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European Heart Journal Advance Access originally published online on April 11, 2005
European Heart Journal 2005 26(16):1633-1639; doi:10.1093/eurheartj/ehi222
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© The European Society of Cardiology 2005. All rights reserved. For Permissions, please e-mail: journals.permissions@oupjournals.org

Lipoprotein (a) and coronary heart disease among women: beyond a cholesterol carrier?

Iris Shai1,2,7,*, Eric B. Rimm1,2,3, Susan E. Hankinson2,3, Carolyn Cannuscio4, Gary Curhan3, JoAnn E. Manson2,3,5, Nader Rifai6, Meir J. Stampfer1,2,3 and Jing Ma2,3

1Department of Nutrition, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA
2Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA
3Channing Laboratory, Department of Medicine, Brigham Women Hospital and Harvard Medical School, Boston, MA, USA
4Merck Research Laboratories, Merck & Co. Inc., Whitehouse Station, NJ, USA
5Division of Preventive Medicine, Department of Medicine, Brigham Women Hospital and Harvard Medical School, Boston, MA, USA
6Department of Laboratory Medicine, Children's Hospital and Harvard Medical School, Boston, MA, USA
7Department of Epidemiology, S. Daniel Abraham International Center for Health and Nutrition, Ben-Gurion University, Beer-Sheva, Israel

Received 21 May 2004; revised 21 December 2004; accepted 17 February 2005; online publish-ahead-of-print 11 April 2005.

* Corresponding author. Tel: +972 8 6477449; fax: +972 8 6477638. E-mail address: ishai{at}hsph.harvard.edu

Aims With its homology with plasminogen, lipoprotein(a) [Lp(a)] may be related to thrombosis and inflammation. We assessed the role of Lp(a) in coronary heart diseases (CHD) by a recently developed assay that is not affected by the plasminogen-like Kringle-type- 2 repeats.

Methods and results Of 32 826 women from the Nurses' Health Study, who provided blood at baseline, we documented 228 CHD events during 8 years of follow-up. Each case was compared with two matched controls. In a multivariable model adjusted for body mass index, family history, hypertension, diabetes, post-menopausal hormone use, physical activity, blood drawing characteristics, and alcohol intake, the odd ratio (OR) for Lp(a) levels ≥30 mg/dL was 1.9(95% CI: 1.3–3.0) when compared with those with Lp(a)<30 mg/dL. Women with high levels of both Lp(a) (≥30 mg/dL) and fibrinogen (≥400 mg/dL) had an OR of 3.2(95% CI: 1.6–6.5) for CHD, when compared with the combination of low levels (P interaction=0.05). Women with high levels of both Lp(a) and C-reactive protein (≥3 mg/L) had an OR of 3.67(95% CI: 2.03–6.64) for CHD, when compared with the combination of low levels (P interaction=0.06).

Conclusion Lp(a) levels >30 mg/dL are associated with twice the risk of CHD events among women and may be related to thrombosis and inflammation.

Key Words: CHD • Lipoprotein(a) • Apolipoprotein(a) • Fibrinogen • C-reactive protein


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