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

西班牙裔/拉丁裔非酒精性脂肪肝和心血管疾病

• 批准号: 10677955
• 负责人: JORGE R KIZER
• 金额: $ 1.93万
• 依托单位: NORTHERN CALIFORNIA INSTITUTE/RES/EDU
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10677955
• 关键词: 3-Dimensional; Abdomen; Acculturation; Address; Adipose tissue; Affect; Antithrombins; Assimilations; Attenuated; Behavioral; Biopsy; Cardiac; Cardiomyopathies; Cardiovascular Diseases; Cardiovascular system; Chronic stress; Cicatrix; Cirrhosis; Clinical; Data; Diabetes Mellitus; Diagnosis; Diffuse; Disease; Dominican; Endothelium; Environmental Risk Factor; Ethnic group; Evaluation; Exhibits; Factor VIII; Fatty Liver; Fatty acid glycerol esters; Functional disorder; Funding; Gene Frequency; Generations; Genetic; Genetic Predisposition to Disease; Genotype; Habits; Health; Heart; Heart Abnormalities; Heart Diseases; Heart Hypertrophy; Heart failure; Hepatic; High Prevalence; Hispanic; Hispanic Community Health Study/Study of Latinos; Hispanic Populations; Imaging Techniques; Immigration; Inflammatory; Insulin Resistance; Iron; Knowledge; Latino Population; Life Style; Link; Lipids; Liver; Liver Fibrosis; Liver diseases; Longitudinal Studies; Magnetic Resonance Imaging; Malignant neoplasm of liver; Measures; Mediation; Mexican; Multi-Ethnic Study of Atherosclerosis; Myocardial; Myocardial dysfunction; Nature; Not Hispanic or Latino; Obesity; Pathogenesis; Pathway interactions; Phenotype; Policies; Population Study; Predisposition; Prevalence; Prevention approach; Puerto Rican; Reporting; Resources; Risk; Risk Factors; Role; South American; Stress; Structure; Study of Latinos; Testing; Thrombin; Time; Tissues; Variant; Visceral; Visceral fat; Visit; Vulnerable Populations; Women' s Interagency HIV Study; abdominal fat; adiponectin; cohort; coronary fibrosis; emotional distress; ethnic diversity; ethnic minority; ethnic minority population; falls; fatty liver disease; genetic variant; heart imaging; high risk; improved; insight; liver biopsy; liver imaging; liver transplantation; low socioeconomic status; mortality; multimodality; non-alcoholic fatty liver disease; non-genetic; nonalcoholic steatohepatitis; protective factors; psychosocial; residence; response; simple steatosis; social; social culture; socioeconomic adversity

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.

项目摘要/摘要 西班牙裔/拉丁裔（H/L）是美国最大的少数民族群体。尽管社会经济地位较低，但H/L 与非西班牙裔白人（NHW）的死亡率低 - “西班牙裔悖论”。这种生存优势下降 随着时间和一代 资源与移民累积压力相结合，以降低健康。纵向研究 缺乏检查这些因素。同时，有证据表明西班牙裔悖论可能不会 适用于主要疾病。 H/L的非酒精性脂肪肝疾病（NAFLD）的燃烧量很高，其中包括更多 晚期形式，非酒精性脂肪性肝炎（NASH），这成为肝脏最常见的原因 在美国的移植。但是，纳什很难研究，因为诊断取决于活检。 虽然H/L的肥胖和糖尿病也不成比例，但这并不能完全解释NAFLD。 同时，发现两种干扰肝脂质加工但不要 肥胖或胰岛素抵抗的易感性引入了“遗传NAFLD”的概念。这可能是 与H/L特别相关，因为在各种H/L遗产组中，这种变体非常普遍。与众不同 NAFLD，H/L的CVD患病率低于NHW，但心脏功能障碍和心力衰竭风险外观 更高。我们组的数据使用肝脏的部分MRI将肝纤维化与心肌纤维化联系起来。这里 我们将为西班牙裔社区健康研究/拉丁裔研究（SOL）的第三次考试提供机会 以及对比度MRI的优势，以解决这个多元化群体中重要的知识差距。我们计划 评估美国居住与MRI确定的肝纤维化和心肌的关系的关系 应变，同时利用生活方式，社会心理和社会文化因素评估的纵向评估 它们对这些表型的累积影响，并探索移民和养育影响的中介。 我们还将研究内脏脂肪和低脂联素水平以及遗传易感性的贡献， 单独和结合使用肝纤维化。最后，我们将评估肝纤维化与 心肌纤维化，以及可能关联两种疾病的促炎和凝聚因子。这 研究将产生对NAFLD和CVD中西班牙裔悖论及其行为和社会心理的关键见解 确定；新来表征H/L及其遗传基础中肝纤维化的燃烧。和 调查肝脏心脏轴和潜在的途径，以此作为对此健康的潜在严重威胁 脆弱的族裔群体。