Date of Award

January 2018

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Aldo Peixoto

Abstract

The purpose of this study was to investigate the different hemodynamic mechanisms underlying isolated diastolic hypertension (IDH) and systolic-diastolic hypertension (SDH) in a population of young healthy adults. We analyzed de-identified data from 207 subjects with diastolic hypertension from the ENIGMA study, a long-term prospective study of 1,668 young adults from university campuses in the United Kingdom. This dataset included age, gender, height, weight, waist size, body mass index (BMI), body surface area (BSA), peripheral and central blood pressure measurements and pulse pressures (PP), augmentation pressure (AP), augmentation index (AIx), ejection duration (ED), cardiac index (CI), stroke volume (SV), peripheral vascular resistance (PVR) and pulse wave velocities. After removing subjects who were taking vasotonic medications and those with incomplete hemodynamic information, we identified 49 subjects with IDH, defined as peripheral diastolic blood pressure (PDBP) ≥90 mmHg and peripheral systolic blood pressures (PSBP) <140 mmHg and 103 subjects with SDH defined as PDBP ≥90 mmHg and PSBP ≥140 mmHg. We performed multiple logistic regression and stepwise linear regression to determine what demographic, hemodynamic, and lab variables were associated with an increased likelihood that a subject would have IDH or increased PDBP respectively. Subjects were then grouped into tertiles of cardiac index (CI), indexed peripheral vascular resistance (PVRI), and carotid-femoral pulse wave velocity (PWVCF). Mean values of all hemodynamic measurements were compared across tertiles to elucidate different hemodynamic mechanisms underlying IDH and SDH. Compared to individuals with IDH, we found that subjects with SDH were significantly older (p=0.0176), taller (p=0.0079), and heavier (p=0.0025). Most subjects with IDH were female (33 out of 49 or 67% were female). In contrast, most subjects with SDH were male (66/103 or 64% were male). There were statistically significant differences in peripheral and central pressures, peripheral and central PP, CI, indexed stroke volume (SVI), PVRI, and pulse wave velocities between the two groups (p<0.01 for all comparisons). In our analysis of the entire cohort of 152 subjects we found statistically significant increases in peripheral PP (p=0.003) from the lowest to highest tertiles of CI, statistically significant decreases in peripheral PP (p<0.0001) between the lowest and highest tertiles of PVRI, and statistically significant increases in PSBP (p<0.0001), PDBP (p=0.0122), peripheral PP (p=0.0031), central systolic blood pressure (p<0.0001), central diastolic blood pressure (p=0.0062), and central PP (p=0.0056) going from the lowest to highest tertiles of PWVCF. We have demonstrated that IDH and SDH in young healthy individuals have significantly different hemodynamic characteristics, and that brachial blood pressure phenotypes encompass a heterogeneous set of hemodynamic features. Systolic hypertension was found to associate with increased CI and increased aortic stiffness, diastolic hypertension was associated with increases in peripheral vascular resistance, increased CI is associated with increased peripheral pulse pressure, and increased aortic stiffness is associated with both increased peripheral and central pulse pressure.

Comments

This thesis is restricted to Yale network users only. It will be made publicly available on 06/25/2100

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