This study examined CIMT progression during childhood growth and development and its cardiometabolic predictors in healthy, overweight Latino youth. Our results indicate that change in CIMT was highly variable. Moreover, 36% of participants showed progression beyond that of the physiological norm (Advanced CIMT Progression Group with CIMT ≥0.01mm over 2 years). Participants in the advanced CIMT progression group had significantly higher baseline LDL and total cholesterol than those in the CIMT non-progression group. Another predictor of CIMT change was baseline glucose effectiveness, which had a negative relationship with CIMT change independent of sex and baseline CIMT, age and height. Finally, the odds of CIMT progression increased 1.03 times (or 3%) for each 1mg/dL increase of baseline LDL-cholesterol, independent of glucose effectiveness and other covariates. These results highlight the baseline effects of LDL-cholesterol in youth that results in advanced CIMT progression.
Contrary to our hypothesis, baseline systolic blood pressure, abdominal adiposity or insulin sensitivity were not associated with change in CIMT over a 2-year period. We have previously shown that Latino children with persistent high blood pressure and high waist circumference, along with children with persistent metabolic syndrome, had a higher CIMT than those children without these risk factors. The cumulative effects of the metabolic syndrome, high blood pressure and waist circumference resulted in elevated CIMT. Our present report shows that these same risk factors were not associated with the rate of CIMT progression. Instead, LDL-cholesterol was the defining cardiometabolic risk factor translated into more CIMT progression. Together, these two studies suggest that multiple risk factors are involved in both elevated CIMT and CIMT progression and that all of these risk factors are important in determining atherosclerosis risk in overweight Latino youth.
The relationship between LDL-cholesterol and CIMT has been well-documented in adults but is still ambiguous in studies of healthy children; 2 studies have observed this relationship (22
) whereas 2 others have not (24
). We have shown a statistically significant relationship with LDL-cholesterol and CIMT progression after only 2 years in overweight Latino youth with a family history of type 2 diabetes. Our data showed that small changes in LDL-cholesterol at baseline were still sufficient to observe differences between CIMT progressors and non-progressors. It is important to note that only 5 participants (all male) had a clinically abnormal level of LDL-cholesterol level (above the 90th
percentile for sex and age) (26
) and 3 of these 5 participants had family histories of hypercholesterolemia. Studies have shown that children with a familial hypercholesterolemia consistently had increased CIMT compared with healthy controls (22
). Based on these studies, we repeated our analyses excluding the 5 participants with abnormal high LDL-cholesterol. We found that baseline LDL- and total cholesterol was still higher in the Advanced CIMT Progression Group (89.3±4.1 mg/dL) versus those in the CIMT Non-progression group (76.5±3.3 mg/dL), after controlling for covariates but the difference was marginally significant (p=0.055), likely caused by a decrease in power.
The findings of our study demonstrate the clinical importance of pediatric risk assessment for sub-clinical atherosclerosis. Currently, there is no screening of subclinical atherosclerosis in high-risk youth, yet there have been recommendations made for asymptomatic adults above the age of 45, in other words, individuals who would theoretically have normative CIMT measures similar to the overweight youth we study. The Primary Prevention Writing Group III for the AHA Prevention Conference V stated the potential value of risk assessment when CIMT measures were used in conjunction with traditional risk factor assessments (27
). Given the growing literature on the early development of atherosclerosis in children, along with added predisposition to metabolic disorders, there may be reasons not to extend this recommendation to children. With respect to treatment, studies have reported improved vascular function and thickness in children that participated in interventions targeted for obesity reduction (28
). These results support the notion that all overweight children should have the opportunity to engage in physical activity and diet interventions in order to gain health benefits.
The strengths of this study include its longitudinal measures of subclinical atherosclerosis using the same sonographer and reader of the ultrasound images. Assessment of cardiovascular risk was done with clinical measures of total and regional body composition (DEXA and MRI scans) and direct measures of insulin sensitivity (FSIVGTT with minimal modeling). In addition, simple and clinically applicable measures using fasting blood were also employed. The use of a homogeneous sample of understudied minority youth contributes to the strengths of this report, but it also limits the generalizability of the results to overweight Latino adolescents with a family history of type 2 diabetes.
Several limitations must also be discussed. First, the moderate sample size and a short time frame of this longitudinal study may have impeded any other predictors of CIMT progression, particularly when one considers the large number of predictors analyzed. This limitation was addressed to some extent by building the multivariate statistical models with only a chosen number of predictors. Another limitation related to this small and highly specific group of overweight Latino youth was the narrow range of BMI change that this children incurred during the 2-year time frame. Most studies of subclinical atherosclerosis in overweight children have shown a relationship between adiposity and CIMT. In contrast, our study has been limited to a small BMI change and we were unable to show this relationship. Broadening the BMI range by adding lean participants would be beneficial to further examine the effects of BMI and adiposity. Lastly, we were unable to statistically control for other important covariates such as physical activity data or for C-reactive protein and other cardiovascular biomarkers, as we did not collect these data or assay blood for these proteins.
These findings extend our previous findings in which persistent metabolic syndrome, high blood pressure and high waist circumference were related to CIMT and suggest that LDL-cholesterol contributes to CIMT and its progression in overweight Latino youth.