Pregnant women with elevated LDL cholesterol have offspring whose cholesterol levels are increased already at 6 to 13 years of age. Cholesterol levels in pregnant women and children with and without familial hypercholesterolemia (FH) is the main focus of Jacob Juel Christensen‘s PhD thesis.
- LDL cholesterol is higher in 6-to-13-year-old children whose mothers had high LDL cholesterol in early pregancy than in offspring whose mothers had low LDL cholesterol.
- Children with maternally inherited familial hypercholesterolemia (FH) do not have higher LDL cholesterol levels than to children with FH inherited from their father.
- FH children have increased levels of pro-inflammatory monocytes in the circulation compared to healthy children, but only if their HDL cholesterol levels are low.
Thesis: Early life cholesterol exposure in children with familial hypercholesterolemia and healthy children
Candidate: Jacob Juel Christensen
Time: August 22, 2017 at 13:15
Place: Oslo University Hospital, Rikshospitalet B: Seminar room 1 (B2.U001)
Link to university website (in Norwegian)
Familial hypercholesterolemia (FH) is caused by a gene mutation, and causes high levels of circulating LDL cholesterol from the first year of life. Individuals with FH have significantly increased risk of cardiovascular disease and death from cardiovascular disease.
(1) Non-statin treated children with maternally inherited FH did not have significantly different plasma levels of LDL cholesterol, total cholesterol, HDL cholesterol or C-reactive protein (CRP) than children with paternal FH inheritance. Thus, lifelong exposure to hypercholesterolemia is probably the main driver of atherosclerosis in FH, rather than from which parent the condition is inherited.
The study included 1063 Norwegian and Dutch FH children younger than 20 years old.
(3) Children with FH have a shift in monocyte subset, characterized by more pro-inflammatory monocytes and less classical monocytes circulating in the blood. The shift was only evident in the half of FH children who had the lowest levels of HDL cholesterol. No difference in the proportion of lymphocyte subpopulation was found between FH and control children.
The results support the notion that FH children have increased inflammatory burden and ongoing early atherosclerosis from childhood, and suggest activation of monocytes at a very early stage of human atherosclerosis. All children included were between 6 and 15 years old, and 23 children with FH were compared with 20 healthy children.
(2) A clinically relevant difference in LDL cholesterol levels were found between healthy children whose mothers had high LDL cholesterol levels at gestational week 14 to 16, compared to children of mothers with low levels of LDL cholesterol. The association was independent of birth weight, and no other measured cardiovascular risk factor differed between the two groups of children.
Only women with the 10 % highest and the 10 % lowest LDL cholesterol levels were included in the study. Christensen and co-workers conclude that affected children may be at increased cardiovascular risk, and encourage pregnant women with hypercholesterolemia and their children to implement a cholesterol-lowering lifestyle.
(1) Narverud, I., van Lennep, J. R., Christensen, J. J., Versmissen, J., Gran, J. M., Iversen, P. O., Aukrust, P., Halvorsen, B., Ueland, T., Ulven, S. M., Ose, L., Veierød, M. B., Sijbrands, E., Retterstøl, K., & Holven, K. B. (2015). Maternal inheritance does not predict cholesterol levels in children with familial hypercholesterolemia. Atherosclerosis, 243(1), 155-160.
(2) Christensen, J. J., Retterstøl, K., Godang, K., Roland, M. C. P., Qvigstad, E., Bollerslev, J., Ueland, T., Henriksen, T., & Holven, K. B. (2016). LDL cholesterol in early pregnancy and offspring cardiovascular disease risk factors. Journal of clinical lipidology, 10(6), 1369-1378.
(3) Christensen, J. J., Osnes, L. T., Halvorsen, B., Retterstøl, K., Bogsrud, M. P., Wium, C., Svilaas, A., Narverud, I., Ulven, S. M, Aukrust, P., & Holven, K. B. (2017). Altered leukocyte distribution under hypercholesterolemia: A cross-sectional study in children with familial hypercholesterolemia. Atherosclerosis, 256, 67-74.