Chee Yingjie, Toh Grace Lx, Lim Chien Joo, Goh Liuh Ling, Dalan Rinkoo
Tan Tock Seng Hospital, Singapore, Singapore.
Department of Metabolic Medicine, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
Front Cardiovasc Med. 2021 Apr 29;8:627691. doi: 10.3389/fcvm.2021.627691. eCollection 2021.
Fibroblast growth factor 21 (FGF21), an emerging metabolic hepatokine, is associated with atherosclerosis. An interaction with sex has been described in various populations. We aimed to study whether sex modulates the relationship between FGF21 and subclinical carotid atherosclerosis in a diabetes-enriched multiethnic population of Singapore. We explore differences in intermediary mechanisms, in terms of hypertension, lipids, and inflammation, between FGF21 and atherosclerosis. We recruited 425 individuals from a single diabetes center in Singapore, and demographics, anthropometry, metabolic profile, FGF21, and carotid ultrasonography were performed. Multivariable logistic regression models were used to study the association between subclinical atherosclerosis and FGF21 adjusting for age, ethnicity, body mass index (BMI), hemoglobin A1c (HbA1c), systolic and diastolic blood pressures, and low-density lipoprotein (LDL)-cholesterol separately for males and females as two groups after an interaction test. An interaction test assessing interaction by sex on the relationship between subclinical atherosclerosis and FGF21 showed a significant interaction with sex (P = 0.033). In the female subgroup, significant independent associations of standardized lnFGF21 with subclinical atherosclerosis were seen, with 1 SD increment in lnFGF21 being associated with 1.48-fold (95% CI: 1.03, 2.12; = 0.036) increase in risk. In the male subgroup, the association of subclinical atherosclerosis with standardized lnFGF21 was not significant [odds ratio (OR) (95% CI): 0.90 (0.63, 1.28); = 0.553]. We found sex interactions with pulse pressure being significantly associated in females only and triglycerides and C-reactive protein being associated with males only. FGF21 is positively associated with subclinical carotid atherosclerosis in women, but not in men. The sex-racial patterns in the mechanisms by which FGF21 causes subclinical atherosclerosis needs to be explored in larger population-based studies and mechanistically studied in greater detail.
成纤维细胞生长因子21（FGF21）是一种新出现的代谢性肝因子，与动脉粥样硬化有关。在不同人群中已描述了其与性别之间的相互作用。我们旨在研究在新加坡一个糖尿病高发的多民族人群中，性别是否会调节FGF21与亚临床颈动脉粥样硬化之间的关系。我们探讨了FGF21与动脉粥样硬化在高血压、血脂和炎症等中介机制方面的差异。我们从新加坡的一个糖尿病中心招募了425名个体，并进行了人口统计学、人体测量学、代谢谱、FGF21和颈动脉超声检查。在进行交互作用检验后，将男性和女性作为两组，使用多变量逻辑回归模型研究亚临床动脉粥样硬化与FGF21之间的关联，并对年龄、种族、体重指数（BMI）、糖化血红蛋白（HbA1c）、收缩压和舒张压以及低密度脂蛋白（LDL）胆固醇进行校正。一项评估性别对亚临床动脉粥样硬化与FGF21之间关系的交互作用的检验显示，性别存在显著交互作用（P = 0.033）。在女性亚组中，标准化lnFGF21与亚临床动脉粥样硬化存在显著的独立关联，lnFGF21每增加1个标准差，风险增加1.48倍（95%CI：1.03，2.12；P = 0.036）。在男性亚组中，亚临床动脉粥样硬化与标准化lnFGF21的关联不显著[比值比（OR）（95%CI）：0.90（0.63，1.28）；P = 0.553]。我们发现，性别交互作用仅在女性中与脉压显著相关，而仅在男性中与甘油三酯和C反应蛋白相关。FGF21与女性的亚临床颈动脉粥样硬化呈正相关，但与男性无关。FGF21导致亚临床动脉粥样硬化的机制中的性别-种族模式需要在更大规模的基于人群的研究中进行探索，并从机制上进行更详细的研究。
