Samar R El Khoudary1, Alexis Nasr1, Jeffrey Billheimer2, Maria M Brooks1, Dan McConnell3, Sybil Crawford4, Trevor J Orchard1, Daniel J Rader2, Karen A Matthews1,5. 1. Department of Epidemiology, University of Pittsburgh, Graduate School of Public Health, Pittsburgh, PA 15261, USA. 2. Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. 3. Department of Epidemiology, University of Michigan, Ann Arbor, MI 48109, USA. 4. Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA. 5. Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Abstract
CONTEXT: Novel metrics of high-density lipoprotein (HDL) (subclasses, lipid content, and function) may improve characterization of the anti-atherogenic features of HDL. In midlife women, changes in these metrics vary by time relative to the final menstrual period (FMP), supporting a contribution of estradiol (E2) and follicle-stimulating hormone (FSH). OBJECTIVE: We tested associations of endogenous E2 and FSH with novel HDL metrics and assessed whether these associations varied by time relative to FMP. METHODS: This study was a longitudinal analysis from the Study of Women's Health Across the Nation (SWAN) HDL study, using a community-based cohort of 463 women, baseline mean age 50.2 (2.7) years. The main outcome measures were HDL cholesterol efflux capacity (HDL-CEC), HDL phospholipids (HDL-PL), HDL triglycerides (HDL-Tg), HDL particles (HDL-P), HDL size, and HDL cholesterol (HDL-C). RESULTS: In multivariable analyses, E2 was positively associated with HDL size, large HDL-P, HDL-CEC, and HDL-Tg, but negatively with medium HDL-P (P values < 0.05). The positive association between E2 and HDL-Tg was stronger 2 years post-FMP than before, (interaction P = 0.031). FSH was positively related to total and medium HDL-P, but negatively to HDL size, large HDL-P, and HDL-CEC per particle (P values < 0.05). Associations of higher FSH with greater total HDL-P and smaller HDL size were only evident at/after menopause (interaction P values < 0.05). CONCLUSION: Some of the associations linking E2 and FSH with novel HDL metrics were vulnerable to time relative to menopause onset. Whether a late initiation of hormone therapy relative to menopause could have a detrimental effect on lipid content of HDL particles should be tested in the future.
CONTEXT: Novel metrics of high-density lipoprotein (HDL) (subclasses, lipid content, and function) may improve characterization of the anti-atherogenic features of HDL. In midlife women, changes in these metrics vary by time relative to the final menstrual period (FMP), supporting a contribution of estradiol (E2) and follicle-stimulating hormone (FSH). OBJECTIVE: We tested associations of endogenous E2 and FSH with novel HDL metrics and assessed whether these associations varied by time relative to FMP. METHODS: This study was a longitudinal analysis from the Study of Women's Health Across the Nation (SWAN) HDL study, using a community-based cohort of 463 women, baseline mean age 50.2 (2.7) years. The main outcome measures were HDL cholesterol efflux capacity (HDL-CEC), HDL phospholipids (HDL-PL), HDL triglycerides (HDL-Tg), HDL particles (HDL-P), HDL size, and HDL cholesterol (HDL-C). RESULTS: In multivariable analyses, E2 was positively associated with HDL size, large HDL-P, HDL-CEC, and HDL-Tg, but negatively with medium HDL-P (P values < 0.05). The positive association between E2 and HDL-Tg was stronger 2 years post-FMP than before, (interaction P = 0.031). FSH was positively related to total and medium HDL-P, but negatively to HDL size, large HDL-P, and HDL-CEC per particle (P values < 0.05). Associations of higher FSH with greater total HDL-P and smaller HDL size were only evident at/after menopause (interaction P values < 0.05). CONCLUSION: Some of the associations linking E2 and FSH with novel HDL metrics were vulnerable to time relative to menopause onset. Whether a late initiation of hormone therapy relative to menopause could have a detrimental effect on lipid content of HDL particles should be tested in the future.
Authors: Samar R El Khoudary; Patrick M Hutchins; Karen A Matthews; Maria M Brooks; Trevor J Orchard; Graziella E Ronsein; Jay W Heinecke Journal: J Clin Endocrinol Metab Date: 2016-07-11 Impact factor: 5.958
Authors: Amit V Khera; Marina Cuchel; Margarita de la Llera-Moya; Amrith Rodrigues; Megan F Burke; Kashif Jafri; Benjamin C French; Julie A Phillips; Megan L Mucksavage; Robert L Wilensky; Emile R Mohler; George H Rothblat; Daniel J Rader Journal: N Engl J Med Date: 2011-01-13 Impact factor: 91.245
Authors: MaryFran R Sowers; Karen A Matthews; Mary Jannausch; John F Randolph; Daniel McConnell; Kim Sutton-Tyrrell; Roderick Little; Bill Lasley; Richard Pasternak Journal: J Clin Endocrinol Metab Date: 2005-08-16 Impact factor: 5.958
Authors: Samar R El Khoudary; Lin Wang; Maria M Brooks; Rebecca C Thurston; Carol A Derby; Karen A Matthews Journal: J Clin Lipidol Date: 2016-04-26 Impact factor: 4.766
Authors: Samar R El Khoudary ( سمر رياض الخضري ); Xirun Chen (陈曦润); Alexis Nasr ( ألكسس نصر ); Jeff Billheimer; Maria Mori Brooks; Dan McConnell; Trevor J Orchard; Sybil L Crawford; Karen A Matthews; Daniel J Rader Journal: Arterioscler Thromb Vasc Biol Date: 2020-12-03 Impact factor: 8.311
Authors: Anna C O'Kelly; Erin D Michos; Chrisandra L Shufelt; Jane V Vermunt; Margo B Minissian; Odayme Quesada; Graeme N Smith; Janet W Rich-Edwards; Vesna D Garovic; Samar R El Khoudary; Michael C Honigberg Journal: Circ Res Date: 2022-02-17 Impact factor: 17.367