1 Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Norway.
2 Faculty of Medicine, KG Jebsen Inflammatory Research Centre, University of Oslo, Norway.
Eur J Prev Cardiol. 2017 Jul;24(11):1161-1167. doi: 10.1177/2047487317703826. Epub 2017 Apr 21.
Aims Extracellular matrix remodelling may influence atherosclerotic progression and plaque stability. We hypothesized that evaluation of extracellular matrix markers, with potentially different roles during atherogenesis, could provide information on underlying mechanisms and risk of myocardial infarction (MI) in apparently healthy individuals. Methods We conducted a case-control study nested within the population-based HUNT2 cohort in Norway. A total of 58,761 men and women, free of known cardiovascular disease, were followed for a first MI. During 11.3 years of follow-up, 1587 incident MIs were registered, and these cases were compared with 3959 age- and sex-matched controls. Circulating levels of the ECM proteins CD147 (ECM metalloproteinase inducer; EMMPRIN), cartilage oligomeric matrix protein (COMP: thrombospondin-5) and YKL-40 (chitinase-3-like-1) were measured by enzyme immunoassays. Results We found an inverse association between COMP (quartile (Q) 4 vs. Q1: hazard ratio 0.81 (95% confidence interval: 0.67-0.98)) and YKL-40 (Q4 vs. Q1: hazard ratio 0.77 (0.62-0.95)) with incidence of MI after full multivariable adjustment. Serum CD147 was not associated with MI risk in adjusted analysis. Conclusion High levels of COMP and YKL-40 were associated with lower risk of incident MI, suggesting a potential beneficial role in promoting plaque stability in individuals without incident cardiovascular disease.
目的 细胞外基质重塑可能影响动脉粥样硬化的进展和斑块稳定性。我们假设，评估细胞外基质标志物（在动脉粥样发生过程中可能具有不同的作用）可以提供有关潜在机制和心肌梗死（MI）风险的信息，而这些信息来自于表面上健康的个体。
方法 我们在挪威基于人群的 HUNT2 队列中进行了一项病例对照研究。共有 58761 名无已知心血管疾病的男性和女性参与研究，随访其首次心肌梗死（MI）。在 11.3 年的随访期间，共登记了 1587 例首发 MI，将这些病例与 3959 名年龄和性别匹配的对照进行比较。通过酶联免疫吸附试验测量细胞外基质蛋白 CD147（细胞外基质金属蛋白酶诱导因子；EMMPRIN）、软骨寡聚基质蛋白（COMP：血小板反应蛋白-5）和 YKL-40（几丁质酶-3 样蛋白-1）的循环水平。
结果 我们发现，在经过充分多变量调整后，COMP（四分位间距（Q）4 与 Q1：风险比 0.81（95%置信区间：0.67-0.98））和 YKL-40（Q4 与 Q1：风险比 0.77（0.62-0.95））与 MI 发生率呈负相关。在调整分析中，血清 CD147 与 MI 风险无关。
结论 高水平的 COMP 和 YKL-40 与 MI 发生率降低相关，这表明在没有心血管疾病事件的个体中，它们可能具有促进斑块稳定的潜在有益作用。
