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1.
N Engl J Med ; 381(12): 1114-1123, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31532959

RESUMO

BACKGROUND: Persons with low socioeconomic status and nonwhite persons in the United States have high rates of cardiovascular disease. The use of combination pills (also called "polypills") containing low doses of medications with proven benefits for the prevention of cardiovascular disease may be beneficial in such persons. However, few data are available regarding the use of polypill therapy in underserved communities in the United States, in which adherence to guideline-based care is generally low. METHODS: We conducted a randomized, controlled trial involving adults without cardiovascular disease. Participants were assigned to the polypill group or the usual-care group at a federally qualified community health center in Alabama. Components of the polypill were atorvastatin (at a dose of 10 mg), amlodipine (2.5 mg), losartan (25 mg), and hydrochlorothiazide (12.5 mg). The two primary outcomes were the changes from baseline in systolic blood pressure and low-density lipoprotein (LDL) cholesterol level at 12 months. RESULTS: The trial enrolled 303 adults, of whom 96% were black. Three quarters of the participants had an annual income below $15,000. The mean estimated 10-year cardiovascular risk was 12.7%, the baseline blood pressure was 140/83 mm Hg, and the baseline LDL cholesterol level was 113 mg per deciliter. The monthly cost of the polypill was $26. At 12 months, adherence to the polypill regimen, as assessed on the basis of pill counts, was 86%. The mean systolic blood pressure decreased by 9 mm Hg in the polypill group, as compared with 2 mm Hg in the usual-care group (difference, -7 mm Hg; 95% confidence interval [CI], -12 to -2; P = 0.003). The mean LDL cholesterol level decreased by 15 mg per deciliter in the polypill group, as compared with 4 mg per deciliter in the usual-care group (difference, -11 mg per deciliter; 95% CI, -18 to -5; P<0.001). CONCLUSIONS: A polypill-based strategy led to greater reductions in systolic blood pressure and LDL cholesterol level than were observed with usual care in a socioeconomically vulnerable minority population. (Funded by the American Heart Association Strategically Focused Prevention Research Network and the National Institutes of Health; ClinicalTrials.gov number, NCT02278471.).


Assuntos
Anti-Hipertensivos/administração & dosagem , Combinação de Medicamentos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hipercolesterolemia/tratamento farmacológico , Hipertensão/tratamento farmacológico , Área Carente de Assistência Médica , Adesão à Medicação/estatística & dados numéricos , Adulto , Alabama , Anlodipino/administração & dosagem , Atorvastatina/administração & dosagem , LDL-Colesterol/sangue , Centros Comunitários de Saúde , Feminino , Humanos , Hidroclorotiazida/administração & dosagem , Hipercolesterolemia/sangue , Hipercolesterolemia/complicações , Hipertensão/complicações , Losartan/administração & dosagem , Masculino , Pessoa de Meia-Idade
2.
Hipertens. riesgo vasc ; 36(3): 162-164, jul.-sept. 2019. ilus, graf
Artigo em Espanhol | IBECS | ID: ibc-183955

RESUMO

En la actualidad son cada vez más los pacientes con hipertensión arterial refractaria (HTAR) que sufren insuficiencia cardiaca (IC) en fases avanzadas y que precisan dispositivos implantables para su tratamiento. Presentamos el caso de un paciente con un desfibrilador automático implantable (DAI) que precisó la colocación de un dispositivo de terapia de activación de barorreceptores (TAB) del seno carotídeo con la doble indicación de IC y HTAR. Hasta donde sabemos, se trata del primer caso realizado en nuestro país


The number of patients who suffer refractory arterial hypertension and chronic heart failure in advanced stages is currently increasing. The case is presented of a patient with an implantable cardioverter defibrillator, and with the dual indication of chronic heart failure and refractory arterial hypertension, who required the implanting of a baroreceptors activation therapy device of the carotid sinus. As far as it is known, it is the first case reported in Spain?


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Insuficiência Cardíaca/complicações , Pressorreceptores/efeitos dos fármacos , Fatores de Risco , Pressorreceptores/metabolismo , Hipercolesterolemia/complicações , Hipercolesterolemia/tratamento farmacológico , Isquemia Miocárdica/complicações
3.
Appl Microbiol Biotechnol ; 103(15): 5993-6006, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31201452

RESUMO

Atherosclerosis is the major cause of cardiovascular diseases, which are considered the fatal ailment globally. Hypercholesterolaemia plays a critical role in the development of atherosclerosis and cardiovascular diseases. Many studies have been stated that probiotics could affect hypercholesterolemia via cholesterol metabolism. Probiotics are live bacteria which are good for our health when administered orally in high amounts. Recently, many studies have revealed the beneficial effects of the nutritional ingestion of probiotics which can decrease serum cholesterol levels. The aim of this review is, firstly, to explore the hypercholesterolemia effect of how it progresses into atherosclerosis and, secondly, to summarize the hypocholesterolaemia effect of probiotics on atherosclerosis and the up-to-date information on their basic mechanisms. The most important mechanisms responsible for the hypocholesterolemic effect of probiotics are the suppression of the reabsorption of bile acids and inhibition of the intestinal cholesterol absorption. Current studies indicate that numerous mechanisms within the cholesterol metabolism, e.g., ones involving the Niemann-Pick C1-Like 1 protein, 3-hydroxy-3-methylglutaryl-CoA reductase, and 7α- and 27α-hydroxylases, have been recommended where regulation may take place after oral intake of probiotics. However, these mechanisms are still poorly understood. Thus, further studies are required to examine the possible mechanisms, whereby probiotics can be utilized safely and considered for the treatment of hypercholesterolemia.


Assuntos
Aterosclerose/prevenção & controle , Aterosclerose/fisiopatologia , Hipercolesterolemia/complicações , Hipercolesterolemia/terapia , Probióticos/administração & dosagem , Probióticos/farmacologia , Animais , Colesterol/metabolismo , Humanos
4.
J Forensic Sci ; 64(6): 1929-1932, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31162647

RESUMO

Hyperostosis frontalis interna is a common phenomenon, which may have been overrated in its significance in the past, and may, currently be underrated in its significance. We present three cases of hyperostosis frontalis interna found during medicolegal autopsies and discuss their forensic considerations. The patients were all middle-aged women with metabolic and endocrine manifestations and psychiatric ailments; thickening of the inner table of the frontal bone of the skull was found during each autopsy. We describe the relationship between hyperostosis frontalis interna, metabolic manifestations, and neuropsychiatric symptoms as part of Morgagni-Stewart-Morel syndrome. There is still considerable disagreement in the scientific community as to whether this syndrome is a clinical entity. Nonetheless, awareness of Morgagni-Stewart-Morel syndrome can be of help in understanding the circumstances surrounding death. In some other cases, hyperostosis frontalis interna could be used by forensic pathologists as criteria for sexing and aging a skeleton.


Assuntos
Hiperostose Frontal Interna/patologia , Autopsia , Feminino , Humanos , Hipercolesterolemia/complicações , Hipotireoidismo/complicações , Transtornos Mentais/complicações , Pessoa de Meia-Idade , Obesidade/complicações , Suicídio
5.
Med. clín (Ed. impr.) ; 152(12): 473-481, jun. 2019. graf, tab
Artigo em Inglês | IBECS | ID: ibc-183317

RESUMO

Background: Recent clinical studies have yielded controversial results regarding the effect of probiotics on lipid profiles. To assess the efficacy of probiotics in lowering serum lipid concentrations, we conducted a meta-analysis of randomized controlled trials (RCTs). Methods: Literature from the PubMed, Embase and Cochrane databases were searched and screened. The effects of probiotics on lipid profiles were assessed by mean difference (MD) and 95% confidence interval (CI). All included studies were analyzed using Review Manager 5.3 (Cochrane Collaboration, 2014). Results: A total of 19 RCTs, including 967 participants, met the inclusion criteria. Probiotic interventions reduced total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) compared to controls (placebo or no treatment) by −0.25mmol/L (95% CI: −0.39, −0.12) and −0.17mmol/L (95% CI: −0.25, −0.09), respectively. No significant effects of probiotics on triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) levels were found. The effects of probiotics on decreasing TC and LDL-C levels were greater for longer intervention times, certain probiotic strains, and in younger mildly hypercholesterolaemic subjects. Conclusion: This meta-analysis revealed that the use of probiotics can significantly lower TC and LDL-C levels in hypercholesterolaemic adults, which brings hope for reducing the risk factors for developing cardiovascular disease


Antecedentes: Los resultados obtenidos por estudios clínicos recientes sobre el efecto de los probióticos en los perfiles lipídicos han generado cierta controversia. Para evaluar la eficacia de los probióticos en la reducción de las concentraciones séricas de lípidos, se realizó un metaanálisis de estudios comparativos aleatorizados (ECA). Métodos: Se realizó una búsqueda y posterior cribado bibliográfico en las bases de datos PubMed, Embase y Cochrane. Se evaluaron los efectos de los probióticos en los perfiles de lípidos mediante la diferencia de medias (DM) y el intervalo de confianza (IC) del 95%. Todos los estudios incluidos se analizaron con Review Manager 5.3 (Cochrane Collaboration, 2014). Resultados: Cumplieron con los criterios de inclusión un total de 19 ECA, que incluyeron 967 participantes. Las intervenciones probióticas redujeron el colesterol total (CT) y el colesterol de lipoproteínas de baja densidad (c-LDL) en −0,25mmol/l (IC 95%: −0,39, −0,12) y −0,17mmol/l (IC 95%: −0,25, −0,09), respectivamente, en comparación con los controles (placebo o ningún tratamiento). No se observaron efectos significativos de los probióticos en los niveles de triglicéridos (TG) y en el colesterol de lipoproteínas de alta densidad (c-HDL). Los efectos de los probióticos en la disminución de los niveles de CT y c-LDL fueron mayores en los casos donde la intervención duró más tiempo, en ciertas cepas probióticas y en sujetos más jóvenes con hipercolesterolemia leve. Conclusión: Este metaanálisis reveló que el uso de probióticos puede reducir significativamente los niveles de CT y c-LDL en adultos hipercolesterolémicos, lo que brinda la esperanza de reducir los factores de riesgo relativos al desarrollo de enfermedad cardiovascular


Assuntos
Adulto , Humanos , Probióticos/administração & dosagem , Metabolismo dos Lipídeos/efeitos dos fármacos , Hipercolesterolemia/complicações , Fatores de Risco , Doenças Cardiovasculares/prevenção & controle , Hipercolesterolemia/tratamento farmacológico , Colesterol/sangue , Anticolesterolemiantes/administração & dosagem , Dislipidemias/sangue , Dislipidemias/terapia
6.
Rev Bras Epidemiol ; 22: e190015, 2019.
Artigo em Português, Inglês | MEDLINE | ID: mdl-31038611

RESUMO

OBJECTIVE: To compare the prevalence of cardiovascular risk factors in the adult population of Vitória, Espírito Santo, Brazil, in two surveys conducted by telephone interview (VIGITEL) or by clinic and laboratory exams during the National Health Interview Survey (NHIS). METHOD: Data were collected from adults (≥ 18 years). In VIGITEL, 1,996 subjects (males = 38%) were interviewed. In NHIS, home visit followed by clinical and laboratory tests was made with 318 individuals (males = 48%) selected in 20 census tracts of the city. The prevalence of risk factors was adjusted to the estimated population of the city in 2013. Data are shown as prevalence and 95% confidence interval (95%CI). RESULTS: Similar values of prevalence were found in VIGITEL and NHIS, respectively, for smoking (8.2%; 95%CI 6.7-9.7% vs 10.0; 95%CI 6.4 - 13.6%) and hypertension (24.8%; 95%CI 22.6 - 27.0% vs 27.2%; 95%CI 21.8 - 32.5%). Statistical differences between surveys (p < 0.01) were found for diabetes (6.7%; 95%CI 5.6 - 7.9% vs 10.7%; 95%CI 7.1 - 14.5%), obesity (16.8%; 95%CI 14.1 - 18.1% vs 25.7%; 95%CI 20.4 - 30.9%) and high cholesterol (≥ 200mg/dL) (20.6%; 95%CI 18.6- 22.6% vs 42.3%; 95%CI 36.9 - 47.7%). The prevalence of diabetes was also higher (p < 0.01) in NHIS (6.7 vs 10.7%). CONCLUSION: Prevalence of smoking and hypertension, but not obesity, was adequately detected in VIGITEL, because there might have been information bias related to body weight during telephone interviews. Datashow the necessity to improve the diagnosis of dyslipidemias in primary care services, as the control of this risk factor is of utmost importance to prevent cardiovascular diseases.


Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Diabetes Mellitus/epidemiologia , Hipercolesterolemia/epidemiologia , Hipertensão/epidemiologia , Obesidade/epidemiologia , Fumar/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Brasil/epidemiologia , Complicações do Diabetes , Feminino , Inquéritos Epidemiológicos , Humanos , Hipercolesterolemia/complicações , Hipertensão/complicações , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Prevalência , Fatores de Risco , Autorrelato , Distribuição por Sexo , Fumar/efeitos adversos , Adulto Jovem
7.
Int J Mol Sci ; 20(9)2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31064116

RESUMO

Hypercholesterolemia may be causally related to heart failure with preserved ejection fraction (HFpEF). We aimed to establish a HFpEF model associated with hypercholesterolemia and type 2 diabetes mellitus by feeding a high-sucrose/high-fat (HSHF) diet to C57BL/6J low-density lipoprotein receptor (LDLr)-/- mice. Secondly, we evaluated whether cholesterol-lowering adeno-associated viral serotype 8 (AAV8)-mediated LDLr gene transfer prevents HFpEF. AAV8-LDLr gene transfer strongly (p < 0.001) decreased plasma cholesterol in standard chow (SC) mice (66.8 ± 2.5 mg/dl versus 213 ± 12 mg/dl) and in HSHF mice (84.6 ± 4.4 mg/dl versus 464 ± 25 mg/dl). The HSHF diet induced cardiac hypertrophy and pathological remodeling, which were potently counteracted by AAV8-LDLr gene transfer. Wet lung weight was 19.0% (p < 0.001) higher in AAV8-null HSHF mice than in AAV8-null SC mice, whereas lung weight was normal in AAV8-LDLr HSHF mice. Pressure-volume loop analysis was consistent with HFpEF in AAV8-null HSHF mice and showed a completely normal cardiac function in AAV8-LDLr HSHF mice. Treadmill exercise testing demonstrated reduced exercise capacity in AAV8-null HSHF mice but a normal capacity in AAV8-LDLr HSHF mice. Reduced oxidative stress and decreased levels of tumor necrosis factor-α may mediate the beneficial effects of cholesterol lowering. In conclusion, AAV8-LDLr gene therapy prevents HFpEF.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Cardiomiopatias Diabéticas/prevenção & controle , Terapia Genética/métodos , Insuficiência Cardíaca/prevenção & controle , Hipercolesterolemia/terapia , Receptores de LDL/genética , Animais , Colesterol/sangue , Dependovirus/genética , Diabetes Mellitus Tipo 2/etiologia , Cardiomiopatias Diabéticas/fisiopatologia , Dieta Hiperlipídica/efeitos adversos , Sacarose na Dieta/efeitos adversos , Feminino , Insuficiência Cardíaca/fisiopatologia , Hipercolesterolemia/complicações , Hipercolesterolemia/etiologia , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Receptores de LDL/metabolismo , Volume Sistólico , Fator de Necrose Tumoral alfa/sangue
8.
Recurso na Internet em Português | LIS - Localizador de Informação em Saúde, LIS-bvsms | ID: lis-LISBR1.1-46422

RESUMO

O infarto do miocárdio, ou ataque cardíaco, é a morte das células de uma região do músculo do coração por conta da formação de um coágulo que interrompe o fluxo sanguíneo de forma súbita e intensa.


Assuntos
Infarto do Miocárdio , Aterosclerose , Vasos Coronários , Infarto , Tabagismo/complicações , Obesidade/complicações , Hipercolesterolemia/complicações , Diabetes Mellitus , Hipertensão
9.
Recurso na Internet em Português | LIS - Localizador de Informação em Saúde, LIS-bvsms | ID: lis-LISBR1.1-46428

RESUMO

A vesícula biliar é um órgão em forma de saco, parecida com uma pera, localizada abaixo do lobo direito do fígado. Sua função é armazenar a bile, líquido produzido pelo fígado que atua na digestão de gorduras no intestino. A bile é formada pela mistura de várias substâncias, entre elas o colesterol, responsável pela imensa maioria da formação de cálculos (pedras), que podem impedir o fluxo da bile para o intestino e causar uma inflamação chamada colecistite.


Assuntos
Colecistite , Cálculos Biliares , Hipercolesterolemia/complicações , Hipertrigliceridemia/complicações , Comportamento Sedentário , Diabetes Mellitus , Obesidade/complicações , Hipertensão/complicações , Tabagismo/complicações , Anticoncepcionais/efeitos adversos , Estrogênios/efeitos adversos , Hereditariedade
10.
Mol Med Rep ; 19(6): 4603-4612, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30957178

RESUMO

As the incidence of osteoporosis (OP) and hypercholesterolaemia in men has increased, male OP has drawn more attention from clinicians worldwide. The present study sought to investigate the effects of cholesterol on male bone. Between July 2015 and October 2015, 216 men (aged ≥18 years) were recruited for this cross­sectional study. To test our clinical hypothesis, we designed two male animal models: Exogenous hypercholesterolaemia induced by a high­cholesterol diet (HCD) and endogenous hypercholesterolaemia induced by apolipoprotein E (ApoE) knockout. Finally, the direct effects of cholesterol on osteoblasts were observed in cell experiments. In our clinical studies, men with hypercholesterolaemia displayed a lower bone mineral density (BMD) and increased beta collagen cross­linking (beta­CTX) and type I anterior collagen amino terminal peptide (PINP) levels compared to those of the control subjects. Serum cholesterol levels were a significant independent predictor of BMD, beta­CTX and PINP and were negatively correlated with BMD and positively correlated with beta­CTX and PINP levels. Our animal experimental results validated our clinical results, as they also indicated that hypercholesterolaemia damages bone microstructure and reduces bone strength. Cholesterol directly increased osteoblast functional gene expression in vitro. Hypercholesterolaemia increases the risk of high­turnover osteoporosis in men at least in part by excessively promoting the activity of the remodelling pathway. In addition, hypercholesterolaemia damages the bone microstructure, resulting in osteopenia or OP and reduced bone strength, leading to a higher risk of fracture in men. We emphasize the importance of preventing and treating hypercholesterolaemia as well as monitoring bone metabolic markers and BMD in men with hypercholesterolemia for the effective prevention of bone loss and subsequent fracture. In addition, our findings provide a theoretical basis for the development of treatments for high cholesterol­induced osteoporosis in men.


Assuntos
Remodelação Óssea , Hipercolesterolemia/sangue , Osteoporose/sangue , Adulto , Animais , Biomarcadores/sangue , Reabsorção Óssea/sangue , Osso e Ossos/metabolismo , Colágeno Tipo I/sangue , Estudos Transversais , Modelos Animais de Doenças , Humanos , Hipercolesterolemia/complicações , Masculino , Pessoa de Meia-Idade , Osteoporose/etiologia , Fragmentos de Peptídeos/sangue , Ratos , Ratos Sprague-Dawley
11.
Int J Mol Med ; 43(6): 2451-2461, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31017253

RESUMO

Ischemic postconditioning (IPoC) has been demonstrated to prevent myocardial ischemia­reperfusion injury (MIRI), but its cardioprotective effect is abrogated by hypercholesterolemia. The aim of the present study was to determine whether lycopene (LP), a type of carotenoid, can restore the cardioprotective effect of IPoC in hypercholesterolemic rats. Male Wistar rats were fed a cholesterol­enriched diet for 12 weeks to establish a hypercholesterolemic model. The rat hearts were isolated and subjected to 30 min ischemia and 60 min reperfusion using a Langendorff apparatus. LP was administered to the rats intraperitoneally for 5 consecutive days prior to ischemia and reperfusion. Myocardial pathological changes, infarct size and cell apoptosis were measured by hematoxylin and eosin, triphenyltetrazolium chloride and TUNEL staining, respectively. The changes in endoplasmic reticulum (ER) stress markers, the reperfusion injury salvage kinase (RISK) pathway and mitochondrial apoptosis­related proteins were detected by western blotting. Overall, the results demonstrated that low­dose LP in combination with IPoC ameliorated myocardial histopathological changes, reduced the infarct size and release of cardiac enzymes, and decreased cardiomyocyte apoptosis in hypercholesterolemic rats, but no beneficial effects were achieved by the same dose of LP or IPoC treatment were used alone. Furthermore, the combination of LP and IPoC inhibited the expression of glucose­regulated protein 78 and C/EBP homologous protein, increased the phosphorylation levels of AKT, ERK1/2 and glycogen synthase kinase­3ß, repressed mitochondrial permeability transition pore opening, and reduced the expression of cytochrome c, cleaved caspase­9 and cleaved caspase­3. Collectively, these findings demonstrated that LP can restore the cardioprotective effects of IPoC on MIRI in hypercholesterolemic rats, and this restoration by LP was mediated by inhibition of ER stress and reactivation of the RISK pathway in hypercholesterolemic rat myocardium.


Assuntos
Hipercolesterolemia/complicações , Pós-Condicionamento Isquêmico , Licopeno/uso terapêutico , Traumatismo por Reperfusão Miocárdica/complicações , Traumatismo por Reperfusão Miocárdica/terapia , Substâncias Protetoras/uso terapêutico , Animais , Hipercolesterolemia/sangue , Hipercolesterolemia/patologia , Pós-Condicionamento Isquêmico/métodos , Lipídeos/sangue , Masculino , Infarto do Miocárdio/sangue , Infarto do Miocárdio/complicações , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Traumatismo por Reperfusão Miocárdica/sangue , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/patologia , Ratos Wistar
13.
Angiology ; 70(8): 726-736, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30871330

RESUMO

Heterozygous familial hypercholesterolemia (HeFH) is a common genetic disorder predisposing affected individuals to lifelong low-density lipoprotein cholesterol (LDL-C) elevation and coronary heart disease. However, whether HeFH increases the risk of peripheral arterial disease (PAD) and ischemic stroke is undetermined. We examined associations between HeFH and these outcomes in a comprehensive systematic review and meta-analysis. We searched MEDLINE, EMBASE, Global Health, the Cochrane Library, and PubMed (for ahead-of-print publications) for relevant English-language studies. Maximally adjusted risk estimates were pooled under random- and fixed-effects meta-analysis to derive odds ratios (ORs) and 95% confidence intervals (CIs). We included 6 studies representing 183 388 participants. Heterozygnous familial hypercholesterolemia was associated with a higher risk of PAD (OR: 3.59 [95% CI: 1.30-9.89]). This trend was nonsignificantly preserved (OR: 2.96 [95% CI: 0.68-12.88]) in sensitivity analyses of genetically defined HeFH. Genetic HeFH was not associated with increased ischemic stroke risk (OR: 0.76 [95% CI: 0.37-1.58]) although possessing an LDL-C >4.9 mmol/L (190 mg/dL) was (OR: 1.42 [95% CI: 1.06-1.89]). We found clinical and genetic diagnoses of HeFH to be associated with increased PAD risk. Genetically confirmed HeFH may not confer an increased risk of ischemic stroke. Modest associations may exist between LDL-C and ischemic stroke risk in HeFH.


Assuntos
Isquemia Encefálica/genética , Doença das Coronárias/genética , Hipercolesterolemia/genética , Doença Arterial Periférica/genética , Anticolesterolemiantes/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Doença das Coronárias/complicações , Doença das Coronárias/tratamento farmacológico , Humanos , Hipercolesterolemia/complicações , Hipercolesterolemia/tratamento farmacológico , Doença Arterial Periférica/complicações , Doença Arterial Periférica/tratamento farmacológico , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/genética
14.
Expert Opin Emerg Drugs ; 24(1): 63-69, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30841759

RESUMO

INTRODUCTION: Despite the consolidated role of statins and ezetimibe to treat hypercholesterolemia, often the desirable low-density lipoprotein cholesterol (LDL-C) values are not achieved, with a consequent increase of the residual cardiovascular (CV) risk. Areas covered: In this review, we summarize the main pharmacological characteristics of new lipid-lowering drugs, such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, cholesteryl ester transfer protein inhibitors, microsomal triglyceride transfer protein inhibitors, ATP citrate lyase inhibitors, antisense oligonucleotides, small interfering RNA, and peroxisome proliferator-activated receptors type α agonists. The available clinical evidence of efficacy and safety as well as the prospects of application, based on the different mechanisms and targets of action, is critically discussed. Expert opinion: Some of these emerging agents represent an excellent therapeutic strategy to treat patients with LDL largely out of target, resistant or intolerant to statins, trying to minimize the residual CV risk, modulating different classes of lipoproteins, not just LDL. The main challenge for the large use of emerging drugs is their cost. Thus, the correct identification of the adequate target population for treatment is a priority. This is particularly true for safe, powerful, and fully developed drugs such as the PCSK9 inhibitors, for which a relatively large use is potentially expected.


Assuntos
Anticolesterolemiantes/farmacologia , LDL-Colesterol/sangue , Hipercolesterolemia/tratamento farmacológico , Anticolesterolemiantes/efeitos adversos , Doenças Cardiovasculares/prevenção & controle , Custos de Medicamentos , Desenvolvimento de Medicamentos/métodos , Humanos , Hipercolesterolemia/complicações , Hipercolesterolemia/fisiopatologia , Pró-Proteína Convertase 9/antagonistas & inibidores , Fatores de Risco
16.
BMC Neurol ; 19(1): 26, 2019 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-30755166

RESUMO

BACKGROUND: Mixed cerebrovascular disease is a diagnostic entity that presents with hemorrhagic and ischemic stroke clinically and/or subclinically. Here, we report a patient with mixed vascular risk factors, who presented with multiple intracerebral hemorrhages and a simultaneously occurring cerebral infarction with hemorrhagic transformation. CASE PRESENTATION: A 63-year-old male with no history of trauma or prior neurological disease presented with a sudden onset of weakness in his right limbs, followed by an episode of focal seizure without impaired awareness. The patient had a 4-year history of deep vein thrombosis in the lower limbs, and a 2-year history of Raynaud's phenomenon in the hands. He also had a family history of hypertension and thrombophilia. Head computed tomography plain scans showed two high densities in the bilateral parietal lobes and one mixed density in the left frontal lobe. The patient was diagnosed with mixed cerebrovascular disease. In this report, we make a systematic clinical reasoning regarding the etiological diagnosis, and discuss the possible pathogenic mechanisms leading to mixed cerebrovascular disease. We exclude coagulopathy, endocarditis, atrial fibrillation, patent foramen ovale, brain tumor, cerebral venous thrombosis, cerebral vascular malformation, cerebral amyloid angiopathy and vasculitis as causative factors. We identify hypertension, hereditary protein S deficiency, hypercholesteremia and hyperhomocysteinemia as contributing etiologies in this case. CONCLUSION: This case presents complex underlying mechanisms of mixed cerebrovascular disease, in which hypertension and hyperhomocysteinemia are considered to play a central role.


Assuntos
Hipercolesterolemia/complicações , Hiper-Homocisteinemia/complicações , Hipertensão/complicações , Deficiência de Proteína S/complicações , Acidente Vascular Cerebral/etiologia , Isquemia Encefálica/etiologia , Hemorragia Cerebral/etiologia , Humanos , Masculino , Pessoa de Meia-Idade
17.
Nutrients ; 11(2)2019 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-30720747

RESUMO

Vegetarian diets may lower symptomatic gallstone disease via cholesterol lowering. This study aimed to examine the risk of symptomatic gallstone disease (GSD) in Taiwanese vegetarians vs. nonvegetarians in a prospective cohort and to explore if this association is related to cholesterol concentration. We prospectively followed 4839 participants, and in the 29,295 person-years of follow-up, 104 new incident GSD cases were confirmed. Diet was assessed through a validated food frequency questionnaire. Symptomatic GSD was ascertained through linkage to the Taiwan National Health Insurance Research Database. Blood cholesterol profiles were measured at recruitment. Cox regression was applied to assess the effect of diet on symptomatic GSD, adjusting for age, education, smoking, alcohol, physical activities, diabetes, kidney diseases, body mass index, lipid-lowering medication, and hypercholesterolemia. Vegetarian diet was associated with a decreased risk of symptomatic GSD compared with nonvegetarian diet in women (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.28⁻0.96) but not in men. In women, nonvegetarians with hypercholesterolemia had 3.8 times the risk of GSD compared with vegetarians with normal cholesterol (HR, 3.81, 95% CI, 1.61⁻9.01). A vegetarian diet may therefore protect against GSD independent of baseline hypercholesterolemia. A nonvegetarian diet and hypercholesterolemia may have an additive effect in increasing GSD risk in women.


Assuntos
Colesterol/sangue , Dieta Vegetariana/efeitos adversos , Cálculos Biliares/etiologia , Hipercolesterolemia/complicações , Adulto , Idoso , Dieta/efeitos adversos , Inquéritos sobre Dietas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Análise de Regressão , Fatores de Risco , Fatores Sexuais , Taiwan
19.
Yakugaku Zasshi ; 139(5): 807-815, 2019 May 01.
Artigo em Japonês | MEDLINE | ID: mdl-30773524

RESUMO

It is reported that statins have inconsistent effects on glycemic status and adiponectin concentrations in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the effect of statins on these variables in patients with T2DM and hypercholesterolemia. A control group comprising 24 patients with T2DM but without hypercholesterolemia was observed for more than 12 weeks, while 24 patients with T2DM and hypercholesterolemia were treated with statins for the same period (statin group). The percentage changes in the glycemic status [blood glucose and glycated hemoglobin (HbA1c)], and levels of plasma adiponectin [total and high molecular weight (HMW)] were compared between the two groups. The statin group had reduced percentage changes in HbA1c, blood glucose, and total and HMW-adiponectin concentration percentage changes that were similar to those in the control group. However, when matched for sex, age (±5 years) and HbA1c (±0.5%) with the control group, the pravastatin group had reduced percentage changes in the plasma HMW-adiponectin concentrations than the matched controls (p=0.023). However, there were no differences in the percentage changes in the plasma total adiponectin (p=0.137), HbA1c (p=0.202), or blood glucose concentrations (p=0.450) between the two groups. Pravastatin treatment had no effect on the glycemic status of patients with T2DM and hypercholesterolemia, but may reduce the percentage changes in the plasma HMW-adiponectin concentrations. Hence, patients with T2DM and hypercholesterolemia receiving long-term treatment with pravastatin might experience increased insulin resistance.


Assuntos
Adiponectina/sangue , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Hemoglobina A Glicada/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hipercolesterolemia/metabolismo , Pravastatina/farmacologia , Idoso , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hipercolesterolemia/complicações , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Peso Molecular , Pravastatina/administração & dosagem
20.
Gastroenterology ; 156(6): 1693-1706.e12, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30660733

RESUMO

BACKGROUND & AIMS: Concerns related to hepatotoxicity frequently lead to discontinuation or non-initiation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase therapy in patients with cirrhosis despite data supporting statin use. We investigated the independent effects of hyperlipidemia and statin exposure on mortality, hepatic decompensation, and hepatocellular carcinoma development in a large national cohort of patients with cirrhosis. METHODS: We performed a retrospective cohort study of patients with newly diagnosed cirrhosis from January 1, 2008 through June 30, 2016 in the Veterans Health Administration. Subjects were divided into 2 cohorts: 21,921 patients with prior statin exposure (existing users) and 51,023 statin-naïve individuals, of whom 8794 subsequently initiated statin therapy (new initiators) and 44,269 did not (non-initiators). Multivariable Cox proportional hazard models with inverse probability weighting were constructed to assess the effects of time-updating lipid profiles and cumulative exposure to statins on survival and hepatic decompensation. Statin-naïve new initiators were propensity matched with non-initiators to simulate a randomized controlled trial of statin use in cirrhosis. RESULTS: In statin-naïve subjects, every 10-mg/dL increase in baseline total cholesterol was associated with a 3.6% decrease in mortality. In existing users, each year of continued statin exposure was associated with a hazard ratio of 0.920 (95% confidence interval 0.0.897-0.943) for mortality. After risk-set matching, each year of statin exposure among new initiators was associated with a hazard ratio of 0.913 (95% confidence interval 0.890-0.937) for mortality. CONCLUSIONS: In a retrospective cohort study of veterans with a new diagnosis of cirrhosis, we associated hypercholesterolemia with well-preserved hepatic function and decreased mortality. Nonetheless, each cumulative year of statin exposure was associated with an independent 8.0%-8.7% decrease of mortality of patients with cirrhosis of Child-Turcotte-Pugh classes A and B.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/complicações , Hipercolesterolemia/tratamento farmacológico , Cirrose Hepática/mortalidade , Neoplasias Hepáticas/epidemiologia , Idoso , Colesterol/sangue , Feminino , Insuficiência Cardíaca/epidemiologia , Humanos , Hipercolesterolemia/sangue , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Pontuação de Propensão , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologia , Taxa de Sobrevida , Estados Unidos/epidemiologia
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