Date of Award

January 2023

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Lubna Pal

Abstract

Objective: The primary objective was to examine if blood pressure (BP) indices are higher and if the prevalence of hypertension (HTN), indices of metabolic syndrome (MetS) and severe obesity are greater in women diagnosed with polycystic ovary syndrome (PCOS) versus age comparable Controls without PCOS diagnosis. The secondary objective was to examine if Non-Hispanic Black (NHB) race and Hispanic ethnicity were relevant to the relationship between PCOS diagnosis and outcomes. Methods: This was a case-control study based on retrospective analysis of cross-sectional data available in the electronic health record (EHR) of an academic tertiary care health care system. Utilizing ICD-10 diagnosis codes, eligible population (cases of PCOS and Controls [women with tubal and/or male factor infertility]) was identified from overall sample of women older than 18 years seeking reproductive health care at a subspecialty practice between October 07, 2011, through December 01, 2021. Individuals for whom information on BP measures and body mass index (BMI) were captured at the time of or following the diagnosis of PCOS or tubal/ male factor infertility were included. We examined the association between diagnosis of PCOS with BP indices, with diagnostic American College of Cardiology (ACC)/ American Heart Association (AHA) defined criteria for BP (elevated BP [ Stage 0 HTN], Stage 1 HTN, Stage 2 HTN, and overall HTN [Stages 1 and 2]), with World Health Organization (WHO) defined classes of obesity, and with pre-MetS (comprised of 2/5 of the International Diabetes Federation [IDF] MetS criteria. Interaction between obesity indices and PCOS diagnosis for BP specified outcomes were found, and analyses examining the relationship between PCOS diagnosis and BP were stratified by BMI (obese, BMI ≥ 30 kg/m2) vs non-obese, BMI < 30 kg/m2). Multivariable linear regression analyses stratified by BMI and adjusting for age, race and ethnicity examined the relationship between PCOS diagnosis (independent variable of interest, versus Controls) and BP indices (continuous data). Multivariable binary logistic regression analyses similarly stratified by BMI and adjusted for age, race and ethnicity examined the association between PCOS diagnosis and dichotomized BP outcomes (elevated BP (Stage 0 HTN), HTN [Stages 1 and 2 HTN]) in the population with BMI ≥ 30 kg/m2 and the population with BMI <30 kg/m2. Multivariable binary logistic regression models adjusting for age, race, and ethnicity were also used to examine the association between PCOS diagnosis and metabolic indices (pre-MetS, severe obesity) in the overall population. The associations are presented as adjusted odds ratio (aOR) and 95% confidence interval (CI) for logistic regression analyses and as β coefficient (SEM) for linear regression analyses. Statistical analyses were performed using SPSS (version 28.0) and a two-sided p value of <0.05 was deemed to reflect statistical significance. Results: After exclusion, 4,479 women with PCOS (Cases) and 771 women with male factor and/or tubal infertility (Controls) were identified by diagnostic codes. Women with PCOS were younger and were of significantly higher BMI than the Controls. On multivariable binary logistic regression analysis adjusting for race, ethnicity, and age, PCOS was associated with an increased likelihood of meeting ACC/ AHA defined criteria for HTN (aOR 1.36, 95% CI 1.05-1.75) in the population with BMI ≥ 30 kg/m2. The association between NHB race and increased likelihood of meeting criteria for HTN (aOR 1.57, 95% CI 1.14-2.17) was only evident in the population with BMI <30 kg/m2, whereas the association between Hispanic ethnicity and HTN showed a divergent relationship in the context of obesity. Interestingly, Hispanic ethnicity was associated with a decreased likelihood of meeting ACC/AHA criteria for Stage 1 HTN (aOR 0.59, 95% CI 0.46-0.75) in the population with BMI ≥ 30 kg/m2 and an increased likelihood of meeting ACC/AHA criteria for Stage 1 HTN (aOR 1.52, 95% CI 1.04-2.24) in the population with BMI < 30 kg/m2. On multivariable binary logistic regression models adjusting for race, ethnicity, and age, PCOS (aOR 2.25, 95% CI 1.77-2.87) and NHB race (aOR 1.83, 95% CI 1.53-2.20) were associated with increased likelihood of meeting criteria for pre-MetS, whereas Hispanic ethnicity was not associated with meeting criteria for pre-MetS. Further, women with PCOS were 6-fold more likely to have severe obesity compared to Controls (class 3 obesity (BMI >40 kg/m2, aOR=6.29, 95% CI=4.60-8.61). Conclusions: In a large population of reproductive age women, we found that PCOS was associated with numerous risk factors for CVD, including an increased likelihood of meeting clinically relevant criteria for HTN and 2/5 of the criteria for MetS. Women with PCOS were also more likely to have more severe obesity compared to Controls. NHB race was independently associated with increased likelihood of HTN (in the population with BMI < 30 kg/m2), increased likelihood of meeting criteria for pre-MetS, and obesity.

Comments

This thesis is restricted to Yale network users only. It will be made publicly available on 07/24/2025

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