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55万例。尽管医学和外科治疗取得了进展，心衰发病后的死亡率仍然很高。鉴于美国老年人数量的不断增长，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，以改善心衰的管理和预防。为此，饮食中摄入长链omega-3脂肪酸已被证明可以降低心肌梗死和高血压的风险——这是心衰的两个主要危险因素。此外，在动物模型中，n-3脂肪酸已被证明可以减轻压力过载引起的心室重构和功能障碍。目前支持n-3脂肪酸对心衰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心衰风险降低有关。然而，目前还没有关于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）的影响的数据。同样，其他脂肪酸，如反式脂肪酸（已知会增加冠心病的风险）或蔬菜中大量存在的短链脂肪酸（比鱼便宜），是否能预防HF的发生，目前尚不清楚。由于缺乏关于n-3脂肪酸补充剂与HF风险之间关系的研究，因此尚不清楚鱼类中的n-3、鱼类中的其他营养物质或与鱼类消费相关的生活方式因素是否对观察到的鱼类摄入对HF风险的影响负责。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。目前的应用不会受到这样的限制，因为它将检查血浆磷脂n-3脂肪酸（长链和短链）与反式脂肪酸和HF之间的关系，在美国男性医生中使用可重复的方法来测量脂肪酸摄入量。此外，我们将评估血浆磷脂n-3脂肪酸与HF亚型以及HF病因之间的关系。这项研究的结果将有助于确定n-3脂肪酸是否在HF的发展中起重要作用，b)为科学界设计饮食和/或补充剂对HF风险的潜在临床试验提供信息，以及c)帮助确定可与其他措施一起使用的饮食因素来预防HF。反式脂肪的研究结果可能会提供额外的证据，支持对反式脂肪酸的使用采取立法行动。事实上，受试者招募、样本收集、关键协变量和混杂因素信息等成本已经由母研究承担，这使得该应用程序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。人们对膳食脂肪酸在心力衰竭风险中的作用知之甚少。如果目前的项目确定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.