- •High-intensity statin therapy (HIST) reduces cardiovascular events, however, sex-related differences in effects are not well characterized.
- •Our current analysis of 3 coronary IVUS trials of HIST suggest that women achieve greater reductions in coronary atheroma volume compared with men.
- •Gender differences seem more related to lower atherogenic lipoprotein levels than inflammatory or anti-atherogenic lipoprotein levels.
- •These findings underscore the importance to improve upon trends of less aggressive lipid therapy in women with known atherosclerotic disease.
Background and aims
High-intensity statin therapy (HIST) reduces cardiovascular events, however, sex-related differences in treatment effects are not well characterized.
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.
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).
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.
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Published online: September 15, 2016
Accepted: September 15, 2016
Received in revised form: August 31, 2016
Received: April 5, 2016
© 2016 Elsevier Ireland Ltd. All rights reserved.