Cardiovascular Risk in Children With Chronic Conditions Study

Overview

Children living with chronic health conditions face a higher risk of developing cardiovascular diseases than their peers, largely due to the accelerated aging of the heart and blood vessels. Although experts recognize this elevated risk and recommend close monitoring and early intervention, the underlying mechanisms driving this phenomenon remain poorly understood. At present, no effective interventions specifically target its root causes. Recent research shows that both large blood vessels (such as the carotid artery) and small vessels (such as those in the retina) can display early signs of damage decades before clinically apparent heart or vascular disease emerges. This accelerated vascular aging can result from multiple factors - including disease-related processes such as persistent inflammation and metabolic disturbances, treatment-related effects such as chemotherapy or long-term steroid use, and lifestyle changes associated with chronic illness, such as reduced physical activity and altered eating habits. However, it is still unclear how these factors influence the development and progression of vascular changes in children as they grow. Importantly, these changes can be monitored through non-invasive methods, offering a unique opportunity to study at-risk patients many years before overt cardiovascular disease develops. Identifying these early changes may enable us to detect and track individuals at heightened risk well in advance of clinical disease. This study aims to deepen our understanding of the causes of increased cardiovascular risk in children with chronic conditions and to lay the groundwork for earlier, more targeted prevention strategies.

Primary outcome measures

• Arterial stiffness [Time frame: At baseline and at the time of annual follow-up]
• Endothelial function of the brachial artery [Time frame: At baseline and at the time of annual follow-up]
• Retinal vessel diameter [Time frame: At baseline and at the time of annual follow-up]
• Retinal vessel fractal dimension and tortuosity [Time frame: At baseline and at the time of annual follow-up]

Secondary outcome measures (2)

• Endothelial function in capillaries [Time frame: At baseline and at the time of annual follow-up]
• Retinal neurovascular coupling [Time frame: At baseline and at the time of annual follow-up]

Eligibility criteria

Inclusion criteria

• Individuals aged between 6 and 25 years;
• Diagnosed with a chronic childhood condition/disease associated with an increased risk of early cardiovascular disease;
• Provided informed consent (if over 18 years old) or had informed consent provided by their legal guardian (if under 18 years old) following appropriate information about the study.

Chronic childhood conditions/diseases associated with increased risk of early cardiovascular disease are defined according to the 2019 American Heart Association recommendations (https://doi.org/10.1161/CIR.0000000000000618), as well as other conditions/diseases for which at least two large-scale epidemiological studies have demonstrated an increased risk of cardiovascular disease.

Exclusion criteria

• Severe intellectual and developmental disability;
• Decompensated heart failure;
• Severe primary immunodeficiency;
• Ongoing intravenous chemotherapy;
• Infectious diseases posing a public health risk; or
• History of regular alcohol or drug use.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Hungary · 3 centers

• Semmelweis University, Department of Surgery, Transplantation and Gastroenterology — Budapest
• Semmelweis University, Pediatric Center — Budapest
• Semmelweis University, Institute of Preventive Medicine and Public Health — Budapest

Publications

• Hanssen H, Moholdt T, Bahls M, Biffi A, Siegrist M, Lewandowski AJ, Biondi-Zoccai G, Cavarretta E, Kokkvoll A, Lochen ML, Maestrini V, Pinto RS, Palermi S, Thivel D, Wojcik M, Hansen D, Van Craenenbroeck EM, Weghuber D, Kraenkel N, Tiberi M. Lifestyle interventions to change trajectories of obesity-related cardiovascular risk from childhood onset to manifestation in adulthood: a joint scientific s PMID 37491406
• Varley BJ, Nasir RF, Skilton MR, Craig ME, Gow ML. Early Life Determinants of Vascular Structure in Fetuses, Infants, Children, and Adolescents: A Systematic Review and Meta-Analysis. J Pediatr. 2023 Jan;252:101-110.e9. doi: 10.1016/j.jpeds.2022.08.033. Epub 2022 Aug 24. PMID 36029824
• Raitakari O, Pahkala K, Magnussen CG. Prevention of atherosclerosis from childhood. Nat Rev Cardiol. 2022 Aug;19(8):543-554. doi: 10.1038/s41569-021-00647-9. Epub 2022 Jan 5. PMID 34987194
• de Ferranti SD, Steinberger J, Ameduri R, Baker A, Gooding H, Kelly AS, Mietus-Snyder M, Mitsnefes MM, Peterson AL, St-Pierre J, Urbina EM, Zachariah JP, Zaidi AN. Cardiovascular Risk Reduction in High-Risk Pediatric Patients: A Scientific Statement From the American Heart Association. Circulation. 2019 Mar 26;139(13):e603-e634. doi: 10.1161/CIR.0000000000000618. PMID 30798614
• Jacobs DR Jr, Woo JG, Sinaiko AR, Daniels SR, Ikonen J, Juonala M, Kartiosuo N, Lehtimaki T, Magnussen CG, Viikari JSA, Zhang N, Bazzano LA, Burns TL, Prineas RJ, Steinberger J, Urbina EM, Venn AJ, Raitakari OT, Dwyer T. Childhood Cardiovascular Risk Factors and Adult Cardiovascular Events. N Engl J Med. 2022 May 19;386(20):1877-1888. doi: 10.1056/NEJMoa2109191. Epub 2022 Apr 4. PMID 35373933
• Townsend N, Kazakiewicz D, Lucy Wright F, Timmis A, Huculeci R, Torbica A, Gale CP, Achenbach S, Weidinger F, Vardas P. Epidemiology of cardiovascular disease in Europe. Nat Rev Cardiol. 2022 Feb;19(2):133-143. doi: 10.1038/s41569-021-00607-3. Epub 2021 Sep 8. PMID 34497402

Identifiers

NCT: NCT07086989 · NNGYK/00994-4/2025

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗