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）在人体健康中的作用。从历史上看，脂肪酸研究主要集中在广泛的膳食脂肪类别上，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。越来越清楚的是，这种宽泛的分类估计有误，也许更重要的是，模糊了这些类别中单个FA对健康影响的主要差异。此外，对脂肪摄入量的膳食估计对许多其他个体FA提供的信息很少，这些FA在人体内主要来自内源性代谢过程，而不是直接来自饮食摄入。因此，我们之前的工作（R01- HL085710）集中在循环FA生物标志物上，这些生物标志物提供了饮食和代谢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）、心房颤动（AF）、冠心病（CHD）和中风。值得注意的是，我们确定了主要来源于饮食的FA和主要来源于代谢过程的FA之间的关系。实验研究支持这些发现，这些和其他个体FA对各种细胞功能和代谢途径的影响。总之，这些结果支持了个体FA在人类健康中的关键潜在作用。几个基本问题依然存在。迄今为止，所有关于FA生物标志物和心血管疾病风险的研究都只使用了单一的基线暴露测量，通常是在中年参与者中。由于心血管疾病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一些新的发现，但FA对生命后期健康的潜在影响，例如，对老年人中的老年人，平均年龄的影响

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.