Exercise, Vascular Function and Cardiovascular Risk in a

有证据表明，由于技术进步，美国人在工作和家里都变得越来越久坐不动。缺乏运动伴随着过量的卡路里摄入，尤其是卡路里含量高的？快速？食物是这个国家肥胖症流行的罪魁祸首。肥胖者和非肥胖者缺乏运动会增加患心血管疾病和全因死亡的风险。过早的心血管疾病会导致工作场所的生产力下降，生活质量受损，医疗保健成本上升。为了回应这些担忧，美国心脏协会提倡大多数时间进行30分钟的有氧运动；然而，繁忙的日程安排加上缺乏方便的锻炼器材(或使用它的动机)，限制了许多人采用定期锻炼。一年前，国家心肺血液研究所(NHLBI)启动了保持节拍计划，鼓励研究所员工在工作日进行15分钟的锻炼，并在特定的工作地点提供锻炼器材以实现这一目标。然而，只有不到10%的NHLBI员工定期参加Keep the Beat，许多最初注册的人未能继续参与。我们前瞻性队列研究的目的是确定参与Keep the Beat计划是否可以通过刺激骨髓来源的内皮祖细胞修复内皮来改善心血管风险的重要指标-动脉内皮功能。我们建议通过在基线和3个月时测量同意参与保持节拍的国立卫生研究院(National Institutes Of Health，NIH)员工的内皮一氧化氮生物活性(由臂动脉对剪切力的反应性和血液中一氧化氮代谢产物确定)以及血管修复潜力(由内皮祖细胞数量和功能确定)来表征血管健康的重要组成部分。二次分析将包括其他风险的生物标志物，如C反应蛋白、血压、体重指数、血脂、空腹血糖/胰岛素和稳态模型评估指数，将在我们的研究和对心血管风险特别高的参与者(10年内20%)、少数族裔和女性的亚组分析中进行测量。血管功能的改善意味着心血管风险的降低，这可能会激励员工更多地参与既定的雇主发起的计划，并促使其他雇主采用类似的计划。如果在血管功能和其他风险生物标志物中不能证明客观的益处，则可能需要修改该计划以降低心血管风险。 目的：内皮功能障碍与心血管疾病的发生发展密切相关。我们的小组先前报道，在没有已知心血管疾病的男性中，内皮祖细胞集落形成单位(EPC-CFU)与内皮功能和通过Framingham Risk Score(FRS)衡量的心血管风险显著相关。我们评估了荷尔蒙状态可能影响女性的假说--S EPC、血管和风险关系。方法：我们招募了66名女性受试者，年龄22-63岁(平均？SD=43？11)，无心血管病史。外周血单个核细胞在纤维连接蛋白包被的孔中培养：EPC-CFU=5天时有内皮生长的细胞团。采用肱动脉血流介导的扩张法(静息内径的百分比)测定内皮功能。结果：血管内皮功能与女性FRS的心血管风险显著相关(r=-0.39，p=0.001)。与男性相比，我们发现EPC-CFU与内皮功能或FRS之间没有显著关系。此外，我们在女性中没有发现EPC-CFU与总胆固醇、低密度脂蛋白胆固醇、高血压和糖尿病频率的关系；这些变量在我们的男性队列中显著相关。为了探索雌激素对女性EPC-CFU和内皮功能的潜在混杂作用，我们根据雌激素与卵泡刺激素(FSH)的比率，按激素状况对队列进行了划分。EPC-CFU与雌二醇/卵泡刺激素比值无相关性，但雌二醇/卵泡刺激素比值最低的妇女内皮功能明显低于雌二醇/卵泡刺激素比值较高的妇女(p&lt；0.05)。正如预期的那样，老年女性的雌二醇/卵泡刺激素低于年轻女性(p&lt；0.001)；然而，在雌激素/卵泡刺激素的三分位数内，内皮功能与年龄之间没有关系。结论：女性的内皮功能与心血管风险相关；然而，与男性的观察结果相反，EPC-CFU不是心血管风险或血管内皮功能的决定因素。我们的数据表明，女性S的荷尔蒙状况与年龄无关，决定了血管内皮功能，进而决定了心血管风险。

Evidence suggests that Americans are becoming increasingly sedentary at work and at home due to technological advances. Physical inactivity coupled with excess caloric intake, especially of calorie- rich ?fast? foods, are responsible for the epidemic of obesity in this country. Physical inactivity in obese and non-obese individuals increases the risk of cardiovascular disease and all-cause mortality. Premature cardiovascular disease leads to lost productivity in the work place, impaired quality of life, and escalating health care costs. In response to these concerns, the American Heart Association advocates 30 minutes of aerobic exercise most days; however, busy schedules coupled with a lack of convenient access to exercise equipment (or motivation to use it) limit adoption of regular exercise by many. One year ago, the National Heart, Lung, and Blood Institute (NHLBI) initiated the Keep the Beat program which encourages Institute employees to engage in fifteen minutes of exercise during the work day, and provides exercise equipment at specific work sites to accomplish this goal. Yet, fewer than 10% of NHLBI employees regularly participate in Keep the Beat and many who initially enrolled have failed to continue participation. The purpose of our prospective cohort study is to determine whether participation in the Keep the Beat program can improve an important measure of cardiovascular risk?arterial endothelial function?by stimulating bone marrow-derived endothelial progenitor cells to repair endothelium. We propose to characterize important components of vascular health by measuring endothelial nitric oxide bioactivity, as determined by brachial artery reactivity to shear stress and nitric oxide metabolites in blood, and vascular repair potential, as determined by endothelial progenitor cell number and function, at baseline and at 3 months in National Institutes of Health (NIH) employees who agree to participate in Keep the Beat. Secondary analyses will include other biomarkers of risk, such as C-reactive protein, blood pressure, body mass index, lipid profile, fasting glucose/insulin, and homeostasis model assessment index, to be measured in our study and subgroup analyses of participants at particularly high cardiovascular risk (> 20% over 10 years), minorities, and women. Demonstration of improved vascular function, with implications of reduced cardiovascular risk, may serve as an incentive for greater employee participation in established employer-initiated programs, and for adoption of similar programs by other employers. If objective benefit cannot be demonstrated in vascular function and other biomarkers of risk, modification of the program may be required to reduce cardiovascular risk. Objective: Endothelial dysfunction has been implicated in the development of cardiovascular disease. Our group previously reported that in men without known cardiovascular disease, endothelial progenitor cells colony-forming units (EPC-CFUs) are significantly related to both endothelial function and cardiovascular risk as measured by the Framingham Risk Score (FRS). We assessed the hypothesis that hormonal status may impact women?s EPC, vascular and risk relationships. Methods: We recruited 66 female subjects aged 22-63 (mean ? SD = 43 ? 11) with no history of cardiovascular disease. Peripheral blood mononuclear cells were cultured in fibronectin-coated wells: EPC-CFUs= cell clusters with endothelial outgrowth at 5 days. Endothelial function was determined by brachial artery flow-mediated dilation (% of resting diameter). Results: Endothelial function was significantly associated (r = -0.39, p = 0.001) with cardiovascular risk derived from the FRS for women. In contrast to men, we found no significant relationship between EPC-CFUs and either endothelial function or FRS. Furthermore, we detected no relationship in women between EPC-CFUs and total cholesterol, LDL cholesterol, or frequency of hypertension and diabetes; these variables were significantly related in our male cohort. To explore the potential confounding effects of estrogen on EPC-CFUs and endothelial function in women, we partitioned our cohort by hormonal status based on the ratio of estradiol to follicle stimulating hormone (FSH). There was no relationship between EPC-CFUs and estradiol/FSH, but endothelial function was significantly lower in women with the lowest estradiol/FSH compared to women with higher estradiol/FSH (p< 0.05). As expected, older women had lower estradiol/FSH than younger women (p< 0.001); however, within the tertiles of estradiol/FSH there was no relationship between endothelial function and age. Conclusions: Endothelial function is associated with cardiovascular risk in women; however, in contrast to observations made in men, EPC-CFUs are not a determinant of cardiovascular risk or endothelial function. Our data suggest that women?s hormonal status, independent of age, determines endothelial function and in turn, cardiovascular risk.