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

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 代表一种代谢驱动的关节病，可以通过饮食和生活方式基本控制 修改.随着美国持续的“西方”生活方式，痛风的患病率和发病率已 在过去几十年中有所增加，据估计3.9%的美国成年人（830万人） 根据美国NHANES的最新数据，这种显著的负担痛风进一步复杂化 由于其高水平的心血管（CV）代谢合并症（例如，高血压占74%， 53%的病例）及其后果（例如，增加未来心肌梗死和过早死亡的风险 死亡）。目前的低嘌呤饮食方法对痛风提供有限的疗效，适口性， 可持续性，并促进增加精制碳水化合物和饱和脂肪的消费， 事实上，通过导致胰岛素抵抗和高水平的 血浆葡萄糖、甘油三酯和LDL-胆固醇。因此，迫切需要一个统一的、 可持续和有效的预防策略，全面解决痛风及其相关疾病 合并症。事实上，有经过验证的有效饮食方法可以减少CV代谢状况 （包括肥胖），也可以降低血清尿酸（SUA）水平和痛风的风险，通过降低 肥胖和胰岛素抵抗。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代谢状况的风险。在这项研究中，我们将建立在我们的 痛风预防研究的广泛经验，以检查这些饮食方法对 SUA和痛风的结果。我们将使用储存的血液样本研究它们对SUA水平的影响 来自6项具有里程碑意义的随机对照试验，这些试验采用各种饮食方法来降低CV代谢 条件（包括地中海、阿特金斯和DASH饮食）（目标1-3）。通过参加 本项目中所有6项试验的PI，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： 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例男性）（目标4）。我们将利用系统收集的高- 经过严格验证的高质量数据，包括超过3，200例确诊的痛风病例。这些 aims有可能彻底改变我们治疗高尿酸血症的非药物降尿酸方法 和痛风通过同时调查多种候选饮食使用高成本效益的研究 设计这些措施还将全面解决与药物滥用增加相关的主要合并症。 痛风的疾病负担凭借我们广泛的痛风研究经验和丰富的数据访问， 我们处于一个独特和无与伦比的地位，以解决美国和其他地区面临的这些关键问题。

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 original 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.