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

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 代表一种新陈代谢驱动的关节病，可通过饮食和生活方式基本控制 修改。随着美国持续的“西式”生活方式，痛风的患病率和发病率 在过去的几十年里有所增加，据估计，3.9%的美国成年人(830万人) 根据美国NHANES的最新数据，他患有痛风。痛风的这种显著负担进一步复杂化 由于其高水平的心血管(CV)代谢合并症(例如，74%的人患有高血压， 53%的病例)及其后果(例如，增加未来心肌梗死和早产的风险 死亡)。目前的低嘌呤饮食方法对痛风的疗效、适口性和 可持续性，并促进增加精制碳水化合物和饱和脂肪的消费， 实际上，痛风的心血管代谢性并存通过导致胰岛素抵抗和升高的水平而恶化 血糖、甘油三酯和低密度脂蛋白-胆固醇。因此，迫切需要一个统一的、 可持续、有效的预防策略，全面解决痛风及其相关问题 合并症。事实上，有一些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)，这也可以降低血清尿酸(SUA)水平和痛风的风险 肥胖和胰岛素抵抗。这些现有的方法可能会提供一种理想的饮食策略 以降低痛风的风险及其相关的心血管代谢状况。在这项研究中，我们将在我们的 在痛风预防研究方面有丰富的经验，以检验这些饮食方法对 尿酸和痛风的结果。我们将使用储存的血液样本来研究它们对血尿酸水平的影响 来自6项具有里程碑意义的随机对照试验，这些试验涉及减少心血管代谢的各种饮食方法 条件(包括地中海饮食、阿特金斯饮食和短跑饮食)(目标1-3)。通过参与的 在这个项目的所有6个试验中，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，我们将基于3个大的前瞻性队列来评估它们对痛风风险的影响：护士的 健康研究(NHS)I(n=121,700名妇女)、NHS II(n=116,430名年轻妇女)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高- 经过严格验证的高质量数据，包括3200例痛风事件确诊病例。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，通过使用一项高成本效益的研究同时调查多个候选饮食 设计。这些措施还将全面解决与经济增长相关的主要问题。 痛风的疾病负担。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.