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Multicenter Study
. 2018 Sep;38(9):2236-2244.
doi: 10.1161/ATVBAHA.118.311017.

HDL (High-Density Lipoprotein) Metrics and Atherosclerotic Risk in Women

Samar R El Khoudary  1 , Indre Ceponiene  2   3 , Saad Samargandy  1 , James H Stein  4 , Dong Li  2 , Matthew C Tattersall  4 , Matthew J Budoff  2
Affiliations
Multicenter Study

HDL (High-Density Lipoprotein) Metrics and Atherosclerotic Risk in Women

Samar R El Khoudary et al. Arterioscler Thromb Vasc Biol. 2018 Sep.

Abstract

Objective- HDL-C (high-density lipoprotein cholesterol) may not always be cardioprotective in postmenopausal women. HDL particles (HDL-P) via ion-mobility may better reflect the antiatherogenicity of HDL. Objectives were (1) to evaluate associations of HDL-C and ion-mobility HDL-P with carotid intima-media thickness (cIMT) and carotid plaque separately and jointly in women; and (2) to assess interactions by age at and time since menopause. Approach and Results- Analysis included 1380 females from the MESA (Multi-Ethnic Study of Atherosclerosis; age: 61.8±10.3; 61% natural-, 21% surgical-, and 18% peri-menopause). Women with unknown or early menopause (age at nonsurgical menopause ≤45 years) were excluded. Adjusting for each other, higher HDL-P but not HDL-C was associated with lower cIMT ( P=0.001), whereas higher HDL-C but not HDL-P was associated with greater risk of carotid plaque presence ( P=0.04). Time since menopause significantly modified the association of large but not small HDL-P with cIMT; higher large HDL-P was associated with higher cIMT close to menopause but with lower cIMT later in life. The proatherogenic association reported for HDL-C with carotid plaque was most evident in women with later age at menopause who were >10 years postmenopausal. Conclusions- Elevated HDL-C may not always be cardioprotective in postmenopausal women. The cardioprotective capacity of large HDL-P may adversely compromise close to menopause supporting the importance of assessing how the menopause transition might impact HDL quality and related cardiovascular disease risk later in life.

Keywords: atherosclerosis; carotid intima-media thickness; cholesterol; perimenopause; postmenopause.

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Figures

Figure 1
Figure 1. Difference in cIMT (μm) per 1 SD Greater A: HDL-C or HDL-P; B: Large HDL-P or Small HDL-P
* Adjusted for age, race, study site, menopausal status, BMI, SBP, smoking, physical activity, anti-hypertensive, lipid lowering medications, ever use hormone replacement therapy, IL-6 and CRP. † * + LDL-P. ‡ * + HDL-C and LDL-P BMI: body mass index; cIMT: carotid intima-media thickness; CRP: C-reactive protein; HDL-C: high-density lipoprotein cholesterol; HDL-P: high-density lipoprotein particles; IL-6: interleukin-6; LDL-P: low-density lipoprotein particle particles; SBP: systolic blood pressure.
Figure 1
Figure 1. Difference in cIMT (μm) per 1 SD Greater A: HDL-C or HDL-P; B: Large HDL-P or Small HDL-P
* Adjusted for age, race, study site, menopausal status, BMI, SBP, smoking, physical activity, anti-hypertensive, lipid lowering medications, ever use hormone replacement therapy, IL-6 and CRP. † * + LDL-P. ‡ * + HDL-C and LDL-P BMI: body mass index; cIMT: carotid intima-media thickness; CRP: C-reactive protein; HDL-C: high-density lipoprotein cholesterol; HDL-P: high-density lipoprotein particles; IL-6: interleukin-6; LDL-P: low-density lipoprotein particle particles; SBP: systolic blood pressure.
Figure 2
Figure 2. Interaction of Large HDL-P with Time since Menopause in relation with cIMT
* Adjusted for age, race, study site, menopausal status, BMI, SBP, smoking, physical activity, anti-hypertensive, lipid lowering medications, ever use hormone replacement therapy, IL-6, CRP, HDL-C, small HDL-P and LDL-P BMI: body mass index; cIMT: carotid intima-media thickness; CRP: C-reactive protein; HDL-C: high-density lipoprotein cholesterol; HDL-P: high-density lipoprotein particles; IL-6: interleukin-6.; LDL-P: low-density lipoprotein particle particles; SBP: systolic blood pressure.
Figure 3
Figure 3. Adjusted Odds Ratio (95% CI) of cPlaque Presence per 1 SD Greater HDL-C, HDL-P, Large HDL-P or Small HDL-P
* Adjusted for age, race, study site, menopausal status, BMI, SBP, smoking, physical activity, antihypertensive, lipid lowering medications, ever use hormone replacement therapy, IL-6 and CRP † * + LDL-P ‡ * + HDL-C and LDL-P BMI: body mass index; cPlaque: carotid plaque; CRP: C-reactive protein; HDL-C: high-density lipoprotein cholesterol; HDL-P: high-density lipoprotein particles; IL-6: interleukin-6; LDL-P: low-density lipoprotein particles; SBP: systolic blood pressure.
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