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Original research article
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
  1. Adam Blyme1,
  2. Camilla Asferg1,
  3. Olav W Nielsen2,
  4. Thomas Sehestedt3,
  5. Y Antero Kesäniemi4,
  6. Christa Gohlke-Bärwolf5,
  7. Kurt Boman6,
  8. Ronnie Willenheimer7,
  9. Simon Ray8,
  10. Christoph A Nienaber9,
  11. Anne Rossebø10,
  12. Kristian Wachtell1 and
  13. Michael H Olsen11,12
  1. 1Department of Cardiology, Glostrup Hospital, University of Copenhagen, Glostrup, Denmark
  2. 2Department of Cardiology, Bispebjerg Hospital, Copenhagen, Denmark
  3. 3Department of Cardiology, Herlev Hospital, Herlev, Denmark
  4. 4Department of Medicine, Institute of Clinical Medicine, University of Oulu and Clinical Research Center, Oulu University Hospital, Oulu, Finland
  5. 5Heart Center Bad Krozingen, Bad Krozingen, Germany
  6. 6Research Unit, Skelelfteå, Institution of Public health and Clinical Medicine, Umeå University, Umeå, Sweden
  7. 7Heart Health Group and Lund University, Malmö, Sweden
  8. 8Department of Cardiology, University Hospitals of South Manchester, Manchester Academic Health Sciences Centre, Manchester, UK
  9. 9Universitätsmedizin Rostock, Zentrum für Innere Medizin, Rostock Univärsitet, Rostock, Germany
  10. 10Cardiology Department, Oslo University Hospital, Ullevål, Oslo
  11. 11The Cardiovascular and Metabolic Preventive Clinic, Department of Endocrinology, Centre for Individualized Medicine in Arterial Diseases (CIMA), Odense University Hospital, Odense, Denmark
  12. 12Hypertension in Africa Research Team (HART), School for Physiology, Nutrition and Consumer Sciences, North-West University, Potchefstroom, South Africa
  1. Correspondence to Dr Adam Blyme; adam_blyme{at}


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.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:

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