Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan.
Department of Cardiology, Kushiro Kojinkai Memorial Hospital, Kushiro, Japan.
Sci Rep. 2021 Feb 17;11(1):4008. doi: 10.1038/s41598-021-83494-5.
Fatty acid-binding protein 4 (FABP4) is secreted from adipose tissue and acts as an adipokine, and an elevated circulating FABP4 level is associated with metabolic disorders and atherosclerosis. However, little is known about the causal link between circulating FABP4 level and mortality in a general population. We investigated the relationship between FABP4 concentration and mortality including cardiovascular death during a 12-year period in subjects of the Tanno-Sobetsu Study, a population-based cohort (n = 721, male/female: 302/419). FABP4 concentration at baseline was significantly higher in female subjects than in male subjects. All-cause death occurred in 123 (male/female: 74/49) subjects, and 34 (male/female: 20/14) and 42 (male/female: 26/16) subjects died of cardiovascular events and cancer, respectively. When divided into 3 groups according to tertiles of FABP4 level at baseline by sex (T1-T3), Kaplan-Meier survival curves showed that there were significant differences in rates of all-cause death and cardiovascular death, but not cancer death, among the groups. Multivariable Cox proportional hazard model analysis with a restricted cubic spline showed that hazard ratio (HR) for cardiovascular death, but not that for all-cause death, significantly increased with a higher FABP4 level at baseline after adjustment of age and sex. The risk of cardiovascular death after adjustment of age, sex, body mass index and levels of brain natriuretic peptide and high-sensitivity C-reactive protein in the 3rd tertile (T3) group (HR: 4.96, 95% confidence interval: 1.20-22.3) was significantly higher than that in the 1st tertile (T1) group as the reference. In conclusion, elevated circulating FABP4 concentration predicts cardiovascular death in a general population.
脂肪酸结合蛋白 4(FABP4)由脂肪组织分泌,作为一种脂肪因子发挥作用,循环 FABP4 水平升高与代谢紊乱和动脉粥样硬化有关。然而,对于一般人群中循环 FABP4 水平与死亡率之间的因果关系知之甚少。我们在 Tanno-Sobetsu 研究中,对一个基于人群的队列(n=721,男/女:302/419)进行了为期 12 年的研究,调查了 FABP4 浓度与死亡率(包括心血管死亡)之间的关系。在基线时,女性受试者的 FABP4 浓度明显高于男性受试者。在所有受试者中,有 123 人(男/女:74/49)死亡,34 人(男/女:20/14)和 42 人(男/女:26/16)死于心血管事件和癌症。根据性别按 FABP4 水平的三分位数(T1-T3)将受试者分为 3 组,Kaplan-Meier 生存曲线显示,各组之间全因死亡和心血管死亡的发生率存在显著差异,但癌症死亡无差异。多变量 Cox 比例风险模型分析显示,经年龄和性别校正后,心血管死亡的风险比(HR)随着基线 FABP4 水平的升高而显著增加,但全因死亡的 HR 则不然。校正年龄、性别、体重指数以及脑钠肽和高敏 C 反应蛋白水平后,第 3 组(T3)的心血管死亡风险(HR:4.96,95%置信区间:1.20-22.3)明显高于第 1 组(T1)作为参考。总之,循环 FABP4 浓度升高可预测一般人群的心血管死亡。