High lipoprotein(a) level promotes both coronary atherosclerosis and myocardial infarction: a path analysis using a large number of autopsy cases
- M Sawabe1,
- N Tanaka2,
- K Nakahara3,
- A Hamamatsu1,
- K Chida1,
- T Arai1,
- K Harada4,
- T Inamatsu4,
- T Ozawa4,
- M M Naka5,
- S Matsushita4
- 1Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan
- 2Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA
- 3Nagasaki Medical Center, Omura, Japan
- 4Department of Internal Medicine, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan
- 5Department of Medical Informatics, Center for Information, Jichi Medical University, Shimotsuke, Japan
- Correspondence to Dr Motoji Sawabe, Department of Pathology, Tokyo Metropolitan Geriatric Hospital, 35-2 Sakae-cho, Itabashi, Tokyo 173-0015, Japan; sawabe{at}tmig.or.jp
- Accepted 11 August 2009
- Published Online First 25 August 2009
Abstract
Objective: To investigate whether hyper-lipoproteinaemia(a) (Lp(a)) promotes coronary atherosclerosis, acute thrombosis resulting in myocardial infarction (MI), or both.
Design: Retrospective chart review.
Setting: A community-based general geriatric hospital.
Patients: 1062 consecutive autopsy cases (609 men, 453 women). The mean age at the time of death was 80 years.
Main outcome measures: A semiquantitative evaluation of the coronary stenosis on cut sections and pathological definition of MI. Lp(a) levels of fresh serum taken antemortem, measured by a latex-enhanced turbidimetric immunoassay.
Results: The prevalence of severe coronary stenosis and pathological MI increased linearly with increasing Lp(a) levels with no apparent threshold. The odds ratios (95% CI) of hyper-Lp(a) (2.99 (1.70 to 5.28) for 200–299 mg/l and 3.25 (1.90 to 5.54) for >300 mg/l) for severe coronary stenosis were larger than those of hypertension (2.61 (1.88 to 3.63)), diabetes mellitus (2.09 (1.41 to 3.11)) and hypercholesterolaemia (2.05 (1.31 to 3.21)). The severe coronary sclerosis was much stronger risk of MI (6.28 (4.33 to 9.11)) than hyper-Lp(a), hypertension and diabetes mellitus. A path analysis showed that the Lp(a) levels affected both coronary sclerosis and MI, with path coefficients of 0.15 and 0.07 (direct effect), respectively. In cases with severe coronary sclerosis Lp(a) affected only MI (0.15).
Conclusions: Lp(a) levels have distinct effects on coronary sclerosis and MI, with about half of the overall effect on MI being via coronary sclerosis. This result supports the prothrombotic and a probable proinflammatory role of Lp(a) in coronary events.
Footnotes
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‣ Additional tables and figures are published online only at http://heart.bmj.com/content/vol95/issue24
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MS and NT contributed equally to this work.
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Funding This study was supported in part by a Grant-in-aid for Scientific Research (C) (No 19590377) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.
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Competing interests None.
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Ethics approval Written informed consent, including consent for the use of the antemortem sera, was obtained from the bereaved family of each of the patients before the autopsy examination. The use of autopsy materials for medical education and research is generally permitted by the Act of Postmortem Examinations of Japan. This study was approved by the ethics committee of Tokyo Metropolitan Geriatric Hospital (#381).
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Provenance and Peer review Not commissioned; externally peer reviewed.
