Non-alcoholic Fatty Liver Disease and Cardiovascular Disease in Hispanics/Latinos

项目概要/摘要 西班牙裔/拉丁裔（H/L）是美国最大的少数民族。尽管社会经济地位低，H/L 死亡率低于非西班牙裔白人（NHW）--“西班牙裔悖论”。这种生存优势下降 随着时间和世代的推移，这导致了一个命题，即健康的生活习惯和社会的侵蚀 资源联合收割机加上移民的累积压力，使健康状况恶化。纵向研究 缺乏对这些因素的研究。与此同时，有证据表明，西班牙裔议员可能不会 适用于重大疾病。H/L遭受非酒精性脂肪性肝病（NAFLD）的高负担，包括其更多 晚期形式，非酒精性脂肪性肝炎（NASH），这正在成为肝脏疾病的最常见原因。 在美国移植。然而，NASH一直难以研究，因为诊断依赖于活检。 虽然H/L也有不成比例的肥胖和糖尿病负担，但这并不能完全解释NAFLD。 与此同时，发现了两种主要的遗传变异，它们干扰肝脏脂质加工，但不 易患肥胖症或胰岛素抵抗的人，引入了“遗传性NAFLD”的概念。这可能是 这与H/L特别相关，因为其中一种变体在各种H/L遗产群体中非常普遍。不像 H/L组NAFLD、CVD的患病率低于NHW组，但心功能不全和心力衰竭风险出现 高我们研究组的部分肝脏MRI数据表明肝纤维化与心肌纤维化有关。这里 我们将利用西班牙裔社区健康研究/拉丁裔研究（SOL）的第三次考试的机会， 和对比MRI的优势，以解决这个多样化群体中的重要知识差距。我们计划 评估出生和美国居住时间与MRI确定的肝纤维化和心肌纤维化的关系。 压力，同时利用对生活方式、社会心理和社会文化因素的纵向评估， 它们对这些表型的累积影响，并探讨移民和文化适应效应的中介作用。 我们还将研究内脏脂肪和低脂联素水平的贡献，以及遗传易感性， 单独和联合治疗对肝纤维化的影响。最后，我们将评估肝纤维化与 心肌纤维化，沿着可能与这两种疾病相关的促炎和促凝血因子。这 这项研究将对NAFLD和CVD中的西班牙裔患者及其行为和心理社会产生重要的见解。 决定因素; H/L中肝纤维化负担的新特征及其遗传基础;以及 调查肝心轴和潜在的途径作为一个潜在的严重威胁的健康， 弱势族群。

PROJECT SUMMARY/ABSTRACT Hispanics/Latinos (H/L) are the largest minority ethnic group in the US. Despite low socioeconomic status, H/L have lower mortality than non-Hispanic whites (NHW) – the “Hispanic Paradox.” This survival advantage declines with time and generation, which has led to the proposition that erosion of healthful lifestyle habits and social resources combine with the cumulative stresses of immigration to degrade health. Longitudinal studies examining these factors are lacking. At the same time, there is evidence that the Hispanic Paradox may not apply to major diseases. H/L suffer a high burden of non-alcoholic fatty liver disease (NAFLD), including its more advanced form, non-alcoholic steatohepatitis (NASH), which is becoming the most common cause of liver transplant in the US. NASH has been difficult to study, however, because the diagnosis has depended on biopsy. While H/L also have a disproportionate burden of obesity and diabetes, this does not fully account for NAFLD. Meanwhile, discovery of two major genetic variants that interfere with hepatic lipid processing, but do not predispose to obesity or insulin resistance, has introduced the concept of “genetic NAFLD.” This may be of particular relevance to H/L, because one such variant is highly prevalent in various H/L heritage groups. Unlike NAFLD, prevalence of CVD is lower in H/L than NHW, but cardiac dysfunction and heart failure risk appear higher. Data from our group using partial MRI of the liver has linked hepatic fibrosis to myocardial fibrosis. Here we will parlay the opportunity for a third exam of the Hispanic Community Health Study/Study of Latinos (SOL), and the strengths of contrast MRI, to address important knowledge gaps in this diverse group. We plan to evaluate relations of nativity and duration of US residence with MRI-determined hepatic fibrosis and myocardial strain, while leveraging longitudinal assessments of lifestyle, psychosocial and sociocultural factors to assess their cumulative impact on these phenotypes, and to explore mediation of immigration and acculturation effects. We will also examine the contributions of visceral fat and low adiponectin levels, as well as genetic susceptibility, alone and in combination, to hepatic fibrosis. Last, we will evaluate the association between hepatic fibrosis and myocardial fibrosis, along with proinflammatory and procoagulant factors that may link the two disorders. This study will yield key insights into the Hispanic Paradox in NAFLD and CVD and their behavioral and psychosocial determinants; newly characterize the burden of hepatic fibrosis in H/L and its genetic underpinnings; and investigate the liver-heart axis and underlying pathways as a potentially serious threat to the health of this vulnerable ethnic group.