Reversing Vascular Dysfunction In Rheumatoid Arthritis: Peroxisome Proliferator-Activated Receptor Gamma Agonist Therapy Improves Augmentation Index But Not Endothelial Function

Michelle J. Ormseth¹, Aihua Bian², Annette M. Oeser², Andrew Cunningham², Ayumi Shintani², S. Bobo Tanner³ and C. Michael Stein⁴, ¹Rheumatology, Vanderbilt Medical Center, Nashville, TN, ²Vanderbilt Medical Center, Nashville, TN, ³Div of Rheumatology & Allergy, Vanderbilt Medical Center, Nashville, TN, ⁴School of Medicine, Division of Clinical Pharmacology, Vanderbilt Medical Center, Nashville, TN

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: Cardiovascular disease, insulin resistance, rheumatoid arthritis (RA) and rheumatoid arthritis, treatment

Session Information

Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis

Session Type: Abstract Submissions (ACR)

Background/Purpose: Rheumatoid arthritis (RA) is associated with insulin resistance and increased cardiovascular (CV) risk. Impaired vascular function, including arterial stiffness and endothelial dysfunction, is associated with insulin resistance and is an important CV risk factor. Pioglitazone, a thiazolidinedione PPAR-γ agonist insulin sensitizing drug, decreased CV risk in diabetes, but little is known about its CV effects in RA. We examined the hypothesis that treatment with pioglitazone would improve vascular function in RA patients.

Methods: We performed a 20-week, single center, randomized, double-blind, placebo-controlled, cross-over study. Patients with RA (n=34) and moderate disease activity on stable disease modifying anti-rheumatic drug therapy were randomized to drug sequence, receiving either pioglitazone 45mg daily or matching placebo for 8 weeks separated by a 4-week washout period and the alternative treatment for 8 weeks. We measured change in augmentation index, aortic pulse wave velocity, reactive hyperemia index, and blood pressure. High sensitivity C-reactive protein (CRP), and the homeostatic model assessment of insulin resistance (HOMA) were also measured. Intention-to-treat analysis and linear mixed-effects models were used to determine the treatment effect of pioglitazone.

Results: Pioglitazone reduced augmentation index by -4.7% units (95% CI, -7.9, -1.5% units) P=0.004 and diastolic blood pressure by -3.0 mmHg (-5.7, -0.2 mmHg) P=0.03, but did not significantly change aortic pulse wave velocity (P=0.33), reactive hyperemia index (P=0.46) or systolic blood pressure (P=0.45). The improvement in augmentation index and diastolic blood pressure were not mediated by pioglitazone’s effect on insulin resistance (HOMA) or inflammation (CRP).

Conclusion: Pioglitazone improves some indices of vascular function, including augmentation index and diastolic blood pressure in patients with RA.

Disclosure:

M. J. Ormseth,
None;

A. Bian,
None;

A. M. Oeser,
None;

A. Cunningham,
None;

A. Shintani,
None;

S. B. Tanner,
None;

C. M. Stein,

NIH,

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/reversing-vascular-dysfunction-in-rheumatoid-arthritis-peroxisome-proliferator-activated-receptor-gamma-agonist-therapy-improves-augmentation-index-but-not-endothelial-function/