Jauhiainen Raimo, Jauhiainen Matti, Vangipurapu Jagadish, Kuulasmaa Teemu, Ala-Korpela Mika, Laakso Markku, Kuusisto Johanna
Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland.
Institute of Biomedicine, Bioinformatics Center, University of Eastern Finland, Kuopio, Finland.
ESC Heart Fail. 2021 Feb;8(1):605-614. doi: 10.1002/ehf2.13132. Epub 2020 Dec 5.
There are only a few studies on novel biomarkers for incident heart failure (HF). We investigated the association of multiple circulating biomarkers with incident HF in a large prospective population-based study.
Conventional risk factors and inflammatory biomarkers were measured, and systemic metabolic measures determined by a high-throughput serum nuclear magnetic resonance platform in a population-based Metabolic Syndrome in Men study including 10 106 Finnish men without HF at baseline. During an 8.8 year follow-up, 172 (1.7%) participants developed HF. Adiponectin, high-sensitivity C-reactive protein (hs-CRP), glycoprotein acetyls, alanine, phenylalanine, glycerol, and pyruvate were associated with incident HF in unadjusted Cox regression analyses, in addition to age, systolic blood pressure, body mass index (BMI), waist circumference, fasting plasma glucose and insulin, haemoglobin A1c (HbA1c), and urinary albumin excretion rate (UAER). After adjustment for age, BMI, diabetes, and statin medication, only adiponectin [hazard ratio (HR) 1.18 (1.10-1.26, P = 4.1E-08)], pyruvate [HR 1.38 (1.28-1.50, P = 8.2E-05)], and UAER [HR 1.15 (1.11-1.18, P = 7.8E-06)] remained statistically significant. In principal component analysis of biomarkers associated with HF in univariate Cox regression analysis, we identified six components, explaining 61.7% of total variance. Four principal components, one with significant loadings on waist, BMI, fasting plasma insulin, interleukin 1 receptor antagonist, and hs-CRP; another on pyruvate, glycoprotein acetyls, alanine, glycerol and HbA1c; third on age and glomerular filtration rate; and fourth on systolic blood pressure, UAER, and adiponectin, significantly associated with incident HF.
Several novel metabolic and inflammatory biomarkers were associated with incident HF, suggesting early activation of respective pathways in the pathogenesis of HF.
关于新发心力衰竭（HF）的新型生物标志物的研究较少。我们在一项基于人群的大型前瞻性研究中调查了多种循环生物标志物与新发HF之间的关联。
在一项名为“男性代谢综合征”的基于人群的研究中，对10106名基线时无HF的芬兰男性测量了传统危险因素和炎症生物标志物，并通过高通量血清核磁共振平台测定了全身代谢指标。在8.8年的随访期间，172名（1.7%）参与者发生了HF。在未调整的Cox回归分析中，除年龄、收缩压、体重指数（BMI）、腰围、空腹血糖和胰岛素、糖化血红蛋白（HbA1c）以及尿白蛋白排泄率（UAER）外，脂联素、高敏C反应蛋白（hs-CRP）、糖蛋白乙酰化物、丙氨酸、苯丙氨酸、甘油和丙酮酸与新发HF相关。在调整年龄、BMI、糖尿病和他汀类药物治疗后，只有脂联素[风险比（HR）1.18（1.10 - 1.26，P = 4.1E - 08）]、丙酮酸[HR 1.38（1.28 - 1.50，P = 8.2E - 05）]和UAER[HR 1.15（1.11 - 1.18，P = 7.8E - 06）]仍具有统计学意义。在单变量Cox回归分析中与HF相关的生物标志物的主成分分析中，我们确定了六个成分，解释了总方差的61.7%。四个主成分，一个在腰围、BMI、空腹血浆胰岛素、白细胞介素1受体拮抗剂和hs-CRP上有显著载荷；另一个在丙酮酸、糖蛋白乙酰化物、丙氨酸、甘油和HbA1c上；第三个在年龄和肾小球滤过率上；第四个在收缩压、UAER和脂联素上，与新发HF显著相关。
几种新型代谢和炎症生物标志物与新发HF相关，提示在HF发病机制中各自途径的早期激活。
