Sex-related differences of coronary atherosclerosis regression following maximally intensive statin therapy: insights from SATURN

Abstract

Objectives: 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).

Trial registration: ClinicalTrials.gov NCT00620542.

Keywords: IVUS; atherosclerosis; atorvastatin; rosuvastatin; statins.