Jordán A, Roldán V, García M, Monmeneu J, de Burgos F G, Lip G Y H, Marín F
Cardiology Department, University General Hospital of Elche, Elche, Spain.
J Intern Med. 2007 Sep;262(3):385-92. doi: 10.1111/j.1365-2796.2007.01823.x.
Structural remodelling of left ventricle is a common feature in the progression of congestive heart failure (CHF). Matrix metalloproteinases (MMPs) have been directly implicated as they degrade extracellular proteins. To test the hypothesis that MMP-and its inhibitor, tissue type inhibitor of matrix metalloproteinases (TIMP-1), could be related to functional status and prognosis in CHF, we examined the relationship of MMP-1 and TIMP-1 to peak oxygen consumption (VO2) and peak minute ventilation/carbon dioxide production relationship (VE/VCO2), and assessed their prognostic value.
We studied 50 patients with CHF, who were compared with 53 controls echocardiogram and ergoespirometry were performed, and serum levels of MMP-1 and TIMP-1 were assayed by ELISA. Patients were followed up for 17.5+/-8.9 months, and total mortality, readmissions for heart failure and cardiac transplantation were recorded.
Patients with CHF had lower levels of MMP-1 (P=0.027), and higher levels of TIMP-1 and TIMP-1/MMP-1 ratio (both P<0.01) than controls. TIMP-1 levels and the TIMP-1/MMP-1 ratio correlated negatively with peak VO2 (Spearman, r:-0.51; P=0.001 and r: -0.42; P=0.030, respectively). During the follow-up period, 23 patients (47.9%) suffered endpoints--these patients had higher baseline peak VE/VCO2 (P=0.001), TIMP-1 (P=0.004), and TIMP-1/MMP-1 ratio values (P=0.002), whereas MMP-1 levels were lower (P=0.027). On multivariate analysis, VE/VCO2, MMP-1 levels and age were the only variables independently related to prognosis (all P<0.05).
Poor functional capacity in CHF can be related to abnormal extracellular matrix turnover. Patients who suffered endpoints had more abnormal indices of matrix turnover, where MMP-1 levels showed independent prognostic value.
左心室结构重塑是充血性心力衰竭（CHF）进展过程中的一个常见特征。基质金属蛋白酶（MMPs）因其可降解细胞外蛋白而被直接牵连其中。为了验证MMP及其抑制剂——基质金属蛋白酶组织抑制剂（TIMP-1）可能与CHF的功能状态和预后相关这一假设，我们研究了MMP-1和TIMP-1与峰值耗氧量（VO2）以及峰值分钟通气量/二氧化碳产生关系（VE/VCO2）之间的关系，并评估了它们的预后价值。
我们研究了50例CHF患者，并与53例对照者进行比较，对他们进行了超声心动图和运动肺功能测试，并通过酶联免疫吸附测定法检测血清MMP-1和TIMP-1水平。对患者进行了17.5±8.9个月的随访，记录了总死亡率、因心力衰竭再次入院情况以及心脏移植情况。
CHF患者的MMP-1水平低于对照组（P=0.027），而TIMP-1水平和TIMP-1/MMP-1比值高于对照组（P均<0.01）。TIMP-1水平和TIMP-1/MMP-1比值与峰值VO2呈负相关（Spearman相关系数分别为r=-0.51；P=0.001和r=-0.42；P=0.030）。在随访期间，23例患者（47.9%）出现了终点事件——这些患者的基线峰值VE/VCO2（P=0.001）、TIMP-1（P=0.004）和TIMP-1/MMP-1比值（P=0.002）较高，而MMP-1水平较低（P=0.027）。多因素分析显示，VE/VCO2、MMP-1水平和年龄是与预后独立相关的仅有的变量（P均<0.05）。
CHF患者功能能力差可能与细胞外基质周转异常有关。出现终点事件的患者有更多异常的基质周转指标，其中MMP-1水平显示出独立预后价值。
