• Journal of Preventive Medicine and Public Health
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• v.55 no.5
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• pp.424-427
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• 2022

A retrospective record-linkage study (RLS) based on medical records containing drug prescription histories involves immortal time bias (ITB). Thus, it is necessary to control for this bias in the research planning and analysis stages. Furthermore, a summary of a meta-analysis including RLSs that did not control for ITB showed that specific drugs had a preventive effect on the occurrence of the disease. Previous meta-analytic results of three systematic reviews evaluating the association between statin intake and gastric cancer risk showed that the summary hazard ratio (sHR) of the RLSs was lower than 1 and was statistically significant. We should consider the possibility of ITB in the sHR of RLSs and interpret the results carefully.

• Korean Journal of Clinical Pharmacy
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• v.28 no.4
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• pp.293-299
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• 2018

Background: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) effectively reduce serum levels of low-density lipoprotein (LDL) and total cholesterol. High-intensity statins are recommended for all patients aged ${\leq}75$ with clinical atherosclerotic cardiovascular disease (ASCVD), diabetes mellitus aged 40-75 with ${\geq}7.5%$ estimated 10-year ASCVD risk and LDL-C ${\geq}190mg/dL$. High-intensity statins associated with more frequent adverse events (AEs) compared to moderate- to low-intensity statins. The aim of this study was to compare AEs between high-intensity and moderate- to low-intensity statin group using the Korea Adverse Event Reporting System (KAERS) database. Methods: Adults (${\geq}18years$) with statin-associated AEs from July 2009-June 2014 were included. Only AEs classified as "certain", "probable" and "possible" based on the WHO-Uppsala Monitoring Center criteria were analyzed. Results: In total, 247 AEs from 196 patients [high-intensity statin group (HG), n = 25 (13%); moderate- to low-intensity statin group (MLG), n = 171 (87%)] were included. Mean age was higher in HG compared with MLG ($67{\pm}14$ vs $62{\pm}12$). The HG showed a significant higher frequency of liver/biliary system disorders (37% vs 14%, p = 0.001). Hepatic function abnormal was reported more frequently in HG compared to MLG (26% vs 9%, p = 0.006). Conclusion: According to KAERS data, liver/biliary system disorders were more frequently reported in HG compared to MLG.

• Development and Reproduction
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• v.11 no.2
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• pp.59-66
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• 2007

Understanding molecular mechanisms that control embryonic stem cell (ESC) self-renewal and differentiation is important for the development of ESC-based therapies. Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), potently reduce cholesterol level. As well as inhibiting cholesterol synthesis, statins inhibit other intermediates in the mevalonate pathway such as farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP), major substrates for protein isoprenylation. Studies showed that pleiotropic effects of statins beyond cholesterol lowering property arise from inhibition of protein isoprenylation that is involved in various cellular functions including proliferation and differentiation. It has been determined that statins have inhibitory effect on ESC self-renewal and stimulatory effect on ESC differentiation into adipogenic/osteogenic lineages. Importantly, statins mediate downregulation of ESC self-renewal by inhibiting RhoA-dependent signaling, independently of their choresterol-lowering properties. Understanding statin's actions on ESCs may provide important insights into the molecular mechanisms that regulate self-renewal or differentiation of ESCs.

• Journal of Korean Neurosurgical Society
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• v.64 no.5
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• pp.693-704
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• 2021

Objective : Endovascular mechanical thrombectomy (MT) has been regarded as one of the standard treatments for acute ischemic stroke caused by large vessel occlusion. Despite the wide use of stent retrievers for MT, arterial intimal damage caused when deployed stent is pulled has been a certain disadvantage. We hypothesized that statin could protect and stabilize vessel damage after endovascular MT using a stent retriever. In this animal study, we observed the protective effects of the statins towards MT-induced vessel wall injury. Methods : Twenty-eight carotid arteries of fourteen rabbits were used in the experiments with MT using stent retriever. We divided the rabbits into four groups as follows : group 1, negative control; group 2, positive control; group 3, statin before MT; and group 4, statin after MT. After MT procedures, we harvested the carotid arteries and performed histomorphological and immunohistochemical analyses. Results : In histomorphological analysis with hematoxylin and eosin and Masson's trichrome stain, significant intimal thickening (p<0.05) was observed in the positive control (group 2), compared to in the negative control (group 1). Intimal thickening was improved in the statin-administered groups (groups 3 and 4 vs. group 2, p<0.05). We also observed that statin administration after MT (group 4) resulted in a more effective decrease in intimal thickness than statin administration before MT (group 3) (p<0.05). We performed immunohistochemical analysis with the antibodies for tumor necrosis factor-alpha (TNF-α), cluster of differentiation (CD)11b, and CD163. In contrast to the negative control (group 1), the stained percentage areas of all immunological markers were markedly increased in the positive control (group 2) (p<0.05). Based on statin administration, the percentage area of TNF-α staining was significantly reduced (p<0.05) in group 3, compared to the positive control group (group 2). However, significant differences were not observed for CD11b and CD163 staining. In group 4, no significant differences were observed for TNF-α, CD11b, and CD163 staining (p≥0.05). The differences in the percentage areas of the different markers between the statin-administered groups (groups 3 and 4) were also not revealed. Conclusion : We presented that statin administration before and after MT exerted protective effects towards vessel wall injury. The efficacy of statins was greater post-administration than pre-administration. Thus, statin administration in routine prescriptions in the peri-procedural period is strongly advised.

• Journal of Medicine and Life Science
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• v.21 no.2
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• pp.40-48
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• 2024

Understanding the effectiveness of statin treatment is essential for developing tailored stroke prevention strategies. We aimed to evaluate the efficacy of statin treatment in preventing recurrent stroke among patients with various ischemic stroke subtypes. Using data from the Clinical Research Collaboration for Stroke-Korea-National Institute for Health (CRCS-K-NIH) registry, we included patients with acute ischemic stroke admitted between January 2011 and July 2020. To evaluate the differential effects of statin treatment based on the ischemic stroke subtype, we analyzed patients with large artery atherosclerosis (LAA), cardio-embolism (CE), and small vessel occlusion (SVO). The primary outcomes were recurrent ischemic stroke and recurrent stroke events. The hazard ratio for outcomes between statin users and nonusers was compared using a Cox proportional hazards model adjusted for covariates. A total of 46,630 patients who met the inclusion criteria were analyzed. Statins were prescribed to 92%, 93%, and 78% of patients with LAA, SVO, and CE subtypes, respectively. The hazards of recurrent ischemic stroke and recurrent stroke in statin users were reduced to 0.79 (95% confidence interval [CI], 0.63-0.99) and 0.77 (95% CI, 0.62-0.95) in the LAA subtype and 0.63 (95% CI, 0.52-0.76) and 0.63 (95% CI, 0.53-0.75) in CE subtype compared to nonusers. However, the hazards of these outcomes did not significantly decrease in the SVO subtype. The effectiveness of statin treatment in reducing the risk of recurrent stroke in patients with LAA and CE subtypes has been suggested. Nonetheless, no significant effect was observed in the SVO subtype, suggesting a differential effect of statins on different stroke subtypes.