Longitudinal trajectories of cholesterol from midlife through late life according to apolipoprotein E allele status
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Updated: Apr 21, 2026

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Published on: June 12, 2019
Brian Downer1, Steven Estus2, Yuriko Katsumata3
1Sealy Center on Aging, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555, USA. brdowner@utmb.edu.
Background:
Previous research indicates that total cholesterol levels increase with age during young adulthood and middle age and decline with age later in life. This is attributed to changes in diet, body composition, medication use, physical activity, and hormone levels. In the current study we utilized data from the Framingham Heart Study Original Cohort to determine if variations in apolipoprotein E (APOE), a gene involved in regulating cholesterol homeostasis, influence trajectories of total cholesterol, HDL cholesterol, and total: HDL cholesterol ratio from midlife through late life.
Methods:
Cholesterol trajectories from midlife through late life were modeled using generalized additive mixed models and mixed-effects regression models.
Results:
APOE e2+ subjects had lower total cholesterol levels, higher HDL cholesterol levels, and lower total: HDL cholesterol ratios from midlife to late life compared to APOE e3 and APOE e4+ subjects. Statistically significant differences in life span cholesterol trajectories according to gender and use of cholesterol-lowering medications were also detected.
Conclusion:
The findings from this research provide evidence that variations in APOE modify trajectories of serum cholesterol from midlife to late life. In order to efficiently modify cholesterol through the life span, it is important to take into account APOE allele status.
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