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Large Scale Cohort Study of the Relationship Between Serum Cholesterol Concentration and Coronary Events With Low-Dose Simvastatin Therapy in Japanese Patients With Hypercholesterolemia: Primary Prevention Cohort Study of the Japan Lipid Intervention Trial (J-LIT)
Open accessAbstract
Hyperlipidemia is a well-established risk factor for primary coronary heart disease (CHD). Although simvastatin is known to lower serum lipid concentrations, the protective effect of such lipid-lowering therapy against primary CHD has not been established in Japanese patients with hypercholesterolemia. The Japan Lipid Intervention Trial was a 6-year, nationwide cohort study of 47,294 patients treated with open-labeled simvastatin (5-10 mg/day) and monitored by physicians under standard clinical conditions. The aim of the study was to determine the relationship between the occurrence of CHD and the serum lipid concentrations during low-dose simvastatin treatment. Simvastatin reduced serum concentrations of total cholesterol (TC), low-density lipoprotein- cholesterol (LDL-C) and triglyceride (TG), by 18.4%, 26.8% and 16.1% on average, respectively, during the treatment period. The risk of coronary events was higher when the average TC concentration was > or =240 mg/dl and the average LDL-C concentration was > or =160 mg/dl. The incidence of coronary events increased in the patients with TG concentration > or =300 mg/dl compared with patients with TG concentration <150 mg/dl. The high-density lipoprotein cholesterol (HDL-C) inversely correlated with the risk of coronary events. The J-curve association was observed between average TC or LDL-C concentrations and total mortality. Malignancy was the most prevalent cause of death. The health of patients should be monitored closely when there is a remarkable decrease in TC and LDL-C concentrations with low-dose statin. A reasonable strategy to prevent coronary events in Japanese hypercholesterolemic patients without prior CHD under low-dose statin treatment might be regulating the serum lipid concentrations to at least <240 mg/dl for TC, <160 mg/dl for LDL-C, <300 mg/dl for TG, and >40 mg/dl for HDL-C.
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“A 9.6-year observational period in NIPPON DATA90 showed that HDL-C was significantly inversely correlated with all deaths as well as stroke-related deaths80).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [80]
In the citing paper
“Women generally have a higher HDL-C level than men46, 80, 85).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [80]
In the citing paper
“It is evident in epidemiological studies and intervention trials conducted in the Western countries that the incidence rate of cardiovascular events is higher in patients with CAD than in primary prevention patients177–179).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [179]
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“Meta-analyses conducted by the Cholesterol Treatment Trialists' Collaboration on large-scale clinical trials using statins confirmed that a decrease in the incidence of cardiovascular events was proportionate to the decrease in LDL-C level, regardless of pretreatment LDL-C level and individual absolute risk177–179, 348).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [179]
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“However, in managing dyslipidemia expressed by hypertriglyceridemia, the non-HDL-C level is more useful than the LDL-C level. This has been reported in a number of studies177–179, 623, 624, 626, 627, 647).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [179]
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Teramoto, T., Sasaki, J., Ueshima, H., Egusa, G., Kinoshita, M., Shimamoto, K., Daida, H., Biro, S., Hirobe, K., Funahashi, T., et al. (2007) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.e554 · Cited by 30
Self-citationModica, R., Salvia, A. L., Liccardi, A., Cannavale, G., Minotta, R., Benevento, E., Faggiano, A., & Colao, A. A. L. (2022) · Metabolites · doi:10.3390/metabo12111057 · Cited by 29
An assessment of risk factors for the complexity of coronary artery disease using the SYNTAX score
Tanaka, T., Seto, S., Yamamoto, K., Kondo, M., & Otomo, T. (2012) · Cardiovascular Intervention and Therapeutics · doi:10.1007/s12928-012-0112-5 · Cited by 29
Unique Features of High-Density Lipoproteins in the Japanese: In Population and in Genetic Factors
Yokoyama, S. (2015) · Nutrients · doi:10.3390/nu7042359 · Cited by 28
“The age-adjusted prevalence of myocardial infarction was obtained as events per year per population of 1000 for every segment of serum LDL-cholesterol and HDL-cholesterol concentration, from the cohort study Japan Lipid Intervention Trial (J-LIT), six-year follow-up study of 47,294 patients treated with low-dose simva…”
MethodStatin Dose in Asians: Is Pharmacogenetics Relevant?
Wang, P. (2011) · Pharmacogenomics · doi:10.2217/pgs.11.98 · Cited by 28
Kim, S., Kim, M.-K., Seo, H. S., Hyun, M., Han, K., Cho, S.-W., Kim, Y.-K., & Park, S. H. (2013) · Clinical Therapeutics · doi:10.1016/j.clinthera.2013.06.020 · Cited by 27
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Shimamoto, K., Fujita, T., Ito, S., Naritomi, H., Ogihara, T., Shimada, K., Tanaka, H., & Yoshiike, N. (2008) · Hypertension Research · doi:10.1291/hypres.31.469 · Cited by 25
Self-citationRelationship of low‐density lipoprotein (LDL) particle size to thyroid function status in Koreans
Kim, C. S., Kang, J. G., Lee, S. J., Ihm, S. H., Yoo, H. J., Nam, J. S., Ahn, C. W., & Kim, K. R. (2008) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2008.03436.x · Cited by 24
Horiuchi, H., Kita, T., Mabuchi, H., Matsuzaki, M., Matsuzawa, Y., Nakaya, N., Oikawa, S., Saitō, Y., Sasaki, J., Shimamoto, K., et al. (2004) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2004.52552.x · Cited by 25
“The overall results of the study clearly showed that the risk of CHD was positively correlated with LDL-C level and inversely correlated with HDL-C level in Japanese patients with hypercholesterolemia.(14,15) In this report, the J-LIT data of patients aged 65 to 70 without prior CHD were compared with those of patient…”
ResultSelf-citationSakabe, K., Fukuda, N., Wakayama, K., Nada, T., Shinohara, H., & Tamura, Y. (2003) · Circulation Journal · doi:10.1253/circj.67.866 · Cited by 25
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Kwon, D., Yi, J., Ohrr, H., & Yi, S. (2019) · Medicine · doi:10.1097/md.0000000000017013 · Cited by 24
Yanai (2014) · Journal of Clinical Medicine Research · doi:10.14740/jocmr1884w · Cited by 24
Pitavastatin and HDL: Effects on plasma levels and function(s)
Pirillo, A., & Catapano, A. L. (2017) · Atherosclerosis Supplements · doi:10.1016/j.atherosclerosissup.2017.05.001 · Cited by 24
Yokoi, H., Nobuyoshi, M., Mitsudo, K., Kawaguchi, A., & Yamamoto, A. (2005) · Circulation Journal · doi:10.1253/circj.69.875 · Cited by 29
Hosomi, R., Fukunaga, K., Arai, H., Kanda, S., Nishiyama, T., & Yoshida, M. (2011) · Journal of Medicinal Food · doi:10.1089/jmf.2011.1620 · Cited by 24
Hashimoto, A., Nakata, T., Wakabayashi, T., Kusuoka, H., & Nishimura, T. (2009) · Circulation Journal · doi:10.1253/circj.cj-09-0212 · Cited by 23
Effect of concomitantly used fish oil and cholesterol on lipid metabolism
Hirako, S., Kim, H. J., Arai, T., Chiba, H., & Matsumoto, A. (2009) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2009.02.013 · Cited by 23
Effect of Atorvastatin on Type 2 Diabetic Dyslipidemia
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“oronary events not g effects but also cular wall.(8) Statins ll cycle progression, lar smooth muscle esses, and benefi-term statin therapy From the Department of Biochemistry (VS, NP) and the Department of Medicine (NM, GR), Lokamanya Tilak Municipal Medical College and General Hospital, Sion, Mumbai, India.”
BackgroundEffect of pravastatin on coronary plaque volume
Ishikawa, K., Tani, S., Watanabe, I., Matsumoto, M., Furukawa, K., Nomoto, K., Nomoto, K., Kushiro, T., Nagao, K., & Kanmatsuse, K. (2003) · The American Journal of Cardiology · doi:10.1016/s0002-9149(03)00982-2 · Cited by 23
Treatment of Hyperlipidemia from Japanese Evidence
Koba, S., & Sasaki, J. D. (2006) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.13.267 · Cited by 22
Self-citationYagi, K., Hifumi, S., Nohara, A., Higashikata, T., Inazu, A., Mizuno, K.-O., Namura, M., Ueda, K., Kobayashi, J., Shimizu, M., et al. (2004) · Circulation Journal · doi:10.1253/circj.68.623 · Cited by 22
Self-citationStatins in cardiometabolic disease: what makes pitavastatin different?
Ginsberg, H. N. (2013) · Cardiovascular Diabetology · doi:10.1186/1475-2840-12-s1-s1 · Cited by 25
Shimamoto, K., Kita, T., Mabuchi, H., Matsuzaki, M., Matsuzawa, Y., Nakaya, N., Oikawa, S., Saitō, Y., Sasaki, J., & Itakura, H. (2005) · Hypertension Research · doi:10.1291/hypres.28.879 · Cited by 21
“The Japan Lipid Intervention Trial (J-LIT) study is a nationwide cohort study including a large number of hypercholesterolemic patients treated with open-labeled simvastatin (5 to 10 mg/day); the J-LIT study was carried out for 6 years by a large number of physicians using standard clinical practices to evaluate the r…”
BackgroundMethodSelf-citationLow-dose statin treatment increases prostate cancer aggressiveness
Caro‐Maldonado, A., Camacho, L., Zabala‐Letona, A., Torrano, V., Fernández‐Ruiz, S., Zamacola, K., Arreal, L., Valcárcel-Jiménez, L., Martín-Martín, N., Flores, J. M., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.22217 · Cited by 23
Coronary heart disease risk in Japan ? an East/West divide?
KITA, T. (2004) · European Heart Journal Supplements · doi:10.1016/j.ehjsup.2004.01.003 · Cited by 21
Self-citation
Metadata
- Authors
- Matsuzaki, M., Kita, T., Mabuchi, H., Matsuzawa, Y., Nakaya, N., Oikawa, S., Saito, Y., Sasaki, J., Shimamoto, K., Itakura, H., & the J-LIT Study Group
- Affiliations
- Yamaguchi University (JP)
- Kyoto University (JP)
- Kanazawa University (JP)
- Osaka University Graduate School of Medicine
- Fussa Hospital (JP)
- Nippon Medical School (JP)
- Chiba University Graduate School of Medicine
- International University Graduate School of Health and Welfare
- Sapporo Medical University (JP)
- Ibaraki Christian University (JP)
- ORCID
- Oikawa, Shinichi
- Venue
- Circulation Journal
- Publisher
- Japanese Circulation Society
- Published
- 2002
- Volume
- 66
- Issue
- 12
- Pages
- 1087-1095
- ISSN
- 1346-9843 (ISSN-L)
- 1347-4820
- OpenAlex
- W2004878568
- Cited by
- 260
- References
- 52
- Citations by year
- 2025: 1 · 2024: 5 · 2023: 7 · 2022: 7 · 2021: 6 · 2020: 6 · 2019: 4 · 2018: 12 · 2017: 4 · 2016: 9 · 2015: 10 · 2014: 17 · 2013: 17 · 2012: 12
- FWCI
- 14.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation Journal (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
- Kanazawa University Repository for Academic Resources (DSpace) (Kanazawa University) (submittedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Keywords
- simvastatin, hypercholesterolemia, coronary artery disease, serum cholesterol, LDL cholesterol, triglycerides, HDL cholesterol, J-curve, lipid-lowering therapy, all-cause mortality, statin therapy, Japanese patients
- MeSH terms
- Adult, Aged, Anticholesteremic Agents, Cholesterol, Coronary Disease, Dose-Response Relationship, Drug, Female, Follow-Up Studies, Humans, Hypercholesterolemia, Lipids, Male, Middle Aged, Osmolar Concentration, Risk Factors, Safety, Cohort Studies, Incidence, Simvastatin
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