Associações de biomarcadores sanguíneos e mudanças estruturais na aterosclerose no Estudo Longitudinal da Saúde do Adulto (ELSA-Brasil): ênfase em mulheres na pré e pós-menopausa

Background: Cardiovascular disease is the leading cause of morbidity and mortality in women worldwide. Cardiovascular risk prediction is incomplete and new markers may help in the early identification of atherosclerosis. Brazilian epidemiological data in women are scarce. Objectives: To review the impact of menopause and diabetes on lipids, lipoprotein subfractions and cardiovascular risk; evaluate cardiometabolic risk in women from the ELSA-Brasil, as well as associations of blood biomarkers [lipoprotein subfractions, insulin resistance index (HOMA-IR) and branched-chain amino acids (BCAA)] and structural changes of atherosclerosis [presence of calcium in the coronary arteries (CAC)] according to age and menopausal status. Methods: Cross-sectional baseline analyzes of 2,258 female participants from the São Paulo site of the ELSA-Brasil, stratified by age and menopausal status, with specific sample and eligibility criteria for each paper. Descriptive statistics, between-group comparisons and multiple regression were performed according to the nature and distribution of the variables for each paper. Results: Paper 1: Literature revision enabled conclusions regarding the association of menopause and diabetes with a worse lipid profile, including hypertriglyceridemia, lower levels of HDL-c and HDL2-c, higher levels of HDL3-c and small dense LDL-c. Postmenopausal diabetic women consist of the highest cardiovascular risk level. Paper 2: Comparing pre- and postmenopausal women categorized according to time since menopause [menopausal duration 45 years and postmenopausal women (n=2047), postmenopausal ones had the worst cardiometabolic risk profile. CAC>0 was found to be associated with TRL-c and dense LDL-c, but not with BCAA levels nor HOMA-IR. Postmenopausal women were about twice as likely to have CAC>0 than younger premenopausal ones [OR 2.37 (95%CI 1.17-4.81)]. Discussion: Our findings suggest that natural menopause is associated with changes in lipoprotein fractions and subfractions (especially in the first 2 years post-menopause) and with calcium deposition in the coronary arteries independently of age and other risk factors, but not with BCAA nor HOMA-IR. Deep investigation on lipid profile and other biomarkers in women approaching to menopause is needed in order to identify cardiovascular risk, prevent cardiovascular outcomes and provide better health conditions.Introdução: A doença cardiovascular se constitui na principal causa de morbimortalidade em mulheres globalmente. A predição de evento cardiovascular é incompleta e novos marcadores de risco cardiometabólico podem auxiliar na identificação precoce da aterosclerose. Dados epidemiológicos brasileiros no sexo feminino são mais escassos. Objetivos: Revisar o impacto da menopausa e diabetes nas lipoproteínas, subfrações e risco cardiovascular; avaliar o perfil de risco cardiometabólico de mulheres do ELSA-Brasil, bem como associações de marcadores sanguíneos [subfrações de lipoproteínas circulantes, índice de resistência à insulina (HOMA-IR) e aminoácidos de cadeia ramificada (BCAA)] e estruturais [cálcio nas artérias coronárias (CAC)] de aterosclerose segundo sua idade e estado menopausal. Métodos: Análise transversal de dados basais de 2258 mulheres acompanhadas no centro de São Paulo do ELSA-Brasil, estratificadas por idade e estado menopausal, respeitando características amostrais estabelecidas para cada artigo. Estatística descritiva, testes de comparação entre grupos e análises de regressão múltipla foram realizadas conforme natureza e distribuição das variáveis para cada artigo. Resultados: Artigo 1: A revisão da literatura permitiu concluir sobre a associação de menopausa e diabetes com pior perfil lipídico, consistindo de hipertrigliceridemia, baixos níveis de HDL-c e HDL2-c e elevados de HDL3-c e LDL-c pequena e densa. Mulheres menopausadas com diabetes apresentam o maior risco cardiovascular. Artigo 2: Comparando-se mulheres pré-menopausadas com as menopausadas, categorizadas segundo tempo de menopausa [duração 45 anos e as menopausadas (n=2047), pior perfil de risco cardiometabólico foi encontrado em mulheres na pós- menopausa. Observou-se associação entre CAC>0 com TRL-c e LDL-c densa, mas não com HOMA-IR e BCAA. Mulheres menopausadas tiveram cerca de 2 vezes mais chance de apresentar CAC>0 quando comparadas com mulheres mais jovens na pré-menopausa [OR 2,37 (IC95% 1,17-4,81)]. Discussão: Nossos achados sugerem que a menopausa natural está associada a alterações no perfil lipídico tradicional e subfrações (especialmente nos primeiros 2 anos pós-menopausa) e ao depósito de cálcio nas artérias coronárias independentemente da idade e de outros fatores de risco, mas não com BCAA e HOMA-IR. Investigação aprofundada do perfil lipídico e outros marcadores de risco cardiovascular em mulheres que se aproximam da menopausa pode melhorar a identificação de risco, prevenção de desfechos cardiovasculares e proporcionar melhores condições de saúde

Impact of menopause and diabetes on atherogenic lipid profile: is it worth to analyse lipoprotein subfractions to assess cardiovascular risk in women?

Abstract Cardiovascular disease is the leading cause of death in women at advanced age, who are affected a decade later compared to men. Cardiovascular risk factors in women are not properly investigated nor treated and events are frequently lethal. Both menopause and type 2 diabetes substantially increase cardiovascular risk in the female sex, promoting modifications on lipid metabolism and circulating lipoproteins. Lipoprotein subfractions suffer a shift after menopause towards a more atherogenic lipid profile, consisted of hypertriglyceridemia, lower levels of both total high density lipoprotein (HDL) and its subfraction HDL2, but also higher levels of HDL3 and small low-density lipoprotein particles. This review discusses the impact of diabetes and menopause to the lipid profile, challenges in lipoprotein subfractions determination and their potential contribution to the cardiovascular risk assessment in women. It is still unclear whether lipoprotein subfraction changes are a major driver of cardiometabolic risk and which modifications are predominant. Prospective trials with larger samples, methodological standardizations and pharmacological approaches are needed to clarify the role of lipoprotein subfractions determination on cardiovascular risk prediction and intervention planning in postmenopausal women, with or without DM

Effects of High-Intensity Training of Professional Runners on Myocardial Hypertrophy and Subclinical Atherosclerosis

<div><p>To evaluate the effects of long-term exposure to high-intensity training among professional runners on cardiac hypertrophy and subclinical atherosclerosis.</p><p>Prospective study included runners of both sexes (n = 52) and age and gender matched controls (n = 57), without classical cardiovascular risk factors. Ventricular hypertrophy was quantified by echocardiography by linear method and carotid intima-media thickness (cIMT) by 2-D images obtained by ultrasonography. Endothelial function was evaluated by flow-mediated dilation (FMD). Steroid hormones were quantified by HPLC followed by LC-MS/MS. Higher left ventricular (LV) mass index was found in male athletes (p<0.0001 vs. other groups). When adjusted for gender, the degree of left ventricular mass index classified as mildly, moderately or severely abnormal was obtained in 26%, 35%, and 30%, respectively, of female athletes, and in 39%, 14%, and 21%, respectively, of male athletes. Higher ratio of the early (E) to late (A) ventricular filling velocities was found in athletes of both genders. Male athletes presented lower cIMT in the right (p = 0.012 vs. male controls) and left (p<0.0001 vs. male controls) common carotid arteries, without differences in cIMT between female athletes and controls. FMD results were similar among groups. Higher serum testosterone levels were found in male athletes (p<0.0001 vs. other groups) and they were correlated with LV mass (r = 0.50, p<0.0001). The chronic exposure of high-intensity training among professional runners of both genders was associated with increased ventricular mass and adaptive remodeling. Less subclinical atherosclerosis was found in male athletes. Differences in steroid hormones may account in part for these findings.</p></div

Carotid intima-media thickness, by study groups.

<p>A- Right common carotid artery (RCCA). B- Left common carotid artery (LCCA). Comparisons were made by ANOVA-Tukey.</p

Echocardiographic parameters, by group.

<p>Echocardiographic parameters, by group.</p

Echocardiographic characteristics of the study population, by group.

<p>A-Left ventricular mass index (LV mass index). B-Left ventricular Ejection Fraction (LVEF). C-Left ventricular mass (LV mass). D-Early (E) to late (A) ventricular filling velocities ratio (E/A ratio). Comparisons were made by ANOVA-Tukey.</p