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Author Spotlight: Assessing the Cardiovascular Profile of Patients with Metabolic Syndrome
Published on: September 27, 2024
Juvenile idiopathic arthritis polygenic risk scores are associated with cardiovascular phenotypes in early adulthood:
Sarah L N Clarke1,2,3, Hannah J Jones4,5,6, Gemma C Sharp4,5,7
1MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK. sarah.clarke@bristol.ac.uk.
Insights
Genetic predisposition to juvenile idiopathic arthritis (JIA) is linked to cardiovascular risk factors, indicating elevated risk early in life. This highlights the importance of cardiovascular risk assessment in JIA patients.
Area of Science:
- Genetics and Cardiovascular Health
- Pediatric Rheumatology
- Public Health
Background:
- Growing concerns exist regarding the long-term cardiovascular health of individuals with juvenile idiopathic arthritis (JIA).
- This study investigates the association between JIA polygenic risk and early-life cardiovascular phenotypes.
Purpose of the Study:
- To assess the relationship between JIA polygenic risk scores (PRSs) and cardiovascular risk factors, atherosclerosis markers, and cardiac structure/function in young adults.
- To determine if these associations manifest early in life.
Main Methods:
- Constructed JIA PRSs for 2,815 participants using genome-wide association study data.
- Employed linear and logistic regression to analyze PRS association with cardiovascular phenotypes at age 24.
- Examined early-life manifestation of associations from age seven onwards.
Main Results:
- JIA PRS was significantly associated with diastolic blood pressure, insulin levels, HOMA2-IR, log hsCRP, waist circumference, fat mass index, and body mass index.
- Suggestive evidence of association between JIA PRS and anthropometric measures/diastolic blood pressure was observed from age seven.
- Findings were robust across multiple sensitivity analyses.
Conclusions:
- Genetic liability to JIA is associated with multiple cardiovascular risk factors, supporting increased cardiovascular risk in JIA.
- Cardiovascular risk appears to be a core feature of JIA, not solely secondary to disease activity or treatment.
- Cardiovascular risk counseling should be integrated into JIA patient care.
Background:
There is growing concern about the long-term cardiovascular health of patients with juvenile idiopathic arthritis (JIA). In this study we assessed the association between JIA polygenic risk and cardiovascular phenotypes (cardiovascular risk factors, early atherosclerosis/arteriosclerosis markers, and cardiac structure and function measures) early in life.
Methods:
JIA polygenic risk scores (PRSs) were constructed for 2,815 participants from the Avon Longitudinal Study of Parents and Children, using the single nucleotide polymorphism (SNP) weights from the most recent JIA genome wide association study. The association between JIA PRSs and cardiovascular phenotypes at age 24 years was assessed using linear and logistic regression. For outcomes with strong evidence of association, further analysis was undertaken to examine how early in life (from age seven onwards) these associations manifest.
Results:
The JIA PRS was associated with diastolic blood pressure (β 0.062, 95% CI 0.026 to 0.099, P = 0.001), insulin (β 0.050, 95% CI 0.011 to 0.090, P = 0.013), insulin resistance index (HOMA2_IR, β 0.054, 95% CI 0.014 to 0.095, P = 0.009), log hsCRP (β 0.053, 95% CI 0.011 to 0.095, P = 0.014), waist circumference (β 0.041, 95% CI 0.007 to 0.075, P = 0.017), fat mass index (β 0.049, 95% CI 0.016 to 0.083, P = 0.004) and body mass index (β 0.046, 95% CI 0.011 to 0.081, P = 0.010). For anthropometric measures and diastolic blood pressure, there was suggestive evidence of association with JIA PRS from age seven years. The findings were consistent across multiple sensitivity analyses.
Conclusions:
Genetic liability to JIA is associated with multiple cardiovascular risk factors, supporting the hypothesis of increased cardiovascular risk in JIA. Our findings suggest that cardiovascular risk is a core feature of JIA, rather than secondary to the disease activity/treatment, and that cardiovascular risk counselling should form part of patient care.
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