Circulating Dietary & Metabolic Fatty Acids, Major CVD Outcomes, & Healthy Aging

描述（由申请人提供）：创新研究已经开始阐明单个脂肪酸（FA）在人类健康中的作用。从历史上看，FA研究主要集中在广泛的膳食脂肪类别，例如饱和脂肪、多不饱和脂肪或单不饱和脂肪，并依赖于饮食问卷中自我报告的估计值。越来越清楚的是，这种广泛的分类估计错误，也许更重要的是，掩盖了这些类别中的个人FA的健康影响的主要差异。此外，膳食脂肪摄入量的估计提供了很少的信息，许多其他个人的FA，在人体内主要是来自内源性代谢过程，而不是从直接的饮食摄入。 因此，我们之前的工作（R 01-HL 085710）集中在循环FA生物标志物上，这些生物标志物提供了膳食和代谢FA暴露的客观测量。我们发现几个关键的个体FA与主要心血管疾病（CVD）结局显著相关，包括充血性心力衰竭（CHF）、房颤（AF）、冠心病（CHD）和卒中。值得注意的是，我们确定了FA的关系，主要来自饮食和FA主要来自代谢过程。实验研究支持这些发现，这些和其他个别FA对各种细胞功能和代谢途径的影响。这些结果共同支持了个体FA在人类健康中的关键潜在作用。 几个基本问题仍然存在。迄今为止，所有关于FA生物标志物和CVD风险的研究都只使用了单一的暴露基线测量，通常在中年参与者中。由于CVD的风险随着年龄的增长而急剧增加，这些先前对中年FA生物标志物的研究排除了对以后生活中潜在影响的强有力的推断。因此，我们之前在心血管健康研究（CHS）中的工作主要集中在基线年龄为65岁的老年男性和女性。虽然这项工作产生了几个新的发现，FA对健康的潜在影响在以后的生活中，例如，在老年人中最年长的，平均年龄 80-第85章不成立这代表了美国一个相当大且快速增长的部分，在这些人中，知道如何预防CVD和增加健康老龄化至关重要。衰老的标志是饮食、生活方式和新陈代谢的变化，每一种变化都会影响循环中的FA。此外，与其他风险因素一样，FA对健康的影响可能会随着年龄的增长而变化。我们先前的工作已经证实，对于许多个体FA，循环水平随着时间的推移而变化很大。因此，在生命后期评估FA是至关重要的，以阐明其对健康的潜在影响，在这一人群。这项建议将建立在我们之前的工作的基础上，并通过评估我们最初措施后6年和13年的CHS中的客观FA生物标志物来扩展我们之前的工作，以提供关于特定个体饮食和内源性FA与CVD和健康老龄化之间关系的重要见解。这项工作将促进对FA如何影响CVD，死亡率和健康老龄化的科学理解，并为生活方式，政策和药物治疗工作提供创新目标和干预措施。

DESCRIPTION (provided by applicant): Innovative research has begun to elucidate the role of individual fatty acids (FA) in human health. Historically, FA research has focused on broad categories of dietary fats, e.g. saturated, polyunsaturated, or monounsaturated fats, and relied on self-reported estimates from diet questionnaires. It is increasingly clear that such broad categorizations are estimated with error and, perhaps more importantly, obscure major differences in health effects of individual FA within these categories. Also, dietary estimates of fat intake provide little information on many other individual FA that in the human body are largely derived from endogenous metabolic processes rather than from direct dietary intake. Consequently, our prior work (R01- HL085710) has focused on circulating FA biomarkers that provide objective measures of exposure to both dietary and metabolic FA. We have found several key individual FA to be significantly associated with major cardiovascular disease (CVD) outcomes, including congestive heart failure (CHF), atrial fibrillation (AF), coronary heart disease (CHD), and stroke. Notably, we identified relations for FA that are largely derived from diet and FA largely derived from metabolic processes. Experimental studies support these findings, with effects of these and other individual FA on a variety of cellular functions and metabolic pathways. Together these results support key potential roles of individual FA in human health. Several fundamental questions remain. To date, all studies of FA biomarkers and CVD risk have utilized only a single baseline measure of exposure, typically among participants in middle-age. Because risk of CVD accelerates dramatically with age, these prior investigations of FA biomarkers in middle-age preclude strong inference on potential effects later in life. Our prior work in the Cardiovascular Health Study (CHS) thus focused on older men and women age 65 at baseline. Whereas this work produced several novel findings, the potential influence of FA on health much later in life, e.g., in the oldest of the old, average age 80- 85 and beyond, is not established. This represents a sizeable and rapidly growing segment of the US, in whom knowing how to prevent CVD and increase healthy aging is critical. Aging is marked by changes in diet, lifestyle, and metabolism, each of which influences circulating FA. Also, as with other risk factors, health effects of FA may vary with aging. Our prior work has confirmed that, for many individual FA, circulating levels change considerably over time. Thus, assessment of FA late in life is crucial to elucidate their potential influence on health in this population. This proposal will build upon and extend our prior work by assessing objective FA biomarkers in CHS at 6 years and 13 years after our initial measures to provide crucial insights into how specific individual dietary and endogenous FA relate to CVD and healthy aging later in life. This work will advance scientific understanding of how FA influence CVD, mortality, and healthy aging and inform innovative targets and interventions for lifestyle, policy, and drug treatment efforts later in life.