ABSTRACT BACKGROUND: Central blood pressure is a factor that may predict cardiovascular events. However, its use in clinical practice is not well consolidated. Therefore, the aim of our study will be to summarize the use of central hemodynamic parameters to predict cardiovascular-related outcomes and all-cause mortality. DESIGN AND SETTING: Protocol for systematic review of longitudinal observational studies conducted in healthcare institutions, as presented in the studies included. METHODS: We will perform a systematic search in the electronic databases MEDLINE (via PubMed), EMBASE and LILACS (via Virtual Health Library (VHL)), using health descriptors terms for elderly people and for hemodynamic indices of central blood pressure. We will include articles that evaluated hemodynamic indices and at least one of the following outcomes: all-cause mortality, total cardiovascular death, total non-cardiovascular death, myocardial infarction, stroke, coronary artery restenosis after percutaneous coronary intervention, revascularization and aortic syndromes. Two independent reviewers will conduct analysis on the abstracts selected and on the full-text articles. Two reviewers will independently perform data extraction and evaluate the methodological quality of the articles selected, and a third reviewer will evaluate any divergences. The methodological quality of the studies will be assessed in accordance with the ROBINS-I tool (Risk Of Bias In Non-randomized Studies of Interventions). RESULTS AND CONCLUSIONS: Through this systematic review, we intend to summarize evidence that supports the use of central hemodynamic parameters for central blood pressure to diagnose and perform prognostics on arterial hypertension in elderly patients within clinical practice and predict future cardiovascular events in this population. REGISTRATION: Prospero - CRD42018085264.

Resumo Fundamentos: Crianças com hipercolesterolemia familiar podem desenvolver dano endotelial precoce, aumentando o risco de desenvolver doenças cardiovasculares. As estatinas tiveram sua eficácia em diminuir níveis de colesterol LDL e eventos cardiovasculares em adultos comprovada. O efeito das estatinas na população pediátrica não está claramente demonstrado. Objetivo: Revisar sistematicamente a literatura para avaliar os efeitos e a segurança de diferentes estatinas e suas dosagens nos níveis de colesterol total em crianças e adolescentes com hipercolesterolêmica familiar. Métodos: Artigos publicados desde o início até fevereiro de 2016 foram pesquisados nas bases PubMed, EMBASE, Bireme, Web of Science, Cochrane Library, SciELO e LILACS. Dois revisores independentes avaliaram a qualidade dos estudos incluídos. Realizamos meta-análise com efeitos aleatórios e variância inversa. Análises de subgrupos foram realizadas. Resultados: Dez ensaios envolvendo 1.543 pacientes preencheram os critérios de inclusão. Em nosso estudo, as análises demostraram reduções nos níveis de colesterol, de acordo com a intensidade das doses de estatina (alta, intermediária e baixa): (-104,61 mg/dl, -67,60 mg/dl, -56,96 mg/dl) e no nível de lipoproteínas de baixa densidade: [-105,03 mg/dl (IC95% -115.76, -94.30), I2 19.2%], [-67.85 mg/dl (IC95% -83.36, -52.35), I2 99.8%], [-58.97 mg/dl (IC95% -67.83, -50.11), I2 93,8%. A duração da terapia com estatina variou de 8 a 104 semanas, impedindo conclusões sobre os efeitos a longo prazo. Conclusão: O tratamento com estatinas é eficiente na redução de lipídios em crianças com hipercolesterolemia familiar. É necessário realizar ensaios controlados randomizados de longo prazo para estabelecer a segurança do uso de estatinas a longo prazo.

Abstract Background: Children with familial hypercholesterolemia may develop early endothelial damage leading to a high risk for the development of cardiovascular disease (CVD). Statins have been shown to be effective in lowering LDL cholesterol levels and cardiovascular events in adults. The effect of statin treatment in the pediatric population is not clearly demonstrated. Objective: To systematically review the literature to evaluate the effects of different statins and dosages in total cholesterol levels in children and adolescents with familial hypercholesterolemia. We also aimed to evaluate statin safety in this group. Methods: PubMed, EMBASE, Bireme, Web of Science, Cochrane Library, SciELO and LILACS databases, were searched for articles published from inception until February 2016. Two independent reviewers performed the quality assessment of the included studies. We performed a meta-analysis with random effects and inverse variance, and subgroup analyses were performed. Results: Ten trials involving a total of 1543 patients met the inclusion criteria. Our study showed reductions in cholesterol levels according to the intensity of statin doses (high, intermediate and low): (-104.61 mg/dl, -67.60 mg/dl, -56.96 mg/dl) and in the low-density lipoprotein cholesterol level: [-105.03 mg/dl (95% CI -115.76, -94.30), I2 19.2%], [-67.85 mg/dl (95% CI -83.36, -52.35), I2 99.8%], [-58.97 mg/dl (95% CI -67.83, -50.11), I2 93.8%. The duration of statin therapy in the studies ranged from 8 to 104 weeks, precluding conclusions about long-term effects. Conclusion: Statin treatment is efficient in lowering lipids in children with FH. There is need of large, long-term and randomized controlled trials to establish the long-term safety of statins.

Resumo Fundamento: A segurança em longo prazo, a eficácia e os critérios para o tratamento com estatinas em crianças são ainda pouco claros na prática clínica. Existem evidências muito limitadas para o uso de medicação em crianças com dislipidemia secundária à obesidade e que não respondem bem à modificação do estilo de vida. Objetivo: Revisão sistemática de ensaios clínicos randomizados de uso de estatinas para o tratamento de crianças e adolescentes com dislipidemia secundária à obesidade. Métodos: Realizamos a busca nas bases de dados PubMed, EMBASE, Bireme, Web of Science, Cochrane Library, SciELO e LILACS para coleta de dados para avaliar o efeito das estatinas sobre: melhora dos marcadores de doença arterial coronariana (DAC) nos resultados clínicos na idade adulta, aumento dos níveis séricos de colesterol total (CT), lipoproteína de baixa densidade (LDL-C) e apolipoproteína B (APOB) e diminuição dos níveis de lipoproteína de alta densidade (HDL-C) desde o início até fevereiro de 2016. Crianças e adolescentes foram incluídos. Resultados: Das 16793 citações potencialmente relevantes recuperadas das bases de dados eletrônicas, nenhum ensaio clínico randomizado atendeu aos critérios de inclusão de crianças com dislipidemia secundária à obesidade. Conclusões: Não encontramos evidência específica para considerar as estatinas no tratamento da hipercolesterolemia secundária à obesidade em crianças. A prática usual de extrapolar achados de estudos em dislipidemia genética ignora as diferenças nos riscos cardiovasculares de longo prazo e os riscos de tratamento de drogas de longo prazo, quando comparada com a recomendação de mudanças de estilo de vida. Ensaios clínicos randomizados são necessários para compreender o tratamento medicamentoso na dislipidemia secundária à obesidade.

Abstract Background: Long-term safety, effectiveness and criteria for treatment with statins in children are still unclear in clinical practice. There is very limited evidence for the use of medication to treat children with dyslipidemia secondary to obesity who do not respond well to lifestyle modification. Objective: Systematic review of randomized clinical trials of statin use to treat children and adolescents with dyslipidemia secondary to obesity. Methods: We performed a search in PubMed, EMBASE, Bireme, Web of Science, Cochrane Library, SciELO, and LILACS for data to evaluate the effect of statins on: improvement of surrogate markers of coronary artery disease in clinical outcomes of adulthood; increased serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and apolipropotein B (APOB); and decreased serum levels of high-density lipoprotein cholesterol (HDL-C) from inception to February 2016. Participants were children and adolescents. Results: Of the 16793 potentially relevant citations recovered from the electronic databases, no randomized clinical trials fulfilled the inclusion criteria for children with dyslipidemia secondary to obesity. Conclusions: We found no specific evidence to consider statins in the treatment of hypercholesterolemia secondary to obesity in children. The usual practice of extrapolating findings from studies in genetic dyslipidemia ignores the differences in long-term cardiovascular risks and the long-term drug treatment risks, when compared to recommendation of lifestyle changes. Randomized clinical trials are needed to understand drug treatment in dyslipidemia secondary to obesity.