Age Associated Changes In Structural And Functional Cardio-Vascular Properties

1)我们试图评估脉搏波速度（PWV），一个动脉硬度的无创指标，是否可以预测收缩压（SBP）的纵向变化和高血压事件。虽然动脉僵硬被认为是与年龄相关的收缩压变化的部分原因，特别是在老年人，但很少有对人类的纵向研究调查了动脉僵硬和血压之间的关系。在基线时测量449名血压正常或未经治疗的高血压志愿者（53 +/- 17岁）的脉搏波速度。在平均4.9 +/- 2.5年的随访期间，反复测量血压。在调整协变量包括年龄、体重指数和平均动脉压后，线性混合效应回归模型显示，PWV是收缩压纵向升高的独立决定因素（与时间的相互作用项p = 0.003）。在306名基线血压正常的受试者中，105人（34%）在中位4.3年（2至12年）的随访期间出现高血压。通过逐步Cox比例风险模型，在随访时间大于中位数的个体中，PWV是高血压事件的独立预测因子（PWV每增加1 m/s的风险比为1.10,95%置信区间为1.00 ~ 1.30,p = 0.03）。因此，脉搏波速度是纵向收缩压升高和高血压事件的独立预测因子。这表明PWV可以帮助识别血压正常的个体，这些个体应该有针对性地实施旨在预防或延缓亚临床动脉硬化和高血压发病的干预措施（J Am Coll Cardiol. 2008;51(14):1377-83）。我们实验室正在进行的研究正在调查动脉僵硬的遗传学。2)高血压加速了与年龄相关的主动脉根直径（AoD）的增加，可能是由于长期升高的扩张压。然而，血压的脉动成分可能与AoD有不同的关系。我们试图评估AoD与脉压（PP）之间的关系，同时考虑左心室和中央动脉的结构和功能特性，这些特性已知会影响PP。研究人群由1256人组成，年龄在30至79岁之间（48%为女性，48%为高血压患者），没有人服用抗高血压药物。采用常规血压计在坐姿测量血压。PP计算为收缩压和舒张压之差。超声心动图法测定心脏舒张末期Valsalva窦水平AoD。采用多元回归分析评价AoD与PP之间的关系。男性PP为50+/-14 mm Hg，女性为54+/-18 mm Hg， AoD为31.9+/-3.5 mm，女性为28.9+/-3.5 mm。在调整了年龄、年龄(2)、身高、体重和平均动脉压后，两性中AoD与PP呈独立负相关。在进一步调整了中央动脉硬度、壁厚、反射波和左心室几何形状后，AoD与PP在男性（系数=-0.48；P=0.0003；模型R(2)=0.51）和女性（系数=-0.40；P=0.01；模型R(2)=0.61）中仍呈负相关。因此，AoD与PP呈负相关，提示小的AoD可能与收缩期高血压的发病机制有关。需要进行纵向研究来检验这种可能性。51(高血压。2008;(2):196 - 202)。3)主动脉根部直径（AoD）随年龄增长而增大，并与体型有关。AoD也被认为会增加高血压。然而，在先前的研究中，在调整年龄和体型后，高血压和正常血压（NT）个体之间的AoD没有差异。高血压是一种具有不同病理生理和年龄分布的多种亚型的异质性疾病。我们评估了不同亚型高血压和非高血压个体的AoD是否不同。在1256名年龄在30-79岁的志愿者中（48%为女性，48%为高血压患者，均未接受治疗），通过经胸超声心动图测量Valsalva鼻窦处的AoD。根据高血压预防、检测、评估和治疗全国联合委员会第七次报告的截止值，受试者被确定为NT(23%)，或高血压前期（PH, 29%），或患有孤立性舒张期（IDH, 6%）、孤立性收缩期（ISH, 12%）或收缩期-舒张期（SDH, 30%）高血压。组间比较采用Bonferroni校正方差分析。AoD随年龄和体表面积（BSA）的增加而增加，男性（r分别为0.25和0.19），女性（r分别为0.30和0.22）（P均< 0.0001）。在男性中，IDH、ISH和SDH患者的AoD均比NT患者高6%（均P < 0.05）。在女性中，ISH和SDH患者的AoD分别比NT患者高10%和8%（均P < 0.05）。在两性中，只有ISH个体比NT个体表现出更大的AoD （P < 0.05）。但是，随着年龄的进一步调整，这些差异不再被观察到。因此，即使单独检查高血压亚型，年龄和BSA，而不是高血压状态，可以解释NT和高血压受试者之间的AoD差异。[J] .地球物理学报。2008;21(5):558-63。4)保留射血分数的心力衰竭常发生于高血压左心室肥厚（HLVH）患者，并涉及多种异常。对保留射血分数（HFpEF）的心力衰竭最特异性的改变的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，这些特征不同于年龄、性别和种族背景相似的HLVH患者，但没有失败。我们进行了一项横断面研究，比较HFpEF患者（n = 37）、无HF的HLVH患者（n = 40）和无LVH的正常血压对照组（n = 56）。所有受试者的EF均为bb50 %，窦性心律，无明显瓣膜或活动性缺血性疾病，各组按年龄、性别和种族进行匹配。进行了全面的超声多普勒和压力分析。HFpEF患者主要是患有高血压、左心室肥厚和肥胖的非裔美国女性。与对照组相比，他们有血管和收缩-心室硬化和舒张功能异常。然而，这些参数中的大多数单独或联合在HLVH组中相似地异常，并且在这些组之间差异不大。与HLVH组相比，HFpEF组有更大的同心LVH和估计的平均肺动脉楔压（20 mm Hg vs. 16 mm Hg）和更短的等容松弛时间。他们也有左心房扩张/功能障碍，不像HLVH和更大的总心外膜容积。左室质量指数与最大左房容积的乘积最能识别HFpEF患者（敏感性84%，特异性82%）。因此，在主要是非裔美国人的城市队列中，HFpEF患者与未衰竭的HLVH患者有许多收缩期、舒张期和血管功能异常，但LVH和LA扩张/衰竭加重。后一种因素可能有助于阐明病理生理学和确定临床试验中重要的HFpEF人群（J Am Coll Cardiol. 2007;49(2):198-207）。

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).