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(Circulation. 2008;117:176-184.)
© 2008 American Heart Association, Inc.

Epidemiology

Extreme Lipoprotein(a) Levels and Risk of Myocardial Infarction in the General Population

The Copenhagen City Heart Study

Pia R. Kamstrup, MD; Marianne Benn, MD, PhD; Anne Tybjærg-Hansen, MD, DMSc; Børge G. Nordestgaard, MD, DMSc

From the Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital (P.R.K., M.B., B.G.N.); Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital (A.T.-H.); and the Copenhagen City Heart Study, Bispebjerg Hospital, Copenhagen University Hospital, University of Copenhagen (A.T.-H., B.G.N.), Copenhagen, Denmark.

Correspondence to Børge G. Nordestgaard, MD, DMSc, Department of Clinical Biochemistry, Herlev University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark. E-mail brno{at}heh.regionh.dk

Received May 21, 2007; accepted October 26, 2007.

Background— Elevated lipoprotein(a) levels are associated with myocardial infarction (MI) in some but not all studies. Limitations of previous studies include lack of risk estimates for extreme lipoprotein(a) levels, measurements in long-term frozen samples, no correction for regression dilution bias, and lack of absolute risk estimates in the general population. We tested the hypothesis that extreme lipoprotein(a) levels predict MI in the general population, measuring levels shortly after sampling, correcting for regression dilution bias, and calculating hazard ratios and absolute risk estimates.

Methods and Results— We examined 9330 men and women from the general population in the Copenhagen City Heart Study. During 10 years of follow-up, 498 participants developed MI. In women, multifactorially adjusted hazard ratios for MI for elevated lipoprotein(a) levels were 1.1 (95% CI, 0.6 to 1.9) for 5 to 29 mg/dL (22nd to 66th percentile), 1.7 (1.0 to 3.1) for 30 to 84 mg/dL (67th to 89th percentile), 2.6 (1.2 to 5.9) for 85 to 119 mg/dL (90th to 95th percentile), and 3.6 (1.7 to 7.7) for 120 mg/dL (>95th percentile) versus levels <5 mg/dL (<22nd percentile). Equivalent values in men were 1.5 (0.9 to 2.3), 1.6 (1.0 to 2.6), 2.6 (1.2 to 5.5), and 3.7 (1.7 to 8.0). Absolute 10-year risks of MI were 10% and 20% in smoking, hypertensive women aged >60 years with lipoprotein(a) levels of <5 and 120 mg/dL, respectively. Equivalent values in men were 19% and 35%.

Conclusions— We observed a stepwise increase in risk of MI with increasing levels of lipoprotein(a), with no evidence of a threshold effect. Extreme lipoprotein(a) levels predict a 3- to 4-fold increase in risk of MI in the general population and absolute 10-year risks of 20% and 35% in high-risk women and men.

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