Background Augmentation index (AIx) and aortic pulse wave velocity (aPWV), the two most common measures of arterial stiffness, are predictors of future cardiovascular disease (CVD) and are increased in patients with inflammatory joint diseases (IJD). Increasing arterial stiffness is associated with hypertension and the presence of carotid artery plaques (CP), which have high prevalences in IJD patients. In addition to lipid lowering, statins have clinically important pleiotropic effects, including a beneficial effect on arterial stiffness, which has previously been reported in small IJD patient cohorts with short follow-up time. In other high CVD risk patients, a pleiotropic antihypertensive effect by statins has also been reported, however this has not yet been ascertained for patients with IJD. Furthermore, the relationship between decreasing arterial stiffness and blood pressure (BP) levels has not been elucidated.
Objectives The aim of the present study was to evaluate the effect of long-term rosuvastatin treatment on arterial stiffness and BP in patients with IJD and CP. A further aim was to evaluate associations between the changes and baseline levels of AIx, aPWV, systolic (sBP) and diastolic BP (dBP).
Methods Eighty-nine statin-naïve IJD patients (rheumatoid arthritis: 55, ankylosing spondylitis: 23, psoriatic arthritis: 11) with ultrasound verified CP received rosuvastatin therapy over 18 months. AIx, aPWV and BP levels were measured at baseline and at the end of the study. Paired-samples t-tests were used to assess the change from baseline to study end in AIx (ΔAIx), aPWV (ΔaPWV), systolic BP (ΔsBP) and diastolic BP (ΔdBP). Linear regression models, adjusted for age, gender and antihypertensive medication, were applied to evaluate for associations between baseline levels and ΔAIx, ΔaPWV, ΔsBP, ΔdBP. Patients for whom antihypertensive medication was initiated or changed during the study period were excluded from analyses with sBP and dBP.
Results AIx, aPWV, sBP and dBP were significantly improved from baseline to study end. The mean reductions (95%CI) were: AIx: 0.3 (0.03, 0.6) % (p=0.03), aPWV: 1.7 (0.2, 3.2) m/s2 (p=0.03), sBP: 5.3 (1.6, 8.9) mmHg (p=0.004) and dBP 2.9 (0.9, 5.0) mmHg (p=0.01) (Figure). Linear regression models revealed that the effect of rosuvastatin in terms of reducing arterial stiffness and BP levels was more pronounced in patients with higher baseline arterial stiffness and BP levels, respectively (p<0.001 for all). Also, linear regression models revealed that ΔaPWV, ΔsBP and ΔdBP were linearly associated (p<0.001 for all), in that a more substantial reduction in aPWV was associated with a larger BP lowering effect.
Conclusions Rosuvastatin therapy for 18 months induced reduction of arterial stiffness and a clinically meaningful BP reduction in IJD patients with atherosclerosis. The effect of statins on arterial stiffness and BP was most pronounced in patients with higher arterial stiffness and BP levels at baseline. In addition, we have shown for the first time that the improvement of aPWV and reduction in BP values were linearly associated, thus providing novel insight into the mechanisms responsible for the pleiotropic effects by statins.
Disclosure of Interest None declared