High sensitivity C reactive protein as a prognostic marker in patients with mild to moderate aortic valve stenosis during lipid-lowering treatment: an SEAS substudy

Adam Blyme, Camilla Asferg, Olav W Nielsen, Thomas Sehestedt, Y Antero Kesäniemi, Christa Gohlke-Bärwolf, Kurt Boman, Ronnie Willenheimer, Simon Ray, Christoph A Nienaber, Anne Rossebø, Kristian Wachtell, Michael H Olsen, Adam Blyme, Camilla Asferg, Olav W Nielsen, Thomas Sehestedt, Y Antero Kesäniemi, Christa Gohlke-Bärwolf, Kurt Boman, Ronnie Willenheimer, Simon Ray, Christoph A Nienaber, Anne Rossebø, Kristian Wachtell, Michael H Olsen

Abstract

Aims: To assess the prognostic importance of high-sensitive C reactive protein (hsCRP) in patients with mild to moderate aortic valve stenosis during placebo or simvastatin/ezetimibe treatment in Simvastatin and Ezetimibe in Aortic Stenosis (SEAS).

Methods and results: In 1620 SEAS patients, we measured lipids and hsCRP at baseline and after 1 year of treatment and registered during 4 years of follow-up major cardiovascular events (MCE) composed of ischaemic cardiovascular events (ICE) and aortic valve-related events (AVE). Simvastatin/ezetimibe reduced low-density lipoprotein cholesterol (3.49 (2.94 to 4.15) to 1.32 (1.02 to 1.69) vs 3.46 (2.92 to 4.08) to 3.34 (2.81 to 3.92) mmol/L) and hsCRP (2.1 (0.9 to 4.1) to 1.2 (0.6 to 2.4) vs 2.2 (0.9 to 4.9) to 1.8 (0.85 to 4.35) mg/L, all p<0.05) during the first year of treatment. In multivariable Cox regression analysis adjusting for traditional risk factors and baseline hsCRP, ICE was associated with a 1-year increase of hsCRP (HR=1.19 (95% CI 1.12 to 1.25), p<0.001) but not with active treatment (HRTreatment=0.86 (0.67 to 1.13), p=0.28). Patients in the top quartile of baseline hsCRP versus the rest were associated with a higher risk of MCE (HR=1.34(1.09 to 1.64), p=0.02). The prognostic benefit of reduction in hsCRP after 1 year was significantly larger (p<0.01 for interaction) in patients with high versus low baseline hsCRP; hence, a reduction in hsCRP abolished the difference in incidence of MCE between high versus low baseline hsCRP in patients with reduced hsCRP (31.1 vs 31.9%, NS) in contrast to patients with increased hsCRP.

Conclusions: The treatment-associated reduction in ICE was in part related to a reduction in hsCRP but not in lipids. hsCRP reduction was associated with less MCE, especially in patients with high baseline hsCRP.

Trial registration: NCT00092677.

Figures

Figure 1
Figure 1
Event-free survival according to baseline and 1-year changes in high-sensitive C reactive protein (hsCRP). Survival free of (A) major cardiovascular event (MCE) and (B) ischaemic cardiovascular event (ICE) according to baseline and 1-year changes in hsCRP.

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