【作者】 曾颖；

【导师】 何国平；

【作者基本信息】 中南大学 ， 护理学， 2012， 博士

【摘要】 背景：心血管疾病(CVD)是人类健康的头号杀手。全球人口老龄化,CVD造成老年人过早死亡和残疾,导致严重的社会经济负担。因此,迫切需要采取措施预防老年人CVD。目前,国际上关于高危人群心血管风险的评估及管理是CVD预防研究的热点。在我国,老年人高血压、糖尿病、高血脂等CVD危险因素未得到有效控制；对老年人心血管风险的评估与管理尚待大力开展。CVD一级预防的干预模式尚不成熟,有待深入研究。本项目拟通过调查老年人心管风险及CVD相关知识知晓现况,探讨CVD相关知识知晓水平与心血管风险的相关性；进一步开展老年人心血管风险评估与综合干预,探索有效的CVD一级预防的干预模式；同时,检测炎症相关因子在评估与监测心血管风险中的作用。目的：1.了解老年人心血管风险及CVD相关知识知晓现况,探讨CVD相关知识知晓水平与心血管风险的相关性；2.通过对老年人的心血管风险的评估与个体化综合干预,探讨综合干预对老年人CVD认知、健康行为依从性、CVD自我管理水平及生活质量、CVD危险因素、心血管风险、血清中炎症相关因子hsCRP、visfatin、IL-6TNF-α水平的影响,并分析炎症相关因子与心血管风险的相关性；3.观察巨噬细胞脂质蓄积及泡沫化与炎症相关因子表达的影响,初步探讨血清中炎症相关因子变化的原因。方法：1.现况研究：采取整群随机抽样方法,抽取衡阳市南华大学附一医院、南华大学附二医院进行健康体检的1200名老年人。利用自制老年人社会人口学及体检一般项目调查表、自制CVD预警症状及危险因素知识问卷,采用面对面访谈、健康指标测量、实验室生化指标检测等方式收集资料；使用2008年WHO/ISH《心血管风险评估与管理袖珍指南》对老年人进行心血管事件10年风险评估。2.随机临床实验研究：从本研究第一部分研究对象中招募200名心血管风险大于10%的老年人作为研究对象,检测血压、血糖、血脂、体重指数(BMI)及炎症相关因子(hsCRP、visfatin、IL-6、TNF-α)等,分析其与心血管风险的相关性；严格遵循匹配原则,采用分层随机法将200名老年人分为对照组与干预组,每组各100人,开展老年人心血管风险评估与综合干预实验研究。对照组根据统一要求开展常规管理,干预组在常规管理的基础上,根据目前衡阳市老年人CVD防治的薄弱环节开展个体化综合干预。利用自制老年人社会人口学及体检一般项目调查表、自制CVD预警症状及危险因素知识问卷、简明生活质量问卷、CVD自我管理问卷,采用面对面访谈、健康指标测量、实验室生化指标检测等方式收集干预前后资料,综合分析干预组与对照组的干预效果。3.实验研究：使用不同剂量oxLDL结合阿托伐他汀处理THP-1巨噬细胞,采用油红O染色观察THP-1巨噬细胞脂质蓄积及泡沫化情况,采用酶联免疫吸附试验检测培养上清中visfatin、 IL-6、TNF-α的表达情况,采用免疫细胞化学法和western blot检测细胞visfatin表达情况。结果：1.本研究的受访对象共计1200名老年人,实际获得1120份有效问卷,对问卷进行综合分析,结果显示：①衡阳市老年人CVD危险因素的控制不理想：高血压、高血脂、高血糖患病率分别为37.5%、36.2%、18.9%,服药率分别为：43.6%、7.6%、16.4%。②衡阳市老年人心血管事件10年风险较高：心血管风险<10%的有222人(19.8%),心血管风险10%-<40%的有510人(45.5%),心血管风险≥40%的有388人(34.6%)。③衡阳市老年人的CVD知识认知水平较低：脑卒中及心脏病发作的预警症状的认知水平很低(平均得分为3.10,总分10分);CVD危险因素的认知水平较低(平均得分为4.98,总分15分)；有心血管病老年人对CVD知识认知水平高于无心血管病老年人(P<0.05)；无心血管病老年人中,CVD知识认知水平越低,心血管风险越高。④CVD知识认知水平与年龄、受教育水平、是否有心血管病史、心血管风险水平等存在不同程度相关性。2.①检测干预前不同心血管事件10年风险老年人的相关指标,结果显示,除甘油三酯外,不同级别心血管风险老年人的收缩压、空腹血糖、总胆固醇、HDL-C、LDL-C、BMI、hsCRP、visfatin、IL-6、 TNF-α的差异均有统计学意义(P<0.05)；随着心血管风险升高,收缩压、空腹血糖、总胆固醇、LDL-C、BMI、血清hsCRP、wisfatin、 IL-6、TNF-α亦升高。②本研究对象200名老年人中,178人(对照组86人,干预组92人)完成了干预六个月后的各项指标的测量,随访率为89%。干预后,两组CVD相关知识平均得分都有显著升高(P<0.05),对照组得分低水平人数明显减少而中水平人数明显增多,干预组得分低水平人数明显减少而得分高水平人数明显增多(P<0.05)；与对照组相比,干预组效果更佳,干预后的CVD知识得分高水平人数明显多于对照组(P<0.05)。③干预后,对照组与干预组健康相关行为、CVD自我管理水平及生活质量均有所提高,且与对照组相比,干预组效果更佳(P<0.05),但在对提高戒烟率及高血压服药率方面,两组效果无显著性差异(P>0.05)。④干预后,干预组收缩压、空腹血糖、TG、TC、LDL-C、BMI均降低,HDL-C升高(P<0.05),而对照组变化不明显(TG除外)(P>0.05)。⑤干预后,干预组有15人心血管风险累计降低了16级,4人累计升高4级,净降低12级,心血管风险≥40%的人数减少5人；干预后,对照组有6人心血管风险累计降低了6级,5人累计升高5级,净降低1级,心血管风险≥40%的人数减少1人。⑥干预后,干预组血清visfatin、IL-6、 TNF-α水平较干预前明显下降(P<0.05)；对照组各项血清炎症因子水平虽有下降,但差异无统计学意义(P>0.05)；干预前后,随着心血管风险的变化血清hsCRP、visfatin、IL-6、TNF-α水平相应变化(P<0.05)。3.①oxLDL能促进THP-1巨噬细胞脂质蓄积及泡沫化,且呈剂量依赖性；阿托伐他汀能减少THP-1巨噬细胞脂质蓄积；②THP-1巨噬细胞脂质蓄积越多,培养上清中visfatin、IL-6、TNF-α表达越高,细胞中visfatin的表达亦越高。结论：1.衡阳市老年人CVD危险因素的控制不理想,CVD知识知晓水平较低,心血管风险水平较高；CVD知识知晓水平与年龄、受教育水平、是否有心血管病史、心血管风险水平存在不同程度相关性。2.综合干预可有效提高老年人CVD知识知晓水平、健康行为依从性、CVD自我管理水平及生活质量,可有效降低老年人血压、血糖、血脂、BMI等CVD危险因素及血管事件10年风险；综合干预对降低心血管风险的效果明显优于常规管理。3.血清炎症因子hsCRP、visfatin、IL-6、TNF-α与心血管风险及泡沫细胞形成存在相关性,可能用于心血管风险评估与监测。更多还原

【Abstract】 Background:Cardiovascular disease (CVD) is the most leading cause of human death worldwide. As the global population aging, CVD causes premature death and disability in the older adults, leading to serious social and economic burden. Therefore, there is an urgent need to take measures to prevent the epidemic of cardiovascular disease in the older adults. Cardiovascular risk assessment and management in high-risk groups is a research hotspot on CVD prevention. In China, hypertension, diabetes, high cholesterol and other CVD risk factors have not been effectively controlled in the older adults. Therefore, it is essential to carry out the assessment and management of cardiovascular risk, in the older adults. And the intervention mode for the primary prevention of cardiovascular disease is not yet mature, needing in-depth study. This project is to to investigate the relationship between cardiovascular risk and awareness of CVD knowledge by investigating the current situation of cardiovascular risk and awareness of CVD knowledge in older adults; and to carry out cardiovascular risk assessment and comprehensive intervention in the older adults to explore effective intervention model for primary prevention of cardiovascular disease; further to detect the role of inflammatory cytokines in the assessing and monitoring of cardiovascular risk.Objectives:The purposes of this study were to:1. describe the current situation of cardiovascular risk and awareness of CVD knowledge in older adults, and to investigate the relationship between cardiovascular risk and awareness of CVD knowledge.2. explore the effect of cardiovascular risk assessment and individualized comprehensive intervention on awareness of CVD knowledge, health behavior adherence, CVD self-management, quality of life, CVD risk factors, cardiovascular risk, and serum inflammatory cytokines hsCRP, visfatin, IL-6, TNF-a levels, and to understand the correlation of inflammatory cytokines with cardiovascular risk.3. observe the effect of lipid accumulation on the expression of inflammatory factors in THP-1macrophage to explore the mechanism on the changes of serum related inflammatory cytokines.Methods:1. A cross-sectional descriptive study.1200older adults were included by a cluster random sampling method, consecutively admitted to the health examination centers of the first and the second affiliated hospitals of University of South China. Socio-demographic data and knowledge of early warning symptoms and risk factors of cardiovascular disease were collected by face-to-face interviews using two self-designed questionnaires. Other data was collected by health measurement and laboratory biochemical detection. The cardiovascular risk of the older adults was assessed using the2008WHO/ISH Pocket Guide for cardiovascular risk assessment and management.2. A randomized clinical experimental study.200older adults with cardiovascular risk greater than10%were recruited from the research subjects in the first part of the study. Blood pressure, blood sugar, blood lipids, body mass index (BMI) and inflammatory factors (hsCRP Visfatin, IL-6, TNF-α) were tested to analyze their correlation with cardiovascular risk.200older adults were divided into control group(n=100) and intervention group(n=100) following the principle of matching and stratified random strictly. An experimental study on cardiovascular risk assessment and comprehensive intervention for the older adults was carried out. The control group was given the routine management, and the intervention group was given the individualized comprehensive intervention on the basis of routine management. Socio-demographic data and knowledge of early warning symptoms and risk factors of cardiovascular disease were collected by face-to-face interviews using two self-designed questionnaires. Status of Quality of Life and CVD self-management were assessed using Quality of Life Questionnaire and CVD self-management questionnaire. Other data was collected by health measurement and laboratory biochemical detection. The cardiovascular risk of the elderly was assessed using the2008WHO/ISH Pocket Guide for cardiovascular risk assessment and management. All data were collected before and after intervention. Comprehensive analysis of the intervention effects of the intervention and the control group was carried out.3. Experimental study. THP-1macrophages were treated using different doses of oxLDL combined with atorvastatin. Lipid accumulation in THP-1macrophages was detected by oil red O staining. Expression of visfatin, IL-6and TNF-a in the culture supernatants were detected by enzyme-linked immunosorbent assay. Expression of visfatin, IL-6and TNF-a in THP-1macrophages were detected using immunocytochemical method and western blot.Results:1. A total of1200older adults people participated in the study, and1120valid questionnaires were obtained.①The control of CVD risk factors of the older adults was not ideal in Hengyang City. The prevalence of hypertension, dyslipidemia, hyperglycemia were37.5%,36.2%,18.9%and rates of medication treatment were:43.6%,7.6%,16.4%respectively. The10-year risk of cardiovascular events was higher in the older adults.②There were222(19.8%) older adults whose cardiovascular risk were<10%,510(45.5%) older adults whose cardiovascular risk were10%～-<40%of, cardiovascular risk≥40%of388(34.6%).③There was a lower level of CVD knowledge awareness in the older adults in Hengyang City. The awareness of stroke and heart attack warning symptoms was low (average score was3.10out of10points), and the awareness of cardiovascular disease risk was low (average score was4.98out of15points). The knowledge level of the older adults with cardiovascular disease was higher than the older adults without cardiovascular disease (P<0.05). The lower the CVD knowledge level, the higher the cardiovascular risk in the older adults.④The education level, history of cardiovascular disease, cardiovascular risk level were significantly associated with the level of CVD knowledge awareness in different degrees (P<0.05).2.①In addition to triglycerides, systolic blood pressure, fasting glucose, total cholesterol, HDL-C, LDL-C; BMI The hsCRP, visfatin, IL-6, TNF-a, the differences were statistically significant associated with the different levels of cardiovascular risk in the older adults (P<0.05). With the increasing of cardiovascular risk, the systolic blood pressure, fasting glucose, total cholesterol, LDL-C, BMI, serum hsCRP, visfatin, IL-6and TNF-a also increased.②A total of200older people participated in this study, and178people (86in control group,92in intervention group) completed all the measurement after the six month intervention. The follow-up rate was89%. After the intervention, the average score of CVD knowledge in the two groups have increased (P<0.05).In the control group, the number of older people with low score decreased and those with intermediate score increased significantly; in the intervention group, the number of older people with low score decreased and those with high score increased significantly (P<0.05). Compared with the control group, the effect of the intervention group was better, the number of older people with high score was significantly more than the control group after the intervention (P<0.05).③After the intervention, the health-related behavior of the control and intervention group, the level of CVD self-management and quality of life have improved. Compared with the control group, the effect of the intervention group was better (P<0.05). But there was no significant difference in the increase of smoking quit rates and the rate of high blood pressure medication taking between the two groups (P>0.05).④After the intervention, except (TG), the systolic blood pressure, fasting glucose, TG, TC, LDL-C, BMI decreased and HDL-C increased in the intervention group (P<0.05), while the control group did not change significantly,(P>0.05).⑤After the intervention, in the intervention group, there were15older adults whose cardiovascular risk reduced16degree cumulatively,4older adults elevated4degree cumulatively, a net reduction of12degree, and a decrease of5older adults with cardiovascular risk≥40%. In the control group, there were6older adults whose cardiovascular risk reduced6degree cumulatively,5older adults elevated5degree cumulatively, a net reduction of5degree, and a decrease of1older adult with cardiovascular risk≥40%.⑥After the intervention, serum visfatin, IL-6, TNF-a levels in the intervention group decreased significantly (P<0.05), but the hsCRP difference was not statistically significant (P>0.05). The level of serum inflammatory factors in the control group decreased after the intervention, but the difference was not significant (P>0.05).3.①oxLDL could promote lipid accumulation in THP-1macrophage in a dose-dependent manner. Atorvastatin can reduce lipid accumulation in THP-1macrophage;②The more lipid accumulation in THP-1macrophage, the higher expression of visfatin, IL-6, TNF-a in culture supernatant, and the higher expression of visfatin THP-1macrophage.Conclusion:1. The control of CVD risk factors of the older adults was not ideal in Hengyang City. The lower awareness of CVD knowledge, the higher cardiovascular risk in the older adults. The education level, history of cardiovascular disease, cardiovascular risk level were significantly associated with the level of CVD knowledge awareness.2. The comprehensive intervention could effectively improve the awareness of CVD knowledge, health behavior adherence, CVD self-management and quality of life; and reduce CVD risk factors, cardiovascular risk, serum inflammatory cytokines. The effect of comprehensive intervention on cardiovascular risk reduction was significantly superior to the routine management.3. There was correlation between serum inflammatory cytokines hsCRP, visfatin, IL-6, TNF-a and cardiovascular risk. These inflammatory cytokines might be used for assessing and monitoring of cardiovascular risk.更多还原