title: Intensive lipid lowering therapy with titrated rosuvastatin yields greater atherosclerotic aortic plaque regression: Serial magnetic resonance imaging observations from RAPID study.
abstract: OBJECTIVE
  Although previous randomized clinical trials established a basis for lipid guidelines worldwide, they employed fixed doses of statins throughout trials (fire-and-forget approach). In the real clinical setting, however, statin doses are titrated to achieve target low-density lipoprotein cholesterol (LDL-C) levels (treat-to-target approach). The major objective was to investigate whether intensive lipid-lowering therapy using the treat-to-target approach yielded greater regression of aortic plaques.
  
  
  METHODS
  We therefore performed a prospective, randomized trial comparing the effects of standard (achieve LDL-C levels recommended by the Japanese guidelines) and intensive (achieve 30% lower LDL-C levels than standard) rosuvastatin therapy for 1 year in 60 hypercholesterolemic patients with a primary endpoint of aortic atherosclerotic plaques evaluated by non-invasive magnetic resonance imaging (MRI).
  
  
  RESULTS
  Average doses were 2.9 ± 3.1 and 6.5 ± 5.1 mg/day for standard (n = 29) and intensive therapy group (n = 31), respectively. Although both therapies significantly reduced LDL-C and high-sensitivity C-reactive protein (hsCRP) levels, LDL-C reduction was significantly greater in the intensive group (-46 vs. -34%). MRI study showed that thoracic aortic plaques were significantly regressed in both groups, with greater regression of thoracic plaque in the intensive group (-9.1 vs. -3.2%, p = 0.01). Multivariate analyses revealed that thoracic plaque regression was significantly correlated with hsCRP reduction, but not with changes in serum lipids, endothelial function, or doses of rosuvastatin.
  
  
  CONCLUSIONS
  Intensive statin therapy with titration targeting lower LDL-C levels resulted in greater thoracic aortic plaque regression compared to standard therapy, which was correlated with hsCRP reduction, suggesting that intensive statin therapy could provide better clinical outcomes.
authors.affiliation: Division of Anti-aging and Vascular Medicine, Department of Internal Medicine, National Defense Medical College, Japan; Department of Neurology, The Jikei University School of Medicine, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Yogo
authors.affiliation: Division of Anti-aging and Vascular Medicine, Department of Internal Medicine, National Defense Medical College, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Division of Anti-aging and Vascular Medicine, Department of Internal Medicine, National Defense Medical College, Japan. Electronic address: ayaori@ndmc.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ayaori
authors.affiliation: Iruma Heart Hospital, Japan.
authors.forename: Teruyoshi
authors.initials: T
authors.lastname: Kihara
authors.affiliation: Department of Public Health and Preventive Medicine, National Defense Medical College, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sato
authors.affiliation: Division of Anti-aging and Vascular Medicine, Department of Internal Medicine, National Defense Medical College, Japan.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Takiguchi
authors.affiliation: Division of Anti-aging and Vascular Medicine, Department of Internal Medicine, National Defense Medical College, Japan.
authors.forename: Harumi
authors.initials: H
authors.lastname: Uto-Kondo
authors.affiliation: Division of Anti-aging and Vascular Medicine, Department of Internal Medicine, National Defense Medical College, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Yakushiji
authors.affiliation: Division of Anti-aging and Vascular Medicine, Department of Internal Medicine, National Defense Medical College, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nakaya
authors.affiliation: Division of Anti-aging and Vascular Medicine, Department of Internal Medicine, National Defense Medical College, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Komatsu
authors.affiliation: Department of Cardiology, National Hospital Organization Tokyo Medical Center, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Momiyama
authors.affiliation: Iruma Heart Hospital, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Nagata
authors.affiliation: Department of Neurology, The Jikei University School of Medicine, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Mochio
authors.affiliation: Department of Neurology, The Jikei University School of Medicine, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Iguchi
authors.affiliation: Division of Anti-aging and Vascular Medicine, Department of Internal Medicine, National Defense Medical College, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Ikewaki
mesh_terms: D000368:Aged; D000886:Anthropometry; D001011:Aorta / Q000473:pathology; D050197:Atherosclerosis; D002097:C-Reactive Protein / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000097:blood*; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D005464:Fluorobenzenes / Q000627:therapeutic use*; D017408:Guidelines as Topic; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000188:drug therapy* / Q000473:pathology*; D011446:Prospective Studies; D011743:Pyrimidines / Q000627:therapeutic use*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D008078:Cholesterol, LDL; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D002097:C-Reactive Protein
keywords: Aortic plaques; Intensive therapy; MRI; Titration of rosuvastatin; hsCRP