). CONCLUSIONS: Intrinsic antioxidative activity of HDL subspecies is impaired in HALP, reflecting altered enzymatic and physicochemical properties.