DD Genotype and Atherosclerosis in Overweight Menopausal Women

Abstract Background Sex-specific pathology of coronary artery disease (CAD) has not been recognized. Women with obstructive or nonobstructive CAD associated with traditional risk factors have similar events; no studies have explored both populations in association with genetic markers. Objective To evaluate the DD genotype in overweight menopausal women and its association with CAD and traditional risk factors. Method This cross-sectional study included 356 menopausal women who underwent coronary angiography as CAD assessment. The patients' DNA was extracted and polymorphisms were detected with a single polymerase chain reaction assay. Two groups were formed based on luminal lesions (normal [n = 134] or pathological [n = 222]) with a cutoff value > 30%, considering overweight and age. The chi-square test, Student's t-test, and multivariate logistic regression were performed as appropriate (p < 0.05) using the following variables: overweight, diabetes, hypertension, dyslipidemia, smoking status, sedentary lifestyle, and a family history of CAD. Results The mean age of the sample was 63 + 8 years, and the mean BMI was 28 + 5 kg/m2. The DD genotype was slightly more prevalent in the pathological group (30.2% vs. 21.6%, p = 0.079), but this significantly changed when BMI > 25 was considered (33% vs. 18%, p = 0.012). In multivariate analysis with two threshold levels (> 50 and > 60 years), diabetes was significantly associated with CAD in both models (p = 0.021 vs. 0.009) but the genotype was only associated with younger age (p = 0.034). Conclusion These data support an association between atherosclerosis and the renin-angiotensin system in overweight menopausal women that is dependent on the age at which the ischemic event occurs.

Economic evaluation in the context of rare diseases: is it possible? / Evaluación económica en el contexto de enfermedades raras: ¿es posible? / Avaliação econômica no âmbito das doenças raras: isto é possível?

This study analyzes the available evidence on the adequacy of economic evaluation for decision-making on the incorporation or exclusion of technologies for rare diseases. The authors conducted a structured literature review in MEDLINE via PubMed, CRD, LILACS, SciELO, and Google Scholar (gray literature). Economic evaluation studies had their origins in Welfare Economics, in which individuals maximize their utilities based on allocative efficiency. There is no widely accepted criterion in the literature to weigh the expected utilities, in the sense of assigning more weight to individuals with greater health needs. Thus, economic evaluation studies do not usually weigh utilities asymmetrically (that is, everyone is treated equally, which in Brazil is also a Constitutional principle). Healthcare systems have ratified the use of economic evaluation as the main tool to assist decision-making. However, this approach does not rule out the use of other methodologies to complement cost-effectiveness studies, such as Person Trade-Off and Rule of Rescue.

El objetivo fue sistematizar las evidencias disponibles sobre la pertinencia de utilizar la evaluación económica para la incorporación/exclusión de tecnología en enfermedades raras. Se realizó una revisión sistemática de la literatura en MEDLINE vía PubMed, CRD, LILACS, SciELO y Google Académico (literatura gris). Los estudios de evaluación económica se originan de la Economía del Bienestar, en la que los individuos maximizan sus utilidades, basándose en la eficiencia de asignación. No existe un criterio ampliamente aceptado para examinar las utilidades, a fin de dar más peso a los individuos con mayores necesidades. Generalmente, los estudios no equilibran asimétricamente las utilidades, todas son consideradas iguales, lo que en Brasil es también un principio constitucional. Los sistemas de salud han ratificado el uso de la evaluación económica como la principal herramienta para ayudar en la toma de decisiones. Sin embargo, este abordaje no excluye el uso de otras metodologías complementarias a los estudios de coste-efectividad, como la técnica de compensación personal o la regla del rescate.

O objetivo deste estudo foi analisar as evidências disponíveis sobre a adequação do uso de avaliação econômica sobre incorporação/exclusão de tecnologias para doenças raras. Foi realizada uma revisão estruturada da literatura, nas bases MEDLINE, via PubMed, CRD, LILACS, SciELO e Google Acadêmico (literatura cinzenta). Os estudos de avaliação econômica têm origem na Economia do Bem-Estar, na qual os indivíduos maximizam suas utilidades, fundamentando-se na eficiência alocativa. Não há um critério amplamente aceito para ponderar as utilidades esperadas, no sentido de dar mais peso aos indivíduos com maiores necessidades em saúde. Geralmente não se ponderam assimetricamente as utilidades; todas são tratadas de forma igualitária, que, no caso brasileiro, também é um princípio constitucional. Os sistemas de saúde têm ratificado o uso de avaliação econômica como principal instrumento para auxiliar na tomada de decisão. No entanto, essa postura não exclui o uso de outras metodologias complementares aos estudos de custo-efetividade, como Person Trade-Off e regra de resgate.

NADPH oxidasa: rol en aterosclerosis y función plaquetaria / NADPH OXIDASE: role in atherosclerosis and platelet function

Reactive oxygen species have emerged as important molecules in cardiovascular function. Recent research has shown that the NADPH oxidases are important sources of superoxide in vascular cells and myocytes. The NADPH oxidases vascular share some, but not all, of the characteristics of the enzyme in neutrophils, both produce superoxide, which is metabolized to hydrogen peroxide, at the same time these reactive oxygen species serve as second messengers activate multiple intracellular signalling pathways. NADPH oxidases are essential in the physiological response of vascular cellsto pathological states such as atherosclerosis, and are functionally relevant in activation and recruitment of platelets. Recent studies suggest a key role for NADPH oxidase in the formation of a specific product from the oxidation of arachidonic acid, and a potential role in the process of recruitment of platelets. Taking into account these characteristics and evidence of the involvement of the NADPH oxidases in cardiovascular diseases as the thrombosis, inhibition of this enzymatic system appears as a promising therapy to treat and prevent these diseases.

Lipasa endotelial y su relación con la enfermedad cardiovascular y diabetes mellitus tipo 2 / The role of endothelial lipase in atherogenesis

Endothelial lipase (EL) is synthetized by endothelial cells and its main substrates are lipoprotein phospholipids. Over expression of EL reduces high density lipoprotein (HDL) cholesterol and phospholipids, in vivo and in vitro. Inhibition of the enzyme achieves the opposite effects. The synthesis of the enzyme is regulated by interleukin 1 and tumor necrosis factor a. These inflammatory cytokines play a role in diabetes and vascular disease. An increase in vascular mechanical forces, that play a role in atherogenesis, also increase the synthesis of EL. There is expression of EL in endothelial cells, macrophages and muscle cells of atherosclerotic lesions of coronary arteries of humans. This evidence leads to the suspicion that EL plays a role in atherogenesis. There are also higher plasma levels of EL in subjects with type 2 diabetes, who are especially susceptible to the development of vascular lesions. Therefore the inhibition of EL could play an important role in HDL metabolism and could be a new therapeutic strategy for the prevention of atherosclerosis.

[Metalloproteinases: therapeutic target in atherosclerosis]

Matrix metalloproteinases are a family of enzymes which collectively can cleave all components of the extracellular matrix. In physiological situations, the expression of matrix metalloproteinases is very low. The increase of their expression leads to several diseases as atherosclerosis, restenosis, rheumatoid arthritis and cancers. In atherosclerosis, metalloproteinases are implicated in the rupture of the atheromatous plaque and contribute to acute vascular accident. Consequently, several studies hypothesized that the inhibition of matrix metalloproteinases activity could reduce the volume of the atheromatous plaque and prevent its destabilisation and therefore could be useful in the treatment of atherosclerosis, However, clinical results have so far been inconclusive because matrix metalloproteinases inhibitors are not very specific. The development of selective inhibitors and gene transfer approaches may better suit the treatment of atherosclerosis