The relationship between sodium intake and mortality: a case-cohort study in a population-based cohort of 148,000 adults with both 24-hour and spot urine samples

项目摘要 迄今为止，关于这一主题的最大规模队列研究发现，估计钠摄入量低的成年人 比那些钠摄入量接近人口平均水平的人有更高的死亡风险。这些发现 “J形”钠死亡率关联的研究对盐的公共卫生工作具有重要意义 因为他们认为，在人群水平上减少钠的摄入量可能会对大量的 人口的比例。许多研究者批评这些队列研究使用了斑点 尿液，而不是黄金标准的24小时尿液样本，以估计钠摄入量。然而，到目前为止， 关于钠死亡率关联形式的争论无法令人信服地得到解决，因为分析 收集24小时尿液样本的队列研究的样本量远小于那些 收集了一点尿液本项目的总体目标是更好地了解 钠摄入量与死亡率的关系，特别是在钠摄入量低于美国人口平均水平时。 中心假设是，一些人报道的钠-死亡率关系的J形 调查者通过使用点滴而不是24小时尿液来评估钠摄入量的偏差 sample.这一中心假设将通过追求三个具体目标来检验：1）确定 成年人的钠摄入量与全因死亡率的最低风险相关; 2）确定 通常报告的低钠摄入量导致死亡风险增加的原因是使用点尿 （而不是黄金标准的24小时尿液），以估计24小时钠摄入量;和3）确定是否 钠摄入量与心血管死亡原因之间的关联是心脏病的主要决定因素。 钠-死亡率关联使用病例队列设计，本项目将分析钠和钾 作为生命线的一部分收集的尿液样本中的浓度，这是一项基于人群的队列研究， 关于荷兰北方的健康老龄化。生命线队列具有三个独特的功能， 研究人员为解决关于J形钠的争议做出了重要贡献， 死亡率相关：1）生命线从参与者中收集了两份24小时尿样; 2）147，888 成年参与者和超过6,000例死亡（超过15年的随访期），生命线队列有更大的 样本量和死亡人数高于任何其他收集24小时尿样的队列;以及3） 生命线还从所有参与者那里收集了一份现场尿样，以便我们能够直接 比较钠-死亡率关联的形状，这取决于是一个点还是金标准24- 使用1小时尿样。该项目意义重大，因为它将为盐的饮食指南提供信息， 公共卫生工作是否应该尝试降低整个人群的钠摄入量（例如，通过 重新制定食物供应）或只关注摄入高水平钠的个人。

PROJECT SUMMARY The largest cohort studies on the subject to date have found that adults with a low estimated sodium intake had a higher risk of mortality than those with a sodium intake close to the population’s average. These findings of a “J-shaped” sodium-mortality association have important implications for public health efforts on salt because they suggest that reducing sodium intake at the population level could cause harm among a large proportion of the population. Many investigators have criticized these cohort studies for their use of a spot urine, rather than the gold-standard 24-hour urine sample, to estimate sodium intake. Thus far, however, the debate on the shape of the sodium-mortality association could not be settled convincingly because analyses of cohort studies that collected 24-hour urine samples have suffered from far smaller sample sizes than of those that collected a spot urine. The overall objective of this project is to better understand the association of sodium intake with mortality, particularly at levels of sodium intake below the population average in the US. The central hypothesis is that the J-shape of the sodium-mortality association that has been reported by some investigators is a result of bias from assessing sodium intake through use of a spot rather than a 24-hour urine sample. This central hypothesis will be tested by pursuing three specific aims: 1) Determine the range of sodium intake among adults that is associated with the lowest risk of all-cause mortality; 2) Determine whether the commonly reported increased risk of mortality at low levels of sodium intake stems from using a spot urine (rather than the gold-standard 24-hour urine) to estimate 24-hour sodium intake; and 3) Establish whether the association of sodium intake with cardiovascular causes of death is the main determinant of the shape of the sodium-mortality association. Using a case-cohort design, this project will analyze the sodium and potassium concentration in urine samples collected as part of Lifelines, which is a population-based cohort study focused on healthy aging in the Northern Netherlands. The Lifelines cohort has three unique features that enable the investigators to make an important contribution to resolving the controversy about the J-shaped sodium- mortality association: 1) Lifelines has collected two 24-hour urine samples from its participants; 2) with 147,888 adult participants and over 6,000 deaths (over a 15-year follow-up period), the Lifelines cohort has a far larger sample size and number of deaths than any other cohorts that have collected 24-hour urine samples; and 3) Lifelines has additionally collected a spot urine sample from all participants such that we are able to directly compare the shape of the sodium-mortality association depending on whether a spot or the gold-standard 24- hour urine sample is used. This project is significant because it will inform dietary guidelines on salt, and whether public health efforts should attempt to lower sodium intake among the entire population (e.g., through reformulation of the food supply) or focus instead only on individuals who consume high levels of sodium.