Ravassa Susana, Kuznetsova Tatiana, Varo Nerea, Thijs Lutgarde, Delles Christian, Dominiczak Anna, Díez Javier, Staessen Jan A
Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, IdiSNA-Navarra Institute for Health Research, Pamplona, Spain.
The Studies Coordinating Centre, Research Unit of Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Belgium.
Int J Cardiol. 2015 Apr 15;185:177-85. doi: 10.1016/j.ijcard.2015.03.046. Epub 2015 Mar 4.
BACKGROUND/OBJECTIVES: The validation of effective screening tools for the identification of patients with subclinical myocardial remodelling is a major clinical need. Thus, we explored the associations of circulating biomarkers of cardiomyocyte injury and stress with subclinical cardiac remodelling and dysfunction, and with biomarkers reflecting collagen turnover.
We randomly recruited 727 subjects from a general population (51.2% women; mean age 51.3 years). Measurements included echocardiographic left atrial (LA) and left ventricular (LV) structure and function, quantification of high sensitivity cardiac Troponin T (hs-cTnT), NT-proBNP, and biomarkers of collagen types I and III turnover.
In unadjusted and adjusted analyses, the prevalence of LA enlargement (LAE), LV hypertrophy (LVH) and LV diastolic dysfunction (LVDD) increased with higher hs-cTnT (P ≤ 0.031). NT-proBNP was independently associated with LVDD (P=0.009). Both biomarkers combined yielded significant integrated discrimination and net reclassification improvements (P ≤ 0.014 and P ≤ 0.009, respectively) for LAE, LVH and LVDD, over the conventional risk factors, and were independently and positively associated with biomarkers of collagen type I turnover. In a sensitivity analysis, after excluding participants with previous cardiac diseases, our findings remained consistent.
Our population-based study suggested that subclinical LV and LA remodelling were associated with hs-cTnT, and that, in combination with NT-proBNP, hs-cTnT showed incremental diagnostic utility over the conventional risk factors. Both biomarkers were associated with biomarkers of collagen type I turnover. Thus, biomarkers of cardiomyocyte microinjury and hemodynamic stress may stimulate fibrosis-related mechanisms and facilitate the diagnosis of subclinical LA and LV remodelling and dysfunction in the general population.
背景/目的：验证有效的筛查工具以识别亚临床心肌重构患者是一项重大临床需求。因此，我们探讨了心肌细胞损伤和应激的循环生物标志物与亚临床心脏重构和功能障碍以及反映胶原转换的生物标志物之间的关联。
我们从普通人群中随机招募了727名受试者（女性占51.2%；平均年龄51.3岁）。测量指标包括超声心动图测量的左心房（LA）和左心室（LV）结构与功能、高敏心肌肌钙蛋白T（hs-cTnT）、N末端B型利钠肽原（NT-proBNP）的定量以及I型和III型胶原转换的生物标志物。
在未调整和调整分析中，hs-cTnT水平越高，LA扩大（LAE）、LV肥厚（LVH）和LV舒张功能障碍（LVDD）的患病率越高（P≤0.031）。NT-proBNP与LVDD独立相关（P=0.009）。与传统危险因素相比，这两种生物标志物联合使用对LAE、LVH和LVDD产生了显著的综合判别改善和净重新分类改善（分别为P≤0.014和P≤0.009），并且与I型胶原转换的生物标志物独立且呈正相关。在敏感性分析中，排除既往有心脏病的参与者后，我们的研究结果仍然一致。
我们基于人群的研究表明，亚临床LV和LA重构与hs-cTnT相关，并且与NT-proBNP联合使用时，hs-cTnT在诊断效用上相对于传统危险因素有增量提升。这两种生物标志物均与I型胶原转换的生物标志物相关。因此，心肌细胞微损伤和血流动力学应激的生物标志物可能刺激纤维化相关机制，并有助于在普通人群中诊断亚临床LA和LV重构及功能障碍。
