Background and Purpose: Serum hs-CRP level has been shown as a reliable marker of vascular inflammation. One of the pleiotropic effect of statin could be anti-inflammation shown as decrease of hs-CRP level. However, it remains unclear whether statin decreases the hs-CRP level in ischemic stroke patients. This is a sub-study of J-STARS, and the primary outcome was change of hs-CRP after statin treatment. The secondary outcome was whether mean hs-CRP level during follow-up period is associated with recurrent stroke and transient ischemic attack (TIA), and all vascular event.
Methods: Among 1578 patients enrolled in J-STARS, 1095 were included in Hs-CRP sub-study. Those were randomly assigned to pravastatin (n=545) or control group (n=550). The pravastatin group patients received 10 mg of pravastatin/day. Blood samples were obtained at baseline and 2, 6 months, 2 and 5 years after randomization. Hs-CRP levels were log-transformed for statistical analysis.
Results: Baseline average hs-CRP level was 691 ng/L. Hs-CRP level was significantly decreased 2 months after pravastatin treatment, and remained significantly lower until the end of study. However, hs-CRP level did not show significant change in the control group. One SD increase of mean hs-CRP level during follow-up tended to increase the risk of stroke/TIA recurrence (HR 1.18, 95%CI 0.99-1.40, p=0.065) and significantly increased the risk of all vascular events (HR1.28, 95%CI 1.10-1.49, p<0.01). After adjustment with risk factors, the association between 1SD increase of hs-CRP and all vascular events remained significant. When cut-off level of hs-CRP level during follow-up was determined as 1000 ng/L, higher CRP level significantly increased the risk of stroke/TIA (HR 1.47, 95%CI 1.04-2.09, p=0.03) and all vascular events (HR 1.63, 95%CI 1.20-2.21, p<0.01). After adjustment, the association with stroke/TIA was of borderline significance (p=0.06) but remained significant with all vascular events (p=0.01).
Conclusion: Low dose pravastatin significantly decreased the level of hs-CRP in ischemic stroke patients. High hs-CRP level during follow-up, particularly beyond 1000 ng/l, tended to increase the stroke/TIA recurrence and was significantly associated with the risk of all vascular events.