The Synergistic Effects of Menopause and HIV on Cardiovascular Disease Risk in Women

Project Summary/Abstract Understanding the contribution of menopause to clinical outcomes in HIV is an emerging health priority. There are over 20 million girls and women living with HIV (WWH) worldwide and over 50% of WWH in the US are experiencing the transition to menopause, a multi-year period characterized by declines in ovarian reserve that spans the premenopausal, perimenopausal, and postmenopausal phases. Perimenopause is a time of increased multi-morbidity risk, highlighting its importance as an optimal time for preventive interventions. HIV and menopause are independently associated with a higher burden of cardiovascular disease (CVD) and other comorbidities, but it is unclear whether HIV and menopause have synergistic effects. Studies of menopause in WWH have been impeded by the irregular menses and amenorrhea caused by chronic illness. As a result, it is unclear how menopause impacts CVD risk in WWH and whether perimenopause is a critical period for CVD prevention in WWH. This proposal leverages the NHLBI-funded MACS/WIHS Combined Cohort Study, which serially measures anti-Müllerian hormone, a biomarker of ovarian reserve, to precisely determine the pre-, peri- , and postmenopausal phases. The overall objective of this proposal is to determine the contribution of HIV and menopausal phase to CVD risk parameters (e.g., insulin resistance, lipids, hypertension) and subclinical atherosclerosis, and to examine the influences of immune activation and adiposity. The specific aims are (1) to determine the association of HIV and menopausal phase with CVD risk parameters; (2) to evaluate the association of HIV and menopausal phase with immune activation and whether immune activation mediates subclinical atherosclerosis using carotid imaging; and (3) to examine the association between MRI-measured adipose tissue volume and immune activation across the menopausal transition in WWH. Determining whether menopause and HIV have a synergistic effect on CVD risk could reveal mechanisms that drive CVD in WWH and identify therapeutic targets to prevent CVD. This K23 proposal also supports the career development of Dr. Rebecca Abelman, Assistant Professor of Medicine at the University of California San Francisco. Dr. Abelman’s long-term goal is to become an independent investigator studying ovarian aging and its role in comorbidity burden and organ dysfunction in WWH. Her short-term career goal is to examine the effect of menopausal phase on the development of cardiometabolic outcomes in WWH. To achieve her career goals, Dr. Abelman proposes training in (1) biomarker testing, analysis, and interpretation; (2) causal mediation and longitudinal data analysis; (3) imaging in patient-oriented studies of menopause and comorbidities; and (4) leading independent ancillary studies in large observational cohorts. To help guide her transition to career independence, Dr. Abelman has assembled a highly experienced mentorship team with deep expertise in HIV, menopause, the inflammatory consequences of HIV infection, biomedical imaging, and biostatistics.