Alexis Nasr1, Karen Matthews1,2, Imke Janssen3, Maria M Brooks1, Emma Barinas-Mitchell1, Trevor J Orchard1, Jeffrey Billheimer4, Norman C Wang5, Dan McConnell6, Daniel J Rader4, Samar R El Khoudary1. 1. Department of Epidemiology, University of Pittsburgh, School of Public Health, Pittsburgh, Pennsylvania, USA. 2. Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. 3. Department of Preventive Medicine, Rush University Medical Center, Chicago, Illinois, USA. 4. Departments of Medicine and Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. 5. Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. 6. Department of Epidemiology, University of Michigan, Ann Arbor, Michigan, USA.
Abstract
CONTEXT: The menopause transition is accompanied by declines in the atheroprotective features of high-density lipoprotein (HDL), which are linked to deleterious cardiovascular (CV) outcomes. OBJECTIVE: This work aimed to assess the relationship between abdominal and CV visceral adipose tissues (VAT) with future HDL metrics in midlife women, and the role of insulin resistance (IR) on these associations. METHODS: Temporal associations compared abdominal and CV fat with later measures of HDL metrics. This community-based cohort comprised 299 women, baseline mean age 51.1 years (SD: 2.8 years), 67% White, 33% Black, from the Study of Women's Health Across the Nation (SWAN) HDL ancillary study. Exposures included volumes of abdominal VAT, epicardial AT (EAT), paracardial AT (PAT), or perivascular AT (PVAT). Main outcomes included HDL cholesterol efflux capacity (HDL-CEC); HDL phospholipids (HDL-PL), triglycerides (HDL-Tgs), and cholesterol (HDL-C); apolipoprotein A-I (ApoA-I), and HDL particles (HDL-P) and size. RESULTS: In multivariable models, higher abdominal VAT was associated with lower HDL-CEC, HDL-PL, HDL-C, and large HDL-P and smaller HDL size. Higher PAT was associated with lower HDL-PL, HDL-C, and large HDL-P and smaller HDL size. Higher EAT was associated with higher small HDL-P. Higher PVAT volume was associated with lower HDL-CEC. The Homeostatic Model Assessment of Insulin Resistance partially mediated the associations between abdominal AT depots with HDL-CEC, HDL-C, large HDL-P, and HDL size; between PVAT with HDL-CEC; and PAT with HDL-C, large HDL-P, and HDL size. CONCLUSION: In midlife women, higher VAT volumes predict HDL metrics 2 years later in life, possibly linking them to future CV disease. Managing IR may preclude the unfavorable effect of visceral fat on HDL metrics.
CONTEXT: The menopause transition is accompanied by declines in the atheroprotective features of high-density lipoprotein (HDL), which are linked to deleterious cardiovascular (CV) outcomes. OBJECTIVE: This work aimed to assess the relationship between abdominal and CV visceral adipose tissues (VAT) with future HDL metrics in midlife women, and the role of insulin resistance (IR) on these associations. METHODS: Temporal associations compared abdominal and CV fat with later measures of HDL metrics. This community-based cohort comprised 299 women, baseline mean age 51.1 years (SD: 2.8 years), 67% White, 33% Black, from the Study of Women's Health Across the Nation (SWAN) HDL ancillary study. Exposures included volumes of abdominal VAT, epicardial AT (EAT), paracardial AT (PAT), or perivascular AT (PVAT). Main outcomes included HDL cholesterol efflux capacity (HDL-CEC); HDL phospholipids (HDL-PL), triglycerides (HDL-Tgs), and cholesterol (HDL-C); apolipoprotein A-I (ApoA-I), and HDL particles (HDL-P) and size. RESULTS: In multivariable models, higher abdominal VAT was associated with lower HDL-CEC, HDL-PL, HDL-C, and large HDL-P and smaller HDL size. Higher PAT was associated with lower HDL-PL, HDL-C, and large HDL-P and smaller HDL size. Higher EAT was associated with higher small HDL-P. Higher PVAT volume was associated with lower HDL-CEC. The Homeostatic Model Assessment of Insulin Resistance partially mediated the associations between abdominal AT depots with HDL-CEC, HDL-C, large HDL-P, and HDL size; between PVAT with HDL-CEC; and PAT with HDL-C, large HDL-P, and HDL size. CONCLUSION: In midlife women, higher VAT volumes predict HDL metrics 2 years later in life, possibly linking them to future CV disease. Managing IR may preclude the unfavorable effect of visceral fat on HDL metrics.
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