Centre d'Investigations Cliniques Plurithématique 1433, Université de Lorraine, INSERM 1116, CHRU de Nancy.
F-CRIN INI-CRCT Cardiovascular and Renal Clinical Trialists Network, Nancy.
J Hypertens. 2023 Mar 1;41(3):402-410. doi: 10.1097/HJH.0000000000003343. Epub 2022 Dec 22.
The associations between childhood adiposity and adult increased carotid intima-media thickness (cIMT) have been well established, which might be corroborated by the association between adiposity in children and inflammation in adults. However, longitudinal data regarding biological pathways associated with childhood adiposity are lacking.
The current study included participants from the STANISLAS cohort who had adiposity measurements at age 5-18 years [ N = 519, mean (SD) age, 13.0 (2.9) years; 46.4% male], and who were measured with cIMT, vascular-related and metabolic-related proteins at a median follow-up of 19 ± 2 years. BMI, waist-to-height ratio and waist circumference were converted to age-specific and sex-specific z -scores.
A minority of children were overweight/obese (16.2% overweight-BMI z -score >1; 1.3% obesity- z -score >2). Higher BMI, waist-height ratio and waist circumference in children were significantly associated with greater adult cIMT in univariable analysis, although not after adjusting for C-reactive protein. These associations were more pronounced in those with consistently high adiposity status from childhood to middle adulthood. Participants with higher adiposity during childhood (BMI or waist-height ratio) had higher levels of insulin-like growth factor-binding protein-1, protein-2, matrix metalloproteinase-3, osteopontin, hemoglobin and C-reactive protein in adulthood. Network analysis showed that IL-6, insulin-like growth factor-1 and fibronectin were the key proteins associated with childhood adiposity.
In a population-based cohort followed for 20 years, higher BMI or waist-to-height ratio in childhood was significantly associated with greater cIMT and enhanced levels of proteins reflective of inflammation, supporting the importance of inflammation as progressive atherosclerosis in childhood adiposity.
儿童肥胖与成人颈动脉内膜中层厚度(cIMT)增加之间的关联已得到充分证实,而儿童肥胖与成人炎症之间的关联也得到了证实。然而,关于与儿童肥胖相关的生物学途径的纵向数据尚缺乏。
本研究纳入了 STANISLAS 队列的参与者,这些参与者在 5-18 岁时进行了肥胖测量[N=519,平均(SD)年龄为 13.0(2.9)岁;46.4%为男性],并在中位随访 19±2 年后进行了 cIMT、血管相关和代谢相关蛋白的测量。BMI、腰高比和腰围被转换为年龄和性别特异性 z 评分。
少数儿童超重/肥胖(16.2%超重-BMI z 评分>1;1.3%肥胖-z 评分>2)。儿童时期 BMI、腰高比和腰围较高与未调整 C 反应蛋白的成人 cIMT 显著相关,但调整后则不相关。这些关联在儿童期至中年期一直保持较高肥胖状态的人群中更为明显。儿童期(BMI 或腰高比)较高的肥胖者在成年期具有更高水平的胰岛素样生长因子结合蛋白-1、蛋白-2、基质金属蛋白酶-3、骨桥蛋白、血红蛋白和 C 反应蛋白。网络分析显示,白细胞介素 6、胰岛素样生长因子 1 和纤维连接蛋白是与儿童肥胖相关的关键蛋白。
在一项以人群为基础、随访 20 年的队列研究中,儿童时期 BMI 或腰高比较高与 cIMT 增加和反映炎症的蛋白水平升高显著相关,支持炎症在儿童肥胖导致动脉粥样硬化进展中的重要性。