Date of Award

January 2023

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

John A. Elefteraides

Abstract

Multiple indicators including low coronary artery calcium score, low carotid intimal media thickness, and low rates of myocardial infarction have previously suggested that ascending thoracic aortic aneurysm (ATAA) disease is protective against systemic late atherosclerosis. However, the mechanism of this paradoxical, protective effect is still unknown and may provide valuable insights into the fundamental pathophysiology of both ATAAs and atherosclerosis. Our aim was to investigate whether ATAA patient lipoprotein levels may help explain this anti-atherogenic phenomenon. To investigate this research question, we carried out a large case-control study in which we compared lipoprotein levels between 532 matched pairs of isolated ATAA patients and controls from the National Health and Nutrition Examination Survey (NHANES) database who were propensity-score matched on age, sex, smoking status, statin prescription, diabetes, hypertension, height, and weight. The absolute mean standardized difference between all covariates for the two groups was less than 10%, indicating excellent matching. A restricted cubic spline model revealed an inverse relationship between LDL levels and odds of ATAA. Lower LDL levels were associated with higher odds of ATAA compared to controls (odds ratio 1.7; 95% CI 1.3 – 2.4) and higher LDL levels were associated with lower odds of ATAA (odds ratio 0.5; 95% CI 0.4-0.6). There was a similarly negative relationship between total cholesterol level and odds of ATAA. We also compared HDL, triglyceride, and CRP levels. Given the known, driving effect of LDL on the development of atherosclerosis, this is a highly significant finding which may point to a mechanism for atherosclerotic protection in ATAA patients that is more upstream than previously hypothesized. A better understanding of the underlying mechanism for this paradoxical protection may advance our understanding of aneurysm disease, atherosclerosis, and potential therapeutic strategies to mitigate these diseases.

Comments

This thesis is restricted to Yale network users only. It will be made publicly available on 07/24/2024

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