Abstract MP36: Changes in High-density Lipoprotein (hdl) Subclasses and Particle Size Over the Menopause Transition are Associated With Higher Levels of Complement Proteins C3 and C4. The Study of Women's Health Across the Nation Hdl Ancillary Study

Objective: High density lipoprotein (HDL) is emerging as a key player in modulating inflammation-related response impacting atherosclerosis development. HDL carries multiple proteins with direct roles in complement system activation including C3 and C4. Postmenopausal women have higher levels of C3 than premenopausal women suggesting a role of the menopause transition (MT) in modulating complement proteins. Preliminary work showed significant declines in large HDL particles (HDL-P) and overall HDL particle size, but increases in small HDL-P during the MT. Whether these changes contribute to higher levels of C3 reported after menopause is not known. Our objectives were to test whether C3 and C4 increase around the final menstrual period (FMP) and whether changes in HDL subclasses over the MT associate with C3 and C4 levels in midlife women. Design: We evaluated 558 women (at baseline: age 49.9(2.8) years; 86.6% perimenopausal) who had nuclear magnetic resonance spectroscopy HDL subclasses, C3 and C4 measured up to 5 times over the MT. Piecewise linear mixed-effects models were used to estimate and compare yearly changes in C3 and C4 at 3 time segments relative to the FMP. Linear mixed effect models were used to test associations between changes in each HDL subclass and overall HDL particle size with C3 and C4 separately. Results: Adjusted annual changes in C3 and C4 varied by time segments relative to FMP with significant increases only observed within 1 year before to 2 years after the FMP ( Figure ). These changes were significantly greater than changes in the other 2 time segments. Greater decreases in large and increases in small HDL-P concentrations and decreases in the overall size of HDL-P were independently associated with higher levels of C3 and C4 over time ( Table ). Conclusions: Complement proteins C3 and C4 significantly rise around menopause with C3 showing the steepest rise. Changes in HDL subclasses and overall size over the MT may play role in modulating inflammation responses known to be related to atherosclerosis.

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HDL (High-Density Lipoprotein) Subclasses, Lipid Content, and Function Trajectories Across the Menopause Transition

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.120.315355 ◽

2020 ◽

Author(s):

Samar R. El Khoudary ◽

Xirun Chen ◽

Alexis Nasr ◽

Jeff Billheimer ◽

Maria Mori Brooks ◽

...

Keyword(s):

High Density Lipoprotein ◽

Lipid Content ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

High Density ◽

Menstrual Period ◽

Resonance Spectroscopy ◽

Hdl Function ◽

Menopause Transition ◽

And Function

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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The effects of nicotinic acid treatment on high density lipoprotein particle size subclass levels in hyperlipidaemic subjects

Atherosclerosis ◽

10.1016/0021-9150(90)90166-g ◽

1990 ◽

Vol 83 (2-3) ◽

pp. 207-216 ◽

Cited By ~ 18

Author(s):

Jan Johansson ◽

Lars A. Carlson

Keyword(s):

Particle Size ◽

High Density Lipoprotein ◽

Nicotinic Acid ◽

Acid Treatment ◽

Density Lipoprotein ◽

High Density ◽

High Density Lipoprotein Particle ◽

Lipoprotein Particle ◽

Lipoprotein Particle Size

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Abstract 3645: Alcohol Volume, Not Drinking Frequency, Increases Plasma High-Density Lipoprotein Sub-Class Particle Concentration

Circulation ◽

10.1161/circ.116.suppl_16.ii_827-b ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Linton R Harriss ◽

Dallas R English ◽

Rory Wolfe ◽

Andrew M Tonkin ◽

Kerin O’Dea ◽

...

Keyword(s):

High Density Lipoprotein ◽

Alcohol Intake ◽

Particle Concentration ◽

Density Lipoprotein ◽

High Density ◽

Resonance Spectroscopy ◽

Cross Sectional ◽

Men And Women ◽

Beverage Type ◽

Drinking Frequency

Introduction: Alcohol intake is positively associated with high-density lipoprotein (HDL) cholesterol, however no studies have investigated the association with lipoprotein sub-classes using nuclear magnetic resonance spectroscopy (NMR). Hypothesis: We assessed the hypothesis that usual daily alcohol intake (volume), beverage type and drinking frequency influence plasma HDL sub-class concentrations as determined by NMR. Methods: Six hundred and ninety volunteers (389 women) aged 40 – 69 years at baseline (1990 –1994) participated in a cross-sectional study using the Melbourne Collaborative Cohort Study, Australia. Measures included self-reported alcohol intake using beverage-specific quantity-frequency questions (volume) and a drinking diary for previous week (frequency). Results: Median alcohol intake was 15.2 g/d (2.7, 32.0) for men and 1.0 g/d (0, 9.6) for women. Alcohol volume was positively associated with total HDL particle concentration in men and women. For men, a 10 g/d increment in alcohol intake increased total HDL particle concentration by 0.62 μmol/L (95% CI: 0.27, 0.98) and small HDL particle concentration by 0.34 μmol/L (0.01, 0.68). For women, total HDL particle concentration increased 1.06 μmol/L (0.60, 1.53) for every 10 g/d increment in alcohol intake. Alcohol volume was positively associated with large HDL particle concentration in premenopausal women [0.67 μmol/L (0.19, 1.15)] and small HDL particle concentration in postmenopausal women [0.82 μmol/L (0.14, 1.51)]. Beer, wine and spirits were all positively associated with total HDL concentration for men. Beer and wine were both positively associated with total HDL concentration for women. Drinking frequency was not associated with total HDL particle concentration or any of its’ sub-classes. Conclusions: Alcohol volume (and not drinking frequency) was positively associated with NMR-determined plasma total HDL particle concentration for men and women. These associations appeared to be regardless of beverage type, although comparison of beverage types was not possible for women. These results suggest that for any given weekly volume of alcohol, the number of drinking days does not influence HDL particle concentration.

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