Long term follow-up of adults has shown that obesity, and high blood pressure, cholesterol and blood sugar increase the risk for future heart attack and stroke. When these cardiovascular (CV) risk factors occur in clusters, the risk for CV disease is greater than if the risk based on individual factors were added. Similarly, autopsy studies in children and adolescents show that clusters of CV risk factors damage the heart and blood vessels well before clinical events occur. Whether ultrasound and other types of non-invasive studies can demonstrate cardiac damage and hardening of the arteries (accelerated CV aging) in adolescents and young adults related to CV risk factor clusters is not known. Furthermore, the normal rate of CV aging in youth must be documented before the effect of individual or clustered risk factors for CV aging can be established. The central hypothesis for this proposal is that more rapid CV aging (thicker heart and carotid arteries, decreased cardiac function, increased arterial stiffness, reduced arterial wall function) will occur over time in youth with CV risk factors, especially those that cluster with obesity such as type 2 diabetes mellitus, as compared to lean, low-risk subjects. This hypothesis will be tested by re-examination 5 to 7 years later, of a group of adolescents and young adults in whom baseline CV measurements (using ultrasound and other non- invasive tests) were already collected.
The aims are to 1) measure the rate of CV aging in adolescents and young adults and 2) determine which clusters of CV risk factors best predict accelerated CV aging (deterioration in CV structure and function). This study will address a knowledge gap by providing data describing the rate of normal CV aging in youth using non-invasive tests. This approach is valuable because it is impractical to measure CV risk factors in children and then follow them for decades until they experience heart attack or stroke. Using these non- invasive tests as the outcome, evidence-based cut-points can be developed to determine when aggressive treatment (like drug therapy) for pediatric CV risk factors should be initiated. This will improve upon the current guidelines which 1) set arbitrary levels defining an abnormal risk factor level that are not based on hard CV data and 2) only address a single risk factor at high level and do not account for the contribution of clusters of CV risk factors at borderline levels to risk for future CV disease. Furthermore, if proven effective in identifying accelerated CV aging, these non-invasive tests can be used to monitor effectiveness of treatment. Successful completion of this project will change the current paradigm in pediatric CV prevention from one of arbitrary cut- points for treatment to one of guidelines based on sound scientific study where primary CV prevention in children focuses aggressive intervention on youth with documented accelerated CV aging.

Public Health Relevance

In adults, clusters of cardiovascular (CV) risk factors such as obesity and high blood pressure, cholesterol and blood sugar increase the chances for heart attack and stroke. This project proposes to use ultrasound and other non-invasive tests to prove that accelerated CV aging (cardiac damage and hardening of the arteries) occurs in adolescents and young adults related to CV risk factor clusters. Successful completion of this project may lead to more accurate guidelines to determine when aggressive treatment (like drug therapy) for pediatric CV risk factors should be initiated to prevent future CV disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL105591-02
Application #
8209257
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Pemberton, Victoria
Project Start
2011-01-01
Project End
2015-12-31
Budget Start
2012-01-01
Budget End
2012-12-31
Support Year
2
Fiscal Year
2012
Total Cost
$580,497
Indirect Cost
$201,087
Name
Cincinnati Children's Hospital Medical Center
Department
Type
DUNS #
071284913
City
Cincinnati
State
OH
Country
United States
Zip Code
45229
Shah, Amy S; Gao, Zhiqian; Urbina, Elaine M et al. (2014) Prediabetes: the effects on arterial thickness and stiffness in obese youth. J Clin Endocrinol Metab 99:1037-43
Maahs, David M; Daniels, Stephen R; de Ferranti, Sarah D et al. (2014) Cardiovascular disease risk factors in youth with diabetes mellitus: a scientific statement from the american heart association. Circulation 130:1532-58
Gordon, Scott M; Davidson, W Sean; Urbina, Elaine M et al. (2013) The effects of type 2 diabetes on lipoprotein composition and arterial stiffness in male youth. Diabetes 62:2958-67
Shah, Amy S; Urbina, Elaine M; Khoury, Philip R et al. (2013) Lipids and lipoprotein ratios: contribution to carotid intima media thickness in adolescents and young adults with type 2 diabetes mellitus. J Clin Lipidol 7:441-5
Shah, Amy S; Dolan, Lawrence M; Gao, Zhiqian et al. (2011) Clustering of risk factors: a simple method of detecting cardiovascular disease in youth. Pediatrics 127:e312-8