Statin Intensification and LDL Cholesterol Reduction are Associated with Longitudinal Changes in Circulating Amyloid-β 1–40 in a Prospective Dyslipidemia Cohort
Abstract
Background Circulating amyloid β 1–40 (Aβ40), a pro-inflammatory and pro-atherogenic peptide, is an emerging biomarker in atherosclerotic cardiovascular disease (ASCVD), but evidence on its modulation by cardiovascular therapies is limited and conflicting. We explored associations between statin therapy and Aβ40 plasma levels. Methods In this prospective study, patients with dyslipidemia ( n = 146) were consecutively recruited. Αβ40 was measured in plasma by enzyme-linked immunosorbent assay at baseline, after a mean follow-up of 5.2 (visit 2 [V2]) and 15 months (visit 3 [V3]). Patients in whom statin treatment was initiated or intensified ( n = 68, intensification group) were compared with patients who were untreated or on stable statin intensity ( n = 78, control group). Results After multivariable adjustment for biologically plausible confounders, increased Aβ40 at baseline associated with ASCVD, heart failure, decreased estimated glomerular filtration rate (eGFR), and diabetes mellitus (DM). Aβ40 increased from baseline to V2 in the intensification group ( p = 0.05 and adjusted p for interaction = 0.031 vs. the control group) and then stabilized. In the control group, Aβ40 increased at V3 compared with V2 ( p = 0.043). Excluding ezetimibe-treated patients did not alter these findings. In patients with low-density lipoprotein cholesterol (LDL-C) reduction ≥ 50% at V3, Aβ40 levels remained unchanged, whereas they increased in the rest of the population (adjusted p for group interaction = 0.030). Conclusion In high-risk patients, statin initiation or intensification is associated with a short-term increase, followed by a long-term return to initial Aβ40 circulating levels, whereas patients achieving LDL-C reduction show long-term stabilization of Aβ40 levels. Further research is warranted to clarify the mechanistic insights of these observations.