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

描述(由申请人提供)：痛风是一种常见且极度疼痛的炎症性关节炎，与高尿酸血症有关。痛风是一种代谢驱动的关节病，可以通过改变饮食和生活方式得到很大程度的控制。随着“西式”生活方式在美国的持续，痛风的患病率和发病率在过去几十年里有所上升，根据美国NHANES的最新数据，估计有3.9%的美国成年人(830万人)患有痛风。这种显著的痛风负担由于其高水平的心血管(CV)代谢共病(例如， 74%的病例患有高血压，53%的病例患有肥胖症)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的疗效、适口性和可持续性有限，并促进精制碳水化合物和饱和脂肪的消费增加，这实际上会导致胰岛素抵抗和血糖、甘油三酯和低密度脂蛋白水平升高，从而恶化痛风的心血管代谢并存。因此，迫切需要一个统一的、可持续的、 有效的预防策略，从整体上解决痛风及其相关的并存问题。事实上，有被证明有效的饮食方法可以减少心血管代谢状况(包括肥胖)，还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潜在地提供一种理想的饮食策略来降低痛风及其相关的心血管代谢状况的风险。在这项研究中，我们将建立在我们在痛风预防研究方面的广泛经验的基础上，检查这些饮食方法对SUA和痛风结果的影响。我们将使用6个里程碑式的随机对照试验的储存血液样本来研究它们对血尿酸水平的影响，这些试验是关于各种饮食方法以减少CV代谢条件的(包括地中海饮食、阿特金斯饮食和DASH饮食)(目标1-3)。通过参与该项目的所有6个试验的PI，我们将充分利用原始的随机对照试验设计和收集的数据。此外，我们将根据3个大的前瞻性队列来评估它们对痛风风险的影响：护士健康研究(NHS)I(n=121,700名女性)、NHS II(n=116,430名年轻女性)和卫生专业人员后续研究(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&gt；3200例痛风事件确诊病例。这些目标有可能通过使用高成本效益的研究设计同时调查多个候选饮食来彻底改变我们治疗高尿酸血症和痛风的非药物降尿酸方法。这些措施还将全面解决与痛风疾病负担上升相关的主要并存问题。凭借我们丰富的痛风研究经验和足智多谋的数据访问，我们处于独特和无与伦比的地位，可以解决美国和其他地区该领域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.