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Blood pressure and cardiovascular disease in type 1 diabetes: an exploration of prediction and control

Guo, Jingchuan (2019) Blood pressure and cardiovascular disease in type 1 diabetes: an exploration of prediction and control. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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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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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee MemberBrooks, Maria
Committee MemberCostacou,
Committee MemberMuldoon, Matthew
Committee MemberNaimi, Ashely
Committee ChairOrchard, Trevor
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: 01 May 2024 05:15

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