Targeting Metabolic and Inflammatory Processes for Coronary Artery Disease Treatment and Prevention.
Abstract: There is a
lack of understanding of how glucose-insulin-potassium (GIK), exert its benefits in
subjects with coronary artery disease (CAD). There is an even greater gap in knowledge
on the relationship between a unique metabolic biomarkers, adiponectin, and CAD. The
aims of this project are: 1) To study the effect of GIK on C-reactive protein (CRP)
levels in subjects with acute coro... read morenary syndrome (ACS), and the association between CRP
and infarct size; 2) To investigate changes in adiponectin levels early in the course of
ACS and its relation to outcomes; and 3) To evaluate current evidence on the association
between adiponectin and primary and secondary CAD. For the first two aims we analyzed
data from the IMMEDIATE Trial on subjects with ACS. Three blood levels were drawn for
biomarkers measurements. Data was collected on infarct size and one-year outcomes. For
aim three we systematically reviewed studies reporting associations between adiponectin
and CAD. We evaluated different associations between primary and secondary events, and
between analyses that do and do not adjust for variables on the causal pathway between
adiponectin and CAD (intermediate variables). For Aim 1, 140 participants were included.
High sensitivity CRP (hs-CRP) values at 12 hours were lower in GIK group compared to
placebo (mean=0.65 mg/L in GIK, 0.84 mg/L in placebo, p=0.053). However, the rate of
change in hs-CRP did not differ by treatment arm using mixed model analysis. The 12 hour
hs-CRP levels were an independent predictor of infarct size. For aim 2, 120 participants
were included. Adiponectin levels decreased by -0.005 μg/mL per hour (p=0.035). No
association was found between adiponectin and outcomes. In aim 3, meta-analysis of
models that did not incorporate intermediate variables, risk of primary CAD events
decreased with higher adiponectin levels (relative risk [RR] 0.73; 95% confidence
interval [CI] 0.63-0.87). For secondary events maximum adjusted models showed that
higher adiponectin levels were associated with higher risk of another CAD event (RR
1.27; 95% CI 1.16-1.39). Results from this study suggests that GIK is less likely to
exert its benefits in subjects with ACS through an inflammatory pathway. It also
illustrates a modest response of adiponectin to the acute phase of ischemia. The
findings from the largest systematic review to date, which incorporated novel
approaches, show that while adiponectin was associated with less incidence CAD, it is
paradoxically linked to an increased risk of subsequent
Thesis (Ph.D.)--Tufts University, 2015.
Submitted to the Dept. of Clinical & Translational Science.
Advisor: Gordon Huggins.
Committee: Harry Selker, Ethan Balk, Jessica Paulus, Robin Ruthazer, Norma Terrin, and Joni Beshansky.
Keywords: Health education, Medicine, and Pharmaceutical sciences.read less