Effects of blood lipids and lipid‐modifying drugs on intracranial aneurysms

Abstract

Background and purpose:We used two-sample Mendelian randomization (MR) to examine the effects of blood lipids and lipid-modifying drugs on intracranial aneurysm (IA). Methods: Genetic variants for the effects of high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B, and triglycerides and targets for lipid-modifying drugs were selected from the genome-wide discovery analyses of the UK Biobank. Summary-level data on IAs were obtained from the International Stroke Genetics Consortium. Univariate and multivariate MR analyses were performed. Results: Univariate MR analyses showed that the HDL-C was negatively correlated with IA (odds ratio [OR] = 0.816, 95% confidence interval [CI] = 0.715-0.932, p = 0.003) and ruptured IA (rIA; OR = 0.775, 95% CI = 0.663-0.906, p = 0.001). The multivariate MRinverse variance weighted analysis showed that the HDL-C was negatively correlated with IA (OR = 0.655, 95% CI = 0.434-0.988, p = 0.043) and rIA (OR = 0.563, 95% CI = 0.347-0.913, p = 0.02), and the LDL-C was negatively correlated with IA (OR = 0.402, 95% CI = 0.191-0.848, p = 0.017) and rIA (OR = 0.376, 95% CI = 0.160-0.883, p = 0.025).Using genetic proxies of known lipid-modifying drugs, we found that the increased HDL-C with cholesterol ester transfer protein proxies was associated with a decreased risk of rIA (OR = 0.852, 95% CI = 0.747-0.973, p = 0.018), and the decreased LDL-C with 3-hydrox y-3-methylglutaryl-coenzyme A reductase proxies was associated with increased risk of IA (OR = 1.772, 95% CI = 1.080-2.908, p = 0.024) and rIA (OR = 1.856, 95% CI = 1.022-3.371, p = 0.042).Conclusions: Genetically determined HDL-C and LDL-C reduce the risk of IA and rIA. The effects of different lipid-modifying drugs on IA need to be further investigated.

Exploring the potential of VGLL3 methylation as a prognostic indicator for intracranial aneurysm with gender-specific considerations

“…Nevertheless, additional research is warranted to elucidate the mechanistic involvement of ApoE in the pathogenesis of arterial aneurysms. According to reports, a negative correlation was observed between HDL and IA as well as ruptured IA [ 25 ]. Additionally, our study revealed a positive correlation between HDL and mean methylation in both males and females.…”

Unruptured intracranial aneurysms: Why should we focus on small aneurysms? A comprehensive update of recent findings

“…2023), with TNF-α being one of the key factors in aneurysm formation and growth [ 50 - 52 ]. High-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were found to reduce the risk of IA and IA rupture [ 53 ].…”

“…Moreover, the presence of interleukins was found to be associated with IA development risk and instability (Monsour et al 2022, Liu et al 2023, with TNFα being one of the key factors in aneurysm formation and growth [5052]. Highdensity lipoprotein cholesterol (HDLC) and lowdensity lipoprotein cholesterol (LDLC) were found to reduce the risk of IA and IA rupture [53].…”

Alcohol flushing syndrome is significantly associated with intracranial aneurysm rupture in the Chinese Han population

“…Statins and antiplatelet agents are commonly used for prevention of stroke in patients with hyperlipidemia and those with a previous ischemic stroke. Several recent studies have emphasized the potential protective effect of these agents for aneurysmal rupture (51)(52)(53)(54)(55)(56). Potential mechanisms include anti-inflammatory effects, stimulation of extracellular matrix production, and chemotactic migration of mesenchymal progenitor cells to stabilize aneurysm walls (57,58).…”