儿童青少年高血压及其危险因素对早期靶器官损害的影响
|
摘要
在过去的20年高血压(hypertension, HTN)患病率急遽上升,已成为全球性公共卫生问题。在成人HTN远未得到有效控制的同时,其流行呈现明显低龄化趋势,正在向儿童青少年蔓延。上世纪70年代以来血压轨迹现象被大量研究证实,即成人HTN源于儿童期,一旦形成,需终生服药,对身心健康和生活质量造成严重影响,带来沉重的疾病负担和社会负担。因此,对高危儿童早发现、早诊断、早治疗的一级预防成为HTN防治事半功倍的治本之策。
血压的准确测量和科学评估是早期发现高危人群的前提,鉴于单次血压测量波动性大,HTN诊断必须建立在血压多次重复测量基础上。与成人相似,近年来非同日多时点血压重复测量也被推荐使用于儿童青少年HTN的判定,但其必要性尚有待循证依据予以证实。临床和科研中常用的血压测量方法是使用血压计对肱动脉血压进行的间接测量,传统的听诊法汞柱立式血压计因其中汞会对环境造成污染,加之测量技术要求的特殊性,操作的复杂性,实际应用中受到一定限制。示波法中的电子血压计因方便、客观、无污染及数据能导入电脑等优点,成为当前血压测量的重要仪器,在临床、科研及家庭血压自主监测中广泛应用。但电子血压计对儿童青少年血压测量的准确性,电子血压计与听诊法对儿童血压测量的一致性尚有待深入研究验证。本研究于筛查HTN儿童过程中,在一子样本中进行了电子血压计与听诊法的比对研究,为电子血压计在儿童青少年人群中推广应用提供循证依据。
来自临床的资料显示即便血压轻度升高的儿童,其伴随的心脏、脑、血管和肾脏等重要靶器官损害(target organ damage, TOD)已不罕见。血压升高使心脏后负荷增加,室壁局部张力增加,促进心肌内蛋白合成,肌纤维成分增加。继而心肌纤维被拉长,心肌组织相对缺氧,代谢产物堆积,通过生物反馈机制,使蛋白合成增加,导致心肌肥厚。美国国家高血压教育项目儿童高血压工作组第四次报告中将左心室肥大(left ventricular hypertrophy, LVH)列为儿童青少年中最常见的TOD,并将心脏二维超声作为评估儿童青少年HTN及其TOD的常规检测。此外,HTN及其并发症的患病率和死亡率还与动脉壁的损害有关,动脉壁结构和功能损害可追溯到HTN早期,即动脉硬化是儿童期得病至成人发病的一种慢性疾病。动脉血管功能改变在儿童期已经开始,动脉脉搏波传导速度(pulse wave velocity, PWV)作为评估动脉弹性的非侵入性手段之一,已受到国内外学者的广泛重视,成为目前心血管疾病无创检测的研究热点。动脉粥样硬化为一种全身性病变,由于颈动脉表浅易于使用超声的手段进行探查,因而颈动脉内膜中层厚度(carotid artery intima-media thickness, cIMT)可作为反映全身动脉粥样硬化的窗口,可能成为早期筛查高危人群的敏感指标,在儿童中存在推广应用的潜在价值。近年来肾脏损害发病年龄也呈提前趋势,鉴于此,肾脏早期损害的推荐指标微量白蛋白尿(Microalbuminuria, MAU)已被写入了2010年《中国高血压防治指南》。
儿童青少年时期的TOD多为功能性改变,在其发展为永久性结构损害之前,如能凭借敏感的筛查指标尽早发现,尽早干预,有望使其有效逆转。然而儿童期HTN多隐匿发病,无任何临床症状,加之敏感筛查指标和手段的缺失,更容易错失早发现、早干预的良机。鉴于既往TOD的研究多局限于临床就诊的HTN患儿或小样本的典型抽样调查,人群中无症状HTN儿童TOD情况如何尚鲜有报道,本研究通过非同日三时点血压筛查,获得HTN及正常血压(normotensive, NT)对照儿童,通过对其TOD情况的评估,研究儿童青少年HTN及其危险因素对早期TOD的影响,为高危儿童敏感筛查指标的选择提供循证依据。
[目的]
1.通过非同日三时点血压筛查,获得HTN及NT对照儿童青少年,并对三时点HTN检出率的分布特征及影响因素进行研究；
2.对筛查获得HTN及NT对照儿童TOD情况进行评估,研究HTN及其危险因素对早期TOD的影响,为高危儿童敏感筛查指标的选择提供循证依据；
3.对电子血压计测量儿童青少年血压的准确性进行评估,为电子血压计在儿童青少年人群中推广使用提供依据。
[方法]
采用分层整群抽样法于2009年3-10月在北京市朝阳、丰台两城区及顺义、昌平两郊区22所中等水平幼儿园、小学及中学,招募3-18岁儿童青少年,各年龄组至少400人,城郊各半、男女各半。测量身高(cm)、体重(kg)及腰围(cm),计算体重指数(body mass index, BMI)(BMI=体重/身高2,kg/m2)；听诊法测量血压,取Korotkoff第Ⅰ音(K1)为收缩压(systolic blood pressure, SBP),第Ⅳ音(K4)为舒张压(diastolic blood pressure, DBP)。问卷调查一般人口学特征、生活行为信息、个人疾病史、HTN家族史等。对第一时点HTN的儿童,15天后第二次测量,第二时点仍为HTN的儿童,15天后第3次测量,三时点均为HTN的儿童方判定为HTN。2011年对筛查获得的HTN儿童,及按照1：2比例为其匹配的同性别同年龄NT儿童,进行TOD情况评估,包括心脏左室质量和室壁厚度、PWV、cIMT及粥样斑块形成、肾脏结构及占位、眼底动脉硬化情况,以及空腹血浆葡萄糖、血脂四项、超敏C反应蛋白(hypersensitive C-reactive protein, hs-CRP)、尿微量白蛋白测定等。在HTN筛查人群中选择1600名3-18岁儿童青少年进行电子血压计与听诊法测量血压的比对试验,每年龄组100人,男女各半,听诊法测量3次,电子血压计测量2次,间隔进行。
本研究涉及诊断标准：超重与肥胖,7-18岁采用中国肥胖问题工作组推荐的“中国学龄儿童超重、肥胖BMI分类标准”,6岁及以下参照"2000年美国疾病预防控制中心生长曲线"BMI性别年龄别P85与P95分位值；HTN,采用“中国儿童青少年血压参照标准”,SBP和DBP均<性别年龄别P90为正常,SBP和/或DBP≥P95为HTN；主动脉僵硬,颈-股PWV (carotid-femoral pulse wave velocity, cfPWV)超过性别年龄别P95；LVH,左心室重量指数(left ventricular mass index, LVMI)超过性别年龄别P95和/或相对壁厚度(relative wall thickness, RWT)超过性别年龄别P95；眼底动脉硬化,Keith-Wagnar分级诊断；MAU,随机尿微量白蛋白介于20-200mg/L；糖尿病,参考2012年美国糖尿病协会的诊断标准；血脂异常,参照2009年发布的“儿童青少年血脂异常防治专家共识”
采用Epidata3.1软件进行数据录入并二次核对,SPSS18.0数据分析,Medcalc比较两种血压计测量结果一致性。非正态分布数据以几何均数与四分位间距表示,经自然对数转换后分析。统计方法包括t检验、x2检验、协方差分析、多元线性回归分析和多因素logistic回归分析,定义P<0.05为差异有统计学意义。
[结果]
1.1总计6692人参加调查,男3326人,占49.7%。三时点HTN检出率分别为18.2%、5.1%和3.1%,其中城区儿童HTN检出率(三时点分别为21.0%、6.1%、3.7%)高于郊区(15.1%、4.0%、2.5%)(P<0.05),男童SBP、DBP水平及HTN检出率高于女童(P<0.05)；第一时点HTN检出率随年龄波动最大,其次第二时点,第三时点相对稳定,规律基本相同：3-5岁检出率最低,6-9岁达高峰,后渐下降或趋平稳,男女间略有不同。
1.2调整可能影响因素性别、年龄、青春期及心率,以三时点HTN为应变量,以体重状态、睡眠时间、父母HTN史、父母教育程度为自变量进行二分类多因素logistic回归分析,结果超重、肥胖及父母HTN史为HTN危险因素,与正常体重相比,超重儿童罹患HTN比值比(Odds Ratio, OR)及95%可信限(confidence interval,CI)在第一、第二及第三时点分别为2.64(2.18-3.31)、3.95(2.65-5.88)、4.54(2.70-7.61),肥胖儿童罹患HTN的OR (95%CI)分别为7.07(5.94-8.42)、17.23(12.63-23.52)、20.63(13.69-31.09)；与无HTN家族史儿童相比,父亲患有HTN儿童,三时点OR (95%CI)分别为1.26(0.98-1.61)、1.35(0.90-2.02)和1.80(1.15-2.81)。
2.对经三时点筛查获得238名儿童青少年(80名HTN及158名NT)进行TOD的评估。依据筛查时点及TOD评估时点血压状态分组,两时点持续NT组152名,血压波动组38名(32名HTN转变为NT,6名NT转变为HTN),持续HTN组48名。三组儿童中baPWV(938±10cm/s、963±21cm/s、1066±19cm/s)、 LVM (93±2g、110±4g、119±3g)、LVMI (28±1g/m2.7、32±1g/m2.7、34±1g/m2.7)、 cIMT (0.46±0.01mm、0.49±0.01mm、0.48±0.01mm)水平逐渐上升(P<0.001)；LVM升高(7.9%、42.1%及33.3%)、LVMI升高(2.0%、10.5%及14.6%)cIMT增厚(12.5%、31.6%、47.9%)及hs-CRP升高(9.7%、22.9%、31.1%)检出率在三组儿童中亦逐渐上升(P<0.001)；多元线性回归筛选对各项TOD有意义的危险因素,再分别对其调整进行logistic回归分析,结果：年龄为多项TOD共同的保护因素,与持续NT儿童相比,血压波动及持续HTN儿童LVM增高的OR (95%CI)分别为5.27(1.57-17.66)和3.28(1.00-10.74)。肥胖儿童LVM升高的风险为正常体重儿童的14.55(4.14-51.22)倍；肥胖儿童LVMI增高的风险是非肥胖儿童22.46(2.14-236.20)倍；女童cIMT增厚的风险小于男童(0.40(0.19-0.87)),血压波动及持续HTN儿童cIMT增厚的风险分别是持续NT儿童的2.88(1.03-8.09)倍和7.25(2.69-19.58)倍。
3.共招募1695名3-18岁儿童青少年参加两种血压计比对试验，男845人,占49.9%。各年龄组电子血压计与听诊法测量结果互有高低,以电子血压计偏高为主。电子血压计与听诊法测量SBP平均误差为3mmHg,标准偏差8mmHg;电子血压计DBP与听诊法K4平均误差-4mmHg,标准偏差10mmHg;电子血压计舒张压与听诊法K5平均误差4mmHg,标准偏差13mmHgo电子血压计与听诊法测量结果差值绝对值<5mmHg,≤10mmHg和≤15mmHg所占比例,对SBP分别为54.2%,82.9%和100%：以听诊法K4为DBP时,3组比例分别为42.3%,70.4%和87.2%,以听诊法K5为DBP时,3组比例分别为46.1%,70.6%和84.8%。电子血压计与听诊法SBP差值95%一致性界限为(-13.5～19.6) mmHg;电子血压计DBP与听诊法K4差值95%一致性界限为(-22.5～15.1) mmHg,与听诊法K5差值95%一致性界限为(-20.3～28.4)mmHg。
[结论]
1.经非同日三时点血压筛查,儿童青少年HTN检出率下降了近6倍,重复测量对儿童青少年HTN判定十分必要；
2.超重、肥胖及父亲HTN疾病史是儿童青少年HTN重要危险因素；
3.两年间持续HTN儿童发生动脉粥样硬化、动脉硬化及左室向心性肥厚的风险高于血压波动儿童,进一步高于持续NT儿童；
4. BaPWV、cIMT、LVM、LVMI高危儿童早期筛查中具有潜在的应用价值；
5.尚未发现持续HTN儿童发生早期肾损害的危险高于血压波动儿童及持续NT儿童；
6.肥胖和糖脂代谢异常与TOD密切相关,及早控制体重及纠正糖脂代谢紊乱是预防的关键；
7.电子血压计与听诊对儿童青少年血压测量结果存在一定差异,但总体尚稳定,一致性尚好,电子血压计可用于儿童青少年血压的测量。
[Background]
Hypertension (HTN) has become an important issue of public health due to its rapid increase in the past two decades. Meanwhile, blood pressure (BP) tracks from childhood to adulthood, and the onset of primary HTN is proved to be traced back to childhood. However, levels of BP are difficult to be efficiently controlled in nearly70%of hypertensive patients. The target organ damages (TOD) are the important problems of HTN study. TOD is the main culprit of the burden of illness and economical load, so primary prevention early from childhood has become the root of the problem.
Recognizing the development of HTN at an earlier age may provide physicians with an opportunity to reduce its risk factors early on. Owing to a large variability in repeated BP measurements obtained on a single visit, the diagnosis of HTN in adults is typically based on repeated BP measurements over several visits. Similar to adults, it was recently recommended that elevated BP in children should be determined from at least three separate visits.
The health hazard of pediatric HTN not only causes the high risks of adult HTN, but also does damage to target organs of artery, heart, brain and kidney. Studies based on clinic have proved that TOD could be observed even in those hypertensive children with BP elevated mildly. However, most of the TOD in childhood are function damage and may be reversed if effective intervention conducted on the premise of early identifying. In view of this the population-based study was designed to investigate the characteristics of HTN and TOD, and studied the association between HTN and other risk factors and early TOD in children and adolescents.
Furthermore, as it's the case in adults, the white coat and the masked hypertension phenomena appear to be common in children. Therefore, assessment of out of-office BP using either electronic sphygmomanometer or home monitoring is often needed in children and adolescents. Limited evidence exists on the accuracy of 电子血压计for blood pressure measurement in children. An additional content of this study is to verify the accuracy of electric sphygmomanometer in measurements of blood pressure based on population survey.
[Objective]
1. To screen hypertensive children and adolescents based on population survey and to prove the necessary of repeated measurements on separate occasions in diagnosing HTN in pediatric population;
2. To analyze the association between HTN and other risk factors with early TOD in pediatric population and to supply some proof evidence-based in identifying, diagnosing and interposing of the high risk population from early time;
3. To verify the assistant between electronic sphygmomanometer and mercury sphygmomanometer in pediatric population based on blood pr electronic sphygmomanometersure population survey.
[Methods]
Children and adolescents aged3to18years (400in each age group) were recruited using a stratified cluster sampling in2009. This survey was conducted in9kindergartens,7primary and5secondary schools selected from2urban and2rural districts in Beijing. BP was measured according to a standard protocol using a mercury sphygmomanometer on right upper arm in the sitting position. Korotkoff phase1(K1) and4(K4) sounds were used to define systolic BP (SBP) and diastolic BP (DBP), respectively. Heart rate was recorded in beats/min. Meanwhile anthropometric measurements including height (cm), weight (kg) and waist circumference (cm) were obtained with body mass index (BMI) being calculated as weight in kilograms divided by the square of height in meters (kg/m2). Those with a BP in≥95th percentile were screened a second or third time at two-week intervals. A questionnaire, which included questions on physical activity, sleep duration, salt intake, familial history of hypertension, and parental educational levels, was completed.
Meanwhile a comparison test between electric sphygmomanometer and mercury sphygmomanometer was conducted in a consecutive pediatric population aged3to18years (100in each age group). Electronic sphygmomanometer (Omron HEM-759P) and mercury sphygmomanometer were used to measure BP two times, respectively, and two instruments were used by turns. Korotkoff K1was recorded as SBP measured by mercury sphygmomanometer (mSBP), K4and K5as DBP by mercury sphygmomanometer (mDBP4and mDBPs), respectively. SBP and DBP measured by lectronic sohygmomanometer were recorded as eSBP and eDBP.
Selected hypertensive and double normotensive matched for gender and age screened from the baseline survey were enrolled in the clinical examination on early TOD in2011. The anthropometric measurements including height, weight, SBP, DBP and heart rate were re-measured with BMI being recalculated. All the participants were divided into3groups (consistent NT, BP change, and consistent HTN) according to the BP levels at the baseline and the clinical examination. Moreover, other indexes such as pulse wave velocity (PWV, cm/s), carotid artery intima-media thickness (cIMT), structure of left ventricular and kidney, retinal artery were measured, blood glucose, lipid spectrum, micro albumin in urine,β2-microglobulin and cystatin C were examined.
'Elevated BP'was defined as SBP or DBP in the≥95th sex-and age-specific percentile of Chinese pediatric population on all the three occasions.'Hypertension' was defined as an'elevated BP' on all three visits. Overweight and obesity in school-aged children were defined according to BMI cutoffs for Chinese children and adolescents. The US2000CDC Growth Chart (CDC2000) was used to clarify the weight status for children aged3-6years. Specifically, BMI in the<85th, between the>85th and<95th, and in the≥95th percentiles was classified as 'normal weight','overweight', and'obese', respectively. Based on the Chinese national survey of students' physical quality data, we also calculated BMI percentiles (i.e.<5th,5th-24th,25th-49th,50th-74th,75th-84th,85th-94th, and≥95th).
Data of investigation and examination were entered and double checked with Epidata software3.1, and analyzed using SPSS18.0. Data of non-normal distribution were turned into normal distribution through natural logarithm transformation before being analyzed. The methods of analyses included student t test, chi-square test, covariance analysis, multivariable linear regression, and multivariate logistic regression.
[Results]
1.1A total of6692consecutive subjects, aged3to18years, were enrolled in the screening. The prevalence of an'elevated BP'was18.2,5.1, and3.1%on the first, second, and third visits, respectively. The prevalence of an'elevated BP'in urban (21.0,6.1, and3.7%on the three visits)were higher than that in rural (15.1,4.0,2.5%)(P<0.05). The BP levels and the prevalence of'elevated SBP' were slightly higher in boys than that in girls on the first and second visits (P<0.05). However, there were no differences between genders on the third visit. Among children with'elevated BP',36.7,45.7, and50.3%of them had isolated elevated SBP on the first, second, and third visits, and38.8,17.9, and14.2%of them had isolated elevated DBP on the three successive visits, respectively. The prevalence of 'elevated BP' in3-5age group were16.6%,1.9%, and0.3%for boys, and20.1%,4.1%, and2.2%for girls; in the6-9age group were24.1%,5.8%, and3.0%for boys, and25.4%,5.1%, and3.1%for girls; in the10-12age group were18.8%,6.5%, and4.1%for boys, and16.5%,5.3%, and3.4%for girls, in the13-15age group were17.1%,7.1%, and4.1%for boys, and9.9%,4.2%, and3.0%for girls; and the16-18age group were17.7%,6.9%, and5.5%for boys, and8.6%,4.1%, and3.2%for girls.
1.2After adjustment for gender, age, puberty status, heart rate, risks of 'elevated BP' and HTN on the3visits were increased with the weight statue and the history of HTN of the parents (P<0.05).The odds ratios (ORs) and95%confidence intervals (CIs) for an'elevated BP'were2.64(2.18-3.31),3.95(2.65-5.88),4.54(2.70-7.61) among overweight children.7.07(5.94-8.42),17.23(12.63-23.52), and20,63(13.69-31.09) among obese children, and1.26(0.98-1.61),1.35(0.90-2.02), and1.80(1.15-2.81) among those with a paternal history of hypertension were on each consecutive visit.
2.1According to BP levels at baseline and the clinical examination152children resided in group with sustained NT,38in group with BP changed (32from HTN to NT,6from NT to HTN), and48group with sustain HTN. After adjustment for gender, age, and puberty status, the levels of baPWV, LVM, LVMI, and cIMT ascended across the3BP groups (P<0.001), and they were (938±10),(963±21),(1066±19)cm/s for baPWV,(93±2),(110±4),(119±3)g for LVM,(28±1),(32±1),(34±1)g/m2.7for LVMI, and (0.46±0.01),(0.49±0.01),(0.48±0.01)mm for cIMT in the3BP change groups accordingly. The prevalence of TOD increased in the3BP change groups in order. They were7.9%,42.1%, and33.3%for elevated LVM,2.0%,10.5%, and14.6%for elevated LVMI,12.5%,31.6%, and47.9%for elevated cIMT,9.7%,22.9%, and31.1%for elevated hs-CRP, respectively (P<0.001).
2.2Adjusted for gender, age, and puberty status, a binary logistic regression was conducted, in which each TOD index was used as dependent variable and the significant effective factors screen through multiple liner regression corresponding to that TOD index were used as independent variables. The results discovered that age was a protective factor for elevated LVM and elevated LVMI, and compared to children with sustained NT the OR (95%CI) were5.27(1.57-17.66) in BP change group and3.28(1.00-10.74) in sustained HTN group. Compared to normal weight children the ORs (95%CIs) in obese children were14.55(4.14-51.22) to suffer from elevated LVM and22.46(2.14-236.20) to suffer from elevated LVMI. Meanwhile age displayed a common protective factor for elevated RWT and LVH. Compared to children in6-9years group the ORs (95%CIs) decreased to0.19(0.06-0.64) for elevated RWT and0.20(0.07-0.63) for LVH in age group of13～15years, and0.08(0.02-0.43) for elevated RWT0.19(0.05-0.71) for LVH in age group16～18years old. The same result was repeated as that age was a protective factor in predicting cIMT increased. The ORs (95%CIs) of elevated cIMT in female is (0.40(1.03-8.09)) compared to male. Compared to children with sustained NT, children with BP changed were at2.88(1.03-8.09) fold and children with sustained HTN were at7.25(2.69-19.58) fold risk of developing elevated cIMT.
3. A total of1695children and adolescents participated in the comparison test between electric sphygmomanometer and mercury sphygmomanometer. The levels of eSBP were higher than mSBP (P<0.05), and eDBP were lower than mDBP4but higher than mDBPs (P<0.05) in both boys and girls. The percentages of absolute difference between electric sphygmomanometer and mercury sphygmomanometer in categories of≤5mmHg,≤10mmHg,≤15mmHg were54.2%,82.9%,100%for SBP;42.3%,70.4%,87.2%for K4; and46.1%,70.6%,84.8%for K5, respectively. The partial correlation coefficients adjusted for gender and age were0.716for SBP (P<0.01),0.448for eDBP and mDBPK4(P<0.01) and0.353for eDBP and mDBPK5(P<0.01). Bland-Altman plots showed good consistency between mercury sphygmomanometer and electric sphygmomanometer for both SBP and DBP.
[Conclusion]
1. It should be recommended that measuring BP on separate visits before characterizing a child as having HTN. Overweight and obesity are the leading cause of pediatric HTN;
2. Hypertensive children were at high risk of developing artery stiffness, concentric left ventricular hypertrophy than the normotensive. Initial treatment should focus on weight loss and rectifying the disorder situation of glucolipid metabolism;
3. The effects of HTN and other risk factors on early kidney damage and retinal artery stiffness didin't present statistical significance in current study;
4. BaPWV, cIMT, LVM, and LVMI may have potencial value in screening high risk population in children and adolescents;
5. Electric sphygmomanometer (Omron HEM-759P) can be used in BP measurement in children and adolescents. However, its application for individual clinical evaluation of HTN needs further studies to evaluate.
血压的准确测量和科学评估是早期发现高危人群的前提,鉴于单次血压测量波动性大,HTN诊断必须建立在血压多次重复测量基础上。与成人相似,近年来非同日多时点血压重复测量也被推荐使用于儿童青少年HTN的判定,但其必要性尚有待循证依据予以证实。临床和科研中常用的血压测量方法是使用血压计对肱动脉血压进行的间接测量,传统的听诊法汞柱立式血压计因其中汞会对环境造成污染,加之测量技术要求的特殊性,操作的复杂性,实际应用中受到一定限制。示波法中的电子血压计因方便、客观、无污染及数据能导入电脑等优点,成为当前血压测量的重要仪器,在临床、科研及家庭血压自主监测中广泛应用。但电子血压计对儿童青少年血压测量的准确性,电子血压计与听诊法对儿童血压测量的一致性尚有待深入研究验证。本研究于筛查HTN儿童过程中,在一子样本中进行了电子血压计与听诊法的比对研究,为电子血压计在儿童青少年人群中推广应用提供循证依据。
来自临床的资料显示即便血压轻度升高的儿童,其伴随的心脏、脑、血管和肾脏等重要靶器官损害(target organ damage, TOD)已不罕见。血压升高使心脏后负荷增加,室壁局部张力增加,促进心肌内蛋白合成,肌纤维成分增加。继而心肌纤维被拉长,心肌组织相对缺氧,代谢产物堆积,通过生物反馈机制,使蛋白合成增加,导致心肌肥厚。美国国家高血压教育项目儿童高血压工作组第四次报告中将左心室肥大(left ventricular hypertrophy, LVH)列为儿童青少年中最常见的TOD,并将心脏二维超声作为评估儿童青少年HTN及其TOD的常规检测。此外,HTN及其并发症的患病率和死亡率还与动脉壁的损害有关,动脉壁结构和功能损害可追溯到HTN早期,即动脉硬化是儿童期得病至成人发病的一种慢性疾病。动脉血管功能改变在儿童期已经开始,动脉脉搏波传导速度(pulse wave velocity, PWV)作为评估动脉弹性的非侵入性手段之一,已受到国内外学者的广泛重视,成为目前心血管疾病无创检测的研究热点。动脉粥样硬化为一种全身性病变,由于颈动脉表浅易于使用超声的手段进行探查,因而颈动脉内膜中层厚度(carotid artery intima-media thickness, cIMT)可作为反映全身动脉粥样硬化的窗口,可能成为早期筛查高危人群的敏感指标,在儿童中存在推广应用的潜在价值。近年来肾脏损害发病年龄也呈提前趋势,鉴于此,肾脏早期损害的推荐指标微量白蛋白尿(Microalbuminuria, MAU)已被写入了2010年《中国高血压防治指南》。
儿童青少年时期的TOD多为功能性改变,在其发展为永久性结构损害之前,如能凭借敏感的筛查指标尽早发现,尽早干预,有望使其有效逆转。然而儿童期HTN多隐匿发病,无任何临床症状,加之敏感筛查指标和手段的缺失,更容易错失早发现、早干预的良机。鉴于既往TOD的研究多局限于临床就诊的HTN患儿或小样本的典型抽样调查,人群中无症状HTN儿童TOD情况如何尚鲜有报道,本研究通过非同日三时点血压筛查,获得HTN及正常血压(normotensive, NT)对照儿童,通过对其TOD情况的评估,研究儿童青少年HTN及其危险因素对早期TOD的影响,为高危儿童敏感筛查指标的选择提供循证依据。
[目的]
1.通过非同日三时点血压筛查,获得HTN及NT对照儿童青少年,并对三时点HTN检出率的分布特征及影响因素进行研究；
2.对筛查获得HTN及NT对照儿童TOD情况进行评估,研究HTN及其危险因素对早期TOD的影响,为高危儿童敏感筛查指标的选择提供循证依据；
3.对电子血压计测量儿童青少年血压的准确性进行评估,为电子血压计在儿童青少年人群中推广使用提供依据。
[方法]
采用分层整群抽样法于2009年3-10月在北京市朝阳、丰台两城区及顺义、昌平两郊区22所中等水平幼儿园、小学及中学,招募3-18岁儿童青少年,各年龄组至少400人,城郊各半、男女各半。测量身高(cm)、体重(kg)及腰围(cm),计算体重指数(body mass index, BMI)(BMI=体重/身高2,kg/m2)；听诊法测量血压,取Korotkoff第Ⅰ音(K1)为收缩压(systolic blood pressure, SBP),第Ⅳ音(K4)为舒张压(diastolic blood pressure, DBP)。问卷调查一般人口学特征、生活行为信息、个人疾病史、HTN家族史等。对第一时点HTN的儿童,15天后第二次测量,第二时点仍为HTN的儿童,15天后第3次测量,三时点均为HTN的儿童方判定为HTN。2011年对筛查获得的HTN儿童,及按照1：2比例为其匹配的同性别同年龄NT儿童,进行TOD情况评估,包括心脏左室质量和室壁厚度、PWV、cIMT及粥样斑块形成、肾脏结构及占位、眼底动脉硬化情况,以及空腹血浆葡萄糖、血脂四项、超敏C反应蛋白(hypersensitive C-reactive protein, hs-CRP)、尿微量白蛋白测定等。在HTN筛查人群中选择1600名3-18岁儿童青少年进行电子血压计与听诊法测量血压的比对试验,每年龄组100人,男女各半,听诊法测量3次,电子血压计测量2次,间隔进行。
本研究涉及诊断标准：超重与肥胖,7-18岁采用中国肥胖问题工作组推荐的“中国学龄儿童超重、肥胖BMI分类标准”,6岁及以下参照"2000年美国疾病预防控制中心生长曲线"BMI性别年龄别P85与P95分位值；HTN,采用“中国儿童青少年血压参照标准”,SBP和DBP均<性别年龄别P90为正常,SBP和/或DBP≥P95为HTN；主动脉僵硬,颈-股PWV (carotid-femoral pulse wave velocity, cfPWV)超过性别年龄别P95；LVH,左心室重量指数(left ventricular mass index, LVMI)超过性别年龄别P95和/或相对壁厚度(relative wall thickness, RWT)超过性别年龄别P95；眼底动脉硬化,Keith-Wagnar分级诊断；MAU,随机尿微量白蛋白介于20-200mg/L；糖尿病,参考2012年美国糖尿病协会的诊断标准；血脂异常,参照2009年发布的“儿童青少年血脂异常防治专家共识”
采用Epidata3.1软件进行数据录入并二次核对,SPSS18.0数据分析,Medcalc比较两种血压计测量结果一致性。非正态分布数据以几何均数与四分位间距表示,经自然对数转换后分析。统计方法包括t检验、x2检验、协方差分析、多元线性回归分析和多因素logistic回归分析,定义P<0.05为差异有统计学意义。
[结果]
1.1总计6692人参加调查,男3326人,占49.7%。三时点HTN检出率分别为18.2%、5.1%和3.1%,其中城区儿童HTN检出率(三时点分别为21.0%、6.1%、3.7%)高于郊区(15.1%、4.0%、2.5%)(P<0.05),男童SBP、DBP水平及HTN检出率高于女童(P<0.05)；第一时点HTN检出率随年龄波动最大,其次第二时点,第三时点相对稳定,规律基本相同：3-5岁检出率最低,6-9岁达高峰,后渐下降或趋平稳,男女间略有不同。
1.2调整可能影响因素性别、年龄、青春期及心率,以三时点HTN为应变量,以体重状态、睡眠时间、父母HTN史、父母教育程度为自变量进行二分类多因素logistic回归分析,结果超重、肥胖及父母HTN史为HTN危险因素,与正常体重相比,超重儿童罹患HTN比值比(Odds Ratio, OR)及95%可信限(confidence interval,CI)在第一、第二及第三时点分别为2.64(2.18-3.31)、3.95(2.65-5.88)、4.54(2.70-7.61),肥胖儿童罹患HTN的OR (95%CI)分别为7.07(5.94-8.42)、17.23(12.63-23.52)、20.63(13.69-31.09)；与无HTN家族史儿童相比,父亲患有HTN儿童,三时点OR (95%CI)分别为1.26(0.98-1.61)、1.35(0.90-2.02)和1.80(1.15-2.81)。
2.对经三时点筛查获得238名儿童青少年(80名HTN及158名NT)进行TOD的评估。依据筛查时点及TOD评估时点血压状态分组,两时点持续NT组152名,血压波动组38名(32名HTN转变为NT,6名NT转变为HTN),持续HTN组48名。三组儿童中baPWV(938±10cm/s、963±21cm/s、1066±19cm/s)、 LVM (93±2g、110±4g、119±3g)、LVMI (28±1g/m2.7、32±1g/m2.7、34±1g/m2.7)、 cIMT (0.46±0.01mm、0.49±0.01mm、0.48±0.01mm)水平逐渐上升(P<0.001)；LVM升高(7.9%、42.1%及33.3%)、LVMI升高(2.0%、10.5%及14.6%)cIMT增厚(12.5%、31.6%、47.9%)及hs-CRP升高(9.7%、22.9%、31.1%)检出率在三组儿童中亦逐渐上升(P<0.001)；多元线性回归筛选对各项TOD有意义的危险因素,再分别对其调整进行logistic回归分析,结果：年龄为多项TOD共同的保护因素,与持续NT儿童相比,血压波动及持续HTN儿童LVM增高的OR (95%CI)分别为5.27(1.57-17.66)和3.28(1.00-10.74)。肥胖儿童LVM升高的风险为正常体重儿童的14.55(4.14-51.22)倍；肥胖儿童LVMI增高的风险是非肥胖儿童22.46(2.14-236.20)倍；女童cIMT增厚的风险小于男童(0.40(0.19-0.87)),血压波动及持续HTN儿童cIMT增厚的风险分别是持续NT儿童的2.88(1.03-8.09)倍和7.25(2.69-19.58)倍。
3.共招募1695名3-18岁儿童青少年参加两种血压计比对试验，男845人,占49.9%。各年龄组电子血压计与听诊法测量结果互有高低,以电子血压计偏高为主。电子血压计与听诊法测量SBP平均误差为3mmHg,标准偏差8mmHg;电子血压计DBP与听诊法K4平均误差-4mmHg,标准偏差10mmHg;电子血压计舒张压与听诊法K5平均误差4mmHg,标准偏差13mmHgo电子血压计与听诊法测量结果差值绝对值<5mmHg,≤10mmHg和≤15mmHg所占比例,对SBP分别为54.2%,82.9%和100%：以听诊法K4为DBP时,3组比例分别为42.3%,70.4%和87.2%,以听诊法K5为DBP时,3组比例分别为46.1%,70.6%和84.8%。电子血压计与听诊法SBP差值95%一致性界限为(-13.5～19.6) mmHg;电子血压计DBP与听诊法K4差值95%一致性界限为(-22.5～15.1) mmHg,与听诊法K5差值95%一致性界限为(-20.3～28.4)mmHg。
[结论]
1.经非同日三时点血压筛查,儿童青少年HTN检出率下降了近6倍,重复测量对儿童青少年HTN判定十分必要；
2.超重、肥胖及父亲HTN疾病史是儿童青少年HTN重要危险因素；
3.两年间持续HTN儿童发生动脉粥样硬化、动脉硬化及左室向心性肥厚的风险高于血压波动儿童,进一步高于持续NT儿童；
4. BaPWV、cIMT、LVM、LVMI高危儿童早期筛查中具有潜在的应用价值；
5.尚未发现持续HTN儿童发生早期肾损害的危险高于血压波动儿童及持续NT儿童；
6.肥胖和糖脂代谢异常与TOD密切相关,及早控制体重及纠正糖脂代谢紊乱是预防的关键；
7.电子血压计与听诊对儿童青少年血压测量结果存在一定差异,但总体尚稳定,一致性尚好,电子血压计可用于儿童青少年血压的测量。
[Background]
Hypertension (HTN) has become an important issue of public health due to its rapid increase in the past two decades. Meanwhile, blood pressure (BP) tracks from childhood to adulthood, and the onset of primary HTN is proved to be traced back to childhood. However, levels of BP are difficult to be efficiently controlled in nearly70%of hypertensive patients. The target organ damages (TOD) are the important problems of HTN study. TOD is the main culprit of the burden of illness and economical load, so primary prevention early from childhood has become the root of the problem.
Recognizing the development of HTN at an earlier age may provide physicians with an opportunity to reduce its risk factors early on. Owing to a large variability in repeated BP measurements obtained on a single visit, the diagnosis of HTN in adults is typically based on repeated BP measurements over several visits. Similar to adults, it was recently recommended that elevated BP in children should be determined from at least three separate visits.
The health hazard of pediatric HTN not only causes the high risks of adult HTN, but also does damage to target organs of artery, heart, brain and kidney. Studies based on clinic have proved that TOD could be observed even in those hypertensive children with BP elevated mildly. However, most of the TOD in childhood are function damage and may be reversed if effective intervention conducted on the premise of early identifying. In view of this the population-based study was designed to investigate the characteristics of HTN and TOD, and studied the association between HTN and other risk factors and early TOD in children and adolescents.
Furthermore, as it's the case in adults, the white coat and the masked hypertension phenomena appear to be common in children. Therefore, assessment of out of-office BP using either electronic sphygmomanometer or home monitoring is often needed in children and adolescents. Limited evidence exists on the accuracy of 电子血压计for blood pressure measurement in children. An additional content of this study is to verify the accuracy of electric sphygmomanometer in measurements of blood pressure based on population survey.
[Objective]
1. To screen hypertensive children and adolescents based on population survey and to prove the necessary of repeated measurements on separate occasions in diagnosing HTN in pediatric population;
2. To analyze the association between HTN and other risk factors with early TOD in pediatric population and to supply some proof evidence-based in identifying, diagnosing and interposing of the high risk population from early time;
3. To verify the assistant between electronic sphygmomanometer and mercury sphygmomanometer in pediatric population based on blood pr electronic sphygmomanometersure population survey.
[Methods]
Children and adolescents aged3to18years (400in each age group) were recruited using a stratified cluster sampling in2009. This survey was conducted in9kindergartens,7primary and5secondary schools selected from2urban and2rural districts in Beijing. BP was measured according to a standard protocol using a mercury sphygmomanometer on right upper arm in the sitting position. Korotkoff phase1(K1) and4(K4) sounds were used to define systolic BP (SBP) and diastolic BP (DBP), respectively. Heart rate was recorded in beats/min. Meanwhile anthropometric measurements including height (cm), weight (kg) and waist circumference (cm) were obtained with body mass index (BMI) being calculated as weight in kilograms divided by the square of height in meters (kg/m2). Those with a BP in≥95th percentile were screened a second or third time at two-week intervals. A questionnaire, which included questions on physical activity, sleep duration, salt intake, familial history of hypertension, and parental educational levels, was completed.
Meanwhile a comparison test between electric sphygmomanometer and mercury sphygmomanometer was conducted in a consecutive pediatric population aged3to18years (100in each age group). Electronic sphygmomanometer (Omron HEM-759P) and mercury sphygmomanometer were used to measure BP two times, respectively, and two instruments were used by turns. Korotkoff K1was recorded as SBP measured by mercury sphygmomanometer (mSBP), K4and K5as DBP by mercury sphygmomanometer (mDBP4and mDBPs), respectively. SBP and DBP measured by lectronic sohygmomanometer were recorded as eSBP and eDBP.
Selected hypertensive and double normotensive matched for gender and age screened from the baseline survey were enrolled in the clinical examination on early TOD in2011. The anthropometric measurements including height, weight, SBP, DBP and heart rate were re-measured with BMI being recalculated. All the participants were divided into3groups (consistent NT, BP change, and consistent HTN) according to the BP levels at the baseline and the clinical examination. Moreover, other indexes such as pulse wave velocity (PWV, cm/s), carotid artery intima-media thickness (cIMT), structure of left ventricular and kidney, retinal artery were measured, blood glucose, lipid spectrum, micro albumin in urine,β2-microglobulin and cystatin C were examined.
'Elevated BP'was defined as SBP or DBP in the≥95th sex-and age-specific percentile of Chinese pediatric population on all the three occasions.'Hypertension' was defined as an'elevated BP' on all three visits. Overweight and obesity in school-aged children were defined according to BMI cutoffs for Chinese children and adolescents. The US2000CDC Growth Chart (CDC2000) was used to clarify the weight status for children aged3-6years. Specifically, BMI in the<85th, between the>85th and<95th, and in the≥95th percentiles was classified as 'normal weight','overweight', and'obese', respectively. Based on the Chinese national survey of students' physical quality data, we also calculated BMI percentiles (i.e.<5th,5th-24th,25th-49th,50th-74th,75th-84th,85th-94th, and≥95th).
Data of investigation and examination were entered and double checked with Epidata software3.1, and analyzed using SPSS18.0. Data of non-normal distribution were turned into normal distribution through natural logarithm transformation before being analyzed. The methods of analyses included student t test, chi-square test, covariance analysis, multivariable linear regression, and multivariate logistic regression.
[Results]
1.1A total of6692consecutive subjects, aged3to18years, were enrolled in the screening. The prevalence of an'elevated BP'was18.2,5.1, and3.1%on the first, second, and third visits, respectively. The prevalence of an'elevated BP'in urban (21.0,6.1, and3.7%on the three visits)were higher than that in rural (15.1,4.0,2.5%)(P<0.05). The BP levels and the prevalence of'elevated SBP' were slightly higher in boys than that in girls on the first and second visits (P<0.05). However, there were no differences between genders on the third visit. Among children with'elevated BP',36.7,45.7, and50.3%of them had isolated elevated SBP on the first, second, and third visits, and38.8,17.9, and14.2%of them had isolated elevated DBP on the three successive visits, respectively. The prevalence of 'elevated BP' in3-5age group were16.6%,1.9%, and0.3%for boys, and20.1%,4.1%, and2.2%for girls; in the6-9age group were24.1%,5.8%, and3.0%for boys, and25.4%,5.1%, and3.1%for girls; in the10-12age group were18.8%,6.5%, and4.1%for boys, and16.5%,5.3%, and3.4%for girls, in the13-15age group were17.1%,7.1%, and4.1%for boys, and9.9%,4.2%, and3.0%for girls; and the16-18age group were17.7%,6.9%, and5.5%for boys, and8.6%,4.1%, and3.2%for girls.
1.2After adjustment for gender, age, puberty status, heart rate, risks of 'elevated BP' and HTN on the3visits were increased with the weight statue and the history of HTN of the parents (P<0.05).The odds ratios (ORs) and95%confidence intervals (CIs) for an'elevated BP'were2.64(2.18-3.31),3.95(2.65-5.88),4.54(2.70-7.61) among overweight children.7.07(5.94-8.42),17.23(12.63-23.52), and20,63(13.69-31.09) among obese children, and1.26(0.98-1.61),1.35(0.90-2.02), and1.80(1.15-2.81) among those with a paternal history of hypertension were on each consecutive visit.
2.1According to BP levels at baseline and the clinical examination152children resided in group with sustained NT,38in group with BP changed (32from HTN to NT,6from NT to HTN), and48group with sustain HTN. After adjustment for gender, age, and puberty status, the levels of baPWV, LVM, LVMI, and cIMT ascended across the3BP groups (P<0.001), and they were (938±10),(963±21),(1066±19)cm/s for baPWV,(93±2),(110±4),(119±3)g for LVM,(28±1),(32±1),(34±1)g/m2.7for LVMI, and (0.46±0.01),(0.49±0.01),(0.48±0.01)mm for cIMT in the3BP change groups accordingly. The prevalence of TOD increased in the3BP change groups in order. They were7.9%,42.1%, and33.3%for elevated LVM,2.0%,10.5%, and14.6%for elevated LVMI,12.5%,31.6%, and47.9%for elevated cIMT,9.7%,22.9%, and31.1%for elevated hs-CRP, respectively (P<0.001).
2.2Adjusted for gender, age, and puberty status, a binary logistic regression was conducted, in which each TOD index was used as dependent variable and the significant effective factors screen through multiple liner regression corresponding to that TOD index were used as independent variables. The results discovered that age was a protective factor for elevated LVM and elevated LVMI, and compared to children with sustained NT the OR (95%CI) were5.27(1.57-17.66) in BP change group and3.28(1.00-10.74) in sustained HTN group. Compared to normal weight children the ORs (95%CIs) in obese children were14.55(4.14-51.22) to suffer from elevated LVM and22.46(2.14-236.20) to suffer from elevated LVMI. Meanwhile age displayed a common protective factor for elevated RWT and LVH. Compared to children in6-9years group the ORs (95%CIs) decreased to0.19(0.06-0.64) for elevated RWT and0.20(0.07-0.63) for LVH in age group of13～15years, and0.08(0.02-0.43) for elevated RWT0.19(0.05-0.71) for LVH in age group16～18years old. The same result was repeated as that age was a protective factor in predicting cIMT increased. The ORs (95%CIs) of elevated cIMT in female is (0.40(1.03-8.09)) compared to male. Compared to children with sustained NT, children with BP changed were at2.88(1.03-8.09) fold and children with sustained HTN were at7.25(2.69-19.58) fold risk of developing elevated cIMT.
3. A total of1695children and adolescents participated in the comparison test between electric sphygmomanometer and mercury sphygmomanometer. The levels of eSBP were higher than mSBP (P<0.05), and eDBP were lower than mDBP4but higher than mDBPs (P<0.05) in both boys and girls. The percentages of absolute difference between electric sphygmomanometer and mercury sphygmomanometer in categories of≤5mmHg,≤10mmHg,≤15mmHg were54.2%,82.9%,100%for SBP;42.3%,70.4%,87.2%for K4; and46.1%,70.6%,84.8%for K5, respectively. The partial correlation coefficients adjusted for gender and age were0.716for SBP (P<0.01),0.448for eDBP and mDBPK4(P<0.01) and0.353for eDBP and mDBPK5(P<0.01). Bland-Altman plots showed good consistency between mercury sphygmomanometer and electric sphygmomanometer for both SBP and DBP.
[Conclusion]
1. It should be recommended that measuring BP on separate visits before characterizing a child as having HTN. Overweight and obesity are the leading cause of pediatric HTN;
2. Hypertensive children were at high risk of developing artery stiffness, concentric left ventricular hypertrophy than the normotensive. Initial treatment should focus on weight loss and rectifying the disorder situation of glucolipid metabolism;
3. The effects of HTN and other risk factors on early kidney damage and retinal artery stiffness didin't present statistical significance in current study;
4. BaPWV, cIMT, LVM, and LVMI may have potencial value in screening high risk population in children and adolescents;
5. Electric sphygmomanometer (Omron HEM-759P) can be used in BP measurement in children and adolescents. However, its application for individual clinical evaluation of HTN needs further studies to evaluate.
引文
[1]Egan BM, Zhao Y, Axon RN. US trends in prevalence, awareness, treatment, and control of hypertension,1988-2008. JAMA.2010.303(20):2043-50.
[2]陈春明.利国利民的信息宝库：中国居民营养与健康状况调查.中华流行病学杂志.2005.26(7)：469-470.
[3]Din-Dzietham R, Liu Y, Bielo MV, Shamsa F. High blood pressure trends in children and adolescents in national surveys,1963 to 2002. Circulation. 2007.116(13):1488-96.
[4]席波,米杰,王俐等.北京市儿童青少年原发性高血压的家庭聚集性分析.中华流行病学杂志.2008.29(9)：849-854.
[5]Chen X, Wang Y. Tracking of blood pressure from childhood to adulthood:a systematic review and meta-regression analysis. Circulation.2008.117(25): 3171-80.
[6]Rothwell PM, Howard SC, Dolan E, et al. Effects of beta blockers and calcium-channel blockers on within-individual variability in blood pressure and risk of stroke. Lancet Neurol.2010.9(5):469-80.
[7]Pickering TG, Hall JE, Appel LJ, et al. Recommendations for blood pressure measurement in humans and experimental animals:part 1:blood pressure measurement in humans:a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Circulation.2005.111(5):697-716.
[8]The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics.2004.114(2 Suppl 4th Report): 555-76.
[9]Hanevold C, Waller J, Daniels S, Portman R, Sorof J. The effects of obesity, gender, and ethnic group on left ventricular hypertrophy and geometry in hypertensive children:a collaborative study of the International Pediatric Hypertension Association. Pediatrics.2004.113(2):328-33.
[10]McNiece KL, Gupta-Malhotra M, Samuels J, et al. Left ventricular hypertrophy in hypertensive adolescents:analysis of risk by 2004 National High Blood Pressure Education Program Working Group staging criteria. Hypertension.2007.50(2):392-5.
[11]Laird WP, Fixler DE. Left ventricular hypertrophy in adolescents with elevated blood pressure:assessment by chest roentgenography, electrocardiography, and echocardiography. Pediatrics.1981.67(2):255-9.
[12]Hanevold C, Waller J, Daniels S, Portman R, Sorof J. The effects of obesity, gender, and ethnic group on left ventricular hypertrophy and geometry in hypertensive children:a collaborative study of the International Pediatric Hypertension Association. Pediatrics.2004.113(2):328-33.
[13]Brady TM, Fivush B, Flynn JT, Parekh R. Ability of blood pressure to predict left ventricular hypertrophy in children with primary hypertension. J Pediatr. 2008.152(1):73-8,78.el.
[14]Varda NM, Gregoric A. A diagnostic approach for the child with hypertension. Pediatr Nephrol.2005.20(4):499-506.
[15]Turin TC, Kita Y, Rumana N, et al. Brachial-ankle pulse wave velocity predicts all-cause mortality in the general population:findings from the Takashima study, Japan. Hypertens Res.2010.33(9):922-5.
[16]Washida N, Wakino S, Hayashi K, Kuwahara T, Itoh H. Brachial-ankle pulse wave velocity predicts silent cerebrovascular diseases in patients with end-stage renal diseases. J Atheroscler Thromb.2010.17(2):165-72.
[17]Tounian P, Aggoun Y, Dubern B, et al. Presence of increased stiffness of the common carotid artery and endothelial dysfunction in severely obese children: a prospective study. Lancet.2001.358(9291):1400-4.
[18]Poredos P. Intima-media thickness:indicator of cardiovascular risk and measure of the extent of atherosclerosis. Vasc Med.2004.9(1):46-54.
[19]Sorof JM, Alexandrov AV, Cardwell G, Portman RJ. Carotid artery intimal-medial thickness and left ventricular hypertrophy in children with elevated blood pressure. Pediatrics.2003.111(1):61-6.
[20]Lande MB, Carson NL, Roy J, Meagher CC. Effects of childhood primary hypertension on carotid intima media thickness:a matched controlled study. Hypertension.2006.48(1):40-4.
[21]Flynn JT. What is the significance of increased carotid intima media thickness in hypertensive adolescents. Hypertension.2006.48(1):23-4.
[22]Barinas-Mitchell E, Kuller LH, Sutton-Tyrrell K, et al. Effect of weight loss and nutritional intervention on arterial stiffness in type 2 diabetes. Diabetes Care.2006.29(10):2218-22.
[23]Tomiyama H, Hashimoto H, Hirayama Y, et al. Synergistic acceleration of arterial stiffening in the presence of raised blood pressure and raised plasma glucose. Hypertension.2006.47(2):180-8.
[24]Munakata M, Miura Y, Yoshinaga K. Higher brachial-ankle pulse wave velocity as an independent risk factor for future microalbuminuria in patients with essential hypertension:the J-TOPP study. J Hypertens.2009.27(7): 1466-71.
[25]Leoncini G, Sacchi G, Ravera M, et al. Microalbuminuria is an integrated marker of subclinical organ damage in primary hypertension. J Hum Hypertens.2002.16(6):399-404.
[26]Mancia G, De Backer G, Dominiczak A, et al.2007 Guidelines for the management of arterial hypertension:The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J.2007.28(12): 1462-536.
[27]Assadi F. Effect of microalbuminuria lowering on regression of left ventricular hypertrophy in children and adolescents with essential hypertension. Pediatr Cardiol.2007.28(1):27-33.
[28]Sorof JM, Turner J, Franco K, Portman RJ. Characteristics of hypertensive children identified by primary care referral compared with school-based screening. J Pediatr.2004.144(4):485-9.
[29]Sizonenko PC, Himes JH. Introduction to the use and interpretation of anthropometry in adolescence. Horm Res.1993.39 Suppl 3:7-8.
[30]Blumenthal S, Epps RP, Heavenrich R, et al. Report of the task force on blood pressure control in children. Pediatrics.1977.59(52 suppl):Ⅰ-Ⅱ,797-820.
[31]Devereux RB, Alonso DR, Lutas EM, et al. Echocardiographic assessment of left ventricular hypertrophy:comparison to necropsy findings. Am J Cardiol. 1986.57(6):450-8.
[32]de Simone G, Daniels SR, Devereux RB, et al. Left ventricular mass and body size in normotensive children and adults:assessment of allometric relations and impact of overweight. J Am Coll Cardiol.1992.20(5):1251-60.
[33]中国肥胖问题工作组.中国学龄儿童青少年超重、肥胖筛查体重指数值分类标准.中华流行病学杂志.2004.25(2)：97-102.
[34]Kuczmarski RJ, Ogden CL, Grummer-Strawn LM, et al. CDC growth charts: United States. Adv Data.2000. (314):1-27.
[35]米杰,王天有,孟玲慧等.中国儿童青少年血压参照标准的研究制定.中国循证儿科杂志.2010.5(1)：4-14.
[36]Reusz GS, Cseprekal O, Temmar M, et al. Reference values of pulse wave velocity in healthy children and teenagers. Hypertension.2010.56(2):217-24.
[37]Khoury PR, Mitsnefes M, Daniels SR, Kimball TR. Age-specific reference intervals for indexed left ventricular mass in children. J Am Soc Echocardiogr. 2009.22(6):709-14.
[38]de Simone G, Daniels SR, Kimball TR, et al. Evaluation of concentric left ventricular geometry in humans:evidence for age-related systematic underestimation. Hypertension.2005.45(1):64-8.
[39]胡大一.心血管疾病防治指南和共识2008.2008.人民卫生出版社.104-119.
[40]胡亚美,江载芳.诸福棠实用儿科学.2008.1593-1595.
[41]Diagnosis and classification of diabetes mellitus. Diabetes Care.2012.35 Suppl 1:S64-71.
[42]Pediatrics TEBoCJo,中华医学会儿科学分会儿童保健学组,中华医学会儿科学分会心血管学组,<,中华儿科杂志>,编辑委员会.儿童青少年血脂异常防治专家共识.中华儿科杂志.2009.47(6)：426-428.
[43]中国疾病预防控制中心.慢病管理业务信息技术规范,2008.15.
[44]Foundation NS.美国国家睡眠基金会对儿童睡眠时间的推荐标准
[45]中国高血压防治指南修订委员会.中国高血压防治指南2010.中华心血管病杂志.2011.39(7)：579-616.
[46]Chiolero A, Cachat F, Burnier M, Paccaud F, Bovet P. Prevalence of hypertension in schoolchildren based on repeated measurements and association with overweight. J Hypertens.2007.25(11):2209-17.
[47]Genovesi S, Giussani M, Pieruzzi F, et al. Results of blood pressure screening in a population of school-aged children in the province of Milan:role of overweight. J Hypertens.2005.23(3):493-7.
[48]Fixler DE, Laird WP, Fitzgerald V, Stead S, Adams R. Hypertension screening in schools:results of the Dallas study. Pediatrics.1979.63(1):32-6.
[49]Sorof JM, Poffenbarger T, Franco K, Bernard L, Portman RJ. Isolated systolic hypertension, obesity, and hyperkinetic hemodynamic states in children. J Pediatr.2002.140(6):660-6.
[50]McNiece KL, Poffenbarger TS, Turner JL, Franco KD, Sorof JM, Portman RJ. Prevalence of hypertension and pre-hypertension among adolescents. J Pediatr. 2007.150(6):640-4,644.e1.
[51]Leung LC, Sung RY, So HK, et al. Prevalence and risk factors for hypertension in Hong Kong Chinese adolescents:waist circumference predicts hypertension, exercise decreases risk. Arch Dis Child.2011.96(9):804-9.
[52]Cornoni-Huntley J, Harlan WR, Leaverton PE. Blood pressure in adolescence. The United States Health Examination survey. Hypertension.1979.1(6): 566-71.
[53]Gugig R, Rosenthal P. Management of portal hypertension in children. World J Gastroenterol.2012.18(11):1176-84.
[54]Shankar RR, Eckert GJ, Saha C, Tu W, Pratt JH. The change in blood pressure during pubertal growth. J Clin Endocrinol Metab.2005.90(1):163-7.
[55]Lurbe E, Cifkova R, Cruickshank JK, et al. Management of high blood pressure in children and adolescents:recommendations of the European Society of Hypertension. J Hypertens.2009.27(9):1719-42.
[56]万燕萍,唐激文,徐仁应,吴颖洁,陈之琦,徐敏.体质指数和腰围对肥胖儿童青少年高血压的影响.上海第二医科大学学报.2004.24(z1)：46-48.
[57]程红,闫银坤,段佳丽,耳玉亮,米杰.儿童肥胖对高血压发病率影响的随访研究.中华预防医学杂志.2011.45(8)：696-701.
[58]刘博伟,尹福在,马春明等.有高血压家族史血压正常的青少年心血管危险因素分析.中华高血压杂志.2008.16(5)：441-444.
[59]李涛,李芸,李艳.有高血压家族史青少年血浆内皮素及相关因素分析.中国儿童保健杂志.2001.9(4)：234-235.
[60]陈慧兰,胡申江,刘超群.高血压家族史对血压正常高值患者血管内皮功能的影响.浙江医学.2011.33(3)：352-354.
[61]Wada K, Tamakoshi K, Yatsuya H, et al. Association between parental histories of hypertension, diabetes and dyslipidemia and the clustering of these disorders in offspring. Prev Med.2006.42(5):358-63.
[62]Burke V, Gracey MP, Beilin LJ, Milligan RA. Family history as a predictor of blood pressure in a longitudinal study of Australian children. J Hypertens. 1998.16(3):269-76.
[63]Fuentes RM, Notkola IL, Shemeikka S, Tuomilehto J, Nissinen A. Familial aggregation of blood pressure:a population-based family study in eastern Finland. J Hum Hypertens.2000.14(7):441-5.
[64]DeStefano AL, Gavras H, Heard-Costa N, et al. Maternal component in the familial aggregation of hypertension. Clin Genet.2001.60(1):13-21.
[65]Bovet P, Gervasoni JP, Ross AG, et al. Assessing the prevalence of hypertension in populations:are we doing it right. J Hypertens.2003.21(3): 509-17.
[66]Lurbe E, Torro I, Alvarez V, et al. Prevalence, persistence, and clinical significance of masked hypertension in youth. Hypertension.2005.45(4): 493-8.
[67]Bao W, Threefoot SA, Srinivasan SR, Berenson GS. Essential hypertension predicted by tracking of elevated blood pressure from childhood to adulthood: the Bogalusa Heart Study. Am J Hypertens.1995.8(7):657-65.
[68]Klumbiene J, Sileikiene L, Milasauskiene Z, Zaborskis A, Shatchkute A. The relationship of childhood to adult blood pressure:longitudinal study of juvenile hypertension in Lithuania. J Hypertens.2000.18(5):531-8.
[69]无.青少年初始血压高者在高血压发生中的预测意义.中华心血管病杂志.1996.24(4)：254-256.
[70]吴光驰,郭素怡.北京地区468名少儿肥胖及血压改变的八年随访观察.中华医学杂志.1997.77(1)：18-21.
[71]Daniels SR, Witt SA, Glascock B, Khoury PR, Kimball TR. Left atrial size in children with hypertension:the influence of obesity, blood pressure, and left ventricular mass. J Pediatr.2002.141(2):186-90.
[72]Park KH, Park WJ, Kim MK, et al. Noninvasive brachial-ankle pulse wave velocity in hypertensive patients with left ventricular hypertrophy. Am J Hypertens.2010.23(3):269-74.
[73]Salvi P, Safar ME, Labat C, Borghi C, Lacolley P, Benetos A. Heart disease and changes in pulse wave velocity and pulse pressure amplification in the elderly over 80 years:the PARTAGE Study. J Hypertens.2010.28(10): 2127-33.
[74]McVeigh GE, Bratteli CW, Morgan DJ, et al. Age-related abnormalities in arterial compliance identified by pressure pulse contour analysis:aging and arterial compliance. Hypertension.1999.33(6):1392-8.
[75]Simon A, Gariepy J, Chironi G, Megnien JL, Levenson J. Intima-media thickness:a new tool for diagnosis and treatment of cardiovascular risk. J Hypertens.2002.20(2):159-69.
[76]Avolio A, Jones D, Tafazzoli-Shadpour M. Quantification of alterations in structure and function of elastin in the arterial media. Hypertension.1998. 32(1):170-5.
[77]Wong M, Edelstein J, Wollman J, Bond MG. Ultrasonic-pathological comparison of the human arterial wall. Verification ofintima-media thickness. Arterioscler Thromb.1993.13(4):482-6.
[78]Kablak-Ziembicka A, Tracz W, Przewlocki T, Pieniazek P, Sokolowski A, Konieczynska M. Association of increased carotid intima-media thickness with the extent ofcoronary artery disease. Heart.2004.90(11):1286-90.
[79]Craven TE, Ryu JE, Espeland MA, et al. Evaluation of the associations between carotid artery atherosclerosis andcoronary artery stenosis. A case-control study. Circulation.1990.82(4):1230-42.
[80]O'Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med.1999.340(1):14-22.
[81]李运刚,李化勇,郭秀风,巩法莲,吴世秀.彩色超声多普勒评价颈动脉粥样硬化与脑梗死发生的相关性.中国临床康复.2005.9(5)：156.
[82]Wong M, Edelstein J, Wollman J, Bond MG. Ultrasonic-pathological comparison of the human arterial wall. Verification of intima-media thickness. Arterioscler Thromb.1993.13(4):482-6.
[83]许竹梅,赵水平,范平.超声测量颈动脉内膜中层厚度与颈动脉斑块的关系.中国动脉硬化杂志.2000.8(2)：165-168.
[84]Wong M EJ, Wollman J. Ultrosonic patrological comparision of human arterial wall:Verification of intima-media thickness. Arteriascler Thromb.1993.13(4): 482-486.
[85]Salcuni M, Di LV, Di SC, Moschini M, Fiorentino P, Rollo M. [The role of Doppler US in the study of carotid system]. Rays.1995.20(4):406-25.
[86]Polak JF, O'Leary DH, Kronmal RA, et al. Sonographic evaluation of carotid artery atherosclerosis in the elderly:relationship of disease severity to stroke and transient ischemic attack. Radiology.1993.188(2):363-70.
[87]Aatola H, Hutri-Kahonen N, Juonala M, et al. Lifetime risk factors and arterial pulse wave velocity in adulthood:the cardiovascular risk in young Finns study. Hypertension.2010.55(3):806-11.
[88]Schram MT, Henry RM, van DRA, et al. Increased central artery stiffness in impaired glucose metabolism and type 2 diabetes:the Hoorn Study. Hypertension.2004.43(2):176-81.
[89]Henry RM, Kostense PJ, Spijkerman AM, et al. Arterial stiffness increases with deteriorating glucose tolerance status:the Hoorn Study. Circulation.2003. 107(16):2089-95.
[90]Nakamura M, Yamashita T, Yajima J, et al. Brachial-ankle pulse wave velocity as a risk stratification index for the short-term prognosis of type 2 diabetic patients with coronary artery disease. Hypertens Res.2010.33(10):1018-24.
[91]Devereux RB, Roman MJ, Paranicas M, et al. Impact of diabetes on cardiac structure and function:the strong heart study. Circulation.2000.101(19): 2271-6.
[92]Lopez RM, Gomez CJ, Barbado HFJ. [Endothelial dysfunction and vasculitis: a close relationship]. Rev Clin Esp.2006.206(4):199-201.
[93]Safar ME, Siche JP, Mallion JM, London GM. Arterial mechanics predict cardiovascular risk in hypertension. J Hypertens.1997.15(12 Pt 2):1605-11.
[94]Yambe M, Tomiyama H, Hirayama Y, et al. Arterial stiffening as a possible risk factor for both atherosclerosis and diastolic heart failure. Hypertens Res. 2004.27(9):625-31.
[95]Stabouli S, Kotsis V, Rizos Z, et al. Left ventricular mass in normotensive, prehypertensive and hypertensive children and adolescents. Pediatr Nephrol. 2009.24(8):1545-51.
[96]Dhuper S, Abdullah RA, Weichbrod L, Mahdi E, Cohen HW. Association of obesity and hypertension with left ventricular geometry and function in children and adolescents. Obesity (Silver Spring).2011.19(1):128-33.
[97]Abel ED, Litwin SE, Sweeney G. Cardiac remodeling in obesity. Physiol Rev. 2008.88(2):389-419.
[98]Daniels SR. Hypertension-induced cardiac damage in children and adolescents. Blood Press Monit.1999.4(3-4):165-70.
[99]Litwin M, Niemirska A, Sladowska J, et al. Left ventricular hypertrophy and arterial wall thickening in children with essential hypertension. Pediatr Nephrol.2006.21(6):811-9.
[100]王飞(综述),卜培莉(审校).高血压早期肾损害的监测指标.心血管病学进展.2009.30(1)：79-83.
[101]Lubrano R, Travasso E, Raggi C, Guido G, Masciangelo R, Elli M. Blood pressure load, proteinuria and renal function in pre-hypertensive children. Pediatr Nephrol.2009.24(4):823-31.
[102]Pose-Reino A, Gomez-Ulla F, Hayik B, et al. Computerized measurement of retinal blood vessel calibre:description, validation and use to determine the influence of ageing and hypertension. J Hypertens.2005.23(4):843-50.
[103]Schmidt RJ, Parrilla JAM, Munoz MJ. [Sources of error in blood pressure measurement]. Rev Enferm.1997.20(223):51-4.
[104]中国血压测量工作组.中国高血压测量指南.中华高血压杂志.2011.19(12)：1-15.
[105]O'Brien E, Pickering T, Asmar R, et al. Working Group on Blood Pressure Monitoring of the European Society of Hypertension International Protocol for validation of blood pressure measuring devices in adults. Blood Press Monit. 2002.7(1):3-17.
[106]高柏青,孙淼,王丽琴.血压的测量和临床评估.现代康复.1999.3(10)：1216-1217.
[107]Geddes LA. Counterpressure:the concept that made the indirect measurement of blood pressure possible. IEEE Eng Med Biol Mag.1998.17(6):85-7.
[108]Ireland J. In praise of mercury sphygmomanometers. Electronic readings of blood pressure seem to be higher than readings obtained with mercury sphygmomanometers. BMJ.2001.322(7296):1249.
[109]朱洁明.欧姆龙BP-203RⅧC型电子血压计和水银柱式血压计测量值比较.现代中西医结合杂志.2009.18(22)：2662-2663.
[110]Chen X, Wang Y, Appel LJ, Mi J. Impacts of measurement protocols on blood pressure tracking from childhood into adulthood:a metaregression analysis. Hypertension.2008.51(3):642-9.
[111]Amoore JN. Oscillometric sphygmomanometers:a critical appraisal of current technology. Blood Press Monit.2012.17(2):80-8.
[112]车承华.电子血压计与汞柱式血压计在临床应用的对照研究.解放军护理杂志.2004.21(1)：15-16.
[113]林奕.两种血压计测量结果比较.中国医疗设备.2009.24(8)：120,119.
[114]盛长生,崔艳,陈寒萼等.高血压合并糖尿病患者家庭自测血压所需天数和读数.中华高血压杂志.2010.18(4)：344-348.
[1]Wu Y, Huxley R, Li L, et al. Prevalence, awareness, treatment, and control of hypertension in China:data from the China National Nutrition and Health Survey 2002. Circulation.2008.118(25):2679-86.
[2]席波,米杰,王俐等.北京市儿童青少年原发性高血压的家庭聚集性分析.中华流行病学杂志.2008.29(9)：849-854.
[3]Nelson MJ, Ragland DR, Syme SL. Longitudinal prediction of adult blood pressure from juvenile blood pressure levels. Am J Epidemiol.1992.136(6): 633-45.
[4]Klumbiene J, Sileikiene L, Milasauskiene Z, Zaborskis A, Shatchkute A. The relationship of childhood to adult blood pressure:longitudinal study of juvenile hypertension in Lithuania. J Hypertens.2000.18(5):531-8.
[5]Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension:analysis of worldwide data. Lancet.2005.365(9455): 217-23.
[6]Hanevold C, Waller J, Daniels S, Portman R, Sorof J. The effects of obesity, gender, and ethnic group on left ventricular hypertrophy and geometry in hypertensive children:a collaborative study of the International Pediatric Hypertension Association. Pediatrics.2004.113(2):328-33.
[7]McNiece KL, Gupta-Malhotra M, Samuels J, et al. Left ventricular hypertrophy in hypertensive adolescents:analysis of risk by 2004 National High Blood Pressure Education Program Working Group staging criteria. Hypertension.2007.50(2):392-5.
[8]Daniels SR, Witt SA, Glascock B, Khoury PR, Kimball TR. Left atrial size in children with hypertension:the influence of obesity, blood pressure, and left ventricular mass. J Pediatr.2002.141(2):186-90.
[9]Parker TG, Schneider MD. Growth factors, proto-oncogenes, and plasticity of the cardiac phenotype. Annu Rev Physiol.1991.53:179-200.
[10]何玲,万国华,李拥军.醛固酮在高血压血管重塑和靶器官损害中的作用.临床荟萃.2005.20(11)：655-657.
[11]Hanevold C, Waller J, Daniels S, Portman R, Sorof J. The effects of obesity, gender, and ethnic group on left ventricular hypertrophy and geometry in hypertensive children:a collaborative study of the International Pediatric Hypertension Association. Pediatrics.2004.113(2):328-33.
[12]Brady TM, Fivush B, Flynn JT, Parekh R. Ability of blood pressure to predict left ventricular hypertrophy in children with primary hypertension. J Pediatr. 2008.152(1):73-8,78.e1.
[13]McNiece KL, Gupta-Malhotra M, Samuels J, et al. Left ventricular hypertrophy in hypertensive adolescents:analysis of risk by 2004 National High Blood Pressure Education Program Working Group staging criteria. Hypertension.2007.50(2):392-5.
[14]Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med.1990.322(22):1561-6.
[15]Varda NM, Gregoric A. A diagnostic approach for the child with hypertension. Pediatr Nephrol.2005.20(4):499-506.
[16]The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics.2004.114(2 Suppl 4th Report): 555-76.
[17]Tounian P, Aggoun Y, Dubern B, et al. Presence of increased stiffness of the common carotid artery and endothelial dysfunction in severely obese children: a prospective study. Lancet.2001.358(9291):1400-4.
[18]Intersalt:an international study of electrolyte excretion and blood pressure.Results for 24 hour urinary sodium and potassium excretion. Intersalt CooperativeResearch Group. BMJ.1988.297(6644):319-28.
[19]Reusz GS, Cseprekal O, Temmar M, et al. Reference values of pulse wave velocity in healthy children and teenagers. Hypertension.2010.56(2):217-24.
[20]王震静PWV/ABI与动脉硬化的诊断.辽宁医学杂志.2009.23(4)：201-204.
[21]Dernellis J, Panaretou M. Aortic stiffness is an independent predictor of progression to hypertension innonhypertensive subjects. Hypertension.2005. 45(3):426-31.
[22]Yamashina A, Tomiyama H, Arai T, et al. Brachial-ankle pulse wave velocity as a marker of atherosclerotic vascular damage and cardiovascular risk. Hypertens Res.2003.26(8):615-22.
[23]王彦隆,闫旭龙.颈动脉内中膜厚度、脉搏波传导速度及踝臂指数对冠状动脉硬化的早期预测.包头医学院学报.2010.26(1)：112-115.
[24]Kawasaki T, Koga N, Hikichi Y, et al. [Diagnostic accuracy of carotid ultrasonography in screening for coronary artery disease]. J Cardiol.2000. 36(5):295-302.
[25]王薇,赵冬,刘静等.中国35～64岁人群心血管病危险因素与发病危险预测模型的前瞻性研究.中华心血管病杂志.2003.31(12)：902-908.
[26]Hogan DB. Did Osler suffer from "paranoia antitherapeuticum baltimorensis"? A comparative content analysis of The Principles and Practice of Medicine and Harrison's Principles of Internal Medicine,11th edition. CMAJ.1999.161(7): 842-5.
[27]Wong M EJ, Wollman J. Ultrosonic patrological comparision of human arterial wall:Verification of intima-media thickness. Arteriascler Thromb.1993.13(4): 482-486.
[28]Wong M, Edelstein J, Wollman J, Bond MG. Ultrasonic-pathological comparison of the human arterial wall. Verification ofintima-media thickness. Arterioscler Thromb.1993.13(4):482-6.
[29]Kablak-Ziembicka A, Tracz W, Przewlocki T, Pieniazek P, Sokolowski A, Konieczynska M. Association of increased carotid intima-media thickness with the extent ofcoronary artery disease. Heart.2004.90(11):1286-90.
[30]Craven TE, Ryu JE, Espeland MA, et al. Evaluation of the associations between carotid artery atherosclerosis andcoronary artery stenosis. A case-control study. Circulation.1990.82(4):1230-42.
[31]O'Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med.1999.340(1):14-22.
[32]李运刚,李化勇,郭秀风,巩法莲,吴世秀.彩色超声多普勒评价颈动脉粥样硬化与脑梗死发生的相关性.中国临床康复.2005.9(5)：156.
[33]Wong M, Edelstein J, Wollman J, Bond MG. Ultrasonic-pathological comparison of the human arterial wall. Verification of intima-media thickness. Arterioscler Thromb.1993.13(4):482-6.
[34]许竹梅,赵水平,范平.超声测量颈动脉内膜中层厚度与颈动脉斑块的关系.中国动脉硬化杂志.2000.8(2)：165-168.
[35]Salcuni M, Di LV, Di SC, Moschini M, Fiorentino P, Rollo M. [The role of Doppler US in the study of carotid system]. Rays.1995.20(4):406-25.
[36]Polak JF, O'Leary DH, Kronmal RA, et al. Sonographic evaluation of carotid artery atherosclerosis in the elderly:relationship of disease severity to stroke and transient ischemic attack. Radiology.1993.188(2):363-70.
[37]Mathiesen EB, Bonaa KH, Joakimsen O. Echolucent plaques are associated with high risk of ischemic cerebrovascular events in carotid stenosis:the tromso study. Circulation.2001.103(17):2171-5.
[38]Xie W, Wu Y, Wang W, et al. A Longitudinal Study of Carotid Plaque and Risk of Ischemic Cardiovascular Disease in the Chinese Population. J Am Soc Echocardiogr.2011.
[39]Ouriel K. Peripheral arterial disease. Lancet.2001.358(9289):1257-64.
[40]Rose SC. Noninvasive vascular laboratory for evaluation of peripheral arterial occlusivedisease:Part Ⅰ--hemodynamic principles and tools of the trade. J Vase Interv Radiol.2000.11(9):1107-14.
[41]Leoncini G, Sacchi G, Ravera M, et al. Microalbuminuria is an integrated marker of subclinical organ damage in primary hypertension. J Hum Hypertens.2002.16(6):399-404.
[42]王飞(综述),卜培莉(审校).高血压早期肾损害的监测指标.心血管病学进展.2009.30(1)：79-83.
[43]郭进,陈雯,王风等.冠心病患者微量白蛋白尿与血管内皮舒张功能关系的探讨.实用医学杂志.2004.20(10)：1112-1113.
[44]蒋海杰,曲鹏,姜艳茹.原发性高血压患者合并低水平白蛋白尿与左室不良构型及舒张功能的关系.中国医师进修杂志.2011.34(4)：13-16.
[45]王鲁雁,孙宁玲,张克良,刘兰燕,刘喜荣.高血压病患者微量白蛋白尿与动脉病变关系的研究.中国循环杂志.2008.23(3)：171-174.
[46]Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation.2000.102(18):2165-8.
[47]Pasceri V, Cheng JS, Willerson JT, Yeh ET. Modulation of C-reactive protein-mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs. Circulation.2001.103(21): 2531-4.
[48]张君苒,陈德兰.高血压眼底改变及视力损伤相关因素分析.中国现代药物应用.2009.3(1)：39-40.
[49]Wong TY, McIntosh R. Systemic associations of retinal microvascular signs:a review of recent population-based studies. Ophthalmic Physiol Opt.2005. 25(3):195-204.
[50]Wong TY. Is retinal photography useful in the measurement of stroke risk. Lancet Neurol.2004.3(3):179-83.
[51]黄中宁,黄杜茹,尹东明等.原发性高血压眼底改变相关因素分析.岭南心血管病杂志.2006.(01)：35-39.
[52]Wong TY, Knudtson MD, Klein R, Klein BE, Hubbard LD. A prospective cohort study of retinal arteriolar narrowing and mortality. Am J Epidemiol. 2004.159(9):819-25.
[53]Wong TY, Hubbard LD, Klein R, et al. Retinal microvascular abnormalities and blood pressure in older people:the Cardiovascular Health Study. Br J Ophthalmol.2002.86(9):1007-13.
[54]Cuspidi C, Meani S, Salerno M, et al. Retinal microvascular changes and target organ damage in untreated essential hypertensives. J Hypertens.2004. 22(11):2095-102.
[55]李东风,刘霞,岳斌等.高血压患者的中心动脉压、肱动脉压、脉压与年龄相关性研究.中西医结合心脑血管病杂志.2010.08(8)：998-999.
[56]刘鹏,周晓芳.中心动脉压临床研究进展.实用医院临床杂志.2009.6(6)：125-129.
[57]孙宁玲.血管弹性功能应作为高血压亚临床损害评估的一个重要靶点.中国循环杂志.2008.23(3)：161-163.
[58]王青,梁英,王红娟.中心动脉压与中心动脉压增强指数的研究进展.山东医药.2010.50(25)：108-109.
[59]Weber T, Auer J, O'Rourke MF, et al. Arterial stiffness, wave reflections, and the risk of coronary artery disease. Circulation.2004.109(2):184-9.
[60]Chirinos JA, Zambrano JP, Chakko S, et al. Aortic pressure augmentation predicts adverse cardiovascular events in patientswith established coronary artery disease. Hypertension.2005.45(5):980-5.
[61]Vlachopoulos C, Kosmopoulou F, Panagiotakos D, et al. Smoking and caffeine have a synergistic detrimental effect on aortic stiffnessand wave reflections. J Am Coll Cardiol.2004.44(9):1911-7.
[62]Van Der Meer IM, De Maat MP, Hak AE, et al. C-reactive protein predicts progression of atherosclerosis measured at varioussites in the arterial tree:the Rotterdam Study. Stroke.2002.33(12):2750-5.
[63]Zhu J, Quyyumi AA, Norman JE, et al. Effects of total pathogen burden on coronary artery disease risk and C-reactiveprotein levels. Am J Cardiol.2000. 85(2):140-6.
[64]Pence S, Yilmaz G, Yilmaz N, et al. Determination of plasma fibronectin and serum C-reactive protein in patients withcerebrovascular events. Int J Clin Pract.2003.57(2):91-5.
[65]Aviles RJ, Martin DO, Apperson-Hansen C, et al. Inflammation as a risk factor for atrial fibrillation. Circulation.2003.108(24):3006-10.
[66]Ridker PM. C-reactive protein and the prediction of cardiovascular events among those atintermediate risk:moving an inflammatory hypothesis toward consensus. J Am Coll Cardiol.2007.49(21):2129-38.
[67]Beeks E, Kessels AG, Kroon AA, der Klauw MM v, de Leeuw PW. Genetic predisposition to salt-sensitivity:a systematic review. J Hypertens.2004.22(7): 1243-9.
[68]Weinberger MH, Fineberg NS, Fineberg SE, Weinberger M. Salt sensitivity, pulse pressure, and death in normal and hypertensive humans. Hypertension. 2001.37(2 Part 2):429-32.
[69]牟建军,杨军,刘治全等.盐敏感性对青少年远期血压变化及高血压发生的影响.中华高血压杂志.2008.16(5)：400-403.
[70]叶涛,刘治全,牟建军等.青少年盐敏感者盐敏感性的远期可重复性及血压的增龄性改变.中华心血管病杂志.2003.31(2)：115-117.
[71]McNiece KL, Gupta-Malhotra M, Samuels J, et al. Left ventricular hypertrophy in hypertensive adolescents:analysis of risk by2004 National High Blood Pressure Education Program Working Group stagingcriteria. Hypertension.2007.50(2):392-5.
[72]Baguet JP, Erdine S, Mallion JM. European Society of Hypertension Scientific Newsletter:Update on HypertensionManagement:Hypertension and dysrhythmias. J Hypertens.2006.24(2):409-11.
[73]Krieger J, Benzoni D, Sforza E, Sassard J. Urinary excretion of prostanoids during sleep in obstructive sleep apnoeapatients. Clin Exp Pharmacol Physiol. 1991.18(8):551-5.
[74]Shamsuzzaman AS, Winnicki M, Lanfranchi P, et al. Elevated C-reactive protein in patients with obstructive sleep apnea. Circulation.2002.105(21): 2462-4.
[75]Nieto FJ, Young TB, Lind BK, et al. Association of sleep-disordered breathing, sleep apnea, and hypertension in alarge community-based study. Sleep Heart Health Study. JAMA.2000.283(14):1829-36.
[76]宋志芳,彭燕,郑泽琪.阻塞性睡眠呼吸暂停综合征对血压、血管内皮功能、肾功能及左室质量的影响研究.中国全科医学.2010.13(35)：3957-3960.
[77]Alonso-Fernandez A, Garcia-Rio F, Racionero MA, et al. Cardiac rhythm disturbances and ST-segment depression episodes in patients withobstructive sleep apnea-hypopnea syndrome and its mechanisms. Chest.2005.127(1): 15-22.
[78]何权瀛.重视阻塞性睡眠呼吸暂停低通气综合征靶器官损害的防治研究.中华结核和呼吸杂志.2005.28(6)：362-363.
[2]陈春明.利国利民的信息宝库：中国居民营养与健康状况调查.中华流行病学杂志.2005.26(7)：469-470.
[3]Din-Dzietham R, Liu Y, Bielo MV, Shamsa F. High blood pressure trends in children and adolescents in national surveys,1963 to 2002. Circulation. 2007.116(13):1488-96.
[4]席波,米杰,王俐等.北京市儿童青少年原发性高血压的家庭聚集性分析.中华流行病学杂志.2008.29(9)：849-854.
[5]Chen X, Wang Y. Tracking of blood pressure from childhood to adulthood:a systematic review and meta-regression analysis. Circulation.2008.117(25): 3171-80.
[6]Rothwell PM, Howard SC, Dolan E, et al. Effects of beta blockers and calcium-channel blockers on within-individual variability in blood pressure and risk of stroke. Lancet Neurol.2010.9(5):469-80.
[7]Pickering TG, Hall JE, Appel LJ, et al. Recommendations for blood pressure measurement in humans and experimental animals:part 1:blood pressure measurement in humans:a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Circulation.2005.111(5):697-716.
[8]The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics.2004.114(2 Suppl 4th Report): 555-76.
[9]Hanevold C, Waller J, Daniels S, Portman R, Sorof J. The effects of obesity, gender, and ethnic group on left ventricular hypertrophy and geometry in hypertensive children:a collaborative study of the International Pediatric Hypertension Association. Pediatrics.2004.113(2):328-33.
[10]McNiece KL, Gupta-Malhotra M, Samuels J, et al. Left ventricular hypertrophy in hypertensive adolescents:analysis of risk by 2004 National High Blood Pressure Education Program Working Group staging criteria. Hypertension.2007.50(2):392-5.
[11]Laird WP, Fixler DE. Left ventricular hypertrophy in adolescents with elevated blood pressure:assessment by chest roentgenography, electrocardiography, and echocardiography. Pediatrics.1981.67(2):255-9.
[12]Hanevold C, Waller J, Daniels S, Portman R, Sorof J. The effects of obesity, gender, and ethnic group on left ventricular hypertrophy and geometry in hypertensive children:a collaborative study of the International Pediatric Hypertension Association. Pediatrics.2004.113(2):328-33.
[13]Brady TM, Fivush B, Flynn JT, Parekh R. Ability of blood pressure to predict left ventricular hypertrophy in children with primary hypertension. J Pediatr. 2008.152(1):73-8,78.el.
[14]Varda NM, Gregoric A. A diagnostic approach for the child with hypertension. Pediatr Nephrol.2005.20(4):499-506.
[15]Turin TC, Kita Y, Rumana N, et al. Brachial-ankle pulse wave velocity predicts all-cause mortality in the general population:findings from the Takashima study, Japan. Hypertens Res.2010.33(9):922-5.
[16]Washida N, Wakino S, Hayashi K, Kuwahara T, Itoh H. Brachial-ankle pulse wave velocity predicts silent cerebrovascular diseases in patients with end-stage renal diseases. J Atheroscler Thromb.2010.17(2):165-72.
[17]Tounian P, Aggoun Y, Dubern B, et al. Presence of increased stiffness of the common carotid artery and endothelial dysfunction in severely obese children: a prospective study. Lancet.2001.358(9291):1400-4.
[18]Poredos P. Intima-media thickness:indicator of cardiovascular risk and measure of the extent of atherosclerosis. Vasc Med.2004.9(1):46-54.
[19]Sorof JM, Alexandrov AV, Cardwell G, Portman RJ. Carotid artery intimal-medial thickness and left ventricular hypertrophy in children with elevated blood pressure. Pediatrics.2003.111(1):61-6.
[20]Lande MB, Carson NL, Roy J, Meagher CC. Effects of childhood primary hypertension on carotid intima media thickness:a matched controlled study. Hypertension.2006.48(1):40-4.
[21]Flynn JT. What is the significance of increased carotid intima media thickness in hypertensive adolescents. Hypertension.2006.48(1):23-4.
[22]Barinas-Mitchell E, Kuller LH, Sutton-Tyrrell K, et al. Effect of weight loss and nutritional intervention on arterial stiffness in type 2 diabetes. Diabetes Care.2006.29(10):2218-22.
[23]Tomiyama H, Hashimoto H, Hirayama Y, et al. Synergistic acceleration of arterial stiffening in the presence of raised blood pressure and raised plasma glucose. Hypertension.2006.47(2):180-8.
[24]Munakata M, Miura Y, Yoshinaga K. Higher brachial-ankle pulse wave velocity as an independent risk factor for future microalbuminuria in patients with essential hypertension:the J-TOPP study. J Hypertens.2009.27(7): 1466-71.
[25]Leoncini G, Sacchi G, Ravera M, et al. Microalbuminuria is an integrated marker of subclinical organ damage in primary hypertension. J Hum Hypertens.2002.16(6):399-404.
[26]Mancia G, De Backer G, Dominiczak A, et al.2007 Guidelines for the management of arterial hypertension:The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J.2007.28(12): 1462-536.
[27]Assadi F. Effect of microalbuminuria lowering on regression of left ventricular hypertrophy in children and adolescents with essential hypertension. Pediatr Cardiol.2007.28(1):27-33.
[28]Sorof JM, Turner J, Franco K, Portman RJ. Characteristics of hypertensive children identified by primary care referral compared with school-based screening. J Pediatr.2004.144(4):485-9.
[29]Sizonenko PC, Himes JH. Introduction to the use and interpretation of anthropometry in adolescence. Horm Res.1993.39 Suppl 3:7-8.
[30]Blumenthal S, Epps RP, Heavenrich R, et al. Report of the task force on blood pressure control in children. Pediatrics.1977.59(52 suppl):Ⅰ-Ⅱ,797-820.
[31]Devereux RB, Alonso DR, Lutas EM, et al. Echocardiographic assessment of left ventricular hypertrophy:comparison to necropsy findings. Am J Cardiol. 1986.57(6):450-8.
[32]de Simone G, Daniels SR, Devereux RB, et al. Left ventricular mass and body size in normotensive children and adults:assessment of allometric relations and impact of overweight. J Am Coll Cardiol.1992.20(5):1251-60.
[33]中国肥胖问题工作组.中国学龄儿童青少年超重、肥胖筛查体重指数值分类标准.中华流行病学杂志.2004.25(2)：97-102.
[34]Kuczmarski RJ, Ogden CL, Grummer-Strawn LM, et al. CDC growth charts: United States. Adv Data.2000. (314):1-27.
[35]米杰,王天有,孟玲慧等.中国儿童青少年血压参照标准的研究制定.中国循证儿科杂志.2010.5(1)：4-14.
[36]Reusz GS, Cseprekal O, Temmar M, et al. Reference values of pulse wave velocity in healthy children and teenagers. Hypertension.2010.56(2):217-24.
[37]Khoury PR, Mitsnefes M, Daniels SR, Kimball TR. Age-specific reference intervals for indexed left ventricular mass in children. J Am Soc Echocardiogr. 2009.22(6):709-14.
[38]de Simone G, Daniels SR, Kimball TR, et al. Evaluation of concentric left ventricular geometry in humans:evidence for age-related systematic underestimation. Hypertension.2005.45(1):64-8.
[39]胡大一.心血管疾病防治指南和共识2008.2008.人民卫生出版社.104-119.
[40]胡亚美,江载芳.诸福棠实用儿科学.2008.1593-1595.
[41]Diagnosis and classification of diabetes mellitus. Diabetes Care.2012.35 Suppl 1:S64-71.
[42]Pediatrics TEBoCJo,中华医学会儿科学分会儿童保健学组,中华医学会儿科学分会心血管学组,<,中华儿科杂志>,编辑委员会.儿童青少年血脂异常防治专家共识.中华儿科杂志.2009.47(6)：426-428.
[43]中国疾病预防控制中心.慢病管理业务信息技术规范,2008.15.
[44]Foundation NS.美国国家睡眠基金会对儿童睡眠时间的推荐标准
[45]中国高血压防治指南修订委员会.中国高血压防治指南2010.中华心血管病杂志.2011.39(7)：579-616.
[46]Chiolero A, Cachat F, Burnier M, Paccaud F, Bovet P. Prevalence of hypertension in schoolchildren based on repeated measurements and association with overweight. J Hypertens.2007.25(11):2209-17.
[47]Genovesi S, Giussani M, Pieruzzi F, et al. Results of blood pressure screening in a population of school-aged children in the province of Milan:role of overweight. J Hypertens.2005.23(3):493-7.
[48]Fixler DE, Laird WP, Fitzgerald V, Stead S, Adams R. Hypertension screening in schools:results of the Dallas study. Pediatrics.1979.63(1):32-6.
[49]Sorof JM, Poffenbarger T, Franco K, Bernard L, Portman RJ. Isolated systolic hypertension, obesity, and hyperkinetic hemodynamic states in children. J Pediatr.2002.140(6):660-6.
[50]McNiece KL, Poffenbarger TS, Turner JL, Franco KD, Sorof JM, Portman RJ. Prevalence of hypertension and pre-hypertension among adolescents. J Pediatr. 2007.150(6):640-4,644.e1.
[51]Leung LC, Sung RY, So HK, et al. Prevalence and risk factors for hypertension in Hong Kong Chinese adolescents:waist circumference predicts hypertension, exercise decreases risk. Arch Dis Child.2011.96(9):804-9.
[52]Cornoni-Huntley J, Harlan WR, Leaverton PE. Blood pressure in adolescence. The United States Health Examination survey. Hypertension.1979.1(6): 566-71.
[53]Gugig R, Rosenthal P. Management of portal hypertension in children. World J Gastroenterol.2012.18(11):1176-84.
[54]Shankar RR, Eckert GJ, Saha C, Tu W, Pratt JH. The change in blood pressure during pubertal growth. J Clin Endocrinol Metab.2005.90(1):163-7.
[55]Lurbe E, Cifkova R, Cruickshank JK, et al. Management of high blood pressure in children and adolescents:recommendations of the European Society of Hypertension. J Hypertens.2009.27(9):1719-42.
[56]万燕萍,唐激文,徐仁应,吴颖洁,陈之琦,徐敏.体质指数和腰围对肥胖儿童青少年高血压的影响.上海第二医科大学学报.2004.24(z1)：46-48.
[57]程红,闫银坤,段佳丽,耳玉亮,米杰.儿童肥胖对高血压发病率影响的随访研究.中华预防医学杂志.2011.45(8)：696-701.
[58]刘博伟,尹福在,马春明等.有高血压家族史血压正常的青少年心血管危险因素分析.中华高血压杂志.2008.16(5)：441-444.
[59]李涛,李芸,李艳.有高血压家族史青少年血浆内皮素及相关因素分析.中国儿童保健杂志.2001.9(4)：234-235.
[60]陈慧兰,胡申江,刘超群.高血压家族史对血压正常高值患者血管内皮功能的影响.浙江医学.2011.33(3)：352-354.
[61]Wada K, Tamakoshi K, Yatsuya H, et al. Association between parental histories of hypertension, diabetes and dyslipidemia and the clustering of these disorders in offspring. Prev Med.2006.42(5):358-63.
[62]Burke V, Gracey MP, Beilin LJ, Milligan RA. Family history as a predictor of blood pressure in a longitudinal study of Australian children. J Hypertens. 1998.16(3):269-76.
[63]Fuentes RM, Notkola IL, Shemeikka S, Tuomilehto J, Nissinen A. Familial aggregation of blood pressure:a population-based family study in eastern Finland. J Hum Hypertens.2000.14(7):441-5.
[64]DeStefano AL, Gavras H, Heard-Costa N, et al. Maternal component in the familial aggregation of hypertension. Clin Genet.2001.60(1):13-21.
[65]Bovet P, Gervasoni JP, Ross AG, et al. Assessing the prevalence of hypertension in populations:are we doing it right. J Hypertens.2003.21(3): 509-17.
[66]Lurbe E, Torro I, Alvarez V, et al. Prevalence, persistence, and clinical significance of masked hypertension in youth. Hypertension.2005.45(4): 493-8.
[67]Bao W, Threefoot SA, Srinivasan SR, Berenson GS. Essential hypertension predicted by tracking of elevated blood pressure from childhood to adulthood: the Bogalusa Heart Study. Am J Hypertens.1995.8(7):657-65.
[68]Klumbiene J, Sileikiene L, Milasauskiene Z, Zaborskis A, Shatchkute A. The relationship of childhood to adult blood pressure:longitudinal study of juvenile hypertension in Lithuania. J Hypertens.2000.18(5):531-8.
[69]无.青少年初始血压高者在高血压发生中的预测意义.中华心血管病杂志.1996.24(4)：254-256.
[70]吴光驰,郭素怡.北京地区468名少儿肥胖及血压改变的八年随访观察.中华医学杂志.1997.77(1)：18-21.
[71]Daniels SR, Witt SA, Glascock B, Khoury PR, Kimball TR. Left atrial size in children with hypertension:the influence of obesity, blood pressure, and left ventricular mass. J Pediatr.2002.141(2):186-90.
[72]Park KH, Park WJ, Kim MK, et al. Noninvasive brachial-ankle pulse wave velocity in hypertensive patients with left ventricular hypertrophy. Am J Hypertens.2010.23(3):269-74.
[73]Salvi P, Safar ME, Labat C, Borghi C, Lacolley P, Benetos A. Heart disease and changes in pulse wave velocity and pulse pressure amplification in the elderly over 80 years:the PARTAGE Study. J Hypertens.2010.28(10): 2127-33.
[74]McVeigh GE, Bratteli CW, Morgan DJ, et al. Age-related abnormalities in arterial compliance identified by pressure pulse contour analysis:aging and arterial compliance. Hypertension.1999.33(6):1392-8.
[75]Simon A, Gariepy J, Chironi G, Megnien JL, Levenson J. Intima-media thickness:a new tool for diagnosis and treatment of cardiovascular risk. J Hypertens.2002.20(2):159-69.
[76]Avolio A, Jones D, Tafazzoli-Shadpour M. Quantification of alterations in structure and function of elastin in the arterial media. Hypertension.1998. 32(1):170-5.
[77]Wong M, Edelstein J, Wollman J, Bond MG. Ultrasonic-pathological comparison of the human arterial wall. Verification ofintima-media thickness. Arterioscler Thromb.1993.13(4):482-6.
[78]Kablak-Ziembicka A, Tracz W, Przewlocki T, Pieniazek P, Sokolowski A, Konieczynska M. Association of increased carotid intima-media thickness with the extent ofcoronary artery disease. Heart.2004.90(11):1286-90.
[79]Craven TE, Ryu JE, Espeland MA, et al. Evaluation of the associations between carotid artery atherosclerosis andcoronary artery stenosis. A case-control study. Circulation.1990.82(4):1230-42.
[80]O'Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med.1999.340(1):14-22.
[81]李运刚,李化勇,郭秀风,巩法莲,吴世秀.彩色超声多普勒评价颈动脉粥样硬化与脑梗死发生的相关性.中国临床康复.2005.9(5)：156.
[82]Wong M, Edelstein J, Wollman J, Bond MG. Ultrasonic-pathological comparison of the human arterial wall. Verification of intima-media thickness. Arterioscler Thromb.1993.13(4):482-6.
[83]许竹梅,赵水平,范平.超声测量颈动脉内膜中层厚度与颈动脉斑块的关系.中国动脉硬化杂志.2000.8(2)：165-168.
[84]Wong M EJ, Wollman J. Ultrosonic patrological comparision of human arterial wall:Verification of intima-media thickness. Arteriascler Thromb.1993.13(4): 482-486.
[85]Salcuni M, Di LV, Di SC, Moschini M, Fiorentino P, Rollo M. [The role of Doppler US in the study of carotid system]. Rays.1995.20(4):406-25.
[86]Polak JF, O'Leary DH, Kronmal RA, et al. Sonographic evaluation of carotid artery atherosclerosis in the elderly:relationship of disease severity to stroke and transient ischemic attack. Radiology.1993.188(2):363-70.
[87]Aatola H, Hutri-Kahonen N, Juonala M, et al. Lifetime risk factors and arterial pulse wave velocity in adulthood:the cardiovascular risk in young Finns study. Hypertension.2010.55(3):806-11.
[88]Schram MT, Henry RM, van DRA, et al. Increased central artery stiffness in impaired glucose metabolism and type 2 diabetes:the Hoorn Study. Hypertension.2004.43(2):176-81.
[89]Henry RM, Kostense PJ, Spijkerman AM, et al. Arterial stiffness increases with deteriorating glucose tolerance status:the Hoorn Study. Circulation.2003. 107(16):2089-95.
[90]Nakamura M, Yamashita T, Yajima J, et al. Brachial-ankle pulse wave velocity as a risk stratification index for the short-term prognosis of type 2 diabetic patients with coronary artery disease. Hypertens Res.2010.33(10):1018-24.
[91]Devereux RB, Roman MJ, Paranicas M, et al. Impact of diabetes on cardiac structure and function:the strong heart study. Circulation.2000.101(19): 2271-6.
[92]Lopez RM, Gomez CJ, Barbado HFJ. [Endothelial dysfunction and vasculitis: a close relationship]. Rev Clin Esp.2006.206(4):199-201.
[93]Safar ME, Siche JP, Mallion JM, London GM. Arterial mechanics predict cardiovascular risk in hypertension. J Hypertens.1997.15(12 Pt 2):1605-11.
[94]Yambe M, Tomiyama H, Hirayama Y, et al. Arterial stiffening as a possible risk factor for both atherosclerosis and diastolic heart failure. Hypertens Res. 2004.27(9):625-31.
[95]Stabouli S, Kotsis V, Rizos Z, et al. Left ventricular mass in normotensive, prehypertensive and hypertensive children and adolescents. Pediatr Nephrol. 2009.24(8):1545-51.
[96]Dhuper S, Abdullah RA, Weichbrod L, Mahdi E, Cohen HW. Association of obesity and hypertension with left ventricular geometry and function in children and adolescents. Obesity (Silver Spring).2011.19(1):128-33.
[97]Abel ED, Litwin SE, Sweeney G. Cardiac remodeling in obesity. Physiol Rev. 2008.88(2):389-419.
[98]Daniels SR. Hypertension-induced cardiac damage in children and adolescents. Blood Press Monit.1999.4(3-4):165-70.
[99]Litwin M, Niemirska A, Sladowska J, et al. Left ventricular hypertrophy and arterial wall thickening in children with essential hypertension. Pediatr Nephrol.2006.21(6):811-9.
[100]王飞(综述),卜培莉(审校).高血压早期肾损害的监测指标.心血管病学进展.2009.30(1)：79-83.
[101]Lubrano R, Travasso E, Raggi C, Guido G, Masciangelo R, Elli M. Blood pressure load, proteinuria and renal function in pre-hypertensive children. Pediatr Nephrol.2009.24(4):823-31.
[102]Pose-Reino A, Gomez-Ulla F, Hayik B, et al. Computerized measurement of retinal blood vessel calibre:description, validation and use to determine the influence of ageing and hypertension. J Hypertens.2005.23(4):843-50.
[103]Schmidt RJ, Parrilla JAM, Munoz MJ. [Sources of error in blood pressure measurement]. Rev Enferm.1997.20(223):51-4.
[104]中国血压测量工作组.中国高血压测量指南.中华高血压杂志.2011.19(12)：1-15.
[105]O'Brien E, Pickering T, Asmar R, et al. Working Group on Blood Pressure Monitoring of the European Society of Hypertension International Protocol for validation of blood pressure measuring devices in adults. Blood Press Monit. 2002.7(1):3-17.
[106]高柏青,孙淼,王丽琴.血压的测量和临床评估.现代康复.1999.3(10)：1216-1217.
[107]Geddes LA. Counterpressure:the concept that made the indirect measurement of blood pressure possible. IEEE Eng Med Biol Mag.1998.17(6):85-7.
[108]Ireland J. In praise of mercury sphygmomanometers. Electronic readings of blood pressure seem to be higher than readings obtained with mercury sphygmomanometers. BMJ.2001.322(7296):1249.
[109]朱洁明.欧姆龙BP-203RⅧC型电子血压计和水银柱式血压计测量值比较.现代中西医结合杂志.2009.18(22)：2662-2663.
[110]Chen X, Wang Y, Appel LJ, Mi J. Impacts of measurement protocols on blood pressure tracking from childhood into adulthood:a metaregression analysis. Hypertension.2008.51(3):642-9.
[111]Amoore JN. Oscillometric sphygmomanometers:a critical appraisal of current technology. Blood Press Monit.2012.17(2):80-8.
[112]车承华.电子血压计与汞柱式血压计在临床应用的对照研究.解放军护理杂志.2004.21(1)：15-16.
[113]林奕.两种血压计测量结果比较.中国医疗设备.2009.24(8)：120,119.
[114]盛长生,崔艳,陈寒萼等.高血压合并糖尿病患者家庭自测血压所需天数和读数.中华高血压杂志.2010.18(4)：344-348.
[1]Wu Y, Huxley R, Li L, et al. Prevalence, awareness, treatment, and control of hypertension in China:data from the China National Nutrition and Health Survey 2002. Circulation.2008.118(25):2679-86.
[2]席波,米杰,王俐等.北京市儿童青少年原发性高血压的家庭聚集性分析.中华流行病学杂志.2008.29(9)：849-854.
[3]Nelson MJ, Ragland DR, Syme SL. Longitudinal prediction of adult blood pressure from juvenile blood pressure levels. Am J Epidemiol.1992.136(6): 633-45.
[4]Klumbiene J, Sileikiene L, Milasauskiene Z, Zaborskis A, Shatchkute A. The relationship of childhood to adult blood pressure:longitudinal study of juvenile hypertension in Lithuania. J Hypertens.2000.18(5):531-8.
[5]Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension:analysis of worldwide data. Lancet.2005.365(9455): 217-23.
[6]Hanevold C, Waller J, Daniels S, Portman R, Sorof J. The effects of obesity, gender, and ethnic group on left ventricular hypertrophy and geometry in hypertensive children:a collaborative study of the International Pediatric Hypertension Association. Pediatrics.2004.113(2):328-33.
[7]McNiece KL, Gupta-Malhotra M, Samuels J, et al. Left ventricular hypertrophy in hypertensive adolescents:analysis of risk by 2004 National High Blood Pressure Education Program Working Group staging criteria. Hypertension.2007.50(2):392-5.
[8]Daniels SR, Witt SA, Glascock B, Khoury PR, Kimball TR. Left atrial size in children with hypertension:the influence of obesity, blood pressure, and left ventricular mass. J Pediatr.2002.141(2):186-90.
[9]Parker TG, Schneider MD. Growth factors, proto-oncogenes, and plasticity of the cardiac phenotype. Annu Rev Physiol.1991.53:179-200.
[10]何玲,万国华,李拥军.醛固酮在高血压血管重塑和靶器官损害中的作用.临床荟萃.2005.20(11)：655-657.
[11]Hanevold C, Waller J, Daniels S, Portman R, Sorof J. The effects of obesity, gender, and ethnic group on left ventricular hypertrophy and geometry in hypertensive children:a collaborative study of the International Pediatric Hypertension Association. Pediatrics.2004.113(2):328-33.
[12]Brady TM, Fivush B, Flynn JT, Parekh R. Ability of blood pressure to predict left ventricular hypertrophy in children with primary hypertension. J Pediatr. 2008.152(1):73-8,78.e1.
[13]McNiece KL, Gupta-Malhotra M, Samuels J, et al. Left ventricular hypertrophy in hypertensive adolescents:analysis of risk by 2004 National High Blood Pressure Education Program Working Group staging criteria. Hypertension.2007.50(2):392-5.
[14]Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med.1990.322(22):1561-6.
[15]Varda NM, Gregoric A. A diagnostic approach for the child with hypertension. Pediatr Nephrol.2005.20(4):499-506.
[16]The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics.2004.114(2 Suppl 4th Report): 555-76.
[17]Tounian P, Aggoun Y, Dubern B, et al. Presence of increased stiffness of the common carotid artery and endothelial dysfunction in severely obese children: a prospective study. Lancet.2001.358(9291):1400-4.
[18]Intersalt:an international study of electrolyte excretion and blood pressure.Results for 24 hour urinary sodium and potassium excretion. Intersalt CooperativeResearch Group. BMJ.1988.297(6644):319-28.
[19]Reusz GS, Cseprekal O, Temmar M, et al. Reference values of pulse wave velocity in healthy children and teenagers. Hypertension.2010.56(2):217-24.
[20]王震静PWV/ABI与动脉硬化的诊断.辽宁医学杂志.2009.23(4)：201-204.
[21]Dernellis J, Panaretou M. Aortic stiffness is an independent predictor of progression to hypertension innonhypertensive subjects. Hypertension.2005. 45(3):426-31.
[22]Yamashina A, Tomiyama H, Arai T, et al. Brachial-ankle pulse wave velocity as a marker of atherosclerotic vascular damage and cardiovascular risk. Hypertens Res.2003.26(8):615-22.
[23]王彦隆,闫旭龙.颈动脉内中膜厚度、脉搏波传导速度及踝臂指数对冠状动脉硬化的早期预测.包头医学院学报.2010.26(1)：112-115.
[24]Kawasaki T, Koga N, Hikichi Y, et al. [Diagnostic accuracy of carotid ultrasonography in screening for coronary artery disease]. J Cardiol.2000. 36(5):295-302.
[25]王薇,赵冬,刘静等.中国35～64岁人群心血管病危险因素与发病危险预测模型的前瞻性研究.中华心血管病杂志.2003.31(12)：902-908.
[26]Hogan DB. Did Osler suffer from "paranoia antitherapeuticum baltimorensis"? A comparative content analysis of The Principles and Practice of Medicine and Harrison's Principles of Internal Medicine,11th edition. CMAJ.1999.161(7): 842-5.
[27]Wong M EJ, Wollman J. Ultrosonic patrological comparision of human arterial wall:Verification of intima-media thickness. Arteriascler Thromb.1993.13(4): 482-486.
[28]Wong M, Edelstein J, Wollman J, Bond MG. Ultrasonic-pathological comparison of the human arterial wall. Verification ofintima-media thickness. Arterioscler Thromb.1993.13(4):482-6.
[29]Kablak-Ziembicka A, Tracz W, Przewlocki T, Pieniazek P, Sokolowski A, Konieczynska M. Association of increased carotid intima-media thickness with the extent ofcoronary artery disease. Heart.2004.90(11):1286-90.
[30]Craven TE, Ryu JE, Espeland MA, et al. Evaluation of the associations between carotid artery atherosclerosis andcoronary artery stenosis. A case-control study. Circulation.1990.82(4):1230-42.
[31]O'Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med.1999.340(1):14-22.
[32]李运刚,李化勇,郭秀风,巩法莲,吴世秀.彩色超声多普勒评价颈动脉粥样硬化与脑梗死发生的相关性.中国临床康复.2005.9(5)：156.
[33]Wong M, Edelstein J, Wollman J, Bond MG. Ultrasonic-pathological comparison of the human arterial wall. Verification of intima-media thickness. Arterioscler Thromb.1993.13(4):482-6.
[34]许竹梅,赵水平,范平.超声测量颈动脉内膜中层厚度与颈动脉斑块的关系.中国动脉硬化杂志.2000.8(2)：165-168.
[35]Salcuni M, Di LV, Di SC, Moschini M, Fiorentino P, Rollo M. [The role of Doppler US in the study of carotid system]. Rays.1995.20(4):406-25.
[36]Polak JF, O'Leary DH, Kronmal RA, et al. Sonographic evaluation of carotid artery atherosclerosis in the elderly:relationship of disease severity to stroke and transient ischemic attack. Radiology.1993.188(2):363-70.
[37]Mathiesen EB, Bonaa KH, Joakimsen O. Echolucent plaques are associated with high risk of ischemic cerebrovascular events in carotid stenosis:the tromso study. Circulation.2001.103(17):2171-5.
[38]Xie W, Wu Y, Wang W, et al. A Longitudinal Study of Carotid Plaque and Risk of Ischemic Cardiovascular Disease in the Chinese Population. J Am Soc Echocardiogr.2011.
[39]Ouriel K. Peripheral arterial disease. Lancet.2001.358(9289):1257-64.
[40]Rose SC. Noninvasive vascular laboratory for evaluation of peripheral arterial occlusivedisease:Part Ⅰ--hemodynamic principles and tools of the trade. J Vase Interv Radiol.2000.11(9):1107-14.
[41]Leoncini G, Sacchi G, Ravera M, et al. Microalbuminuria is an integrated marker of subclinical organ damage in primary hypertension. J Hum Hypertens.2002.16(6):399-404.
[42]王飞(综述),卜培莉(审校).高血压早期肾损害的监测指标.心血管病学进展.2009.30(1)：79-83.
[43]郭进,陈雯,王风等.冠心病患者微量白蛋白尿与血管内皮舒张功能关系的探讨.实用医学杂志.2004.20(10)：1112-1113.
[44]蒋海杰,曲鹏,姜艳茹.原发性高血压患者合并低水平白蛋白尿与左室不良构型及舒张功能的关系.中国医师进修杂志.2011.34(4)：13-16.
[45]王鲁雁,孙宁玲,张克良,刘兰燕,刘喜荣.高血压病患者微量白蛋白尿与动脉病变关系的研究.中国循环杂志.2008.23(3)：171-174.
[46]Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation.2000.102(18):2165-8.
[47]Pasceri V, Cheng JS, Willerson JT, Yeh ET. Modulation of C-reactive protein-mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs. Circulation.2001.103(21): 2531-4.
[48]张君苒,陈德兰.高血压眼底改变及视力损伤相关因素分析.中国现代药物应用.2009.3(1)：39-40.
[49]Wong TY, McIntosh R. Systemic associations of retinal microvascular signs:a review of recent population-based studies. Ophthalmic Physiol Opt.2005. 25(3):195-204.
[50]Wong TY. Is retinal photography useful in the measurement of stroke risk. Lancet Neurol.2004.3(3):179-83.
[51]黄中宁,黄杜茹,尹东明等.原发性高血压眼底改变相关因素分析.岭南心血管病杂志.2006.(01)：35-39.
[52]Wong TY, Knudtson MD, Klein R, Klein BE, Hubbard LD. A prospective cohort study of retinal arteriolar narrowing and mortality. Am J Epidemiol. 2004.159(9):819-25.
[53]Wong TY, Hubbard LD, Klein R, et al. Retinal microvascular abnormalities and blood pressure in older people:the Cardiovascular Health Study. Br J Ophthalmol.2002.86(9):1007-13.
[54]Cuspidi C, Meani S, Salerno M, et al. Retinal microvascular changes and target organ damage in untreated essential hypertensives. J Hypertens.2004. 22(11):2095-102.
[55]李东风,刘霞,岳斌等.高血压患者的中心动脉压、肱动脉压、脉压与年龄相关性研究.中西医结合心脑血管病杂志.2010.08(8)：998-999.
[56]刘鹏,周晓芳.中心动脉压临床研究进展.实用医院临床杂志.2009.6(6)：125-129.
[57]孙宁玲.血管弹性功能应作为高血压亚临床损害评估的一个重要靶点.中国循环杂志.2008.23(3)：161-163.
[58]王青,梁英,王红娟.中心动脉压与中心动脉压增强指数的研究进展.山东医药.2010.50(25)：108-109.
[59]Weber T, Auer J, O'Rourke MF, et al. Arterial stiffness, wave reflections, and the risk of coronary artery disease. Circulation.2004.109(2):184-9.
[60]Chirinos JA, Zambrano JP, Chakko S, et al. Aortic pressure augmentation predicts adverse cardiovascular events in patientswith established coronary artery disease. Hypertension.2005.45(5):980-5.
[61]Vlachopoulos C, Kosmopoulou F, Panagiotakos D, et al. Smoking and caffeine have a synergistic detrimental effect on aortic stiffnessand wave reflections. J Am Coll Cardiol.2004.44(9):1911-7.
[62]Van Der Meer IM, De Maat MP, Hak AE, et al. C-reactive protein predicts progression of atherosclerosis measured at varioussites in the arterial tree:the Rotterdam Study. Stroke.2002.33(12):2750-5.
[63]Zhu J, Quyyumi AA, Norman JE, et al. Effects of total pathogen burden on coronary artery disease risk and C-reactiveprotein levels. Am J Cardiol.2000. 85(2):140-6.
[64]Pence S, Yilmaz G, Yilmaz N, et al. Determination of plasma fibronectin and serum C-reactive protein in patients withcerebrovascular events. Int J Clin Pract.2003.57(2):91-5.
[65]Aviles RJ, Martin DO, Apperson-Hansen C, et al. Inflammation as a risk factor for atrial fibrillation. Circulation.2003.108(24):3006-10.
[66]Ridker PM. C-reactive protein and the prediction of cardiovascular events among those atintermediate risk:moving an inflammatory hypothesis toward consensus. J Am Coll Cardiol.2007.49(21):2129-38.
[67]Beeks E, Kessels AG, Kroon AA, der Klauw MM v, de Leeuw PW. Genetic predisposition to salt-sensitivity:a systematic review. J Hypertens.2004.22(7): 1243-9.
[68]Weinberger MH, Fineberg NS, Fineberg SE, Weinberger M. Salt sensitivity, pulse pressure, and death in normal and hypertensive humans. Hypertension. 2001.37(2 Part 2):429-32.
[69]牟建军,杨军,刘治全等.盐敏感性对青少年远期血压变化及高血压发生的影响.中华高血压杂志.2008.16(5)：400-403.
[70]叶涛,刘治全,牟建军等.青少年盐敏感者盐敏感性的远期可重复性及血压的增龄性改变.中华心血管病杂志.2003.31(2)：115-117.
[71]McNiece KL, Gupta-Malhotra M, Samuels J, et al. Left ventricular hypertrophy in hypertensive adolescents:analysis of risk by2004 National High Blood Pressure Education Program Working Group stagingcriteria. Hypertension.2007.50(2):392-5.
[72]Baguet JP, Erdine S, Mallion JM. European Society of Hypertension Scientific Newsletter:Update on HypertensionManagement:Hypertension and dysrhythmias. J Hypertens.2006.24(2):409-11.
[73]Krieger J, Benzoni D, Sforza E, Sassard J. Urinary excretion of prostanoids during sleep in obstructive sleep apnoeapatients. Clin Exp Pharmacol Physiol. 1991.18(8):551-5.
[74]Shamsuzzaman AS, Winnicki M, Lanfranchi P, et al. Elevated C-reactive protein in patients with obstructive sleep apnea. Circulation.2002.105(21): 2462-4.
[75]Nieto FJ, Young TB, Lind BK, et al. Association of sleep-disordered breathing, sleep apnea, and hypertension in alarge community-based study. Sleep Heart Health Study. JAMA.2000.283(14):1829-36.
[76]宋志芳,彭燕,郑泽琪.阻塞性睡眠呼吸暂停综合征对血压、血管内皮功能、肾功能及左室质量的影响研究.中国全科医学.2010.13(35)：3957-3960.
[77]Alonso-Fernandez A, Garcia-Rio F, Racionero MA, et al. Cardiac rhythm disturbances and ST-segment depression episodes in patients withobstructive sleep apnea-hypopnea syndrome and its mechanisms. Chest.2005.127(1): 15-22.
[78]何权瀛.重视阻塞性睡眠呼吸暂停低通气综合征靶器官损害的防治研究.中华结核和呼吸杂志.2005.28(6)：362-363.