Fatty Acids and Heart Failure in the Physicians' Health Study

描述（由申请人提供）：心力衰竭（HF）是美国老年人住院的主要原因，年发病率为550，000例。尽管内科和外科治疗取得了进展，但HF发作后的死亡率仍然很高。鉴于美国老年人的数量越来越多，预防这种情况的发生势在必行。这就要求进行创新研究，提供具有成本效益的干预工具，以改善HF的管理和预防。为此，饮食中摄入长链ω-3（n-3）脂肪酸已被证明可以降低心肌梗死和高血压的风险-HF的两个主要风险因素。此外，在动物模型中，n-3脂肪酸已显示出减弱由压力超负荷诱导的心室重构和功能障碍。目前支持n-3脂肪酸对HF有益作用的流行病学证据来自心血管健康研究，其中自我报告的鱼类消费与老年人HF风险降低相关。然而，没有关于n-3脂肪酸对HF亚型（收缩期与舒张期HF）或HF病因（例如：缺血性与非缺血性HF）影响的数据。同样，目前还不清楚其他脂肪酸，如反式脂肪酸（已知会增加冠心病的风险）或在蔬菜中大量发现的短链脂肪酸（比鱼便宜）是否可以预防HF的发生。由于缺乏研究检查n-3脂肪酸补充剂与HF风险之间的关系，目前尚不清楚鱼类中的n-3、鱼类中的其他营养素或与鱼类消费相关的生活方式因素是否是观察到的鱼类摄入量对HF风险的影响的原因。更重要的是，自我报告数据固有的偏见可能会导致错误的结论。本申请将不会受到这样的限制，因为它将使用可重复的方法来测量脂肪酸摄入，在美国男性医生中检查血浆磷脂n-3脂肪酸（长链和短链两者）和反式脂肪酸与HF之间的关联。此外，我们将评估血浆磷脂n-3脂肪酸和HF亚型以及HF病因之间的关系。本研究的发现将a）有助于确定n-3脂肪酸在HF的发展中是否重要，B）为科学界设计未来可能的饮食和/或补充剂对HF风险的临床试验提供信息，以及c）有助于确定可以沿着其他预防HF措施的饮食因素。反式脂肪的结果可能会提供额外的证据，以支持反式脂肪酸使用的立法行动。受试者招募、样本采集、关键协变量和混杂因素信息等的成本已由母研究涵盖，这一事实使得该应用具有很高的成本效益。公共卫生相关性：作为美国老年人住院的主要原因，心力衰竭仍然是一个主要的公共卫生问题。关于膳食脂肪酸对心力衰竭风险的作用知之甚少。如果目前的项目确定了影响心力衰竭风险的饮食因素，那么这些信息可以帮助重塑饮食指南，作为旨在降低人群心力衰竭风险的预防策略的主要组成部分。

DESCRIPTION (provided by applicant): Heart failure (HF) is the leading cause of hospitalization among elderly people in the US with an annual incidence rate of 550,000 cases. Despite advances in medical and surgical treatment, mortality after the onset of HF remains high. Given the growing number of older adults in the US, it is imperative to prevent the occurrence of this condition. This calls for innovative research that could provide cost-effective intervention tools to improve the management and prevention of HF. To this end, dietary intake of long-chain omega-3 (n-3) fatty acids has been shown to lower the risk of myocardial infarction and hypertension - two major risk factors for HF. In addition, n-3 fatty acids have been shown to attenuate ventricular remodeling and dysfunction induced by pressure overload in animal models. Current epidemiologic evidence to support such beneficial effect of n-3 fatty acids on HF comes from the Cardiovascular Health Study in which self-reported fish consumption was associated with a lower risk of HF in older adults. However, no data are available on the effects of n-3 fatty acids on HF subtypes (systolic vs. diastolic HF) or HF etiology (for example: ischemic vs. non-ischemic HF). Likewise, it is not clear whether other fatty acids such as trans fatty acids (known to increase the risk of coronary heart disease) or short-chain fatty acids found abundantly in vegetables (and cheaper than fish) could prevent the occurrence of HF. In the absence of a study examining the relation between n-3 fatty acid supplements and risk of HF, it is unclear whether n-3 in fish, other nutrients in fish, or lifestyle factors associated with fish consumption were responsible for the observed effects of fish intake on HF risk. More importantly, bias inherent to self-reported data might lead to erroneous conclusions. The current application will not suffer from such limitations as it will examine the association between plasma phospholipid n-3 fatty acids (both long-chain and short- chain) and trans fatty acids and HF among US male physicians using a reproducible method to measure fatty acid intake. Furthermore, we will assess the relation between plasma phospholipid n-3 fatty acids and HF subtypes as well as HF etiology. Findings of this study will a) help determine whether n-3 fatty acids are important in the development of HF, b) inform the scientific community in designing potential future clinical trials of diet and/or supplements on the risk of HF, and c) help identify dietary factors that could be use along with other measures to prevent HF. Results on trans fats may provide additional evidence to support legislative action on the usage of trans fatty acids. The fact that the costs for subject recruitment, sample collection, information on key covariates and confounders, etc, have been covered by the parent study makes this application highly cost-efficient. PUBLIC HEALTH RELEVANCE: As the leading cause of hospitalization among elderly people in the US, heart failure is still a major public health issue. Little is known about the role of dietary fatty acids on the risk of heart failure. If the current project identifies dietary factors that influence the risk of heart failure, then such information could help reshape dietary guidelines as a major component of prevention strategies designed to lower the risk of heart failure in the population.