Key Dates

Related Announcements

• PA-20-183 - NIH Research Project Grant (Parent R01 Clinical Trial Required)

• PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

Related Notices

• August 30, 2021 NHLBI Announces Interest in Promoting Cardiovascular and Cardiometabolic Health in Early Stages of the Lifecourse: Pre-adolescence Through Adolescence to Young Adulthood. See Notice NOT-HL-21-020

Issued by

National Heart, Lung, and Blood Institute (NHLBI)

Purpose

Purpose

This Notice of Special Interest (NOSI) calls for research to understand and promote cardiovascular and cardiometabolic health during transitionary phases across the lifecourse, from pre-adolescence (6-10 years) through adolescence (11-18 years) to young adulthood (19-39 years).

This initiative would support research to: 1) understand the mechanisms and the pathogenesis of cardiometabolic health and cardiovascular disease (CVD) risk in vulnerable groups throughout transitionary phases from pre-adolescence into adolescence and adolescence into young adulthood, and 2) develop precision prevention interventions (at the individual and populations levels) to address cardiovascular and cardiometabolic risk across these transitionary phases.

Background

Cardiometabolic and cardiovascular health declines during periods of critical growth, such as from adolescence through young adulthood. Several risk factors contribute to this decline, including modifiable health factors such as poor diet, sedentary lifestyle and physical inactivity, smoking (including vaping and second hand smoke), and obesity. Other risk factors, such as high blood pressure and impaired glucose and lipid metabolism, also contribute to the decline during adolescence into young adulthood.

Pediatric obesity is a leading risk factor contributing to cardiometabolic risk in adolescents. Roughly 20% of the pediatric population is obese, with 6.1% having severe obesity. Of these obese children, 70% have at least one cardiovascular risk factor, including hypertension, insulin resistance, dyslipidemia, and increased arterial stiffness and thickness. The cardiovascular risk factors that accumulate in obese youth act synergistically on CVD severity. Additionally, given the increased prevalence of childhood obesity among racial/ethnic minority groups, this also has long-term implications on disparities of cardiometabolic health outcomes into adulthood.

Obesity-related cardiometabolic risk factors, including type 2 diabetes, high blood pressure and dyslipidemia, are increasingly prevalent in adolescents, and these risk factors may continue through young adulthood. The mechanisms associated with these transitional factors are poorly understood. In addition, social determinants of health factors including socioeconomic disparities, adverse childhood experiences, neighborhood and environmental factors are major contributors to cardiometabolic health.

The combination of comorbidities such as obesity and hypertension, obesity and type 2 diabetes, or high blood pressure and dyslipidemia may persist and over time lead to cardiovascular diseases in young adulthood. Understanding these factors and trajectories of change in cardiometabolic health could provide information for targeting interventions. Modifiable lifestyle behaviors, such as physical inactivity and poor diet, which have key consequences for cardiometabolic health, are important intervention points during these transitionary periods of development. In addition, research is needed to understand epigenetic changes during adolescence and transition into young adulthood.

Overall, given that cardiometabolic risk factors act in concert and independently during youth to influence adult cardiometabolic health, it is critical to stimulate research into how the cardiometabolic risk factors that arise throughout transitionary phases of the lifespan from pre-adolescence through adolescence into young adulthood accelerate the pathogenic processes that give rise to adult CVD. A host of factors genetics, behavioral, psychosocial, environmental and socioeconomic may contribute to the progression and development of CVD-related processes in adolescence and into young adulthood, therefore increasing the risk for co-morbidities. The interrelationship between these factors and the key research questions that remain unanswered provide an area of opportunity for future research.

Note: the NHLBI only allows mechanistic clinical trials via the parent R01, Clinical Trial Required FOA (PA-20-183) or its reissue. Efficacy CTs in response to this NOSI submitted to NHLBI via the Parent R01, Clinical Trial Required FOA (PA-20-183) or its reissue will be withdrawn. Applicants interested in submitting an efficacy clinical trial to NHLBI should refer to NOT-HL-21-020 for more information.

Research topics within the scope of this NOSI may include but are not limited to:

• Research studies on the mechanisms by which physical, pubertal, familial, social, and behavioral changes of childhood/adolescence impinge on adult cardiometabolic health. Including, studies that examine resilience resources, that may mitigate the impact of adverse Social Determinants of Health (SDoH) in environments
• Studies to understand the modifiable SDoH factors that could have major impact on cardiometabolic health and the development of CVH disparities during adolescents and transition into adulthood
• Studies of mechanistic links between adult cardiovascular health and child-to-adult BMI and BP trajectories
• Identification and functional studies of genetic variants involved in pathogenesis of obesity-induced hypertension; gene-environment interaction studies of variants suspected of involvement
• Research studies examining metabolically healthy obesity (MHO) and its degeneration into metabolically unhealthy obesity (MUO) in adolescents during transition into young adulthood
• Studies elucidating the mechanisms underlying persistence of favorable cardiometabolic health into adulthood for youth with sustained obesity
• Age-period-cohort analyses addressing how different birth cohorts vary by exposure to CVD risk factors during childhood and how these varied exposures have conferred differential risk for CVD during adulthood
• Studies aiming to identify novel loci for shared genetic risk for both CHD and CVD
• Studies on epigenetic changes in pre-adolescents and adolescents and transition into young adulthood
• Research into the pathogenesis of CVD in vulnerable groups within the pediatric population
• Mechanistic trials assessing the timing of obesity/hypertension treatments and the extent to which they delay the deteriorative processes underlying CVD
• Studies that conduct secondary data analysis using data sets from cohorts such as CARDIA, ABCD, ECHO, and the Framingham Offspring Cohort to explore cardiovascular risk and comorbidities in pre-adolescents, adolescents, and young adults

Application and Submission Information

This notice applies to due dates on or after October 5, 2021 and subsequent receipt dates through June 5, 2026.

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcement through the expiration date of this notice.

• PA-20-183 - NIH Research Project Grant (Parent R01 Clinical Trial Required)
• PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allow)

NOTE: The NHLBI only permits mechanistic clinical trials via the Parent R01, Clinical Trial Required FOA (PA-20-183) or its reissue. Efficacy CTs in response to this NOSI submitted to NHLBI via the Parent R01, Clinical Trial Required FOA (PA-20-183) or its reissue will be withdrawn. Applicants interested in submitting an efficacy clinical trial on the topic of this NOSI to NHLBI should refer to NOT-HL-21-020 for more information.

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

• For funding consideration, applicants must include NOT-HL-21-015 (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.

Inquiries

Scientific/Research Contact(s)

Alison G.M. Brown, PhD, MS, RDN
National Heart Lung and Blood Institute (NHLBI)
National Institutes of Health
Telephone: 301 435 0583
Email: [email protected]

Laurie Donze, PhD
National Heart Lung and Blood Institute (NHLBI)
National Institutes of Health
Telephone: 301-827-1408
Email: [email protected]

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Julie Delgado
National Heart Lung and Blood Institute (NHLBI)
Telephone: 301-435-0833
Email: [email protected]