Open AccessThe Peroxisome Proliferator Activated Receptor‐γ Pioglitazone Improves Vascular Function and Decreases Disease Activity in Patients With Rheumatoid Arthritis
Author(s) -
Marder Wendy,
Khalatbari Shokoufeh,
Myles James D.,
Hench Rita,
Lustig Susan,
Yalavarthi Srilakshmi,
Parameswaran Aishwarya,
Brook Robert D.,
Kaplan Mariana J.
Publication year - 2013
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.113.000441
Subject(s) - medicine , pioglitazone , pulse wave velocity , rheumatoid arthritis , arterial stiffness , reactive hyperemia , placebo , diabetes mellitus , endocrinology , cardiology , gastroenterology , type 2 diabetes , blood pressure , pathology , vasodilation , alternative medicine
Background Rheumatoid arthritis ( RA ) is associated with heightened mortality due to atherosclerotic cardiovascular disease ( CVD ). Inflammatory pathways in RA negatively affect vascular physiology and promote metabolic disturbances that contribute to CVD . We hypothesized that the peroxisome proliferator activated receptor‐γ ( PPAR ‐γ) pioglitazone could promote potent vasculoprotective and anti‐inflammatory effects in RA . Methods and Results One hundred forty‐three non‐diabetic adult RA patients (76.2% female, age 55.2±12.1 [mean± SD ]) on stable RA standard of care treatment were enrolled in a randomized, double‐blind placebo controlled crossover trial of 45 mg daily pioglitazone versus placebo, with a 3‐month duration/arm and a 2‐month washout period. Pulse wave velocity of the aorta ( PWV ), brachial artery flow mediated dilatation ( FMD ), nitroglycerin mediated dilatation ( NMD ), microvascular endothelial function (reactive hyperemia index [ RHI ]), and circulating biomarkers of inflammation, insulin resistance, and atherosclerosis risk all were quantified. RA disease activity was assessed with the 28‐Joint Count Disease Activity Score ( DAS ‐28) C‐reactive protein ( CRP ) and the Short Form (36) Health Survey quality of life questionnaire . When added to standard of care RA treatment, pioglitazone significantly decreased pulse wave velocity (ie, aortic stiffness) ( P =0.01), while FMD and RHI remained unchanged when compared to treatment with placebo. Further, pioglitazone significantly reduced RA disease activity ( P =0.02) and CRP levels ( P =0.001), while improving lipid profiles. The drug was well tolerated. Conclusions Addition of pioglitazone to RA standard of care significantly improves aortic elasticity and decreases inflammation and disease activity with minimal safety issues. The clinical implications of these findings remain to be established. Clinical Trial Registration URL: ClinicalTrials.gov Unique Identifier: NCT 00554853.