High Cholesterol in the Womb May Affect Adult Levels

Marlene Busko

October 21, 2013

MONTREAL, QC — The risk for high cholesterol in adults may be partly explained by intrauterine exposure to high cholesterol, researchers presenting a new study at the Canadian Cardiovascular Congress (CCC) 2013 say[1].

Using multigenerational data from the Framingham Heart Study , they found that if mothers had high prepregnancy LDL levels (a surrogate for intrauterine exposure), their offspring had a fivefold higher risk of having dyslipidemia themselves, as young adults—independent of obesity, smoking, and genetic risk factors for high LDL cholesterol.

This study hints that epigenetics—where genes are switched on or off by environmental factors such as exposure to high cholesterol in the womb—may have a lasting effect on regulating cholesterol levels decades later. Importantly, other research suggests that this is a potentially modifiable risk factor, Dr Michael Mendelson (Boston Children's Hospital, MA) told the audience.

The findings were stronger than expected, he commented to heartwire . Young women of childbearing age who have dyslipidemia need to be identified, and they should follow a healthy lifestyle to reduce their LDL cholesterol, "not only for themselves but also for their [future] children."

The group is conducting further studies to see if DNA methylation—one way that the genome can be modified without changing the nucleotide sequence—might explain the effect, Mendelson added.

Session moderator Dr Sylvia Abadir (Sainte-Justine Mother and Child University Hospital Centre, Montreal, QC) said that this study opened her eyes about epigenetics—by showing that "the child that is born is not just the result of heredity. . . . What the mother is going through has repercussions on the child." Dyslipidemia is so prevalent and such a key risk factor for heart disease that being able to modify or reverse this risk would have important implications, she noted.

High LDL Cholesterol in the Womb

According to NHANES data from 2007 to 2008, about one in four women of childbearing age has high LDL cholesterol, defined as being above 3.36 mmol/L (130 mg/dL), Mendelson explained. The current study was the first to look at the general adult population to determine whether lipid levels in adults are affected by exposure to high intrauterine lipid levels.

From about 9000 offspring in second- and third-generation cohorts of the Framingham Heart Study, the researchers identified 493 individuals whose mothers had total-cholesterol and LDL-cholesterol levels determined before pregnancy. The mothers also had lipid levels determined concurrently with their young-adult offspring.

The mothers had a baseline age of around 31, a body-mass index (BMI) of around 22.9, and about 49% were smokers. The offspring had a mean age of about 24.2, a BMI of about 24.2, and about 26% were smokers.

The offspring had a 3.1-fold increased risk of having hypercholesterolemia—total cholesterol above 5.17 mmol/L (200 mg/dL)— if their mothers had hypercholesterolemia prior to pregnancy.

Their risk was only 1.9-fold higher if their mothers had hypercholesterolemia after pregnancy.

If their mothers had high LDL cholesterol—above 3.36 mmol/L—prepregnancy, young adults had a fivefold higher risk of having this type of dyslipidemia themselves. The risk was attenuated but still significant after accounting for obesity, smoking, and genetic variants associated with LDL cholesterol.

Odds of Offspring Dyslipidemia With Maternal Dyslipidemia*

Adjusted for Odds ratio (95% CI) p
Age and sex (M1) 5.0 (2.2–11.1) <0.0001
M1 + BMI + smoking (M2) 4.7 (2.0–10.9) 0.0004
M2 + genetic risk score 3.7 (1.5–9.0) 0.004

*Dyslipidemia=LDL cholesterol >3.36 mmol/L

The enhanced risk of offspring dyslipidemia was about twice as high if the mothers had high LDL cholesterol before pregnancy as opposed to after pregnancy.

Adult offspring without prebirth exposure to high LDL cholesterol had LDL-cholesterol levels that were 0.5 mmol/L lower. This is "a potentially clinically meaningful difference," according to Mendelson, since a meta-analysis of randomized controlled trials of statins showed that a similar drop in LDL cholesterol was linked with a 20% decline in ischemic heart disease events.

In reply to a question from the audience asking, "What about the fathers?" he explained that in a follow-up study that they plan to present at the American Heart Association meeting, so far, they found that whereas the effect of high maternal prebirth LDL cholesterol on offspring lipid levels persisted, even after corrections for obesity and genetic risk, the effect of high paternal LDL cholesterol did not.

Mendelson had no conflict of interest to declare.

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