Guo, Jingchuan
(2019)
Blood pressure and cardiovascular disease in type 1 diabetes: an exploration of prediction and control.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
This is the latest version of this item.
Abstract
This dissertation provides, in a type 1 diabetes (T1D) cohort followed for 25 years, a comprehensive examination of both blood pressure (BP) as a cardiovascular disease risk predictor and the role of the renin-angiotensin system (RAS) inhibition in reducing cardiovascular risk. Data are from the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study of childhood-onset diabetes.
First, we observed that all five BP indices (systolic [SBP], diastolic [DBP], pulse [PP], mean arterial [MAP] and mid-blood pressure [MidBP]) predicted incident coronary artery disease (CAD) independently of other risk factors. Although PP was less effective in the entire cohort, its prognostic significance improved, and became comparable to SBP, in participants age 35 years and older and/or with poor glycemic control. This likely reflects an early onset of glycation-included vascular stiffening in T1D.
Second, using time-weighted variables that reflected long-term exposure to high BP from youth throughout midlife, we found dose-gradient associations of SBP, DBP and MAP with CAD outcomes, beginning at approximately 120, 80 and 90 mmHg, respectively. This suggests a lower BP goal (i.e.,120/80 mmHg) is needed than currently recommended (140/90 mmHg) for young T1D adults.
In the third analysis, an examination of the RAS inhibition effect on CAD outcomes in T1D, appropriate statistical methods (inverse probability treatment weight, marginal structural model, and causal mediation analysis) were used under a causal-inference framework. RAS inhibitors, but not β blockers or calcium channel blockers, reduced CAD risk, though the results did not reach statistical significance. Mediation analysis indicated that cardiovascular protective effect of RAS inhibitors was partially achieved through pathways beyond lowering BP and urinary albumin, the two prominent effects of this antihypertensive class. Though not significant, these findings suggest a greater potential for RAS inhibitors to offer superior cardioprotection, compared to β blockers and calcium channel blockers, in T1D.
Overall, the dissertation findings have contributed to filling some critical gaps in our understanding of the magnitude of cardiovascular risk associated with BP and how to effectively control hypertension in T1D. This body of work thus has important public health relevance, given the enormous contribution of cardiovascular disease to T1D mortality and morbidity.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
26 June 2019 |
| Date Type: |
Publication |
| Defense Date: |
11 December 2018 |
| Approval Date: |
26 June 2019 |
| Submission Date: |
13 March 2019 |
| Access Restriction: |
5 year -- Restrict access to University of Pittsburgh for a period of 5 years. |
| Number of Pages: |
159 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Public Health > Epidemiology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
None |
| Date Deposited: |
26 Jun 2019 17:51 |
| Last Modified: |
26 Jun 2019 17:51 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/36158 |
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Blood pressure and cardiovascular disease in type 1 diabetes: an exploration of prediction and control. (deposited 26 Jun 2019 17:51)
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