UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
Eur J Heart Fail. 2011 Oct;13(10):1087-95. doi: 10.1093/eurjhf/hfr079. Epub 2011 Jun 30.
Hypertension is one of the main drivers of the heart failure (HF) epidemic. The aims of this study were to profile fibro-inflammatory biomarkers across stages of the hypertensive heart disease (HHD) spectrum and to examine whether particular biochemical profiles in asymptomatic patients identify a higher risk of evolution to HF.
This was a cross-sectional observational study involving a population of 275 stable hypertensive patients divided into two different cohorts: Group 1, asymptomatic hypertension (AH) (n= 94); Group 2, HF with preserved ejection fraction (n= 181). Asymptomatic hypertension patients were further subdivided according to left atrial volume index ≥34 mL/m(2) (n= 30) and <34 mL/m(2) (n= 64). Study assays involved inflammatory markers [interleukin 6 (IL6), interleukin 8 (IL8), monocyte chemoattractant protein 1 (MCP1), and tumour necrosis factor α], collagen 1 and 3 metabolic markers [carboxy-terminal propeptide of collagen 1, amino-terminal propeptide of collagen 1, amino-terminal propeptide of collagen 3 (PIIINP), and carboxy-terminal telopeptide of collagen 1 (CITP)], extra-cellular matrix turnover markers [matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), and tissue inhibitor of metalloproteinase 1 (TIMP1)], and the brain natriuretic peptide. Data were adjusted for age, sex, systolic blood pressure, and creatinine. Heart failure with preserved ejection fraction was associated with an increased inflammatory signal (IL6, IL8, and MCP1), an increased fibrotic signal (PIIINP and CITP), and an increased matrix turnover signal (MMP2 and MMP9). Alterations in MMP and TIMP enzymes were found to be significant indicators of greater degrees of asymptomatic left ventricular diastolic dysfunction.
These data define varying fibro-inflammatory profiles throughout different stages of HHD. In particular, the observations on MMP9 and TIMP1 raise the possibility of earlier detection of those at risk of evolution to HF which may help focus effective preventative strategies.
高血压是心力衰竭（HF）流行的主要驱动因素之一。本研究的目的是分析高血压性心脏病（HHD）谱各阶段的纤维炎症生物标志物，并探讨无症状患者中特定的生化特征是否能识别出向 HF 发展的更高风险。
这是一项横断面观察性研究，涉及 275 名稳定高血压患者的人群，分为两个不同的队列：第 1 组为无症状高血压（AH）（n=94）；第 2 组为射血分数保留的心力衰竭（HFpEF）（n=181）。无症状高血压患者根据左心房容积指数≥34ml/m²（n=30）和<34ml/m²（n=64）进一步分为两组。研究检测指标包括炎症标志物[白细胞介素 6（IL6）、白细胞介素 8（IL8）、单核细胞趋化蛋白 1（MCP1）和肿瘤坏死因子 α]、胶原 1 和 3 代谢标志物[胶原 1 羧基末端前肽、胶原 1 氨基末端前肽、胶原 3 氨基末端前肽（PIIINP）和胶原 1 羧基末端肽（CITP）]、细胞外基质转换标志物[基质金属蛋白酶 2（MMP2）、基质金属蛋白酶 9（MMP9）和金属蛋白酶组织抑制剂 1（TIMP1）]和脑钠肽。数据根据年龄、性别、收缩压和肌酐进行调整。HFpEF 与炎症信号（IL6、IL8 和 MCP1）增加、纤维化信号（PIIINP 和 CITP）增加和基质转换信号（MMP2 和 MMP9）增加有关。发现 MMP 和 TIMP 酶的改变是无症状左心室舒张功能障碍程度较大的重要指标。
这些数据定义了 HHD 不同阶段的不同纤维炎症特征。特别是 MMP9 和 TIMP1 的观察结果提出了更早发现向 HF 发展风险的可能性，这可能有助于集中实施有效的预防策略。
