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Clinical Chemistry 50: 1364-1371, 2004. First published May 20, 2004; 10.1373/clinchem.2003.030031
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Right arrow Lipids, Lipoproteins, and Cardiovascular Risk Factors
(Clinical Chemistry. 2004;50:1364-1371.)
© 2004 American Association for Clinical Chemistry, Inc.


Lipids, Lipoproteins, and Cardiovascular Risk Factors

Apolipoprotein(a) Size and Lipoprotein(a) Concentration and Future Risk of Angina Pectoris with Evidence of Severe Coronary Atherosclerosis in Men: The Physicians’ Health Study

Nader Rifai1,a, Jing Ma2, Frank M. Sacks4, Paul M. Ridker3, Wendy Jade L. Hernandez4, Meir J. Stampfer2,4,5 and Santica M. Marcovina6

1 Department of Laboratory Medicine, Children’s Hospital and Harvard Medical School, Boston, MA. 2 Channing Laboratory and 3 Center for Cardiovascular Disease Prevention, Divisions of Preventive Medicine and Cardiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA. Departments of 4 Nutrition and 5 Epidemiology, Harvard School of Public Health, Boston, MA. 6 Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, WA.

aAddress correspondence to this author at: Department of Laboratory Medicine, Children’s Hospital, 300 Longwood Ave., Boston MA 02115. Fax 617-713-4347; e-mail nader.rifai{at}tch.harvard.edu.

Background: The relationship of lipoprotein (a) [Lp(a)] concentrations with risk of coronary heart disease needs clarification, especially for threshold values for increased risk and for possible interactions with LDL-cholesterol concentrations and apolipoprotein (a) [apo(a)] size polymorphism. This study was designed to examine the ability of baseline Lp(a) concentration and apo(a) size to predict future severe angina pectoris in apparently healthy men.

Methods: Baseline Lp(a) concentration and apo(a) size were determined in 195 men who subsequently developed angina and in 195 men who remained free of cardiovascular disease for 5 years.

Results: Cases had higher median Lp(a) concentrations than did controls (30.6 vs 22.5 nmol/L; P = 0.02). Lp(a) concentration was predictive of angina [relative risk (RR) from lowest to highest quintiles: 1.0, 1.5, 1.0, 1.8, and 2.6; P for trend = 0.015]. The increased risk was ~4-fold (95% confidence interval, 1.4- to 11-fold) among men who had Lp(a) above the 95th percentile (>158 nmol/L). Men with Lp(a) concentrations in the highest quintile and LDL-cholesterol concentrations >1600 mg/L had a 12-fold increased risk (95% confidence interval, 1.5- to 43-fold). Small apo(a) size isoforms also significantly predicted risk of angina (RR for lowest quintile = 4.1; P for trend = 0.004). When the independent effect of Lp(a) concentration and apo(a) size was assessed by including them in the same multivariate model, only the association between apo(a) size and risk remained significant.

Conclusions: High Lp(a) predicts risk of angina, and the risk is substantially increased with high concomitant LDL-cholesterol. Small apo(a) size predicts angina with greater strength and independence than Lp(a) concentration.




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