LDL Cholesterol and the Development of Stroke Subtypes and Coronary Heart Disease in a General Japanese Population: The Hisayama Study
Abstract
Background and Purpose— Although the relation between serum LDL cholesterol level and coronary heart disease (CHD) is well established, its relation with stroke subtypes is less clear. Methods— A total of 2351 inhabitants age ≥40 years in a Japanese community were followed up for 19 years. Results— During follow-up, 271 subjects developed stroke and 144 developed CHD. Whereas the age- and sex-adjusted incidences of CHD significantly increased with increasing LDL cholesterol levels ( P for trend <0.001), the associations between LDL cholesterol level and the incidences of ischemic or hemorrhagic stroke were not significant. The age- and sex-adjusted incidences of atherothrombotic infarctions (ATIs) and lacunar infarctions (LIs) significantly increased with increasing LDL cholesterol level ( P for trend=0.03 for ATIs and=0.02 for LIs), but no such association was observed for cardioembolic infarction. After multivariate adjustment, the positive associations of LDL cholesterol level with the risks of ATI and CHD remained significant ( P for trend=0.02 for ATIs and=0.03 for CHD), whereas the association with LIs was not significant. The risk of ATI significantly increased in the fourth quartile of LDL cholesterol compared with the first quartile (multivariate-adjusted hazard ratio=2.84; 95% CI, 1.17 to 6.93). The multivariate-adjusted risks for developing nonembolic infarction (ATIs and LIs) and CHD were significantly elevated in the groups with elevated LDL cholesterol values with and without the metabolic syndrome. Conclusions— Our findings suggest that an elevated LDL cholesterol level is a significant risk factor for developing ATI as well as CHD, and these associations are independent of the metabolic syndrome.
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The increase in hazard ratio for CAD incidence and mortality following LDL-C elevation has been validated in Japanese cohort studies.
“the increase in hazard ratio for the CAD incidence and mortality following an elevation in LDL-C has been validated in cohort studies involving the Japanese36–40).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [36]
Elevated LDL-C increases the risk for cerebral thrombosis, except lacunar infarction, among ischemic stroke subtypes.
“An elevated LDL-C level also increased the risk for cerebral thrombosis (except lacunar infarction) among the subtypes of ischemic stroke36).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [36]
Among stroke cases, the percentage of atherothrombotic cerebrovascular disease in which LDL-C was a risk factor is approximately 20%.
“among stroke cases, the percentage of atherothrombotic cerebrovascular disease in which LDL-C was a risk factor is approximately 20%36)”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [36]
LDL-C is a risk factor for atherothrombotic cerebral infarction.
“LDL-C is also a risk factor for atherothrombotic cerebral infarction36), and the effectiveness of statins to decrease the incidence of atherothrombotic cerebral infarction was confirmed in a Japanese population by the J-STARS study619).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [36]
The Hisayama study demonstrated that the LDL-C level is a risk factor for atherothrombotic cerebral infarction.
“The results of the Hisayama study, which investigated cerebral infarction risk by type, demonstrated that the LDL-C level is a risk factor for atherothrombotic cerebral infarction.”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [36]
Epidemiological studies conducted in Japan have indicated that there is no significant relationship between the serum cholesterol levels (TC, LDL-C, and non-HDL-C) and the incidence rate of noncardiogenic cerebral infarction.
“However, the results of epidemiological studies conducted in Japan have indicated that there is no significant relationship between the serum cholesterol levels (TC, LDL-C, and non-HDL-C) and the incidence rate of noncardiogenic cerebral infarction36, 38, 40, 57, 64, 78, 337).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [36]
The LDL-C level is not related to the incidence of other types of cerebral infarction.
“However, the LDL-C level is not related to the incidence of other types of cerebral infarction36).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [36]
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- Authors
- Imamura, T., Doi, Y., Arima, H., Yonemoto, K., Hata, J., Kubo, M., Tanizaki, Y., Ibayashi, S., Iida, M., & Kiyohara, Y.
- Affiliations
- Kyushu University (JP)
- Venue
- Stroke
- Published
- 2009-02
- Volume
- 40
- Issue
- 2
- Pages
- 382-388
- ISSN
- 0039-2499 (ISSN-L)
- 1524-4628
- OpenAlex
- W2053503164
- Cited by
- 235
- References
- 37
- Citations by year
- 2026: 11 · 2025: 11 · 2024: 13 · 2023: 16 · 2022: 14 · 2021: 9 · 2020: 16 · 2019: 22 · 2018: 20 · 2017: 10 · 2016: 12 · 2015: 7 · 2014: 9 · 2013: 18 · 2012: 9
- FWCI
- 13.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Stroke (publishedVersion)
- PubMed (publishedVersion)
- Funders
- H2020 European Research Council
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Risk Factors
- Keywords
- LDL cholesterol, stroke subtypes, coronary artery disease, atherothrombotic infarction, lacunar infarction, cardioembolic stroke, metabolic syndrome, stroke risk factors, Japanese population
- MeSH terms
- Age Factors, Aged, Analysis of Variance, Cardiovascular Diseases, Coronary Disease, Female, Follow-Up Studies, Health Surveys, Humans, Japan, Cholesterol, LDL, Male, Middle Aged, Myocardial Infarction, Terminology as Topic, Prospective Studies, Risk Factors, Sex Factors, Cohort Studies, Stroke
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