衰老导致的舒张功能障碍与心肌结构无关，但与血浆晚期糖基化终产物水平有关。
Diastolic dysfunction of aging is independent of myocardial structure but associated with plasma advanced glycation end-product levels.
机构信息
St. Vincent's Institute of Medical Research, Fitzroy, Australia.
出版信息
PLoS One. 2012;7(11):e49813. doi: 10.1371/journal.pone.0049813. Epub 2012 Nov 26.
BACKGROUND
Heart failure is associated with abnormalities of myocardial structure, and plasma levels of the advanced glycation end-product (AGE) N(ε)-(carboxymethyl)lysine (CML) correlate with the severity and prognosis of heart failure. Aging is associated with diastolic dysfunction and increased risk of heart failure, and we investigated the hypothesis that diastolic dysfunction of aging humans is associated with altered myocardial structure and plasma AGE levels.
METHODS
We performed histological analysis of non-ischemic left ventricular myocardial biopsies and measured plasma levels of the AGEs CML and low molecular weight fluorophores (LMWFs) in 26 men undergoing coronary artery bypass graft surgery who had transthoracic echocardiography before surgery. None had previous cardiac surgery, myocardial infarction, atrial fibrillation, or heart failure.
RESULTS
The patients were aged 43-78 years and increasing age was associated with echocardiographic indices of diastolic dysfunction, with higher mitral Doppler flow velocity A wave (r = 0.50, P = 0.02), lower mitral E/A wave ratio (r = 0.64, P = 0.001), longer mitral valve deceleration time (r = 0.42, P = 0.03) and lower early diastolic peak velocity of the mitral septal annulus, e' (r = 0.55, P = 0.008). However, neither mitral E/A ratio nor mitral septal e' was correlated with myocardial total, interstitial or perivascular fibrosis (picrosirius red), immunostaining for collagens I and III, CML, and receptor for AGEs (RAGE), cardiomyocyte width, capillary length density, diffusion radius or arteriolar dimensions. Plasma AGE levels were not associated with age. However, plasma CML levels were associated with E/A ratio (r = 0.44, P = 0.04) and e' (r = 0.51, P = 0.02) and LMWF levels were associated with E/A ratio (r = 0.49, P = 0.02). Moreover, the mitral E/A ratio remained correlated with plasma LMWF levels in all patients (P = 0.04) and the mitral septal e' remained correlated with plasma CML levels in non-diabetic patients (P = 0.007) when age was a covariate.
CONCLUSIONS
Diastolic dysfunction of aging was independent of myocardial structure but was associated with plasma AGE levels.
背景
心力衰竭与心肌结构异常有关，血浆中晚期糖基化终产物（AGE）N（ε）-（羧甲基）赖氨酸（CML）的水平与心力衰竭的严重程度和预后相关。衰老与舒张功能障碍和心力衰竭风险增加有关，我们假设衰老人群的舒张功能障碍与心肌结构改变和血浆 AGE 水平有关。
方法
我们对 26 名接受冠状动脉旁路移植术的男性患者进行了非缺血性左心室心肌活检的组织学分析，并在术前进行了经胸超声心动图检查，测量了血浆中 AGE 的 CML 和低分子量荧光体（LMWF）水平。这些患者均无既往心脏手术、心肌梗死、心房颤动或心力衰竭史。
结果
患者年龄 43-78 岁，年龄增长与舒张功能障碍的超声心动图指标相关，表现为二尖瓣多普勒血流速度 A 波升高（r=0.50，P=0.02）、二尖瓣 E/A 波比值降低（r=0.64，P=0.001）、二尖瓣瓣口减速时间延长（r=0.42，P=0.03）以及二尖瓣间隔瓣环舒张早期峰值速度，e'降低（r=0.55，P=0.008）。然而，二尖瓣 E/A 比值和二尖瓣间隔 e'均与心肌总纤维化、间质纤维化或血管周围纤维化（苦味酸天狼星红染色）、I 型和 III 型胶原免疫染色、CML 以及 AGE 受体（RAGE）、心肌细胞宽度、毛细血管长度密度、扩散半径或小动脉直径无关。血浆 AGE 水平与年龄无关。然而，血浆 CML 水平与 E/A 比值相关（r=0.44，P=0.04），LMWF 水平与 E/A 比值相关（r=0.49，P=0.02）。此外，在所有患者中，二尖瓣 E/A 比值与血浆 LMWF 水平仍相关（P=0.04），在非糖尿病患者中，二尖瓣间隔 e'与血浆 CML 水平仍相关（P=0.007），当年龄为协变量时。
结论
衰老引起的舒张功能障碍与心肌结构无关，但与血浆 AGE 水平有关。
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