title: High dose and long-term statin therapy accelerate coronary artery calcification.
abstract: BACKGROUND
  In randomized clinical trials statins and placebo treated patients showed the same degree of coronary artery calcium (CAC) progression. We reanalyzed data from two clinical trials to further investigate the time and dose dependent effects of statins on CAC. Additionally, we investigated whether CAC progression was associated with incident cardiovascular events.
  
  
  RESULTS
  Data were pooled from two clinical trials: St. Francis Heart Study (SFHS) (419 and 432 patients treated with placebo and 20 mg atorvastatin daily, respectively) and EBEAT Study (164 and 179 patients respectively treated with 10 mg and 80 mg atorvastatin daily). CAC scores were assessed at baseline, 2 years and 4-6 years in SFHS; in EBEAT they were measured at baseline and 12 months. After a short-term follow-up (12 to 24 months) placebo and low dose atorvastatin showed a similar CAC increase, although 80 mg/daily atorvastatin increased CAC an additional 12-14% over placebo (p<0.001). In the long-term, atorvastatin caused a greater progression of CAC compared to placebo (additional 1.1%, p=0.04). In SFHS 42 cardiovascular events occurred after the second CT scan. The baseline and progression of CAC were greater in patients with events. However, only baseline CAC and family history of premature cardiovascular disease but not CAC progression were independent predictors of events.
  
  
  CONCLUSIONS
  Despite a greater CAC increase with high dose and long-term statin therapy, events did not occur more frequently in statin treated patients. This suggests that CAC growth under treatment with statins represents plaque repair rather than continuing plaque expansion.
authors.affiliation: Department of Public Health and Clinical Medicine, Umeå University and Heart Centre, Umeå, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Henein
authors.affiliation: Department of Radiation Sciences, Biomedical Engineering, Umeå University, Umeå, Sweden.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Granåsen
authors.affiliation: Department of Radiation Sciences, Biomedical Engineering, Umeå University, Umeå, Sweden.
authors.forename: Urban
authors.initials: U
authors.lastname: Wiklund
authors.affiliation: Bethanien Hospital, Frankfurt, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Schmermund
authors.affiliation: St. Francis Heart Hospital, Roslyn, NY, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Guerci
authors.affiliation: Department of Cardiology, Essen University, Hufelandstr, Essen, Germany.
authors.forename: Raimund
authors.initials: R
authors.lastname: Erbel
authors.affiliation: Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada. Electronic address: raggi@ualberta.ca.
authors.forename: Paolo
authors.initials: P
authors.lastname: Raggi
mesh_terms: D000368:Aged; D003324:Coronary Artery Disease / Q000139:chemically induced / Q000175:diagnosis* / Q000453:epidemiology; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D061205:Vascular Calcification / Q000139:chemically induced / Q000175:diagnosis* / Q000453:epidemiology
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: Computed tomography; Coronary artery calcium; Statins