AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Intermittent Statin Administration Impairs LDL Control and Accelerates Atherosclerotic Plaque Development in ApoE-/- Mice
By Sprehe LK, Zhu J, Dhuppar S et al.
Background: Hyperlipidemia is a major risk factor for atherosclerotic cardiovascular disease. Prior studies suggest that early intermittent hyperlipidemia induced by a Western diet accelerates atherosclerosis development. Statins are among the most prescribed medications for hyperlipidemia, but many patients do not take them consistently over time. Research Question: Does intermittent statin administration worsen atherosclerosis development compared with continuous treatment. Methods: Thirty ApoE-knockout mice fed a high-fat, high-cholesterol diet were randomized at 10 weeks of age into six groups (n=5/group): PBS control (PC), continuous statin (CS; Atorvastatin 15 mg/kg), intermittent 1:1 (IS 1:1; alternating weekly PBS/Atorvastatin), intermittent 3:4 (IS 3:4; 4 days PBS + 3 days Atorvastatin/week), intermittent 1:6 (IS 1:6; Atorvastatin once weekly), and late-onset statin (LOS; PBS weeks 1-3, Atorvastatin weeks 4-6). Serum lipids and circulating leukocytes were assessed at baseline and at weeks 4, 6, and 8. Aortic roots were stained with Oil Red O and quantified in a blinded manner. Leukocyte populations in spleen, heart, and bone marrow were analyzed by flow cytometry. Results: At week 8, CS treatment reduced circulating T cells, neutrophils and Ly6C-high monocytes compared to PC treatment, whereas B cells and total monocytes were not significantly reduced. In the bone marrow, CS was also associated with significantly lower T cells and Ly6C-high monocytes. These changes were not observed in the IS 1:6 and LOS groups. CS showed a trend toward lower cholesterol and reduced plaque area versus PC. In contrast, IS 1:1 and LOS mice had significantly higher LDL levels and a trend toward greater plaque area compared to CS. Conclusion: Intermittent statin administration impairs LDL control and is associated with greater plaque development compared to continuous statin treatment. Weekly alternating dosing and late-onset initiation appeared most detrimental. These findings suggest that statin non-adherence may diminish, and potentially reverse, cardiovascular benefit, underscoring the importance of consistent treatment.