Fatty Acids and Major Cardiovascular Outcomes

描述（由申请人提供）：随着年龄的增长，充血性心力衰竭（CHF）、房颤（AF）和卒中的发病率和患病率急剧上升，造成发病率和死亡率的重大负担。膳食中n-3脂肪酸和反式脂肪酸的摄入会影响许多心血管疾病（CVD）风险因素，包括CHF、AF和卒中的风险因素。然而，n-3和反式脂肪酸与这些主要CVD终点之间的关系尚未明确。在先前的研究中，我们已经证明了报告的饮食习惯与老年人CVD事件的发生率独立相关。我们特别关注不同鱼粉的影响，并假设所观察到的与疾病风险的关系可能是由于n-3或反式脂肪酸。使用饮食调查问卷估计特定脂肪酸的饮食摄入量可能具有挑战性。在以前的工作中，使用病例对照设计，我们已经证明，直接测量磷脂n-3和反式脂肪酸提供了一个客观的措施暴露，并允许直接调查这些脂肪酸和冠心病的风险之间的关系。我们建议在心血管健康研究（一项基于人群的心血管疾病风险多中心队列研究）中测量4，766名老年人储存样本中的血浆磷脂脂肪酸，以前瞻性研究n-3和反式脂肪酸与CHF、AF、卒中和总死亡率的相关性。将使用1992年储存的血浆评估脂肪酸，并前瞻性确定和裁定事件。对于这些结果中的每一个，我们假设n-3脂肪酸（海鲜和植物来源的）将与较低的风险相关，而反式脂肪酸将与较高的风险相关。作为次要目的，我们将通过评估这些脂肪酸与血流动力学、心脏结构和功能、电生理学、胰岛素敏感性、炎症、内皮功能和肥胖的关系来阐明CVD效应的潜在机制。这些目标直接涉及NIH的目标，即调查营养因素对CHF病因或预防的作用。 这项拟议研究的结果将与公共卫生高度相关，确定可能影响老年人主要疾病终点风险的饮食因素，包括心力衰竭，房颤，中风和死亡。

DESCRIPTION (provided by applicant): With advancing age, the incidence and prevalence of congestive heart failure (CHF), atrial fibrillation (AF), and stroke rise dramatically, producing major burdens of morbidity and mortality. Dietary intakes of n-3 fatty acids and trans-fatty acids influence many cardiovascular disease (CVD) risk factors, including risk factors for CHF, AF, and stroke. However, relations between n-3 and trans-fatty acids and these major CVD endpoints are not well-established. In prior studies, we have demonstrated that reported dietary habits are independently associated with incidence of CVD events in older adults. We have particularly focused on effects of different fish meals and hypothesized that the observed relations with disease risk may be due to n-3 or trans-fatty acids. Estimation of dietary intake of specific fatty acids using diet questionnaires can be challenging. In prior work using case-control designs, we have demonstrated that direct measurement of phospholipid n-3 and trans-fatty acids provides an objective measure of exposure and allows direct investigation of relations between these fatty acids and risk of coronary heart disease. We propose to measure plasma phospholipid fatty acids in stored samples among 4,766 older adults in the Cardiovascular Health Study, a population-based, multicenter cohort study of CVD risk, to investigate prospectively the association between n-3 and trans-fatty acids and incidence of CHF, AF, stroke, and total mortality. Fatty acids will be assessed using plasma stored in 1992, with events prospectively ascertained and adjudicated. For each of these outcomes, we hypothesize that n-3 fatty acids (both seafood and plant-derived) will be associated with lower risk, while trans-fatty acids will be associated with higher risk. As a secondary aim, we will elucidate potential mechanisms for CVD effects by evaluating the relations of these fatty acids with measures of hemodynamics, cardiac structure and function, electrophysiology, insulin sensitivity, inflammation, endothelial function, and obesity. These aims directly address the NIH's goal to investigate the role of nutritional factors for causation or prevention of CHF. The results of this proposed research will be highly relevant to public health, identifying dietary factors which may influence risk of major disease endpoints in older adults, including heart failure, atrial fibrillation, stroke, and death.