title: Sex-related differences of coronary atherosclerosis regression following maximally intensive statin therapy: insights from SATURN.
abstract: OBJECTIVE
  The study sought to explore sex-related differences in coronary atheroma regression following high-intensity statin therapy.
  
  
  BACKGROUND
  Guidelines now recommend high-intensity statins in all individuals with atherosclerotic cardiovascular disease.
  
  
  METHODS
  SATURN (Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin Versus Atorvastatin) employed serial intravascular ultrasound measures of coronary atheroma volume in patients treated with rosuvastatin 40 mg or atorvastatin 80 mg for 24 months. The treatment groups did not differ significantly in change from baseline of percent atheroma volume (PAV) or total atheroma volume (TAV) on intravascular ultrasound, nor in safety or clinical outcomes.
  
  
  RESULTS
  Compared with men (n = 765), women (n = 274) were older (p < 0.001) and more likely to have hypertension (p < 0.001), diabetes (p = 0.002), and higher low-density lipoprotein cholesterol (LDL-C) (p = 0.01), high-density lipoprotein cholesterol (p < 0.001), and C-reactive protein (CRP) (p = 0.004) levels. At follow-up, women had higher high-density lipoprotein cholesterol (p < 0.001) and CRP (p < 0.001), but similar LDL-C (p = 0.46) levels compared with men. Compared with men, women had lower baseline PAV (34.0 ± 8.0% vs. 37.2 ± 8.2%, p < 0.001) and TAV (122.4 ± 55 mm(3) vs. 151.9 ± 63 mm(3), p < 0.001), yet demonstrated greater PAV regression (-1.52 ± 0.18% vs. -1.07 ± 0.10%, p = 0.03) and TAV regression (-8.27 ± 0.9 mm(3) vs. -6.59 ± 0.50 mm(3), p = 0.11) following treatment. Greater PAV regression in women versus men occurred with rosuvastatin (p = 0.004), those with diabetes (p = 0.01), stable coronary disease (p = 0.01), higher baseline LDL-C (p = 0.02), and higher CRP (p = 0.04) levels. On multivariable analysis, female sex was independently associated with PAV regression (p = 0.01), and a sex-treatment interaction was found (p = 0.036). For participants with on-treatment LDL-C levels <70 mg/dl, women achieved greater PAV regression (-1.81 ± 0.22% vs. -1.12 ± 0.13%, p = 0.007) and TAV regression (-10.1 ± 1.1 mm(3) vs. -7.16 ± 0.65 mm(3), p = 0.023) than men, whereas PAV and TAV regression did not differ by sex, with LDL-C levels ≥70 mg/dl.
  
  
  CONCLUSIONS
  Women with coronary disease demonstrate greater coronary atheroma regression than men when empirically prescribed guideline-driven potent statin therapy. This benefit appears in the setting of lower on-treatment LDL-C levels. (CRESTOR Athero Imaging Head to Head IVUS Study [SATURN]; NCT000620542).
authors.affiliation: Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio; C5Research, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Rishi
authors.initials: R
authors.lastname: Puri
authors.affiliation: Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Nissen
authors.affiliation: C5Research, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Shao
authors.affiliation: Section of Cardiovascular Research, Baylor College of Medicine, and the Methodist DeBakey Heart and Vascular Center, Houston, Texas.
authors.forename: Christie M
authors.initials: CM
authors.lastname: Ballantyne
authors.affiliation: Centre for Vascular Research, University of New South Wales, Sydney, Australia.
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Barter
authors.affiliation: INSERM Dyslipidaemia and Atherosclerosis Research Unit, Pitié-Salpetriere University Hospital, Paris, France.
authors.forename: M John
authors.initials: MJ
authors.lastname: Chapman
authors.affiliation: West German Heart Center, Essen, Germany.
authors.forename: Raimund
authors.initials: R
authors.lastname: Erbel
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Peter
authors.initials: P
authors.lastname: Libby
authors.affiliation: AstraZeneca, Wilmington, Delaware.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Raichlen
authors.affiliation: Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Uno
authors.affiliation: South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia.
authors.forename: Yu
authors.initials: Y
authors.lastname: Kataoka
authors.affiliation: C5Research, Cleveland Clinic, Cleveland, Ohio; South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia. Electronic address: stephen.nicholls@sahmri.com.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Nicholls
mesh_terms: D000368:Aged; D000069059:Atorvastatin; D002097:C-Reactive Protein / Q000032:analysis; D015897:Comorbidity; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000453:epidemiology; D003925:Diabetic Angiopathies / Q000453:epidemiology; D005260:Female; D005464:Fluorobenzenes / Q000008:administration & dosage*; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006973:Hypertension / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000008:administration & dosage*; D011758:Pyrroles / Q000008:administration & dosage*; D000068718:Rosuvastatin Calcium; D012737:Sex Factors; D013449:Sulfonamides / Q000008:administration & dosage*; D018084:Ultrasonography, Interventional
chemical_list: D005464:Fluorobenzenes; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D002097:C-Reactive Protein; D000069059:Atorvastatin
keywords: IVUS; atherosclerosis; atorvastatin; rosuvastatin; statins