Coronary atheroma progression rates in men and women following high-intensity statin therapy: A pooled analysis of REVERSAL, ASTEROID and SATURN

Atherosclerosis. 2016 Nov:254:78-84. doi: 10.1016/j.atherosclerosis.2016.09.059. Epub 2016 Sep 15.

Abstract

Background and aims: High-intensity statin therapy (HIST) reduces cardiovascular events, however, sex-related differences in treatment effects are not well characterized.

Methods: A patient-level post hoc pooled analysis of 3 randomized trials utilizing serial coronary intravascular ultrasound was undertaken, testing the anti-atherosclerotic effects of HIST in coronary disease patients. Sex-related differences in changes (Δ) in coronary percent atheroma volume (PAV) were ascertained following 18-24 months of HIST (atorvastatin 80 mg or rosuvastatin 40 mg daily), and further characterized according to on-treatment lipid and lipoprotein levels.

Results: In women (n = 451) compared with men (n = 1190), on-treatment levels of LDL-C (68 ± 24 vs. 67 ± 22 mg/dl, p=0.62) and apoB (77 ± 23 vs. 76 ± 20 mg/dL, p=0.51) were similar; levels of HDL-C (53 ± 12 vs. 47 ± 11 mg/dl, p < 0.001), apoA1 (154 ± 26 vs. 140 ± 24 mg/dl, p < 0.001), triglycerides [122 (95, 158) vs. 114 (89, 154) mg/dl, p=0.012] and CRP [1.7 (0.9, 3.8) vs. 1.1 (0.6, 2.7) mg/l, p < 0.001] were higher; while the total cholesterol/HDL-C (TC/HDL-C) ratio was lower (2.9 ± 0.8 vs. 3.1 ± 0.8, p < 0.001). Compared with men, women harbored significantly lower baseline PAV (34.8 ± 8.7 vs. 38.3 ± 8.8%, p < 0.001), yet demonstrated significantly greater PAV regression (ΔPAV -1.07 ± 0.26 vs. -0.66 ± 0.23%, p=0.02). When achieved on-treatment levels of LDL-C were <64 mg/dl, apoB <73 mg/dl, non-HDL-C <88.8 mg/dl, and TC/HDL-C <2.99, women demonstrated significantly greater PAV regression than men. Multivariable analysis revealed female sex to independently associate with PAV regression (coefficient -0.66, p=0.02).

Conclusions: Women demonstrate greater degrees of coronary plaque regression compared with men following long-term HIST, especially in the setting of lower achieved atherogenic lipoprotein levels.

Keywords: Atherosclerosis; Cholesterol; Coronary artery disease; Lipids; Ultrasound; Women.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Atherosclerosis / blood
  • Atherosclerosis / drug therapy*
  • Atorvastatin / pharmacology
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Coronary Artery Disease / drug therapy*
  • Disease Progression
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Linear Models
  • Lipids / blood
  • Male
  • Middle Aged
  • Plaque, Atherosclerotic / drug therapy*
  • Rosuvastatin Calcium / pharmacology
  • Sex Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Cholesterol, HDL
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipids
  • Rosuvastatin Calcium
  • Atorvastatin