We demonstrated in this study that high-risk youth have increased vascular thickness and stiffness compared with low-risk youth. In addition, clustering cardiovascular risks into low- and high-risk groups is associated with abnormal vascular structure and function after adjustment for age, race, and gender. In our population, both risk-factor clustering and the modified PDAY score were associated with abnormal vascular structure and function, suggesting that clustering of cardiovascular risks is a reliable tool for assessing abnormal vascular function. Its simplicity compared with PDAY risk score assessment likely provides an advantageous tool for the clinician.
Clustering cardiovascular risks is an established method to predict atherosclerosis and coronary heart disease. The Framingham Heart Study first demonstrated the importance of multiple cardiovascular risk factors in the prediction of clinical coronary heart disease in adults.5
Similarly, other large cohort studies, such as the PDAY and Bogalusa Heart Study, also have used cardiovascular risks to predict preclinical atherosclerotic lesions on autopsy examinations in young and middle-aged adults.2,20
With the development of noninvasive cardiovascular-imaging techniques, autopsy studies are no longer the only means to detect preclinical cardiovascular changes in youth. Vascular imaging is an established method to detect early changes in vessel thickness and stiffness that relate to cardiovascular risk factors and an increased risk for coronary artery disease and stroke.21,22
In this study, we demonstrate for all noninvasive measures of the vasculature, that adolescents with 2 or more cardiovascular risk factors had thicker and stiffer vessels compared with their counterparts with 0 to 1 cardiovascular risk factors. The PDAY score also predicted abnormal vessel structure and function, suggesting that these studies are a valid method for assessing target organ damage in high-risk youth.
Previous work has shown that atherosclerosis begins in childhood and progresses to clinical coronary artery disease by the age of 30 years.18,23
Fatty streaks and plaque formation are the result of additive modifiable risk factors such as obesity, dyslipidemia, hypertension, and hyperglycemia.1
In the late 1990s, the Framingham Heart Study was the first to quantify the additive effect of cardiovascular risks to predict clinical coronary events.24
Subsequently, the PDAY score was developed for use in young people to assess the risk for atherosclerotic lesions using data from autopsy studies.8
These scores have been reproduced in different age groups.9,10,25
Although risk scoring is helpful, it can be time consuming. In this study, we demonstrate that a simple, yet practical, technique of risk-factor clustering into low- and high-risk groups also is associated with abnormalities in the vasculature.
We statistically compared low and high clustering risk scoring to the both a dichotomous and continuous PDAY score to determine which assessment was a better predictor of abnormal vasculature. Regression modeling demonstrated that clustering of cardiovascular risks explained more of the variance in carotid thickness and stiffness. For each measure, the low- and high-risk clustering score produced a higher R2 value compared with the PDAY score, except in the internal carotid, where R2 values were similar.
Finally, we assessed whether using other cardiovascular risk factors in our models could increase R2
values of each of the structure and function outcomes. Using BMI as single risk factor, and using a combination of BMI and BP, substituting homeostasis model assessment of insulin resistance for glucose and insulin or adding inflammatory markers did not improve our models. These findings suggest that adiposity is a major risk factor for adverse changes in the vasculature of adolescents. For the purposes of this article, only the model including BMI, BP, hyperglycemia, and lipid measurements was chosen so that it compares with the modified PDAY score. However, it should be noted, as documented in the Fourth Report of Blood Pressure Management in Children and Adolescents,14
adolescents with obesity and elevated BP are at significantly increased risk to develop other components of the metabolic syndrome (high triglycerides, low high-density lipoprotein, and hyperinsulinemia), suggesting that a comprehensive risk-factor profile should be assessed in these individuals.
This study has limitations. First, when developing an easy tool for clinicians, we included risk factors in the PDAY score. Thus, our clustering mechanism is not inclusive of all known cardiovascular risks. Inflammatory markers were omitted because they were not used in the PDAY score and are infrequently measured in pediatric patients. Smoking also was omitted from our clustering score because there were only 11 smokers in our population. Second, we found that in youth with 2 or more cardiovascular risk factors, higher carotid vascular thickness and stiffness compared with those with 0 to 1 risk factor. To date, normal values for this age group have not been established. Therefore, we can not say whether there are no vascular changes in the low-risk group. Finally, our cross-sectional design does not allow us detect when changes occur in the vasculature in relation to the development to risk factors. Similarly, we can not prove that increased cardiovascular risk factors lead to vasculature changes. Longitudinal evaluation is needed to make these conclusions.