Age Associated Changes In Structural And Functional Cardio-Vascular Properties

与年龄相关的心血管结构和功能的变化

• 批准号: 7732332
• 负责人: Edward G Lakatta
• 金额: $ 31.11万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7732332
• 关键词: Accounting; African American; Age; Age Distribution; Age-Years; Aging; Analysis of Variance; Antihypertensive Agents; Attenuated; Blood Pressure; Blood Vessels; Body Size; Body Surface Area; Body mass index; Caliber; Cardiovascular Diseases; Cardiovascular system; Clinical; Clinical Trials; Condition; Confidence Intervals; Cox Proportional Hazards Models; Cross-Sectional Studies; Detection; Diastole; Diastolic blood pressure; Disease; Disease regression; EFRAC; Echocardiography; Ethnic Origin; Evaluation; Exhibits; Failure; Functional disorder; Gender; Genetic; Genetic Determinism; Heart Atrium; Heart failure; Height; High Blood Pressure; Human; Hypertension; Individual; Intervention; Joints; Laboratories; Left; Left Ventricular Hypertrophy; Left Ventricular Mass; Longitudinal Studies; Measurement; Measures; Mission; Modeling; Modification; Multiple Abnormalities; Obesity; Outcome; Pathogenesis; Patients; Pharmaceutical Preparations; Physiologic pulse; Plant Roots; Population; Population Study; Positioning Attribute; Prevention; Prevention strategy; Property; Pulmonary Wedge Pressure; Pulse Pressure; Pulse taking; Range; Regression Analysis; Relaxation; Reporting; Risk Factors; Sinus; Specificity; Structure; Succinate Dehydrogenase; Thick; Time; Valsalva sinus; Ventricular; Weight; Woman; Work; age difference; aged; arterial stiffness; base; body system; cardiovascular risk factor; cohort; follow-up; hazard; indexing; men; modifiable risk; neglect; normotensive; pressure; prevent; sex; systolic hypertension; volunteer

1) We sought to evaluate whether pulse wave velocity (PWV), a noninvasive index of arterial stiffness, is a predictor of the longitudinal changes in systolic blood pressure (SBP) and of incident hypertension. Although arterial stiffness is believed to underlie, in part, the age-associated changes in SBP, particularly at older ages, few longitudinal studies in humans have examined the relationship between arterial stiffness and blood pressure. Pulse wave velocity was measured at baseline in 449 normotensive or untreated hypertensive volunteers (age 53 +/- 17 years). Repeated measurements of blood pressure were performed during an average follow-up of 4.9 +/- 2.5 years. After adjusting for covariates including age, body mass index, and mean arterial pressure, linear mixed effects regression models showed that PWV was an independent determinant of the longitudinal increase in SBP (p = 0.003 for the interaction term with time). In a subset of 306 subjects who were normotensive at baseline, hypertension developed in 105 (34%) during a median follow-up of 4.3 years (range 2 to 12 years). By stepwise Cox proportional hazards models, PWV was an independent predictor of incident hypertension (hazard ratio 1.10 per 1 m/s increase in PWV, 95% confidence interval 1.00 to 1.30, p = 0.03) in individuals with a follow-up duration greater than the median. Thus, pulse wave velocity is an independent predictor of the longitudinal increase in SBP and of incident hypertension. This suggests that PWV could help identify normotensive individuals who should be targeted for the implementation of interventions aimed at preventing or delaying the progression of subclinical arterial stiffening and the onset of hypertension (J Am Coll Cardiol. 2008;51(14):1377-83). Ongoing studies in our laboratory are investigating the genetics of arterial stiffness. 2) Hypertension accelerates the age-associated increase in aortic root diameter (AoD), likely because of chronically elevated distending pressures. However, the pulsatile component of blood pressure may have a different relationship with AoD. We sought to assess the relationship between AoD and pulse pressure (PP) while accounting for left ventricular and central arterial structural and functional properties, which are known to influence PP. The study population was composed of 1256 individuals, aged 30 to 79 years (48% women and 48% hypertensive), none of whom were on antihypertensive medications. Blood pressure was measured in the sitting position with conventional sphygmomanometry. PP was calculated as the difference between systolic and diastolic blood pressures. AoD was measured at end diastole at the level of the sinuses of Valsalva with echocardiography. The relationship between AoD and PP was evaluated with multiple regression analyses. PP was 50+/-14 mm Hg in men and 54+/-18 mm Hg in women, and AoD was 31.9+/-3.5 mm in men and 28.9+/-3.5 mm in women. After adjusting for age, age(2), height, weight, and mean arterial pressure, AoD was independently and inversely associated with PP in both sexes. After further adjustments for central arterial stiffness and wall thickness, reflected waves, and left ventricular geometry, AoD remained inversely associated with PP in both men (coefficient=-0.48; P=0.0003; model R(2)=0.51) and women (coefficient=-0.40; P=0.01; model R(2)=0.61). Thus, AoD is inversely associated with PP, suggesting that a small AoD may contribute to the pathogenesis of systolic hypertension. Longitudinal studies are needed to examine this possibility. (Hypertension. 2008;51(2):196-202). 3) Aortic root diameter (AoD) increases with aging and is related to body size. AoD is also presumed to increase in hypertension. In prior studies, however, after adjusting for age and body size, AoD did not differ between hypertensive and normotensive (NT) individuals. Hypertension is a heterogeneous condition with various subtypes that differ in pathophysiology and age distribution. We assessed whether AoD differs among subjects with the various subtypes of hypertension and nonhypertensive individuals. In 1,256 volunteers aged 30-79 years (48% women, 48% hypertensive; all untreated), AoD was measured at the sinuses of Valsalva with transthoracic echocardiography. Using cutoff values based on the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, subjects were identified as NT (23%), or prehypertensive (PH, 29%), or as having isolated diastolic (IDH, 6%), isolated systolic (ISH, 12%), or systolic-diastolic (SDH, 30%) hypertension. Groups were compared using analysis of variance with Bonferroni's correction. AoD increased with age and body surface area (BSA) in both men (r = 0.25 and 0.19, respectively) and women (r = 0.30 and 0.22, respectively) (all P < 0.0001). In men, those identified as having IDH, ISH, and SDH each had a 6% larger AoD than NT individuals (all P < 0.05). In women, those identified with ISH and SDH had a 10 and 8% larger AoD than NT individuals, respectively (all P < 0.05). In both sexes, after indexing to BSA, only ISH individuals exhibited larger AoD compared with NT individuals (both P < 0.05). But, with further adjustment for age, these differences were no longer observed. Thus, even when the subtypes of hypertension are examined separately, age and BSA, not hypertension status, account for the AoD differences between NT and hypertensive subjects. (Am J Hypertens. 2008;21(5):558-63). 4) Heart failure with preserved ejection fraction often develops in hypertensive left ventricular hypertrophy (HLVH) patients and involves multiple abnormalities. Clarification of changes most specific to heart failure with preserved ejection fraction (HFpEF) may help elucidate underlying pathophysiology. We sought to identify cardiovascular features of patients with HFpEF that differ from those in individuals with HLVH of similar age, gender, and racial background but without failure. We performed a cross-sectional study that compared HFpEF patients (n = 37), HLVH subjects without HF (n = 40), and normotensive control subjects without LVH (n = 56). All subjects had an EF of >50%, sinus rhythm, and insignificant valvular or active ischemic disease, and groups were matched for age, gender, and ethnicity. Comprehensive echo-Doppler and pressure analysis was performed. The HFpEF patients were predominantly African-American women with hypertension, LVH, and obesity. They had vascular and systolic-ventricular stiffening and abnormal diastolic function compared with the control subjects. However, most of these parameters either individually or combined were similarly abnormal in the HLVH group and poorly distinguished between these groups. The HFpEF group had quantitatively greater concentric LVH and estimated mean pulmonary artery wedge pressure (20 mm Hg vs. 16 mm Hg) and shorter isovolumic relaxation time than the HLVH group. They also had left atrial dilation/dysfunction unlike in HLVH and greater total epicardial volume. The product of LV mass index and maximal left atrial (LA) volume best identified HFpEF patients (84% sensitivity, 82% specificity). Thus, in an urban, principally African American, cohort, HFpEF patients share many abnormalities of systolic, diastolic, and vascular function with nonfailing HLVH subjects but display accentuated LVH and LA dilation/failure. These latter factors may help clarify pathophysiology and define an important HFpEF population for clinical trials (J Am Coll Cardiol. 2007;49(2):198-207).

1）我们试图评估脉冲波速度（PWV）是动脉刚度的无创指数，是收缩压（SBP）纵向变化和入射高血压的纵向变化的预测指标。尽管据信动脉僵硬在某种程度上是基于年龄相关的SBP的变化，尤其是在年龄较大的年龄，但在人类中很少有纵向研究检查了动脉僵硬与血压之间的关系。脉冲波速度在基线时在449个正常性或未经治疗的高血压志愿者（53岁+/- 17岁）中测量。在平均随访期为4。9 +/- 2。5年中，对血压进行了重复测量。在调整包括年龄，体重指数和平均动脉压在内的协变量后，线性混合效应回归模型表明，PWV是SBP纵向增加的独立决定因素（与时间相互作用的p = 0.003）。在基线时有正常性的306名受试者的子集中，在中位随访期间，高血压在105（34％）中出现了4。3年（范围2至12年）。通过逐步的COX比例危害模型，PWV是入射高血压的独立预测指标（危险比1.10每1 m/s增加PWV，95％置信区间1.00至1.30，P = 0.03，p = 0.03）的随访时间大于中间。因此，脉搏波速度是SBP纵向增加和入射高血压的独立预测指标。这表明PWV可以帮助识别出正常的人，这些人应针对旨在防止或延迟亚临床动脉僵硬和高血压发作的干预措施的实施（J Am CollCardiol。2008; 51（14）：1377-83）。我们实验室正在进行的研究正在研究动脉僵硬的遗传学。 2）高血压加速了与年龄相关的主动脉根直径（AOD）的增加，这可能是由于长期升高的压力升高。但是，血压的脉动成分与AOD可能不同。我们试图评估AOD和脉压（PP）之间的关系，同时考虑左心室和中央动脉结构和功能特性，这些特性已知会影响PP。该研究人群由1256名患者组成，年龄在30至79岁（48％的女性和48％的高血压）中，其中一个人都没有使用降压药。通过常规的血压计在坐姿中测量血压。 PP计算为收缩压和舒张压之间的差异。 AOD在带有超声心动图的Valsalva的鼻窦水平下在末端舒张期测量。通过多个回归分析评估了AOD和PP之间的关系。男性的PP为50 +/- 14毫米汞柱，女性为54 +/- 18毫米汞柱，男性为31.9 +/- 3.5毫米，女性为28.9 +/- 3.5毫米。调整年龄，年龄（2），身高，体重和平均动脉压后，AOD在两性中都独立并与PP成反相关。在对中央动脉刚度和壁厚，反射波和左心室几何形状进行进一步调整后，AOD与男性的PP呈呈呈呈反相关（系数= -0.48; p = 0.0003; p = 0.0003; model r（2）= 0.51）和女性（系数= -0.40; p = -0.40; p = 0.01; p = 0.01; p = 0.01; p = 0.01; model R（2）= 0.61 = 0.61 = 0.61 = 0.61）。因此，AOD与PP成反比，表明小型AOD可能有助于收缩高压​​的发病机理。需要纵向研究来检查这种可能性。 （Hypermension。2008; 51（2）：196-202）。 3）主动脉根直径（AOD）随着衰老而增加，与体型有关。还假定AOD可以增加高血压。然而，在先前的研究中，在调整了年龄和体型后，高血压和正常人（NT）个体之间的AOD没有差异。高血压是一种异质疾病，具有各种亚型，在病理生理学和年龄分布方面有所不同。我们评估了AOD在高血压和非高血压个体的各种亚型的受试者之间是否有所不同。在30-79岁的1,256名志愿者中（48％的女性，48％的高血压；全部未经治疗），在valsalva的鼻窦上测量了AOD，并具有经胸膜超声心动图。使用基于预防，检测，评估和高血压联合治疗联合委员会的第七次报告，将受试者确定为NT（23％）（23％）或型前术前（pH，29％）或具有孤立的舒张期（IDH，6％），孤立的（6％），孤立的（ISH，12％），或Systolotic-hypertolocic（ISH，12％），或Systoloist-hypertoical（Systolotic-hypert）。使用Bonferroni校正的方差分析比较组。 AOD随着男性（分别为r = 0.25和0.19）和女性（分别为r = 0.30和0.22）的年龄和身体表面积（BSA）增加（r = 0.30和0.22）（全p <0.0001）。在男性中，被识别为具有IDH，ISH和SDH的人，每个人的AOD都比NT个体高6％（ast p <0.05）。在女性中，被ISH和SDH识别的人分别比NT个体大10％和8％（所有p <0.05）。在两个性别中，在索引BSA之后，与NT个体相比，只有ISH个体显示出更大的AOD（均P <0.05）。但是，随着年龄的进一步调整，不再观察到这些差异。因此，即使分别检查高血压的亚型，年龄和BSA，而不是高血压状态，也解释了NT和高血压受试者之间的AOD差异。 （Am JHypertens。2008; 21（5）：558-63）。 4）保留射血分数的心力衰竭通常在高血压左心室肥大（HLVH）患者中发展，并涉及多种异常。用保留的射血分数（HFPEF）对心力衰竭最特定的变化澄清可能有助于阐明潜在的病理生理学。我们试图确定HFPEF患者的心血管特征，这些特征与年龄相似，性别和种族背景但没有失败的患者的患者不同。我们进行了一项横断面研究，该研究比较了HFPEF患者（n = 37），没有HF的HLVH受试者（n = 40）和没有LVH的正常控制受试者（n = 56）。所有受试者的EF均为50％，鼻窦节奏和微不足道的瓣膜或活性缺血性疾病，并且成群的年龄，性别和种族匹配。进行了全面的回声多普勒和压力分析。 HFPEF患者主要是患有高血压，LVH和肥胖症的非裔美国妇女。与对照组相比，它们具有血管和收缩期室性僵硬和异常舒张功能。但是，这些参数中的大多数单独或组合在HLVH组中类似地异常，并且这些组之间的区分很差。与HLVH组相比，HFPEF组具有更大的同心LVH和估计的平均肺动脉楔压（20 mM Hg vs. 16 mm Hg）和短的异伏液弛豫时间。与HLVH不同，他们还留下了心房扩张/功能障碍，并且总心外膜量更大。 LV质量指数和最大左心房（LA）体积最佳鉴定的HFPEF患者的乘积（84％的敏感性，82％的特异性）。因此，在城市，主要是非裔美国人的队列中，HFPEF患者具有许多收缩期，舒张期和血管功能的异常，具有非轻率的HLVH受试者，但表现出突出的LVH和LA扩张/失败。这些后一个因素可能有助于阐明病理生理学并定义用于临床试验的重要HFPEF人群（J Am CollCardiol。2007; 49（2）：198-207）。

项目成果

Arterial aging and subclinical arterial disease are fundamentally intertwined at macroscopic and molecular levels.

• DOI: 10.1016/j.mcna.2009.02.008
• 发表时间: 2009-05
• 期刊: The Medical clinics of North America
• 作者: Lakatta EG;Wang M;Najjar SS
• 通讯作者: Najjar SS

Rapid titration of carvedilol in patients with congestive heart failure: a randomized trial of automated telemedicine versus frequent outpatient clinic visits.

充血性心力衰竭患者卡维地洛的快速滴定：自动远程医疗与频繁门诊就诊的随机试验。

• DOI: 10.1016/j.ahj.2005.06.044
• 发表时间: 2006
• 期刊: American heart journal
• 影响因子: 4.8
• 作者: Spaeder,Jeffrey;Najjar,SamerS;Gerstenblith,Gary;Hefter,Gail;Kern,Linda;Palmer,JamesG;Gottlieb,SheldonH;Kasper,EdwardK
• 通讯作者: Kasper,EdwardK