Background Endothelial dysfunction is an early step in the formation of atherosclerotic lesions and can be quantified by the degree of flow mediated vasodilation (FMD) of the brachial artery. FMD is a predictor of cardiovascular (CV) events in the general population (1% lower FMD is associated with 13% increase in risk of future CV events) and is lower in patients with inflammatory joint diseases (IJD) compared to the general population. Furthermore, restoration of endothelial function to normal levels has been proposed as one of the important factors being involved in the regression of atherosclerotic plaques.
Objectives Our aim was to investigate the effect of long-term rosuvastatin therapy on FMD in patients with IJD and who had carotid artery plaque(s). Furthermore, we evaluated associations between change in FMD (ΔFMD) and change in carotid plaque height, arterial stiffness [aortic pulse wave velocity (aPWV) and augmentation index (AIx)], lipids, rheumatic disease activity and inflammatory variables.
Methods Eighty-five statin naïve patients with IJD and ultrasound verified carotid artery plaques (rheumatoid arthritis: 53, ankylosing spondylitis: 24, psoriatic arthritis: 8) received rosuvastatin treatment for 18 months to obtain low density lipoprotein cholesterol goal ≤1.8 mmol/L. All patients underwent assessment of FMD, aPWV, AIx and carotid ultrasound at baseline and at study end. Change in FMD from baseline to study end was analyzed using paired-samples t-test. Furthermore, multiple linear regression analyses, adjusted for age, gender and use of biologic disease-modifying anti-rheumatic drugs, were applied to evaluate associations between ΔFMD and change in carotid artery plaque height, aPWV, AIx, lipids, disease activity/inflammatory variables and medication. In addition, the mean diameter of the brachial artery as a result of FMD was plotted against time at baseline and 18 months.
Results The patient cohort had a median (IQR) age of 61.0 (56.0-67.0), a predominance of females (60%) and a median (IQR) disease duration of 18.0 (8.3-26.0) years. The mean ± SD FMD was significantly improved from 7.10±3.14% at baseline to 8.70±2.98% at study end (p<0.001). Multiple linear regression analyses with ΔFMD as the dependent variable revealed that the FMD improvement was linearly associated with the improvement in arterial stiffness as measured by AIx: β (CI): -0.09 (-0.18, 0.00) (p=0.05) and carotid plaque height regression: β (CI): -3.10 (-4.95, -1.25) (p=0.001). ΔFMD was not associated with changes in lipid levels, disease activity, inflammatory variables or medication. The mean diameter of the brachial artery as a result of FMD was plotted against time at baseline and 18 months is shown in figure.
Conclusions Long-term intensive lipid lowering with rosuvastatin improved endothelial function measured by FMD in IJD patients with atherosclerotic disease. The statin-induced improvement in endothelial function was linearly associated with reduced arterial stiffness and carotid artery plaque regression. Thus, our results support the hypothesis that restoration of endothelial function plays an important role in the regression process of atherosclerosis.
Disclosure of Interest None declared
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