Impact of the statin escape phenomenon on long-term clinical outcomes in patients with acute myocardial infarction: Subgroup analysis of the Nagoya Acute Myocardial Infarction Study (NAMIS)

Ota, Terukazu; Ishii, Hideki; Suzuki, Susumu; Shibata, Yohei; Tatami, Yosuke; Harata, Seiko; Shimbo, Yusaku; Takayama, Yoshiaki; Tanaka, Akihito; Kawamura, Y.; Osugi, Naohiro; Maeda, Kengo; Kondo, Takahisa; Murohara, Toyoaki

doi:10.1016/j.atherosclerosis.2015.07.012

Cited by 5 publications

(13 citation statements)

References 29 publications

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“…Our results showing an initial marked LDL-C reduction but followed by a > 10% LDL-C increase after prolonged statin treatment in subjects exhibiting the statin escape phenomenon are in line with the results of these studies[ 3 , 5 , 7 ]. Similar to previous studies, we did not find any predictors for this phenomenon[ 3 , 5 , 7 ]. A recent study showed that statin escape phenomenon not only exists, but also might be an independent predictor of cardiovascular disease[ 3 ].…”

Section: Discussionsupporting

confidence: 92%

“…Two small studies including patients with familial hypercholesterolemia were the first to notice a paradox rebound cholesterol increase following statin dose increase[ 4 , 5 ]. Since then, the EXCEL study along with others, have described this so called statin escape phenomenon[ 3 , 5 - 7 ]. Our results showing an initial marked LDL-C reduction but followed by a > 10% LDL-C increase after prolonged statin treatment in subjects exhibiting the statin escape phenomenon are in line with the results of these studies[ 3 , 5 , 7 ].…”

Section: Discussionmentioning

confidence: 99%

“…Since then, the EXCEL study along with others, have described this so called statin escape phenomenon[ 3 , 5 - 7 ]. Our results showing an initial marked LDL-C reduction but followed by a > 10% LDL-C increase after prolonged statin treatment in subjects exhibiting the statin escape phenomenon are in line with the results of these studies[ 3 , 5 , 7 ]. Similar to previous studies, we did not find any predictors for this phenomenon[ 3 , 5 , 7 ].…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, a notable cardiovascular risk remains in statin-treated individuals, which has been attributed to other residual factors, such as hypertension, diet and adherence to therapy[ 2 ]. Recently, the so called “statin escape” phenomenon has been reported as an independent cardiovascular risk factor in patients with acute myocardial infarction on prolonged statin treatment[ 3 ]. This phenomenon was first described in small studies including patients with familial hypercholesterolemia[ 4 , 5 ] and afterwards in the Expanded Clinical Evaluation of Lovastatin (EXCEL) study[ 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Statin escape phenomenon: Fact or fiction?

Barkas

Elisaf

Klouras

et al. 2017

WJEM

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AIMTo evaluate the presence of the so called “statin escape” phenomenon among hyperlipidemic subjects attending a lipid clinic.METHODSThis was a retrospective analysis of 1240 hyperlipidemic individuals followed-up for ≥ 3 years. We excluded those individuals meeting one of the following criteria: Use of statin therapy at baseline visit, discontinuation of statin treatment at most recent visit, change in statin treatment during follow-up and poor compliance to treatment. Statin escape phenomenon was defined as an increase in low-density lipoprotein cholesterol (LDL-C) levels at the most recent visit by > 10% compared with the value at 6 mo following initiation of statin treatment.RESULTSOf 181 eligible subjects, 31% exhibited the statin escape phenomenon. No major differences regarding baseline characteristics were found between statin escapers and non-statin escapers. Both escapers and non-escapers had similar baseline LDL-C levels [174 (152-189) and 177 (152-205) mg/dL, respectively]. In comparison with non-escapers, statin escapers demonstrated lower LDL-C levels at 6 mo after treatment initiation [88 (78-97) mg/dL vs 109 (91-129) mg/dL, P < 0.05], but higher levels at the most recent visit [103 (96-118) mg/dL vs 94 (79-114) mg/dL, P < 0.05].CONCLUSIONThese data confirm the existence of an escape phenomenon among statin-treated individuals. The clinical significance of this phenomenon remains uncertain.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Statin escape phenomenon: Fact or fiction?

Barkas

Elisaf

Klouras

et al. 2017

WJEM

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“…The study outcome supports the benefits of controlling the LDL-C level at < 100 mg/dL rather than basing the treatment on the strength of statin. It has been reported that the risk of cardiovascular events increased in patients with the escape phenomenon (i.e., re-elevation in LDL-C level of ≥ 10% after a reduction) following the start of statin treatment 634 ) . However, patients with the escape phenomenon had an LDL-C level of 106 mg/dL; whereas the comparison group had an LDL-C level of 90 mg/dL.…”

Section: Comprehensive Risk Managementmentioning

confidence: 99%

Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2017

Kinoshita

Yokote

Arai

et al. 2018

J Atheroscler Thromb

622

569

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Regulation of Cholesterol Homeostasis by a Novel Long Non-coding RNA LASER

Wen

et al. 2019

Sci Rep

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Genome-wide association studies (GWAS) have identified many genetic variants in genes related to lipid metabolism. However, how these variations affect lipid levels remains elusive. Long non-coding RNAs (lncRNAs) have been implicated in a variety of biological processes. We hypothesize lncRNAs are likely to be located within disease or trait-associated DNA regions to regulate lipid metabolism. The aim of this study was to investigate whether and how lncRNAs in lipid- associated DNA regions regulate cholesterol homeostasis in hepatocytes. In this study, we identified a novel long non-coding RNA in Lipid Associated Single nucleotide polymorphism gEne Region (LASER) by bioinformatic analysis. We report that LASER is highly expressed in both hepatocytes and peripheral mononuclear cells (PBMCs). Clinical studies showed that LASER expression is positively related with that of cholesterol containing apolipoprotein levels. In particular, we found that LASER is positively correlated with plasma PCSK9 levels in statin free patients. siRNAs mediated knock down of LASER dramatically reduces intracellular cholesterol levels and affects the expression of genes involved in cholesterol metabolism. Transcriptome analyses show that knockdown of LASER affects the expression of genes involved in metabolism pathways. We found that HNF-1α and PCSK9 were reduced after LASER knock-down. Interestingly, the reduction of PCSK9 can be blocked by the treatment of berberine, a natural cholesterol-lowering compound which functions as a HNF-1α antagonist. Mechanistically, we found that LASER binds to LSD1 (lysine-specific demethylase 1), a member of CoREST/REST complex, in nucleus. LASER knock-down enhance LSD1 targeting to genomic loci, resulting in decreased histone H3 lysine 4 mono-methylation at the promoter regions of HNF-1α gene. Conversely, LSD1 knock-down abolished the effect of LASER on HNF-1α and PCSK9 expressions. Finally, we found that statin treatment increased LASER expression, accompanied with increased PCSK9 expression, suggesting a feedback regulation of cholesterol on LASER expression. This observation may partly explain the statin escape during anti-cholesterol treatment. These findings identified a novel lncRNA in cholesterol homeostasis. Therapeutic targeting LASER might be an effective approach to augment the effect of statins on cholesterol levels in clinics.

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Impact of the statin escape phenomenon on long-term clinical outcomes in patients with acute myocardial infarction: Subgroup analysis of the Nagoya Acute Myocardial Infarction Study (NAMIS)

Cited by 5 publications

References 29 publications

Statin escape phenomenon: Fact or fiction?

Statin escape phenomenon: Fact or fiction?

Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2017

Regulation of Cholesterol Homeostasis by a Novel Long Non-coding RNA LASER

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