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The developmental origins of chronic rheumatic heart disease
Johan G Eriksson1, Eero Kajantie, David I W Phillips
1Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland; Department of General Practice and Primary Health Care, University of Helsinki, Finland; Vasa Central Hospital, Finland; Folkhälsan Research Centre, Helsinki, Finland; Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland.
Insights
A longer umbilical cord in utero may program increased susceptibility to chronic rheumatic heart disease, particularly mitral valve disease, following Streptococcus pyogenes infection.
Area of Science:
- Cardiovascular Science
- Developmental Biology
- Infectious Disease Epidemiology
Background:
- Prenatal programming influences adult health, with evidence linking in utero exposures to cardiovascular disease.
- Susceptibility to chronic rheumatic heart disease (CRHD) following Streptococcus pyogenes infection may be influenced by early developmental factors.
Purpose of the Study:
- To investigate whether early-life programming, specifically related to umbilical cord characteristics, influences the risk of developing chronic rheumatic heart disease (CRHD).
- To explore the association between umbilical cord length and CRHD, and its specific impact on mitral versus aortic valve disease.
Main Methods:
- A retrospective cohort study of 20,431 individuals born in Helsinki, Finland (1924-1944) was conducted.
- Hospital admissions and deaths related to CRHD were analyzed in relation to birth parameters, including umbilical cord length.
- Statistical analysis, including hazard ratios, was used to determine associations.
Main Results:
- A longer umbilical cord was significantly associated with an increased risk of CRHD (HR 1.23 per 10 cm increase, P=0.02).
- This association was particularly strong for mitral valve disease (HR 1.5, P<0.0001) but not for aortic valve disease (HR 1.0, P=0.97).
- Growing up in large households also increased the risk of CRHD.
Conclusions:
- Longer umbilical cords, with increased spiraling, may increase fetal cardiac workload, potentially predisposing heart valves to damage.
- The mitral valve's larger size and greater wall stress might explain its increased vulnerability to Streptococcus pyogenes-induced autoimmune processes.
- These findings suggest a potential prenatal programming mechanism for rheumatic heart disease susceptibility.
Objectives:
Programming is the phenomenon whereby the body's structures and functions are permanently set by nutrition and other influences during early development. There is increasing evidence that programming in utero initiates cardiovascular disease. We hypothesized that susceptibility to developing chronic rheumatic heart disease on exposure to Streptococcus pyogenes is programmed.
Methods:
We studied hospital admissions and deaths from chronic rheumatic heart disease in 20,431 people born in Helsinki, Finland, during 1924-1944. One hundred and one people, 56 men, and 45 women, had chronic rheumatic heart disease.
Results:
The disease was not associated with body or placental size at birth. It was, however, associated with a long umbilical cord so that the hazard ratio for the disease was 1.23 (95% CI 1.04-1.45, P = 0.02) for every 10 cm increase in cord length. This association was present in people with mitral valve disease, hazard ratio 1.5 (1.20-1.89, P < 0.0001), but not in people with aortic valve disease, hazard ratio 1.0 (0.76-1.33, P = 0.97). Growing up in large households increased the risk of rheumatic heart disease.
Conclusion:
Longer umbilical cords have more spirals and a greater density of spirals per unit of length. Increased spiraling will increase the resistance to flow and the pressure load on the fetal heart. This could affect the development of the heart's valves and make them more vulnerable to the autoimmune process initiated by Streptococcus pyogenes. The mitral valve may be more vulnerable than the aortic valve because the valve leaflets are larger and therefore have greater wall stress.
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