Impact of Cardiovascular and Weight Loss diets on Uric Acid and Gout Risk

描述（由申请人提供）：痛风是一种常见的、疼痛难忍的炎性关节炎，与高尿酸血症有关。痛风是一种代谢驱动的关节病，可以通过饮食和生活方式的改变来控制。随着美国持续的“西方”生活方式，痛风的患病率和发病率在过去几十年中有所增加，根据最新的美国NHANES数据，估计3.9%的美国成年人（830万人）患有痛风。痛风的这种显著负担因其高水平的心血管（CV）代谢合并症（例如， 74%的高血压和53%的肥胖）及其后果（例如，增加未来心肌梗死和过早死亡的风险）。目前的低嘌呤饮食方法对痛风提供有限的疗效，适口性和可持续性，并促进精制碳水化合物和饱和脂肪的消费增加，实际上可以通过导致胰岛素抵抗和血浆葡萄糖，甘油三酯和LDL胆固醇水平升高来恶化痛风的CV代谢合并症。因此，迫切需要一个统一的、可持续的、 和有效的预防策略，从整体上解决痛风及其相关的合并症。事实上，有经证实的有效饮食方法可以减少CV代谢状况（包括肥胖），也可以通过降低肥胖和胰岛素抵抗来降低血清尿酸（SUA）水平和痛风风险。这些现有的方法可能提供一种理想的饮食策略，以降低痛风及其相关CV代谢疾病的风险。在这项研究中，我们将根据我们在痛风预防研究方面的丰富经验，研究这些饮食方法对SUA和痛风结果的影响。我们将使用来自6项里程碑式随机对照试验的储存血液样本研究其对SUA水平的影响，这些试验采用各种饮食方法来减少CV代谢状况（包括地中海饮食、阿特金斯饮食和DASH饮食）（目标1-3）。通过所有6项试验的PI参与本项目，我们将充分利用原始RCT设计和收集的数据。此外，我们将基于3个大型前瞻性队列评估其对痛风风险的影响：护士健康研究（NHS）I（n= 121，700名女性），NHS II（n= 116，430名年轻女性）和卫生专业人员随访研究（HPFS; n= 51，529名男性）（目标4）。我们将利用系统收集的经过严格验证的高质量数据，包括>3,200例确诊的偶发痛风病例。这些目标具有革命性的潜力，我们的非药物降尿酸方法，高尿酸血症和痛风，同时调查多种候选饮食使用一个高度成本效益的研究设计。这些措施还将全面解决与痛风疾病负担上升相关的主要合并症。凭借我们丰富的痛风研究经验和资源丰富的数据访问，我们处于独特和无与伦比的地位，以解决美国及其他地区面临的这些关键问题。

DESCRIPTION (provided by applicant): Gout is a common and excruciatingly painful inflammatory arthritis associated with hyperuricemia. Gout represents a metabolically-driven arthropathy that could be substantially controlled through dietary and lifestyle modifications. With the continued "western" lifestyle in the US, the prevalence and incidence of gout have increased over the last few decades and it is estimated that 3.9% of US adults (8.3 million individuals) have had gout according to the latest US NHANES data. This remarkable burden of gout is further complicated by its high level of cardiovascular (CV)-metabolic comorbidities (e.g., hypertension in 74% and obesity in 53% of cases) and their consequences (e.g., increased future risk of myocardial infarction and premature death). The current low-purine dietary approach to gout offers limited efficacy, palatability, and sustainability, and promotes increased consumption of refined carbohydrates and saturated fat that can actually worsen gout's CV-metabolic comorbidities by leading to insulin-resistance and increased levels of plasma glucose, triglycerides, and LDL-cholesterol. Therefore, there is an urgent need for a unifying, sustainable, and effective prevention strategy that holistically addresses both gout and its associated comorbidities. In fact, there are proven, effective dietary approaches to reduce CV-metabolic conditions (including obesity) that could also lower serum uric acid (SUA) levels and the risk of gout by lowering adiposity and insulin resistance. These existing approaches could potentially provide an ideal dietary strategy to reduce both the risk of gout and its associated CV-metabolic conditions. In this study, we will build upon our extensive experience with gout prevention research to examine the impact of these dietary approaches on the outcomes of both SUA and gout. We will investigate their effects on SUA levels using stored blood samples from 6 landmark randomized controlled trials of various dietary approaches to reduce CV-metabolic conditions (including the Mediterranean, Atkins, and DASH diets) (Aims 1-3). Through participation of the PIs of all 6 trials in this project, we will take full advantage of the originl RCT designs and collected data. Further, we will evaluate their impact on the risk of gout based on 3 large prospective cohorts: the Nurses' Health Study (NHS) I (n=121,700 women), NHS II (n=116,430 younger women), and the Health Professionals Follow-up Study (HPFS; n=51,529 men) (Aim 4). We will take advantage of systematically collected high- quality data that have undergone rigorous validation including >3,200 confirmed cases of incident gout. These aims hold the potential to revolutionize our non-pharmacological urate-lowering approaches to hyperuricemia and gout by simultaneously investigating multiple candidate diets using a highly cost-effective study design. These measures will also comprehensibly address the major comorbidities associated with the rising disease burden of gout. With our extensive gout research experience combined with resourceful data access, we are in a unique and unparalleled position to address these key issues facing the field in the US and beyond.