Carotid intima-media thickness (cIMT) and carotid-femoral pulse wave velocity (cfPWV), indicators of arterial stiffness, are crucial markers for subclinical atherosclerotic cardiovascular morbidity and mortality. Given the global cardiovascular disease burden, managing lifetime risk factors is vital for prevention. Cumulative exposure to childhood obesity, often estimated using BMI, has been linked to faster cfPWV and thicker cIMT. However, BMI's inability to differentiate between fat and lean mass has led to questions about the accuracy of these findings. Some studies suggest that previous associations between body composition (assessed by BMI) and vascular measures might be misinterpreted. A Mendelian randomization study even found no causal link between BMI and cfPWV/cIMT at age 17. This study aims to clarify these associations by using dual X-ray energy absorptiometry (DEXA) to quantify body composition, providing a more precise assessment of cardiovascular risk than traditional anthropometrics. Furthermore, the study investigates the cumulative effects of blood pressure (BP) from childhood, since a previous study demonstrated a strong association between persistent high BP (ages 18-39) and increased cardiovascular event risk in late adulthood, but lacked childhood data. Utilizing data from the Avon Longitudinal Study of Parents and Children (ALSPAC) UK birth cohort, this study prospectively examines the associations of cumulative exposures to fat mass, lean mass, BMI, and BP from ages 9-24 years with cfPWV and cIMT progression from ages 17-24 years.

The literature review highlights the established links between cIMT and cfPWV and cardiovascular risk. Existing research emphasizes the importance of lifetime risk factor management to mitigate future cardiovascular events. Studies have associated cumulative exposure to childhood obesity (using BMI as a proxy) with accelerated vascular aging, indicated by higher cfPWV and cIMT. However, the limitations of BMI in distinguishing fat and lean mass prompted further investigation. Some recent studies using more precise body composition measurements questioned the previous findings, suggesting a need for clarification using techniques like DEXA scans. The importance of early life blood pressure exposure on later cardiovascular health was also discussed, leading to the inclusion of BP as a key variable in this study.

The study utilized data from the ALSPAC birth cohort, a large longitudinal study following individuals from birth. A total of 3863 participants with complete cfPWV and cIMT measurements at ages 17 and 24 were included in the prospective analysis. Body composition (fat mass, lean mass) was measured using DEXA scans at ages 9, 17, and 24. Blood pressure was measured at ages 9, 17, and 24. cfPWV and cIMT were measured at ages 17 and 24. Cardiometabolic and lifestyle factors (fasting glucose, insulin, hsCRP, LDL-C, triglycerides, smoking, physical activity, family history of cardiovascular disease) were also collected. Cross-sectional analyses used multiple linear regression to examine associations at age 24. Longitudinal analyses used linear mixed-effect models to assess the cumulative effects of exposures from ages 9-24 on changes in cfPWV and cIMT from ages 17-24. Models were adjusted for sex, age, time, cardiometabolic factors, and lifestyle factors. Multiple imputation was used to handle missing data.

Cross-sectional analysis at age 24 showed positive associations between lean mass and systolic/diastolic BP with cfPWV, while BMI showed a negative association. Lean mass, LMI, and systolic BP were positively associated with cIMT, while BMI was negatively associated. No significant associations were observed between fat mass and cfPWV/cIMT. Longitudinal analysis revealed that cumulative high exposures to lean mass, systolic BP, and diastolic BP were positively associated with increased cfPWV over 7 years. Cumulative high exposures to lean mass, LMI, BMI, and systolic BP were associated with higher cIMT at age 24. Sex differences were observed in the association between cumulative high lean mass exposure and the 7-year increase in cfPWV, with a positive association in males and a negative association in females. Importantly, total fat mass and trunk fat mass showed no association with cfPWV or cIMT progression. The results remained consistent after adjusting for various cardiometabolic and lifestyle factors.

The findings indicate that increased lean mass and BP, but not fat mass, are key drivers of arterial remodeling in young adulthood. This challenges previous assumptions linking childhood obesity (as measured by BMI) to accelerated vascular aging. The study's strengths include its longitudinal design, use of DEXA for precise body composition assessment, and adjustment for multiple confounders. The sex-specific differences in the relationship between lean mass and cfPWV warrant further investigation, potentially exploring hormonal or other biological factors. The lack of association between fat mass and vascular measures suggests that interventions targeting lean mass and BP might be more effective in preventing early vascular aging.

This study demonstrates that cumulative high exposures to lean mass and blood pressure, not fat mass, are significantly associated with increased arterial stiffness and carotid intima-media thickness in young adults. These findings highlight the importance of focusing on lean mass management and blood pressure control, rather than solely targeting fat mass reduction, for preventing early vascular aging. Future research should investigate the underlying mechanisms driving these associations and explore potential sex-specific interventions.

While the study included a large sample size and addressed many confounders, some limitations exist. The reliance on self-reported data for some lifestyle factors might introduce some bias. The study population was primarily from a single geographic region, limiting generalizability. Further research in diverse populations is needed to confirm the findings. The lack of data on anti-hypertensive medication use at age 24 may have slightly affected the interpretation of BP's impact.