Risk factors for stroke and lipid-lowering effect of pravastatin on the risk of stroke in Japanese patients with hypercholesterolemia: Analysis of data from the MEGA Study, a large randomized controlled trial
Abstract
Background The aims of this study were to clarify the risk factors for stroke, and to investigate the effect of low-density lipoprotein cholesterol (LDL-C) lowering with pravastatin on the risk of stroke, in Japanese mild-to-moderately hypercholesterolemic patients enrolled in the MEGA Study.Methods Multivariate Cox proportional hazard model was used to determine the baseline risk factors for stroke. The proportion of treatment effect (PTE) explained by on-treatment LDL-C levels was estimated.Results In 7832 patients at risk, a total of 99 strokes were observed during the 5-year follow-up period. Significant relationships were observed between stroke and traditional risk factors such as male sex, advanced age, low high-density lipoprotein cholesterol (HDL-C), high lipoprotein(a) (Lp[a]), hypertension, diabetes, obesity, and smoking. In the pravastatin group, hazard ratio (HR) for stroke adjusted by on-treatment lipid level was lower than the unadjusted value versus control (HR [95%CI], 0.48 [0.26-0.87] and 0.59 [0.38-0.92], respectively)--giving a negative PTE of -38.6% and suggesting that the risk reduction could not be explained by LDL-C lowering alone.Conclusions Male sex, aging, hypertension, diabetes, low HDL-C, high Lp(a), obesity, and smoking were determined as risk factors for stroke in Japanese patients with hypercholesterolemia, and the observed risk reduction could not be explained by pravastatin's LDL-C-lowering effect alone, suggesting pleiotropic effects.
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The effectiveness of statins to decrease the incidence of atherothrombotic cerebral infarction was confirmed in a Japanese population by the J-STARS study.
“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 [619]
Statin therapy may prevent the development of cerebral infarction.
“Statin therapy may prevent the development of cerebral infarction. (Evidence level: 2, recommendation level: A)”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [619]
In terms of secondary prevention of noncardiogenic cerebral infarction, statin therapy has suppressive effects on atherothrombotic cerebral infarction incidence.
“In terms of secondary prevention of noncardiogenic cerebral infarction, these results suggest that statin therapy has suppressive effects on atherothrombotic cerebral infarction incidence.”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [619]
In J-STARS, the incidence rate of intracranial hemorrhage was the same as the non-statin group (hazard ratio 1.00).
“Meanwhile, the incidence rate of intracranial hemorrhage was the same as the non-statin group (hazard ratio 1.00)619).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [619]
Regarding the results of SPARCL, which are contrary to those of a meta-analysis, it has been shown that hemorrhage incidence does not increase in the Japanese.
“Moreover, in regard to the results of SPARCL, which are contrary to those of a meta-analysis348) in which increased incidence of cerebral hemorrhage because of statin administration was not observed, it has been shown that hemorrhage incidence does not increase in the Japanese.”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [619]
In J-STARS, Japanese subjects with ischemic stroke excluding those with cardiogenic cerebral embolism, the pravastatin group had a significantly decreased incidence rate of atherothrombotic cerebral infarction (hazard ratio 0.33) compared with the non-pravastatin group.
“The J-STARS study involved Japanese subjects with ischemic stroke, excluding those with cardiogenic cerebral embolism. The results of a comparison between the pravastatin group and the non-pravastatin group revealed that the former had a significantly decreased incidence rate of atherothrombotic cerebral infarction (hazard ratio 0.33).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [619]
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- Authors
- Uchiyama, S., Nakaya, N., Mizuno, K., Ohashi, Y., Tajima, N., Kushiro, T., Teramoto, T., & Nakamura, H.
- Affiliations
- Tokyo Women's Medical University (JP)
- Nippon Medical School (JP)
- The University of Tokyo (JP)
- Jikei University School of Medicine (JP)
- Nihon University (JP)
- Teikyo University (JP)
- Mitsukoshi Health and Welfare Foundation (JP)
- Corresponding author
- Uchiyama, Shinichiro
- Venue
- Journal of the Neurological Sciences
- Publisher
- Elsevier BV
- Published
- 2009-09
- Volume
- 284
- Issue
- 1-2
- Pages
- 72-76
- ISSN
- 0022-510X (ISSN-L)
- OpenAlex
- W1979783879
- Cited by
- 32
- References
- 36
- Citations by year
- 2024: 1 · 2023: 3 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 1 · 2015: 3 · 2014: 7 · 2013: 3 · 2012: 3
- FWCI
- 2.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the Neurological Sciences (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- stroke risk factors, pravastatin, hypercholesterolemia, LDL cholesterol lowering, MEGA study, Japanese patients, lipoprotein(a), HDL cholesterol, hypertension, diabetes mellitus, obesity, smoking, pleiotropy
- MeSH terms
- Adult, Aged, Alcohol Drinking, Cholesterol, Combined Modality Therapy, Diabetes Mellitus, Female, Follow-Up Studies, Humans, Hypercholesterolemia, Hypertension, Japan, Male, Middle Aged, Obesity, Risk Factors, Sex Factors, Smoking, Comorbidity, Incidence, Proportional Hazards Models, Randomized Controlled Trials as Topic, Pravastatin, Lipoprotein(a), Hydroxymethylglutaryl-CoA Reductase Inhibitors, Stroke
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