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Effects of an Inhibitor of 3-Hydroxy-3-Methylglutaryl Coenzyme a Reductase on Serum Lipoproteins and Ubiquinone-10 Levels in Patients with Familial Hypercholesterolemia
Abstract
We studied the effects of ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on serum levels of lipoproteins and ubiquinone-10-in seven heterozygous patients with familial hypercholesterolemia. ML-236B was given at doses of 30 to 60 mg per day for 24 weeks. Serum cholesterol decreased from 390 +/- 9 to 303 +/- 8 mg per deciliter (101 +/- 0.2 to 7.88 +/- 0.2 mmol per liter, mean +/- S.E.M.; p less than 0.001) and serum triglyceride decreased from 137 +/- 18 to 87 +/- 9 mg per deciliter (1.55 +/- 0.20 to 0.98 +/- 0.01 mmol per liter; p less than 0.05). Intermediate-density-lipoprotein (DL) cholesterol, IDL triglyceride, low-density-lipoprotein (LDL) cholesterol, and LDL triglyceride decreased significantly (p less than 0.01, P less than 0.001, and P less than 0.001, respectively). However, there were no significant changes in very-low-density-lipoprotein (VLDL) cholesterol and triglyceride or high-density-lipoprotein (HDL) cholesterol. Serum ubiquinone-10 levels did not change, and LDL levels of ubiquinone-10 decreased by 50 per cent, from 0.39 +/- 0.07 to 0.20 +/- 0.01 microgram per milliliter (P less than 0.05). No adverse effects were observed. We conclude that ML-236B is effective in lowering serum cholesterol without lowering serum ubiquinone-10 in heterozygous patients with familial hypercholesterolemia.
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“Meanwhile, the co-administration of a nicotinic acid derivative (niacin) and statin to increase HDL-C levels did not have a suppressive effect on cardiovascular events in the AIM-HIGH653) and HPS2-THRIVE654) studies.”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [654]
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Metadata
- Authors
- Mabuchi, H., Haba, T., Tatami, R., Miyamoto, S., Sakai, Y., Wakasugi, T., Watanabe, A., Koizumi, J., & Takeda, R.
- Affiliations
- Kanazawa University (JP)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1981-08-27
- Volume
- 305
- Issue
- 9
- Pages
- 478-482
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2051105453
- Cited by
- 262
- References
- 41
- Citations by year
- 2025: 2 · 2024: 6 · 2023: 8 · 2022: 2 · 2021: 6 · 2020: 5 · 2019: 3 · 2018: 3 · 2017: 6 · 2016: 3 · 2015: 3 · 2014: 5 · 2013: 2 · 2012: 2
- FWCI
- 25.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
- Keywords
- ML-236B, statins, familial hypercholesterolemia, serum cholesterol, serum triglycerides, lipoproteins, LDL cholesterol, intermediate density lipoprotein, ubiquinone-10
- MeSH terms
- Adult, Aged, Cholesterol, Female, Heterozygote, Humans, Hyperlipoproteinemia Type II, Lipoproteins, Lipoproteins, HDL, Lipoproteins, LDL, Lipoproteins, VLDL, Lovastatin, Male, Middle Aged, Naphthalenes, Triglycerides, Ubiquinone, Hydroxymethylglutaryl-CoA Reductase Inhibitors
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