Nonesterified Fatty Acids and Cardiovascular Aging

根据2003年NIA试点研究资助计划公告PAR-03-056（心脑血管衰老），研究心血管自主控制的年龄相关变化与非酯化脂肪酸（NEFA）增加的关系。与NEFA水平直接相关的内脏脂肪增加与迷走神经控制下降和交感神经活动增加有关。在人类衰老过程中，自主神经控制也发生了类似的变化。随着年龄的增长，内脏脂肪和NEFA水平的增加可能会导致心血管衰老的标志——压力反射敏感性下降，肌肉交感神经外流增加和血管僵硬。然而，NEFA水平对自主神经功能的直接影响尚未得到很好的研究。因此，具体目的是确定NEFAs升高是否与年龄相关的压力反射敏感性下降、交感神经活动增加和血管僵硬有关；并确定急性NEFAs升高是否会进一步降低健康老年人的压力反射敏感性，增加血管交感血流和血管僵硬。在体压变化期间，将结合直接交感神经记录和同时超声衍生的颈动脉图像来测量逐拍动脉压变化、R-R间隔和脉搏波速度的标准心血管测量。这将同时评估心脏迷走神经和血管交感压力反射增益，同时估计动脉压力传导到压力感觉区域的拉伸。假设较低的压力反射控制、较大的交感神经外流和血管僵硬度与NEFA水平高有关，在低NEFA的患者中，压力反射控制可急剧下降，交感神经活动和血管僵硬度均随NEFA水平的短期升高而增加。年龄较大（55-70岁）的正常和超重受试者将被研究，以提供广泛的循环NEFA水平，以检查NEFA与血管特性、功能和系统自主循环控制的关系。急性NEFA升高对血管扩张性、压力反射敏感性和交感神经流出的影响将被评估。这项工作具有临床意义，因为这些关联可能为心血管疾病发病率随年龄增长而增加的病因学提供见解。

Examining the relation of age-related changes in cardiovascular autonomic control to increases in nonesterified fatty acids (NEFA) is proposed in response to 2003 NIA Pilot Research Grant program announcement PAR-03-056 (Cardiovascular and Cerebrovascular Aging). Increased visceral adiposity, which directly related to NEFA levels, is associated with decreased vagal control and increased sympathetic activity. Analogous changes in autonomic control occur with human aging. Increased visceral adiposity and NEFA levels with age could contribute to the hallmarks of cardiovascular aging - decreased baroreflex sensitivity, increased muscle sympathetic nervous outflow and vascular stiffening. However, direct effects of NEFA levels on autonomic function have not been well examined. Accordingly, the specific aims are to determine whether elevated NEFAs are associated with the age-related decrease in baroreflex sensitivity, increase in sympathetic nervous activity and vascular stiffness; and to determine whether acute elevations of NEFAs can further decrease baroreflex sensitivity, increase vascular sympathetic outflow and vessel stiffness in healthy older adults. Standard cardiovascular measures of beat-by-beat arterial pressure changes, R-R intervals and pulse wave velocity will be combined with direct sympathetic nerve recordings and concurrent ultrasound-derived carotid images during systemic pressure changes. This will assess cardiac vagal and vascular sympathetic baroreflex gain simultaneously while estimating arterial pressure transduction into stretch of a barosensory region. It is hypothesized that lower baroreflex control, greater sympathetic outflow and vascular stiffness are related to high NEFA level and that in those with low NEFAs, baroreflex control can be acutely decreased, sympathetic nervous activity and vessel stiffness both increased with short-term elevation of NEFAs. Older (55-70) normal and overweight subjects will be studied to provide a broad range of circulating NEFA levels to examine the relation of NEFAs to vascular character, function, and systemic autonomic circulatory control. Effects of acute NEFA elevation on vascular distensibility, baroreflex sensitivity, and sympathetic outflow will be assessed. This work is clinically relevant because these associations may provide insight into the etiology of the increased incidence of cardiovascular disease with age.