Rosuvastatin Improves Arterial Stiffness in Patients with Inflammatory Joint Diseases

Eirik Ikdahl¹, Silvia Rollefstad¹, Jonny Hisdal², Inge C. Olsen³, Ingar Holme⁴, Terje R. Pedersen⁵, Tore Kvien⁶ and Anne Grete Semb¹, ¹Preventive Cardio-Rheuma clinic, Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway, ²Section of Vascular Investigations, Oslo University Hospital Aker, Oslo, Norway, ³Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway, ⁴Department of biostatistics, epidemiology and health economics, Oslo University Hospital, Oslo, Norway, ⁵Faculty of Medicine, University of Oslo, Oslo, Norway, ⁶Dept of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway

Meeting: ACR/ARHP Annual Meeting 2014

Keywords: Atherosclerosis, Biomarkers, Cardiovascular disease, inflammatory arthritis and statins

Session Information

Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy: Safety of Biologics and Small Molecules in Rheumatoid Arthritis

Session Type: Abstract Submissions (ACR)

Background/Purpose

Arterial stiffness, as pulse wave velocity (PWV) and augmentation index (AIx) has emerged as early risk markers of cardiovascular disease (CVD) in patients with inflammatory joint diseases (IJD). In IJD patients, statin treatment has demonstrated a significant improvement in arterial stiffness. Furthermore, we have shown that statin treatment induced carotid plaque (CP) regression in IJD patients. However, the effect of statins on arterial stiffness in IJD patients with established atherosclerosis is still not elucidated. The aim of the present study was therfore to evaluate the effect of rosuvastatin on arterial stiffness in patients with IJD who had CP. We also evaluated the association between the change in arterial stiffness and change in inflammation markers, disease activity, low-density lipoprotein cholesterol (LDL-c), blood pressure (BP), CP height and intima-media thickness (IMT) after 18 months of rosuvastatin treatment.

Methods

The study population included 89 statin naïve patients with IJD (55 with rheumatoid arthritis, 23 with ankylosing spondylitis and 11 with psoriatic arthritis). All patients had B-mode ultrasound verified CP and received rosuvastatin therapy over 18 months to obtain LDL-c goals (<1.8mmol/L). The arterial stiffness variables PWV and AIx were measured prior to, and at the end of the study, using the Sphygmocor device. We used paired-samples t-tests to assess change from baseline, and regression analysis to assess the association between change in arterial stiffness and other outcome measures.

Results

Study population demographics are presented in table 1. After 18 months rosuvastatin therapy, a significant reduction in Aix was observed, from mean (SD) 27.9 (7.7) % to 26.2 (8.2) % (p=0.026). Furthermore, PWV decreased from 8.1 (1.6) m/s² to 7.8 (1.5) m/s² (p=0.031). In a logistic regression model where change in arterial stiffness was the dependent variable (defined as either increasing or decreasing related to baseline value), change in and exposure of systolic blood pressure during the study period influenced PWV significantly: odds ratio (95% CI): 1.06 (1.02, 1.09)(p=0.005) and 0.97 (0.94; 1.00)(p=0.035). Change in CP height and rosuvastatin dose predicted change in AIx 5.72 significantly: odds ratio (95% CI): (1.25, 26.25)(p=0.025) and 1.22 (1.05, 1.41)(p=0.009).

Conclusion

This is the first clinical trial showing that rosuvastatin treatment improves arterial stiffness in IJD patients with atherosclerosis.

Fig. 1

Legends Fig 1: AIx: augmentation index, PWV: pulse wave velocity

	RA	AS	PsA	All	p-value RA/AS/PsA
Number n (%)	55 (61.8)	23 (25.8)	11 (12.4)	89	–
Age median (IQR)	62.0 (57.0-68.0)	59.0 (53.0-64.0)	60.0 (52.0-64.0)	61.0 (56.0-67.0)	0.07
Sex male/female n (%)	14/41 (25.5/74.5)	15/8 (65.2/34.8)	5/6 (45.5/54.5)	34/55 (38.2/61.8)	0.004
Disease duration median (IQR)	16.0 (6.5-22.3)	22.0 (16.0-30.0)	13.0 (2.0-30.0)	16.0 (8.0-26.0)	0.11
*CV risk factors*
Smoke n (%)	11 (20.0)	3 (13.0)	3 (27.3)	17 (19.1)	0.59
Body mass index mean±SD	25.0±2.9	25.2±2.7	26.1±3.7	25.2±2.9	0.55
Total cholesterol (mmol/L) mean±SD	6.43±1.24	6.19±0.90	6.62±1.07	6.39±1.13	0.54
HDL-c (mmol/L) mean±SD	1.78±0.48	1.53±0.45	1.60±0.51	1.69±0.49	0.09
Triglycerides (mmol/L) median (IQR)	1.2 (0.9-1.6)	1.4 (0.9-1.9)	1.1 (0.7-2.9)	1.2 (0.9-1.8)	0.67
LDL-c (mmol/L) mean±SD	3.95±0.96	3.97±0.86	4.32±1.00	4.00±0.94	0.48
Systolic blood pressure (mm Hg) mean±SD	142.6±19.8	144.8±14.2	147.4±24.6	143.7±19.0	0.71
Diastolic blood pressure (mm Hg) mean±SD	82.7±8.9	85.2±8.2	87.9±10.8	84.0±9.0	0.16
*Co morbidities* n (%)
Hypertension	31 (56.4)	16 (69.6)	6 (54.5)	53 (59.6)	0.52
Diabetes	3 (5.5)	2 (8.7)	0 (0.0)	5 (5.6)	0.59
Cardiovascular disease	6 (10.9)	2 (8.7)	0 (0.0)	8 (9.0)	0.51
Carotid artery plaque median (range)	1 (1-5)	1 (1-3)	2 (1-3)	1 (1-5)	0.34
*Haematology* mean±SD
ESR (mm/h)	15.8±10.3	12.9±9.8	13.9±5.7	14.8±9.7	0.47
CRP (mg/L) median (IQR)	3.0 (1-4)	1 (1-3)	3 (2-6)	2 (1-4)	0.22
*Medication* n (%)
Prednisolone	21 (38.2)	2 (8.7)	2 (18.2)	25 (28.1)	0.02
NSAIDs	21 (38.2)	12 (52.2)	5 (45.5)	38 (42.7)	0.52
Synthetic DMARDs	36 (65.5)	5 (21.7)	9 (81.8)	50 (56.2)	0.002
Biologic DMARDs	15 (27.3)	8 (34.8)	5 (45.5)	28 (31.5)	0.53
Antihypertensive medication	16 (29.1)	4 (17.4)	2 (18.2)	22 (24.7)	0.48

Disclosure:

E. Ikdahl,
None;

S. Rollefstad,
None;

J. Hisdal,
None;

I. C. Olsen,
None;

I. Holme,
None;

T. R. Pedersen,
None;

T. Kvien,
None;

A. G. Semb,
None.

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