1.
Effects of simvastatin on white matter integrity in healthy middle-aged adults.
Vogt, NM, Hunt, JFV, Ma, Y, Van Hulle, CA, Adluru, N, Chappell, RJ, Lazar, KK, Jacobson, LE, Austin, BP, Asthana, S, et al
Annals of clinical and translational neurology. 2021;(8):1656-1667
Abstract
BACKGROUND The brain is the most cholesterol-rich organ and myelin contains 70% of total brain cholesterol. Statins are potent cholesterol-lowing medications used by millions of adults for prevention of vascular disease, yet the effect of statins on cholesterol-rich brain white matter (WM) is largely unknown. METHODS We used longitudinal neuroimaging data acquired from 73 healthy, cognitively unimpaired, statin-naïve, middle-aged adults during an 18-month randomized controlled trial of simvastatin 40 mg daily (n = 35) or matching placebo (n = 38). ANCOVA models (covariates: age, sex, APOE-ɛ4) tested the effect of treatment group on percent change in WM, gray matter (GM), and WM hyperintensity (WMH) neuroimaging measures at each study visit. Mediation analysis tested the indirect effects of simvastatin on WM microstructure through change in serum total cholesterol levels. RESULTS At 18 months, the simvastatin group showed a significant preservation in global WM fractional anisotropy (β = 0.88%, 95% CI 0.27 to 1.50, P = 0.005), radial diffusivity (β = -1.10%, 95% CI -2.13 to -0.06, P = 0.039), and WM volume (β = 0.72%, 95% CI 0.13 to 1.32, P = 0.018) relative to the placebo group. There was no significant effect of simvastatin on GM or WMH volume. Change in serum total cholesterol mediated approximately 30% of the effect of simvastatin on WM microstructure. CONCLUSIONS Simvastatin treatment in healthy, middle-aged adults resulted in preserved WM microstructure and volume at 18 months. The partial mediation by serum cholesterol reduction suggests both peripheral and central mechanisms. Future studies are needed to determine whether these effects persist and translate to cognitive outcomes. TRIAL REGISTRATION NCT00939822 (ClinicalTrials.gov).
2.
Prognostic impact of estimated remnant-like particle cholesterol in patients with differing glycometabolic status: an observational cohort study from China.
Zhao, Q, Zhang, TY, Cheng, YJ, Ma, Y, Xu, YK, Yang, JQ, Zhou, YJ
Lipids in health and disease. 2020;(1):179
Abstract
BACKGROUND It is uncertain whether estimated remnant-like particle cholesterol (RLP-C) could predict residual risk in patients with different glycometabolic status. This study aimed to evaluate the relationship between estimated RLP-C and adverse prognosis in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) treated with percutaneous coronary intervention (PCI) and to identify the potential impact of glycometabolism on the predictive value of estimated RLP-C. METHODS The study assessed 2419 participants with NSTE-ACS undergoing PCI at Beijing Anzhen Hospital from January to December 2015. Estimated RLP-C was calculated as follows: total cholesterol (TC) minus low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). The adverse events included all-cause death, non-fatal myocardial infarction (MI), and ischemia-driven revascularization. RESULTS Estimated RLP-C was prominently associated with adverse prognosis in the total population [hazard ratio (HR) 1.291 per 1-SD increase, 95% confidence interval (CI) 1.119-1.490, P < 0.001], independent of confounding risk factors. However, subgroup analysis showed that increasing estimated RLP-C was related to a higher risk of adverse events in the diabetic population only [HR 1.385 per 1-SD increase, 95% CI 1.183-1.620, P < 0.001]. Estimated RLP-C failed to be a significant determinant of adverse prognosis in non-diabetic and pre-diabetic subgroups. The addition of estimated RLP-C to a baseline model including traditional risk factors enhanced the predictive performance both in total and diabetic populations. CONCLUSIONS High estimated RLP-C level is a significant predictor for recurrent adverse events in patients with diabetes and NSTE-ACS treated with PCI.