Effect of atorvastatin on C-reactive protein and benefits for cardiovascular disease in patients with type 2 diabetes: analyses from the Collaborative Atorvastatin Diabetes Trial.

Sabita S Soedamah-Muthu,Coen D A Stehouwer,David A Demicco,Casper G Schalkwijk,Helen M Colhoun,Graham A Hitman,D John Betteridge,Weihang Bao,John H Fuller,Paul N Durrington,Shona J Livingstone,Valentine Charlton-Menys,H Andrew W Neil,Gregory M Preston

doi:10.1007/s00125-015-3586-8

Abstract

Aims/hypothesisWe investigated whether atorvastatin 10 mg daily lowered C-reactive protein (CRP) and whether the effects of atorvastatin on cardiovascular disease (CVD) varied by achieved levels of CRP and LDL-cholesterol.MethodsCRP levels were measured at baseline and 1 year after randomisation to atorvastatin in 2,322 patients with type 2 diabetes (40–75 years, 69% males) in a secondary analysis of the Collaborative Atorvastatin Diabetes Study, a randomised placebo-controlled trial. We used Cox regression models to test the effects on subsequent CVD events (n = 147) of CRP and LDL-cholesterol lowering at 1 year.ResultsAfter 1 year, the atorvastatin arm showed a net CRP lowering of 32% (95% CI −40%, −22%) compared with placebo. The CRP response was highly variable, with 45% of those on atorvastatin having no decrease in CRP (median [interquartile range, IQR] per cent change −9.8% [−57%, 115%]). The LDL-cholesterol response was less variable, with a median (IQR) within-person per cent change of −41% (−51%, −31%). Baseline CRP did not predict CVD over 3.8 years of follow-up (HRper SD log 0.89 [95% CI 0.75, 1.06]), whereas baseline LDL-cholesterol predicted CVD (HRper SD 1.21 [95% CI 1.02, 1.44]), as did on-treatment LDL-cholesterol. There was no significant difference in the reduction in CVD by atorvastatin, with above median (HR 0.57) or below median (HR 0.52) change in CRP or change in LDL-cholesterol (HR 0.61 vs 0.50).Conclusions/interpretationCRP was not a strong predictor of CVD. Statin efficacy did not vary with achieved CRP despite considerable variability in CRP response. The use of CRP as an indicator of efficacy of statin therapy on CVD risk in patients with type 2 diabetes is not supported by these data.Trial registration NCT00327418Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-015-3586-8) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Highlights

Aims/hypothesis We investigated whether atorvastatin 10 mg daily lowered C-reactive protein (CRP) and whether the effects of atorvastatin on cardiovascular disease (CVD) varied by achieved levels of CRP and LDL-cholesterol
We investigated whether CRP predicted CVD events, whether atorvastatin 10 mg daily lowered CRP and whether the effects of atorvastatin on CVD differed by achieved post-treatment CRP levels in a large sample of patients with type 2 diabetes from the Collaborative Atorvastatin Diabetes Study (CARDS)
A comparison of the baseline characteristics by treatment arm in those with CRP data showed that both treatment arms were well balanced in terms of all characteristics, except for slightly lower baseline CRP levels in the atorvastatin compared with the placebo arm

Summary

Introduction

Aims/hypothesis We investigated whether atorvastatin 10 mg daily lowered C-reactive protein (CRP) and whether the effects of atorvastatin on cardiovascular disease (CVD) varied by achieved levels of CRP and LDL-cholesterol. It is controversial whether CRP should be used as a target biomarker to assess the effects of statin treatment [14] Most of these previous studies [6, 12, 13] primarily evaluated patients without type 2 diabetes. As there is evidence that CRP levels are higher in patients with type 2 diabetes, we investigated whether there was evidence to support the clinical relevance of changing CRP levels during 1 year of follow-up with low-dose atorvastatin in a diabetes-specific trial without restrictions on the initial CRP level. We investigated whether CRP predicted CVD events, whether atorvastatin 10 mg daily lowered CRP and whether the effects of atorvastatin on CVD differed by achieved post-treatment CRP levels in a large sample of patients with type 2 diabetes from the Collaborative Atorvastatin Diabetes Study (CARDS). Several studies show that statins reduce the inflammatory biomarker high-sensitivity C-reactive protein (CRP), an effect that is thought to be independent of change in LDL-cholesterol, based on low correlations (

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Conclusion