Division of Cardiovascular Diseases Strategic Plan

Goals in Cardiovascular Clinical Problems or Disease States

2.2a. Develop and evaluate preventive and therapeutic strategies for cardiovascular risk factors for acquired heart disease beginning in childhood

Table of Contents

• Overview
• Strategies to Accomplish This Goal May Entail
  • Basic Research
  • Translational Research
  • Clinical Research
• Contributing Sources

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Overview

Every adult once had the heart of a child. It is becoming increasingly clear that unhealthy CV status in childhood, as manifested by identifiable factors, portends increased risk in adulthood. Identified risk factors include obesity, hypertension, hyperlipidemia, diabetes, smoking, sedentary lifestyle, and a high-fat, high-carbohydrate diet. We know that some risk factors track from childhood into adulthood, and that some risk factors are associated with adverse changes in intermediate cardiac end-points, such as carotid intimal-medial thickness. What we do not know is the extent to which risk factor reduction in childhood might lead to improvement in hard clinical end-points in adulthood, when to begin risk factor reduction, how best to reduce risk factors, and how much reduction might be needed to achieve clinical benefit years later.

Strategies to Accomplish this Goal May Entail:

Basic Research:

• Investigate biological mechanisms of the etiology of CV risk factors from fetus to adolescent.
• Evaluate in animal models the effect of maternal nutrition, including caloric intake, fat composition, and sodium intake on CV risk in the offspring.
• Encourage the use of existing and the development of novel animal models of fetal programming, pre-hypertension, pre-atherosclerosis, hypertension, and atherosclerosis in youth.
• Develop intermediate markers to assess the progression of atherosclerosis in juvenile animal models.
• Using established animal models of high-risk conditions, such as familial hypcholesterolemia (FH) or type 1 hyperlipidemia (extremely elevated triglyceride levels), identify potential therapeutic targets for preventing CV disease.
• Identify genetic markers associated with elevated CV risk factors.

Translational Research:

• Initiate mechanistic studies in children to understand the development of CV risk or protective factors and identify factors that predict or protect against future CV complications, such as hypertension, atherosclerosis, and dyslipidemia in later life.
• Identify and validate biomarkers to predict adverse vascular changes in children and adolescents and to monitor treatment effectiveness.
• Investigate time windows during development and throughout childhood when intervention might be effective in preventing/reducing CV risk, especially in high-risk children such as those with a strong family history of CV disease.
• Explore the CV risk factors and the impact of aggressive risk factor reduction in high-risk pediatric populations, such as those with cardiac transplant recipients, chronic renal disease, or lupus.

Clinical Research:

• Develop and support a long-term clinical research strategy to evaluate who should be treated with medication, at what age treatment should begin, and whether treating in infancy, childhood, or adolescence influences later CV outcomes.
• Conduct trials of lifestyle interventions during infancy, childhood and adolescence to prevent or reduce CV risk, such as weight control, increased physical activity, or dietary changes.
• Test novel pharmacologic approaches for pediatric hypertension.
• Create a new cohort of adults by pooling subjects from NHLBI-funded studies of children from 30+ years ago (e.g., Bogalusa, Muscatine, Princeton, Beaver County, Minnesota BP study) to evaluate the persistence of risk factors identified in childhood, the extent of subclinical atherosclerosis assessed noninvasively, and current clinical CV status. Evaluation of this cohort could answer one of the most critical questions in prevention: does the presence of risk factors in childhood lead to earlier and more severe atherosclerotic disease in adult life?

Contributing Sources:

• NHLBI Strategic Plan Goals 1 and 2
• Recommendations from the NHLBI Strategic Plan Level One Final Reports:
  • Vascular Diseases and Hypertension
• NHLBI Workshops and Working Groups:
  • NHLBI Long-term Plan for Research and Translation in Hypertension for Enhancing Public Health, 2005.
  • The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents, NHLBI, August 2004.
  • NHLBI Task Force Report on Research in Pediatric Cardiovascular Disease, May 2002.

September 2008