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1.
Int Heart J ; 61(5): 872-878, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32921669

RESUMO

In-stent restenosis (ISR) still exists after drug-eluting stent (DES) implantation, even up to one year. The incidence and risk factors for neoatherosclerosis in patients with early ISR have not yet been elucidated. Here, we used optical coherence tomography (OCT) to evaluate the incidence and predictors of neoatherosclerosis in patients with early ISRs.OCT was performed on ISR lesions in 185 patients in order to detect neoatherosclerosis. The median follow-up was 180 days, and neoatherosclerosis was detected in 37% of early ISR lesions. According to the presence of neoatherosclerosis, patients with ISR were divided into two groups: neoatherosclerosis (group A, n = 69) and non-neoatherosclerosis (group B, n = 116) groups.The risk factors were similar, except for hypercholesterolemia. Moreover, the tissue characteristics were not significantly different between patients with and without neoatherosclerosis. Follow-up low-density lipoprotein-cholesterol (LDL-C) levels were divided into three grades (LDL < 70 mg/dL, 70 mg/dL≤ LDL < 100 mg/dL, and LDL ≥ 100 mg/dL). The incidence of neoatherosclerosis was significantly lower (23% versus 57%, P < 0.0001) in the LDL < 70 mg/dL group. There was no significant difference in the incidence of neoatherosclerosis in patients with lipid levels between 70 and 100 mg/dL (P = 0.53). However, neoatherosclerosis was significantly more common in patients with a follow-up LDL-C level > 100 mg/dL (45% versus 15%, P < 0.0001).In patients with early ISR lesions, the LDL-C levels may be related to the formation and progression of early neoatherosclerosis, and poor LDL-C control may be a risk factor for the occurrence of early-stage neoatherosclerosis following DES implantation.


Assuntos
LDL-Colesterol/sangue , Doença da Artéria Coronariana/epidemiologia , Reestenose Coronária/epidemiologia , Stents Farmacológicos , Hipercolesterolemia/epidemiologia , Neointima/epidemiologia , Idoso , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Reestenose Coronária/diagnóstico por imagem , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Incidência , Masculino , Pessoa de Meia-Idade , Neointima/diagnóstico por imagem , Fatores de Risco , Tomografia de Coerência Óptica
2.
Med Hypotheses ; 143: 110127, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32759008

RESUMO

Fenofibrate, which is a PPAR-alfpha agonist, increases the level of sulfatide. In this letter we hypothesize on the background of various findings that this is beneficial against COVID-19. Fenofibrate has been used for decades against hypercholesterolemia and has no serious side effects. Therefore, a trial giving fenofibrate to patients with corona virus infection is recommended.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/tratamento farmacológico , Fenofibrato/farmacologia , Hipolipemiantes/farmacologia , Pandemias , Pneumonia Viral/tratamento farmacológico , Sulfoglicoesfingolipídeos/sangue , Adulto , Envelhecimento/sangue , Criança , Reposicionamento de Medicamentos , Fenofibrato/uso terapêutico , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/complicações , Hipertensão/sangue , Hipertensão/complicações , Hipolipemiantes/uso terapêutico , PPAR alfa/antagonistas & inibidores , Internalização do Vírus
3.
PLoS Med ; 17(7): e1003121, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32673317

RESUMO

BACKGROUND: Bempedoic acid is a first-in-class lipid-lowering drug recommended by guidelines for the treatment of hypercholesterolemia. Our objective was to estimate its average effect on plasma lipids in humans and its safety profile. METHODS AND FINDINGS: We carried out a systematic review and meta-analysis of phase II and III randomized controlled trials on bempedoic acid (PROSPERO: CRD42019129687). PubMed (Medline), Scopus, Google Scholar, and Web of Science databases were searched, with no language restriction, from inception to 5 August 2019. We included 10 RCTs (n = 3,788) comprising 26 arms (active arm [n = 2,460]; control arm [n = 1,328]). Effect sizes for changes in lipids and high-sensitivity C-reactive protein (hsCRP) serum concentration were expressed as mean differences (MDs) and 95% confidence intervals (CIs). For safety analyses, odds ratios (ORs) and 95% CIs were calculated using the Mantel-Haenszel method. Bempedoic acid significantly reduced total cholesterol (MD -14.94%; 95% CI -17.31%, -12.57%; p < 0.001), non-high-density lipoprotein cholesterol (MD -18.17%; 95% CI -21.14%, -15.19%; p < 0.001), low-density lipoprotein cholesterol (MD -22.94%; 95% CI -26.63%, -19.25%; p < 0.001), low-density lipoprotein particle number (MD -20.67%; 95% CI -23.84%, -17.48%; p < 0.001), apolipoprotein B (MD -15.18%; 95% CI -17.41%, -12.95%; p < 0.001), high-density lipoprotein cholesterol (MD -5.83%; 95% CI -6.14%, -5.52%; p < 0.001), high-density lipoprotein particle number (MD -3.21%; 95% CI -6.40%, -0.02%; p = 0.049), and hsCRP (MD -27.03%; 95% CI -31.42%, -22.64%; p < 0.001). Bempedoic acid did not significantly modify triglyceride level (MD -1.51%; 95% CI -3.75%, 0.74%; p = 0.189), very-low-density lipoprotein particle number (MD 3.79%; 95% CI -9.81%, 17.39%; p = 0.585), and apolipoprotein A-1 (MD -1.83%; 95% CI -5.23%, 1.56%; p = 0.290). Treatment with bempedoic acid was positively associated with an increased risk of discontinuation of treatment (OR 1.37; 95% CI 1.06, 1.76; p = 0.015), elevated serum uric acid (OR 3.55; 95% CI 1.03, 12.27; p = 0.045), elevated liver enzymes (OR 4.28; 95% CI 1.34, 13.71; p = 0.014), and elevated creatine kinase (OR 3.79; 95% CI 1.06, 13.51; p = 0.04), though it was strongly associated with a decreased risk of new onset or worsening diabetes (OR 0.59; 95% CI 0.39, 0.90; p = 0.01). The main limitation of this meta-analysis is related to the relatively small number of individuals involved in the studies, which were often short or middle term in length. CONCLUSIONS: Our results show that bempedoic acid has favorable effects on lipid profile and hsCRP levels and an acceptable safety profile. Further well-designed studies are needed to explore its longer-term safety.


Assuntos
Anticolesterolemiantes/uso terapêutico , Ácidos Dicarboxílicos/uso terapêutico , Ácidos Graxos/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Anticolesterolemiantes/efeitos adversos , Apolipoproteínas B/sangue , Colesterol/sangue , LDL-Colesterol/sangue , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Ácidos Dicarboxílicos/efeitos adversos , Ácidos Graxos/efeitos adversos , Humanos , Hipercolesterolemia/sangue , Fragmentos de Peptídeos/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Arterioscler Thromb Vasc Biol ; 40(9): 2310-2321, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32611242

RESUMO

OBJECTIVE: Plant stanol ester supplementation (2-3 g plant stanols/d) reduces plasma LDL (low-density lipoprotein) cholesterol concentration by 9% to 12% and is, therefore, recommended as part of prevention and treatment of atherosclerotic cardiovascular disease. In addition to plasma LDL-cholesterol concentration, also qualitative properties of LDL particles can influence atherogenesis. However, the effect of plant stanol ester consumption on the proatherogenic properties of LDL has not been studied. Approach and Results: Study subjects (n=90) were randomized to consume either a plant stanol ester-enriched spread (3.0 g plant stanols/d) or the same spread without added plant stanol esters for 6 months. Blood samples were taken at baseline and after the intervention. The aggregation susceptibility of LDL particles was analyzed by inducing aggregation of isolated LDL and following aggregate formation. LDL lipidome was determined by mass spectrometry. Binding of serum lipoproteins to proteoglycans was measured using a microtiter well-based assay. LDL aggregation susceptibility was decreased in the plant stanol ester group, and the median aggregate size after incubation for 2 hours decreased from 1490 to 620 nm, P=0.001. Plant stanol ester-induced decrease in LDL aggregation was more extensive in participants having body mass index<25 kg/m2. Decreased LDL aggregation susceptibility was associated with decreased proportion of LDL-sphingomyelins and increased proportion of LDL-triacylglycerols. LDL binding to proteoglycans was decreased in the plant stanol ester group, the decrease depending on decreased serum LDL-cholesterol concentration. CONCLUSIONS: Consumption of plant stanol esters decreases the aggregation susceptibility of LDL particles by modifying LDL lipidome. The resulting improvement of LDL quality may be beneficial for cardiovascular health. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01315964.


Assuntos
Dieta , Ésteres/administração & dosagem , Hipercolesterolemia/dietoterapia , Lipoproteínas LDL/sangue , Fitosteróis/administração & dosagem , Agregados Proteicos , Adulto , Idoso , Biomarcadores/sangue , LDL-Colesterol/sangue , Método Duplo-Cego , Feminino , Finlândia , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/diagnóstico , Lipidômica , Masculino , Pessoa de Meia-Idade , Proteoglicanas/sangue , Esfingomielinas/sangue , Fatores de Tempo , Resultado do Tratamento , Triglicerídeos/sangue , Adulto Jovem
5.
Am J Cardiol ; 128: 163-167, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32650914

RESUMO

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are novel drugs that provide striking lowering of low-density lipoprotein cholesterol (LDL-C) when added to maximum tolerated therapy in patients with hypercholesterolemia. Ceramides, novel cardiac risk markers, have been associated with increased cardiovascular mortality, independent of traditional cardiovascular risk factors. The Ceramide Risk Score (CRS) predicts the likelihood of adverse cardiovascular events within 1 to 3 years in patients with coronary artery disease. The effect of PCSK9 inhibition on plasma ceramides is not well known. The study examines the effect of PCSK9 inhibitors on plasma ceramides and CRS in patients with clinical indication for this therapy. Retrospective chart review of consecutive patients with hypercholesterolemia on PCSK9 inhibitors was conducted (n = 24; Mayo Clinic 2015 to 2018). Plasma ceramides were measured before the initiation of PCSK9 inhibitors and 2 to 12 months after treatment. CRS was calculated before and after therapy based on individual plasma concentrations of 4 ceramides. Treatment with PCSK9 inhibitors was associated with significant reduction in mean CRS and individual ceramides levels (p <0.0001). CRS significantly improved with PCSK9 therapy. PCSK9 inhibitors significantly decreased LDL-C levels by 63% (p <0.0001). The absolute reduction in CRS did not correlate with the absolute reduction in LDL-C (r = 0.31; confidence interval -0.10 to 0.64), indicating that CRS may evaluate a different pathway for risk reduction beyond LDL-C lowering. In conclusion, treatment with PCSK9 inhibitors is associated with significant reduction in CRS and distinct ceramide levels.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticolesterolemiantes/uso terapêutico , Ceramidas/sangue , Hipercolesterolemia/tratamento farmacológico , Pró-Proteína Convertase 9/antagonistas & inibidores , 1-Alquil-2-acetilglicerofosfocolina Esterase/sangue , Idoso , Apolipoproteína A-I/sangue , Apolipoproteínas B/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Hipercolesterolemia/sangue , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Lipoproteína(a)/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
6.
Am J Cardiol ; 128: 28-34, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32650921

RESUMO

Involvement of atherosclerosis in extracardiac vascular territories may identify coronary artery disease (CAD) patients at higher risk for adverse events. We investigated the long-term prognostic implications of polyvascular disease in patients with CAD, and further analyzed lipid goal attainment and its relation to patient outcomes. The study was a retrospective analysis of 10,297 patients who underwent coronary revascularization, categorized as having CAD alone (83.1%) or with multisite artery disease (MSAD) (16.9%) including cerebrovascular disease (CBVD) and/or peripheral artery disease (PAD). Incidence rates and hazard ratios (HR) for major adverse cardiovascular events (MACE) (myocardial infarction, ischemic stroke, or all-cause death) according to vascular territories involved, and in relation to most-recent lipid levels attained, were analyzed. Patients with MSAD were older with higher burden of co-morbidities. The rate of MACE (myocardial infarction, ischemic stroke, or all-cause death) and its individual components increased with the number of affected vascular beds. Adjusted HR (95% confidence interval) for MACE was 1.41 (1.24 to 1.59) in patients with CAD and CBVD, 1.46 (1.33 to 1.62) in CAD and PAD, and 1.69 (1.49 to 1.92) in those with CAD and CBVD and PAD, compared with CAD alone. Most-recent low-density lipoprotein cholesterol (LDL-C) levels <55 mg/dl and <70 mg/dl were attained by 21.8% and 44.6% of patients with CAD alone, in comparison to 22.7% and 43.3% in MSAD. Compared with patients with most-recent LDL-C > 100 mg/dl, attaining LDL-C < 70 mg/dl had an adjusted HR for MACE of 0.52 (0.47 to 0.57) in CAD only patients and 0.66 (0.57 to 0.78) in MSAD patients. In conclusion, the presence of CBVD and/or PAD in patients with CAD is associated with higher burden of co-morbidities and progressive increase in long-term MACE. More than half of CAD patients with or without MSAD do not achieve lipid goals, which are associated with a significantly lower risk for adverse events.


Assuntos
Transtornos Cerebrovasculares/epidemiologia , Doença da Artéria Coronariana/cirurgia , Hipercolesterolemia/terapia , Infarto do Miocárdio/epidemiologia , Revascularização Miocárdica , Doença Arterial Periférica/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Angina Instável/epidemiologia , Angina Instável/cirurgia , Aneurisma da Aorta Abdominal/epidemiologia , Causas de Morte , LDL-Colesterol/sangue , Comorbidade , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/epidemiologia , Feminino , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/epidemiologia , Incidência , Israel/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mortalidade , Infarto do Miocárdio sem Supradesnível do Segmento ST/epidemiologia , Infarto do Miocárdio sem Supradesnível do Segmento ST/cirurgia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia
7.
Nature ; 582(7810): 73-77, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32494083

RESUMO

High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular risk-changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million-4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.


Assuntos
LDL-Colesterol/sangue , Hipercolesterolemia/sangue , Hipercolesterolemia/epidemiologia , Internacionalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Teorema de Bayes , HDL-Colesterol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/sangue , Isquemia Miocárdica/epidemiologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia , Triglicerídeos/sangue , Adulto Jovem
8.
Internist (Berl) ; 61(6): 573-586, 2020 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-32394074

RESUMO

The treatment of elevated plasma lipids plays an important role in atherosclerosis prevention. Low-density lipoprotein (LDL) cholesterol lowering with statins and, if required, additional inhibition is of the utmost importance. Lifestyle modification plays only a minor role in LDL cholesterol lowering. Absolute cardiovascular risk determines whether and at what intensity lipid lowering therapy should be implemented. Thus, in patients at very high risk, an LDL cholesterol level <55 mg/dl (<1.4 mmol/l) and a 50% reduction from baseline should be achieved. With respect to elevated triglyceride concentrations, treatment goals are less clearly defined, despite the fact that elevated triglyceride concentrations are causally linked to atherosclerotic events. Lifestyle modification can significantly reduce triglyceride concentrations and are often more effective than specific triglyceride lowering medications. New lipid lowering drugs still need to prove their clinical benefit in endpoint trials.


Assuntos
Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipolipemiantes/uso terapêutico , LDL-Colesterol , Dislipidemias/sangue , Medicina Baseada em Evidências/tendências , Humanos , Hipercolesterolemia/sangue , Hiperlipoproteinemias/sangue , Hipertrigliceridemia/sangue , Triglicerídeos/sangue
9.
Nutr Metab Cardiovasc Dis ; 30(7): 1137-1146, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32456947

RESUMO

BACKGROUND AND AIMS: The increased risk of cardiovascular disease under hypercholesterolemia is due to associations between oxidized low-density lipoprotein (ox-LDL) and lipoprotein-associated phospholipase A2 (Lp-PLA2) and between ox-LDL and coagulant profiles. We investigated the impact of different ox-LDL levels on coagulation time and plasma metabolomes in subjects with borderline hypercholesterolemia. METHODS AND RESULTS: One hundred thirty-one subjects with borderline hypercholesterolemia (serum cholesterol ≥200 mg/dL) were divided into low ox-LDL (n = 66) and high ox-LDL (n = 65) groups. After adjusting for confounding factors, the high ox-LDL group exhibited a significantly decreased activated partial thromboplastin time (aPTT) and prothrombin time (PT) and increased Lp-PLA2 activity. Compared to the low ox-LDL group, the high ox-LDL group exhibited significantly increased intensities of 17 lysophosphatidylcholines (lysoPCs) and 7 lysophosphatidylethanolamines (lysoPEs). Ox-LDL was inversely correlated with aPTT and PT and positively correlated with Lp-PLA2 activity. Positive correlations were also found among ox-LDL, Lp-PLA2 activity, lysoPCs, and lysoPEs. LysoPCs and lysoPEs were inversely correlated with PT and aPTT. The identified plasma metabolites, including amino acids, fatty acid amides, acylcarnitines, and lysophospholipids, were significantly upregulated in the high ox-LDL group. CONCLUSION: High ox-LDL levels may be involved in the development of a procoagulant state in subjects with borderline hypercholesterolemia by increasing Lp-PLA2 activity and lysoPC and lysoPE levels.


Assuntos
1-Alquil-2-acetilglicerofosfocolina Esterase/sangue , Fatores de Coagulação Sanguínea/análise , Coagulação Sanguínea , Hipercolesterolemia/sangue , Lipoproteínas LDL/sangue , Lisofosfatidilcolinas/sangue , Lisofosfolipídeos/sangue , Biomarcadores/sangue , Feminino , Humanos , Hipercolesterolemia/diagnóstico , Hipercolesterolemia/enzimologia , Masculino , Metabolômica , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Regulação para Cima
10.
Clín. investig. arterioscler. (Ed. impr.) ; 32(2): 49-58, mar.-abr. 2020. tab, graf
Artigo em Inglês | IBECS | ID: ibc-187146

RESUMO

Background and aims: The first line of therapy in children with hypercholesterolaemia is therapeutic lifestyle changes (TLSC). The efficacy of lifestyle intervention in children with familial hypercholesterolaemia (FH), where LDL-C levels are genetically driven, deserves a focused study. Aims: To evaluate the impact of a lifestyle education program, focused on food patterns and physical activity, on lipid profiles assessed by nuclear magnetic resonance (NMR) in children with FH vs. non-FH. Methods: Phase 1 was a cross-sectional study of baseline characteristics, and phase 2 was a prospective TLSC intervention study. In total, the study included 238 children (4 to 18 years old; 47% girls) attending the lipid unit of our hospital due to high cholesterol levels. Eighty-five were diagnosed with FH (72% genetic positive), and 153 were diagnosed with non-Familial hypercholesterolaemia. A quantitative food frequency questionnaire (FFQ) including 137 items was used. Physical activity (PA) was assessed by the Minnesota questionnaire. The lipid profile was assessed using the 2D-1H-NMR (Liposcale test). A total of 127 children (81 in the FH group) participated in the prospective phase and were re-assessed after 1 year of the TLSC intervention, consisting of education on lifestyle changes delivered by a specialized nutritionist. Results: The FH and non-FH groups were similar in anthropometry and clinical data, except that those in the FH were slightly younger than those in the non-FH group. Both the FH and non-FH groups showed a similar diet composition characterized by a high absolute calorie intake and a high percentage of fat, mainly saturated fat. The PA was below the recommended level in both groups. After one year of TLSC, the percentage of total and saturated fats was reduced, and the amount of fiber increased significantly in both groups. The percentage of protein increased slightly. The number of children engaged in at least 1 hour/day of PA increased by 56% in the FH group and by 53% in the non-FH group, and both these increases were significant. The total and small-LDL particle numbers were reduced in both groups, although the absolute change was greater in the FH group than in the non-FH group. Conclusions: Educational strategies to implement TLSC in children lead to empowerment, increased adherence, and overall metabolic improvement in children with high blood cholesterol, including those with FH


Antecedentes y objetivos: La primera línea de terapia en niños con hipercolesterolemia son los cambios terapéuticos en el estilo de vida (TLSC). La eficacia de la intervención en el estilo de vida en niños con hipercolesterolemia familiar (HF), en los que los niveles de LDL-C son generados genéticamente, merece un estudio específico. Objetivos: Evaluar el impacto de un programa de educación sobre el estilo de vida, centrado en los patrones alimentarios y la actividad física, sobre el perfil lipídico evaluado por resonancia magnética nuclear (RMN) en niños con HF versus no HF. Métodos: La fase 1 fue un estudio transversal de las características basales, y la fase 2 fue un estudio prospectivo de intervención mediante TLSC. En total, el estudio incluyó a 238 niños (de 4 a 18 años; 47% niñas) que asistieron a la unidad de lípidos de nuestro hospital debido a los altos niveles de colesterol. Ochenta y cinco fueron diagnosticados con HF (72% genéticamente positivos), y 153 fueron diagnosticados de no HF. Se utilizó un cuestionario cuantitativo de frecuencia de alimentos (FFQ) que incluye 137 ítems. La actividad física (AF) se evaluó mediante el cuestionario de Minnesota. El perfil lipídico se evaluó mediante la prueba 2D-1H-NMR (Liposcale Test). Un total de 127 niños (81 en el grupo HF) participaron en la fase prospectiva y fueron reevaluados después de 1 año de la intervención mediante TLSC, que consistió en educación sobre cambios en el estilo de vida impartida por una nutricionista especializada. Resultados: Los grupos HF y no HF fueron similares en los datos antropométricos y clínicos, excepto que los HF eran ligeramente más jóvenes que los no HF. Los participantes de ambos grupos mostraron una composición de dieta similar caracterizada por un alto consumo de calorías totales y un alto porcentaje de grasas, principalmente grasas saturadas. La AF estuvo por debajo del nivel recomendado en ambos grupos. Después de un año de TLSC, se redujo el porcentaje de grasas totales y saturadas, y la cantidad de fibra aumentó significativamente en ambos grupos. El porcentaje de proteína aumentó ligeramente. El número de niños involucrados en al menos 1 hora/día de AF aumentó en un 56% en el grupo de HF y en un 53% en el grupo sin HF, y ambos aumentos fueron significativos. Los números de partículas LDL totales y pequeñas se redujeron en ambos grupos, aunque el cambio absoluto fue mayor en el grupo HF que en el grupo no HF. Conclusiones: Las estrategias educativas para implementar TLSC en niños conducen al empoderamiento, al aumento de la adherencia y a la mejora metabólica general en niños con colesterol alto en sangre, incluidos aquellos con HF


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Hipercolesterolemia/sangue , Hipercolesterolemia/terapia , Estilo de Vida , Educação de Pacientes como Assunto , Lipoproteínas LDL/sangue , Dietoterapia , Terapia por Exercício , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/terapia , Ressonância Magnética Nuclear Biomolecular , Estudos Transversais , Estudos Prospectivos , Resultado do Tratamento
11.
Nutr Metab Cardiovasc Dis ; 30(6): 907-914, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32249143

RESUMO

BACKGROUND AND AIM: General population awareness about cardiovascular risk factors is usually low. The aim of the present study was to evaluate the vascular aging of subjects aware and not aware to be hypertensive, hypercholesterolemic, hypertriglyceridemic or diabetics in a general population sample. METHODS AND RESULTS: We interviewed 1652 subjects without atherosclerotic cardiovascular diseases (M: 46.6%, F: 53.4%) about their awareness of hypertension, hypercholesterolemia, hypertriglyceridemia or type 2 diabetes. Then we compared the augmentation index and pulse wave velocity of subjects aware and not aware of the investigated cardiovascular risk factors. 1049 participants declared not to be hypertensive, while 32 were not sure. Among them, respectively, 23.5% and 50% were hypertensive. Subjects not aware of their hypertension had significantly higher aortic blood pressure than aware ones (p < 0.001). 841 participants declared not to be hypercholesterolemic, while 60 were not sure. Among them, respectively, 18.1% and 40% were hypercholesterolemic. Subjects not aware of their hypercholesterolemia had significantly higher augmentation index than the aware ones (p < 0.05). 1226 participants declared not to be hypertriglyceridemic, while 200 were not sure. Among them, respectively, 19.2% and 44% were hypertriglyceridemic. Subjects not aware of their hypertriglyceridemia had significantly higher TG levels aware ones (p < 0.05), although this seemed to not related to increased arterial stiffness. 1472 participants declared not to be diabetic, while 20 were not sure. Among them, respectively, 2.0% and 25.0% were diabetics. Subjects not aware of their diabetes had significantly higher augmentation index than the aware ones (p < 0.05). CONCLUSIONS: In conclusion, the lack of awareness of hypertension and hypercholesterolemia is relatively frequent in the general population and is associated to significantly higher arterial stiffness.


Assuntos
Envelhecimento , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus/epidemiologia , Hipercolesterolemia/epidemiologia , Hipertensão/epidemiologia , Hipertrigliceridemia/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Glicemia/metabolismo , Pressão Sanguínea , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Colesterol/sangue , Estudos Transversais , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Feminino , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/diagnóstico , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Hipertrigliceridemia/sangue , Hipertrigliceridemia/diagnóstico , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Triglicerídeos/sangue , Rigidez Vascular , Adulto Jovem
12.
Stroke ; 51(5): 1546-1554, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32312223

RESUMO

Background and Purpose- The PCSK9 (proprotein convertase subtilisin-kexin type 9) monoclonal antibody evolocumab lowered LDL (low-density lipoprotein) cholesterol by 59% to 0.8 (0.5-1.2) mmol/L and significantly reduced major vascular events in the FOURIER trial (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk). Herein, we report the results of a prespecified analysis of cerebrovascular events in the overall trial population and in patients stratified by prior stroke. Methods- FOURIER was a randomized, double-blind trial comparing evolocumab versus placebo in patients with established atherosclerosis, additional risk factors, and LDL cholesterol levels ≥1.8 (or non-HDL [high-density lipoprotein] ≥2.6 mmol/L) on statin therapy. The median follow-up was 2.2 years. We analyzed the efficacy of evolocumab to reduce overall stroke and stroke subtypes, as well as the primary cardiovascular composite end point by subgroups according to a history of stroke. Results- Among the 27 564 patients, 469 (1.7%) experienced a total of 503 strokes of which 421 (84%) were ischemic. Prior ischemic stroke, diabetes mellitus, elevated CRP (C-reactive protein), history of heart failure, older age, nonwhite race, peripheral arterial disease, and renal insufficiency were independent predictors of stroke. Evolocumab significantly reduced all stroke (1.5% versus 1.9%; hazard ratio, 0.79 [95% CI, 0.66-0.95]; P=0.01) and ischemic stroke (1.2% versus 1.6%; hazard ratio, 0.75 [95% CI, 0.62-0.92]; P=0.005), with no difference in hemorrhagic stroke (0.21% versus 0.18%; hazard ratio, 1.16 [95% CI, 0.68-1.98]; P=0.59). These findings were consistent across subgroups, including among the 5337 patients (19%) with prior ischemic stroke in whom the hazard ratios (95% CIs) were 0.85 (0.72-1.00) for the cardiovascular composite, 0.90 (0.68-1.19) for all stroke, and 0.92 (0.68-1.25) for ischemic stroke (P interactions, 0.91, 0.22, and 0.09, respectively, compared with patients without a prior ischemic stroke). Conclusions- Inhibition of PCSK9 with evolocumab added to statin in patients with established atherosclerosis reduced ischemic stroke and cardiovascular events in the total population and in key subgroups, including those with prior ischemic stroke. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT01764633.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticolesterolemiantes/uso terapêutico , Aterosclerose/tratamento farmacológico , Hipercolesterolemia/tratamento farmacológico , Infarto do Miocárdio/epidemiologia , Doença Arterial Periférica/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Idoso , Aterosclerose/epidemiologia , LDL-Colesterol/sangue , Método Duplo-Cego , Feminino , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia
13.
PLoS One ; 15(4): e0231506, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32298312

RESUMO

Hypercholesterolaemia is considered an important cause of atherosclerotic cardiovascular disease. In a previous investigation, we demonstrated that cultured hepatoma cells treated with hypercholesterolaemic sera compared with cells treated with normocholesterolaemic sera show overexpression of mRNAs related to mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase (HMGCS2). In the present work, using an NMR metabolomic analysis, we demonstrate that the hypercholesterolaemic blood sera previously used to treat cultured hepatoma cells are characterized by a metabolomic profile that is significantly different from the normocholesterolaemic sera. Acetate, acetone, 2-hydroxybutyrate, cysteine, valine, and glutamine are the metabolites distinguishing the two groups. Abnormalities in the concentrations of these metabolites reflect alterations in energy-related pathways, such as pantothenate and CoA biosynthesis, pyruvate, glycolysis/gluconeogenesis, the citrate cycle, and ketone bodies. Regarding ketone bodies, the pathway is regulated by HMGCS2; therefore, serum samples previously found to be able to increase HMGCS2 mRNA levels in cultured cells also contain higher amounts of the metabolites of its encoded enzyme protein product.


Assuntos
Hipercolesterolemia/sangue , Metabolômica , Adulto , Carcinoma Hepatocelular/metabolismo , Estudos de Casos e Controles , Linhagem Celular Tumoral , Expressão Gênica/fisiologia , Humanos , Hidroximetilglutaril-CoA Sintase/metabolismo , Hipercolesterolemia/metabolismo , Neoplasias Hepáticas/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Redes e Vias Metabólicas , Pessoa de Meia-Idade
14.
Am J Cardiol ; 125(9): 1312-1316, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32143815

RESUMO

Sitosterolemia is a rare lipid metabolism disease with heterogeneous manifestations. Atherosclerosis can occur in children, and therefore, early detection, diagnosis, and treatment of this disease are important. We studied 18 pediatric patients with sitosterolemia who showed a significant increase in plasma lipid levels and analyzed their clinical, biochemical, and genetic characteristics. We recorded the initial serum lipid results and clinical manifestations of the patients. Lipid and plant sterol levels were measured after homozygous or compound heterozygous mutations of ABCG5 or ABCG8 were identified by genetic testing. Plasma plant sterol levels were analyzed by gas chromatography. Fourteen cases of sitosterolemia were examined by ultrasound and echocardiography. The initial total cholesterol and low-density lipoprotein levels of the children were significantly increased, but then markedly decreased after diet control or drug treatment, and even reached normal levels. Carotid atherosclerosis and aortic valve regurgitation were present in three of 14 patients. Serum lipid levels of children with sitosterolemia and xanthomas were notably higher than those without xanthomas. There were no significant differences in clinical manifestations between patients with different genotypes. In conclusion, sitosterolemia should be considered in children with hyperlipidemia who do not present with xanthomas, especially with a significant increase in total cholesterol and low-density lipoprotein levels. There does not appear to be a correlation between clinical phenotype and genotype.


Assuntos
Hipercolesterolemia/diagnóstico , Enteropatias/diagnóstico , Erros Inatos do Metabolismo Lipídico/diagnóstico , Fitosteróis/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Hipercolesterolemia/sangue , Lactente , Enteropatias/sangue , Erros Inatos do Metabolismo Lipídico/sangue , Masculino , Fitosteróis/sangue
15.
N Engl J Med ; 382(16): 1507-1519, 2020 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-32187462

RESUMO

BACKGROUND: Inclisiran inhibits hepatic synthesis of proprotein convertase subtilisin-kexin type 9. Previous studies suggest that inclisiran might provide sustained reductions in low-density lipoprotein (LDL) cholesterol levels with infrequent dosing. METHODS: We enrolled patients with atherosclerotic cardiovascular disease (ORION-10 trial) and patients with atherosclerotic cardiovascular disease or an atherosclerotic cardiovascular disease risk equivalent (ORION-11 trial) who had elevated LDL cholesterol levels despite receiving statin therapy at the maximum tolerated dose. Patients were randomly assigned in a 1:1 ratio to receive either inclisiran (284 mg) or placebo, administered by subcutaneous injection on day 1, day 90, and every 6 months thereafter over a period of 540 days. The coprimary end points in each trial were the placebo-corrected percentage change in LDL cholesterol level from baseline to day 510 and the time-adjusted percentage change in LDL cholesterol level from baseline after day 90 and up to day 540. RESULTS: A total of 1561 and 1617 patients underwent randomization in the ORION-10 and ORION-11 trials, respectively. Mean (±SD) LDL cholesterol levels at baseline were 104.7±38.3 mg per deciliter (2.71±0.99 mmol per liter) and 105.5±39.1 mg per deciliter (2.73±1.01 mmol per liter), respectively. At day 510, inclisiran reduced LDL cholesterol levels by 52.3% (95% confidence interval [CI], 48.8 to 55.7) in the ORION-10 trial and by 49.9% (95% CI, 46.6 to 53.1) in the ORION-11 trial, with corresponding time-adjusted reductions of 53.8% (95% CI, 51.3 to 56.2) and 49.2% (95% CI, 46.8 to 51.6) (P<0.001 for all comparisons vs. placebo). Adverse events were generally similar in the inclisiran and placebo groups in each trial, although injection-site adverse events were more frequent with inclisiran than with placebo (2.6% vs. 0.9% in the ORION-10 trial and 4.7% vs. 0.5% in the ORION-11 trial); such reactions were generally mild, and none were severe or persistent. CONCLUSIONS: Reductions in LDL cholesterol levels of approximately 50% were obtained with inclisiran, administered subcutaneously every 6 months. More injection-site adverse events occurred with inclisiran than with placebo. (Funded by the Medicines Company; ORION-10 and ORION-11 ClinicalTrials.gov numbers, NCT03399370 and NCT03400800.).


Assuntos
Anticolesterolemiantes/uso terapêutico , LDL-Colesterol/sangue , Doença da Artéria Coronariana/tratamento farmacológico , Hipercolesterolemia/tratamento farmacológico , Pró-Proteína Convertase 9/antagonistas & inibidores , RNA Interferente Pequeno/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anticolesterolemiantes/efeitos adversos , Anticolesterolemiantes/farmacocinética , Doenças Cardiovasculares , Doença da Artéria Coronariana/complicações , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/sangue , Hipercolesterolemia/complicações , Injeções Subcutâneas/efeitos adversos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , RNA Interferente Pequeno/efeitos adversos , RNA Interferente Pequeno/farmacocinética , Fatores de Risco
16.
J Pharmacol Sci ; 143(1): 45-51, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32169433

RESUMO

The leaves of Lindera aggregate (Sims) Kosterm. are traditionally used as healthy tea for the prevention and treatment of hyperlipidemia in Chinese. The aim of this study was to evaluate the antihyperlipidemic effects and potential mechanisms of the aqueous extracts from L. aggregate leaves (AqLA-L) on normal and hypercholesterolemic (HCL) mice. HCL mice were induced by high fat diet (HFD) and orally administrated with or without AqLA-L for ten days. The results showed that AqLA-L (0.3, 0.6, 1.2 g/kg) significantly reduced serum TG, ALT, but elevated fecal TG in normal mice. AqLA-L (0.3, 0.6, 1.2 g/kg) also remarkably lowered serum TC, TG, LDL, N-HDL, ALT, GLU, APOB, hepatic GLU and increased serum HDL, APOA-I, fecal TG levels in HCL mice. These results revealed that AqLA-L treatment regulated the disorders of the serum lipid and liver function, reduced hepatic GLU contents both in normal and HCL mice. The potential mechanisms for cholesterol-lowering effects of AqLA-L might be up-regulation of cholesterol 7-alpha-hydroxylase (CYP7A1) and ATP-binding cassette transporter A1 (ABCA1), as well as down-regulation of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR). The data indicated that AqLA-L has potential therapeutic value in treatment of hyperlipidemia with great application security.


Assuntos
Hipercolesterolemia/sangue , Hipercolesterolemia/metabolismo , Lindera/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Extratos Vegetais/farmacologia , Folhas de Planta/química , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Administração Oral , Animais , Colesterol 7-alfa-Hidroxilase/metabolismo , Hidroximetilglutaril-CoA Redutases/metabolismo , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/fisiopatologia , Fígado/fisiopatologia , Masculino , Camundongos Endogâmicos ICR , Fitoterapia , Extratos Vegetais/administração & dosagem , Regulação para Cima/efeitos dos fármacos , Água
18.
PLoS One ; 15(2): e0219412, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32106257

RESUMO

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) has a wide spectrum, eventually leading to cirrhosis and hepatic carcinogenesis. We previously reported that a series of microRNAs (miRNAs) mapped in the 14q32.2 maternally imprinted gene region (Dlk1-Dio3 mat) are related to NAFLD development and progression in a mouse model. We examined the suitability of miR-379, a circulating Dlk1-Dio3 mat miRNA, as a human NAFLD biomarker. METHODS: Eighty NAFLD patients were recruited for this study. miR-379 was selected from the putative Dlk1-Dio3 mat miRNA cluster because it exhibited the greatest expression difference between NAFLD and non-alcoholic steatohepatitis in our preliminary study. Real-time PCR was used to examine the expression levels of miR-379 and miR-16 as an internal control. One patient was excluded due to low RT-PCR signal. RESULTS: Compared to normal controls, serum miR-379 expression was significantly up-regulated in NAFLD patients. Receiver operating characteristic curve analysis suggested that miR-379 is a suitable marker for discriminating NAFLD patients from controls, with an area under the curve value of 0.72. Serum miR-379 exhibited positive correlations with alkaline phosphatase, total cholesterol, low-density-lipoprotein cholesterol and non-high-density-lipoprotein cholesterol levels in patients with early stage NAFLD (Brunt fibrosis stage 0 to 1). The correlation between serum miR-379 and cholesterol levels was lost in early stage NAFLD patients treated with statins. Software-based predictions indicated that various energy metabolism-related genes, including insulin-like growth factor-1 (IGF-1) and IGF-1 receptor, are potential targets of miR-379. CONCLUSIONS: Serum miR-379 exhibits high potential as a biomarker for NAFLD. miR-379 appears to increase cholesterol lipotoxicity, leading to the development and progression of NAFLD, via interference with the expression of target genes, including those related to the IGF-1 signaling pathway. Our results could facilitate future research into the pathogenesis, diagnosis, and treatment of NAFLD.


Assuntos
Hipercolesterolemia/sangue , MicroRNAs/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Hipercolesterolemia/etiologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Regulação para Cima
19.
Am J Cardiol ; 125(6): 874-879, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31952841

RESUMO

Treatment guidelines recommend monitoring of lipids to assess efficacy and adherence to lipid lowering therapy. We assessed whether lipid profile monitoring is associated with intensification of cholesterol lowering therapy. Patients from the Veterans Affairs (VA) healthcare system with atherosclerotic cardiovascular disease and at least one primary care visit between October 2013 and September 2014 were included (n = 1,061,753). Treatment intensification was defined as the initiation of a statin, an increase in the intensity or dose of statin therapy and/or the addition of ezetimibe. An association between the number of lipid panels and treatment intensification was assessed with adjusted regression models. During the study period, 87.1% of included patients had ≥1 lipid panel. Patients with ≥1 lipid panel were more likely to undergo treatment intensification compared with individuals with 0 lipid panels (9.3% vs 5.4%, respectively, p <0.001). Among individuals not on statin therapy at the index date (n = 287,636), those with ≥1 lipid panel were more likely to have a statin initiated compared those who without a lipid panel (21.5% vs 8.7%, p <0.001). On regression analysis (odds ratio [OR] [95% confidence interval {CI}]), patients with 1 lipid panel (1.55 [1.50 to 1.59]), 2 to 3 lipid panels (1.76 [1.71 to 1.81]) and >3 lipid panels (3.02 [2.90 to 3.14]) showed greater odds of treatment intensification compared with individuals without a lipid panel. In conclusion, lipid monitoring is associated with higher rates of treatment intensification in patients with atherosclerotic cardiovascular disease. This has important clinical implications as higher intensity regimens with statins and in combination with select nonstatin therapies is associated with improved cardiovascular outcomes.


Assuntos
LDL-Colesterol/sangue , Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Lipídeos/sangue , Monitorização Fisiológica , Serviços de Saúde para Veteranos Militares , Idoso , Idoso de 80 Anos ou mais , Anticolesterolemiantes/uso terapêutico , Aterosclerose/sangue , Aterosclerose/tratamento farmacológico , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/tratamento farmacológico , Ezetimiba/uso terapêutico , Feminino , Fidelidade a Diretrizes , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Razão de Chances , Resultado do Tratamento , Estados Unidos
20.
Lipids Health Dis ; 19(1): 1, 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31900179

RESUMO

BACKGROUND: The aim of this study was to compare and summarize the lipid-altering effects of combination therapy with ezetimibe and statins (E/S) and a double dose of statin (D/S) monotherapy on patients with hypercholesterolemia. METHODS: We conducted search on 2 medical databases, PubMed and EMBASE to identify all relevant studies. A meta-analysis was performed to clarify the efficacy in the two groups. Only double-blind Randomized controlled study (RCTs) of efficacy evaluation in the two groups with ezetimibe and statins and a double dose of statin in participants with hypercholesterolemia that examined low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and high-density lipoprotein (HDL) were included. Two reviewers extracted data from all primary studies independently. The primary data were the level of LDL-C, TC and HDL-C concentrations at the end point and are expressed as mean and standard deviation (SD). RESULTS: A total of 11 double-blind, active or placebo-controlled studies with 1926 hypercholesterolemia adults randomized to ezetimibe 10 mg added to ongoing statins (N = 994) or statin titration (doubling) (N = 932) were pooled for the global meta-analysis. The effect size between treatment groups within individual studies was assessed by weighted mean difference (MD) using a random- or fixed-effect model. The result showed that the participants in E/S group get obvious lower LDL-C [MD = -13.14 mg/dL, 95%CI (-16.83, -9.44), p = 0.00001] and TC concentration [MD = -23.79 mg/dL, 95%CI (-38.65, -8.93), p = 0.002] from baseline to follow-up, comparing to the D/S group. Besides, no significant between-group differences were observed for concentrations of HDL-C [MD = 0.46 mg/dL, 95%CI (- 1.14, 2.06), p = 0.57]. According to subgroup analysis, the combination of ezetimibe and atorvastatin (10 mg) [MD = -16.98 mg/dL, p < 0 .0001] or simvastatin (20 mg) [MD = -17.35 mg/dL, p < 0 .0001] showed stronger ability of reducing LDL-C than combination of ezetimibe and rosuvastatin (10 mg) [MD = -9.29 mg/dL, p = 0.05]. The efficacy of short-term (endpoint time between 6 to 16 week) and long-term (52 week) treatment in the LDL-C between two groups did not show significant differences. Besides, only participants from Asia treated with combination therapy were associated with a significant lower LDL-C concentration [MD = -14.7 mg/dL, p < 0 .0001]. CONCLUSIONS: The addition of ezetimibe to statin appears to be more effective on reducing LDL-C and TC concentrations than doubling the statin dose. Moreover, the ability to reduce cholesterol levels of combinations therapy with ezetimibe and different statins or to participants from different geographic location may vary, based on this meta-analysis, while more samples are needed to verify.


Assuntos
Combinação de Medicamentos , Ezetimiba/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Idoso , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/patologia , Masculino , Pessoa de Meia-Idade
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