Early-Life Risk Factors for Carotid Intima-Media Thickness and Carotid Stiffness in Adolescence

Abstract

Importance: Atherogenesis starts during childhood, making childhood and adolescence an important window of opportunity to prevent atherosclerotic cardiovascular disease later in life.

Objective: To identify early-life risk factors for preclinical atherosclerosis in adolescence.

Design, setting, and participants: This cohort study is part of the ongoing Wheezing Illness Study in Leidsche Rijn (WHISTLER) prospective birth cohort study, which includes 3005 healthy newborns born between December 2001 and December 2012 in the Leidsche Rijn area of Utrecht, the Netherlands. Eligible participants included those from the WHISTLER cohort who visited the clinic between March 2019 and October 2020 for adolescent follow-up. This study's analyses were performed in January 2024.

Exposures: Early-life growth was assessed at birth to 6 months, 5 years, and 12 to 16 years. Abdominal ultrasonography determined abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) depth. Blood pressure (BP) percentiles and body mass index (BMI) z scores were used.

Main outcomes and measures: Carotid ultrasonography was performed at age 12 to 16 years to assess carotid intima-media thickness (cIMT) and the distensibility coefficient (DC), established measures of preclinical atherosclerosis. Multivariable linear regression models were used to identify early-life risk factors for cIMT and DC in adolescence.

Results: In total, 232 adolescents (median [IQR] age, 14.9 [13.7-15.8] years; 121 female [52.2%]) were included. More postnatal weight gain (B = 12.34; 95% CI, 2.39 to 22.39), higher systolic BP at 5 years (B = 0.52; 95% CI, 0.02 to 1.01), more VAT at 5 years (B = 3.48; 95% CI, 1.55 to 5.40), and a larger change in VAT between 5 and 12 to 16 years (B = 3.13; 95% CI, 1.87 to 4.39) were associated with a higher cIMT in adolescence. A higher BMI (B = -2.70, 95% CI,-4.59 to -0.80) and VAT at 5 years (B = -0.56; 95% CI, -0.87 to -0.25), as well as a larger change in BMI between 5 and 12 to 16 years (B = -3.63; 95% CI, -5.66 to -1.60) were associated with a higher carotid stiffness in adolescence. On the contrary, a larger change in SAT between 5 and 12 to 16 years (B = 0.37; 95% CI, 0.16 to 0.58) was associated with a higher carotid DC in adolescence.

Conclusions and relevance: In this cohort study of 232 participants, early-life growth parameters, and particularly abdominal VAT development, were associated with a higher cIMT and carotid stiffness in adolescence. These findings suggest that assessment of adipose tissue development during childhood can aid characterization of lifetime risk trajectories and tailoring of cardiovascular prevention and risk management strategies.