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Published on: November 10, 2017
HDL (High-Density Lipoprotein) Subclasses, Lipid Content, and Function Trajectories Across the Menopause Transition:
Samar R El Khoudary ( سمر رياض الخضري )1, Xirun Chen (陈曦润)1, Alexis Nasr ( ألكسس نصر )1
1Graduate School of Public Health (S.R.E., X.C., A.N., M.M.B., T.J.O.), University of Pittsburgh, PA.
Insights
High-density lipoprotein (HDL) cholesterol levels rise during menopause transition, but HDL particle subclasses and function decline, potentially increasing cardiovascular risk. Changes around the final menstrual period are particularly notable.
Area of Science:
- Cardiovascular Science
- Endocrinology
- Lipid Metabolism
Background:
- The cardioprotective role of high-density lipoprotein (HDL) cholesterol after menopause is debated.
- HDL subclasses, lipid composition, and functionality may offer superior cardiovascular risk prediction compared to standard HDL cholesterol.
- Characterization of these HDL parameters during the menopause transition (MT) relative to the final menstrual period is lacking.
Purpose of the Study:
- To characterize changes in HDL particle subclasses, lipid content, and cholesterol efflux capacity (HDL-CEC) across the menopause transition.
- To investigate the timing of these HDL changes in relation to the final menstrual period.
- To assess the association between HDL measures and HDL-CEC throughout the MT.
Main Methods:
- Longitudinal study of 471 women across the menopause transition.
- Measurement of HDL particle (HDL-P) subclasses, HDL size, HDL phospholipids, HDL triglycerides, and HDL-CEC using nuclear magnetic resonance spectroscopy and other assays.
- Data collected at up to 5 time points per participant across the MT.
Main Results:
- HDL cholesterol and total HDL-P concentrations increased during the MT.
- Large HDL-P and HDL size decreased, while small HDL-P and HDL triglycerides increased within 1-2 years around the final menstrual period.
- HDL-CEC per HDL-P declined, indicating reduced function per particle, despite an overall increase in HDL-CEC.
Conclusions:
- Menopause transition is associated with adverse shifts in HDL subclasses and function, despite rising HDL cholesterol.
- The efficiency of large HDL particles in promoting cholesterol efflux may decrease during the MT.
- These functional changes in HDL during menopause may have implications for cardiovascular risk.
Objective:
The cardioprotective capacity of HDL (high-density lipoprotein) cholesterol postmenopause has been challenged. HDL subclasses, lipid contents, and function might be better predictors of cardiovascular risk than HDL cholesterol. Changes in these measures have not been characterized over the menopause transition (MT) with respect to timing relative to the final menstrual period. Approach and Results: Four hundred seventy-one women with HDL particle (HDL-P) subclasses (nuclear magnetic resonance spectroscopy total, large, medium, and small HDL-P and HDL size), HDL lipid content (HDL phospholipids and triglycerides), and HDL function (cholesterol efflux capacity [HDL-CEC]) measured for a maximum of 5 time points across the MT were included. HDL cholesterol and total HDL-P increased across the MT. Within the 1 to 2 years bracketing the final menstrual period, large HDL-P and HDL size declined while small HDL-P and HDL-triglyceride increased. Although overall HDL-CEC increased across the MT, HDL-CEC per HDL-P declined. Higher concentrations of total, large, and medium HDL-P and greater HDL size were associated with greater HDL-CEC while of small HDL-P were associated with lower HDL-CEC. Associations of large HDL-P and HDL size with HDL-CEC varied significantly across the MT such that higher large HDL-P concentrations and greater HDL size were associated with lower HDL-CEC within the 1 to 2 years around the final menstrual period.
Conclusions:
Although HDL cholesterol increased over the MT, HDL subclasses and lipid content showed adverse changes. While overall HDL-CEC increased, HDL-CEC per HDL-P declined, consistent with reduced function per particle. Large HDL-P may become less efficient in promoting HDL-CEC during the MT.
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