Long-Term Adiposity and Midlife Carotid Intima-Media Thickness Are Linked Partly Through Intermediate Risk Factors

Abstract

OBJECTIVE: This study aims to determine quantitatively the mediation effects of multiple cardiovascular risk factors on the associations of childhood body mass index (BMI) and its cumulative burden with adult carotid intima-media thickness (cIMT). METHODS: The longitudinal cohort consisted of 1391 adults who had been examined for BMI 4-15 times over 35.0 years on average since childhood and had data on adult cIMT, systolic blood pressure, low-density lipoprotein cholesterol, atherogenic index of plasma, and serum glucose. The area under the curve was used as a measure of cumulative burden of BMI. RESULTS: After adjusting for covariates, the total effects (standardized regression coefficient) of childhood BMI (0.138), adult BMI (0.111), and BMI area under the curve (0.150) on cIMT were all significant ( P <0.001) without mediators included in the model. The mediation effects of adult systolic blood pressure, glucose, atherogenic index of plasma and low-density lipoprotein cholesterol were 8.0%, 4.3%, 3.6%, and 0.0%, respectively, in the model with childhood BMI as the predictor, 23.4%, 15.3%, 12.6%, and 7.2%, respectively, with adult BMI as the predictor, and 14.7%, 8.7%, 6.0%, and 2.0%, respectively, with BMI area under the curve as the predictor. The direct effects on cIMT were 0.117 ( P <0.001) for childhood BMI, 0.046 ( P =0.224) for adult BMI, and 0.103 ( P <0.001) for BMI area under the curve after removing the mediation effects. CONCLUSIONS: The long-term deleterious impact of adiposity on subclinical changes in vascular structure begins early in life and is accumulated over lifetime. Excess adiposity and higher cIMT are linked partly through other cardiovascular risk factors in later life, especially elevated blood pressure and glucose.

Associations of Epigenetic Age Acceleration With CVD Risks Across the Lifespan

“…Prior to mediation analyses, we confirmed results of previous studies, 38 , 39 , 40 , 41 , 42 demonstrating significant associations of childhood BMI, BP, lipids, and glucose AUC with adulthood cIMT in the BHS ( Supplemental Table 5 ). The results of analyses investigating the potentially mediating effects of identified EAA measures on known associations of childhood BMI, TGs, and HDL-C with cIMT are shown in Figure 4 and Supplemental Table 6 .…”

Development trends of etiological research contents and methods of noncommunicable diseases

“…Conventional trajectory analysis methods include growth curve fitting based on Z scores, multilevel modeling, group‐based trajectory modeling, and latent class mixed effects models [ 32 , 33 ]. Zhang et al [ 34 ] performed life course trajectory analysis and mediation analysis to quantify the life course cumulative burden of childhood to adulthood obesity and showed that the adverse effects of obesity on cardiovascular health began in childhood and accumulated over the life course. This study provides new evidence for the early‐life origins of cardiovascular disease and has significant implications for formulating early prevention strategies and measures related to obesity‐associated atherosclerosis.…”

Obesity in children and adolescents: Overview of the diagnosis and management

“…5 Childhood obesity has been shown to remain through adulthood with a low rate of spontaneous remission, especially for severely obese children. [6][7][8] The cumulative effect of increased adiposity spans through the life course, and it has been shown in large birth cohorts that childhood obesity is associated with impaired glucose metabolism and increased carotid intima-media thickness in adulthood 8,9 On the other hand, it has been shown in large-scale longitudinal studies that adverse effects of childhood obesity on future risk of T2D could be reversed with normalization of body mass index (BMI) before adulthood. 8,10 As a result, vigorous management of childhood obesity should be the logical upstream approach to prevent obesity-related adverse health outcomes in adulthood.…”