Low-Density Lipoprotein Cholesterol Concentrations and Death Due to Intraparenchymal Hemorrhage: The Ibaraki Prefectural Health Study
Abstract
Background— Few studies have examined the association between low levels of low-density lipoprotein (LDL) cholesterol and risk of intraparenchymal hemorrhage. Methods and Results— A total of 30 802 men and 60 417 women, 40 to 79 years of age with no history of stroke or coronary heart disease, completed a baseline risk factor survey in 1993 under the auspices of the Ibaraki Prefectural Health Study. Systematic mortality surveillance was performed through 2003, and 264 intraparenchymal hemorrhage deaths were identified. LDL cholesterol levels were calculated with the Friedewald formula. Persons with LDL cholesterol ≥140 mg/dL had half the sex- and age-adjusted risk of death due to intraparenchymal hemorrhage of those with LDL cholesterol <80 mg/dL. After adjustment for cardiovascular risk factors, the multivariable hazard ratio compared with persons with LDL cholesterol <80 mg/dL was 0.65 (95% CI 0.44 to 0.96) for those with LDL cholesterol 80 to 99 mg/dL, 0.48 (0.32 to 0.71) for 100 to 119 mg/dL, 0.50 (0.33 to 0.75) for 120 to 139 mg/dL, and 0.45 (0.30 to 0.69) for ≥140 mg/dL. These inverse associations were not altered substantially after the exclusion of persons with hypertriglyceridemia, after analysis with a Cox proportional hazard model with time-dependent covariates, or in sensitivity analysis for the potential effect of competing risks. Conclusions— Low LDL cholesterol levels are associated with elevated risk of death due to intraparenchymal hemorrhage.
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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 [40]
High LDL-C levels are negatively related to hemorrhagic stroke, primarily intracerebral hemorrhage.
“there was a negative relationship between hemorrhagic stroke (primarily intracerebral hemorrhage) and a decrease in hazard ratio in the groups with high LDL-C levels40).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [40]
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 [40]
Many reports, including those from Japan, have stated that hypocholesterolemia is a risk factor for cerebral hemorrhage.
“Many reports, including those from Japan, have stated that hypocholesterolemia is a risk factor for cerebral hemorrhage40, 858).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [40]
In Japan, an LDL-C level of 80 mg/dL or less has been reported to increase the cerebral hemorrhage incidence.
“In Japan, an LDL-C level of 80 mg/dL or less has also been reported to increase the cerebral hemorrhage incidence40).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [40]
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- Authors
- Noda, H., Iso, H., Irie, F., Sairenchi, T., Ohtaka, E., Doi, M., Izumi, Y., & Ohta, H.
- Affiliations
- Ministry of the Environment (JP)
- Venue
- Circulation
- Published
- 2009-04-28
- Volume
- 119
- Issue
- 16
- Pages
- 2136-2145
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W1979346724
- Cited by
- 150
- References
- 40
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 3 · 2023: 8 · 2022: 15 · 2021: 6 · 2020: 12 · 2019: 9 · 2018: 8 · 2017: 5 · 2016: 7 · 2015: 9 · 2014: 7 · 2013: 8 · 2012: 7
- FWCI
- 8.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Centers for Disease Control and Prevention
- Topics
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Keywords
- LDL cholesterol, intraparenchymal hemorrhage, low LDL cholesterol, stroke risk factors, hypertriglyceridemia, competing risks, Friedewald formula
- MeSH terms
- Adult, Aged, Female, Follow-Up Studies, Humans, Japan, Cholesterol, LDL, Male, Middle Aged, Prospective Studies, Risk Factors, Survival Rate, Multivariate Analysis, Proportional Hazards Models, Intracranial Hemorrhages, Asian People
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