(Circulation. 2000;102:1082.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Lipoprotein(a) and Coronary Heart Disease
Meta-Analysis of Prospective Studies
From the Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Clinical Medicine, University of Oxford, Radcliffe Infirmary, Oxford, UK.
Correspondence to Dr John Danesh, CTSU, Radcliffe Infirmary, Oxford OX2 6HE, UK.
Background—Studies of the association between the plasma concentration of lipoprotein(a) [Lp(a)] and coronary heart disease (CHD) have reported apparently conflicting findings. We report a meta-analysis of the prospective studies with at least 1 year of follow-up published before 2000.
Methods and Results—The following information was abstracted for each study: geographical location of study, size, type of cohort (population-based or selected because of previous disease), mean age, follow-up duration, blood storage temperature and duration, assay methods, degree of adjustment for potential confounders, and relationship of baseline Lp(a) measurement with subsequent CHD risk. There were 5436 deaths from CHD or nonfatal myocardial infarctions during a weighted mean follow-up of 10 years in the 27 eligible studies. Comparison of individuals in the top third of baseline plasma Lp(a) measurements with those in the bottom third in each study yielded a combined risk ratio of 1.6 (95% CI 1.4 to 1.8, 2P<0.00001), with similar findings when the analyses were restricted to the 18 studies of general populations (combined risk ratio 1.7, 95% CI 1.4 to 1.9; 2P<0.00001). Despite differences among studies in blood storage techniques and assay methods, there was no significant heterogeneity among the results from the 18 population-based studies or among those from the 9 studies of patients with previous disease. Lp(a) was only weakly correlated with classical vascular risk factors, and adjustment for those that had been recorded made little difference to the reported risk ratios.
Conclusions—These prospective studies demonstrate a clear association between Lp(a) and CHD, but further studies are needed to determine the extent to which this is causal.
Key Words: lipoproteins • coronary disease • meta-analysis
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K. Hoffmann, B.-C. Zyriax, H. Boeing, and E. Windler A dietary pattern derived to explain biomarker variation is strongly associated with the risk of coronary artery disease Am. J. Clinical Nutrition, September 1, 2004; 80(3): 633 - 640. [Abstract] [Full Text] [PDF]
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N. Rifai, J. Ma, F. M. Sacks, P. M. Ridker, W. J. L. Hernandez, M. J. Stampfer, and S. M. Marcovina 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 Clin. Chem., August 1, 2004; 50(8): 1364 - 1371. [Abstract] [Full Text] [PDF]
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P. M Ridker, N. J. Brown, D. E. Vaughan, D. G. Harrison, and J. L. Mehta Established and Emerging Plasma Biomarkers in the Prediction of First Atherothrombotic Events Circulation, June 29, 2004; 109(25_suppl_1): IV-6 - IV-19. [Full Text] [PDF]
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S. C. Smith Jr, R. V. Milani, D. K. Arnett, J. R. Crouse III, M. M. McDermott, P. M Ridker, R. S. Rosenson, K. A. Taubert, and P. W.F. Wilson Atherosclerotic Vascular Disease Conference: Writing Group II: Risk Factors Circulation, June 1, 2004; 109(21): 2613 - 2616. [Full Text] [PDF]
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H. D. Wu, L. Berglund, C. Dimayuga, J. Jones, R. R. Sciacca, M. R. Di Tullio, and S. Homma High lipoprotein(a) levels and small apolipoprotein(a) sizes are associated with endothelial dysfunction in a multiethnic cohort J. Am. Coll. Cardiol., May 19, 2004; 43(10): 1828 - 1833. [Abstract] [Full Text] [PDF]
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E. R. Christ, M. H. Cummings, N. Jackson, M. Stolinski, P. J. Lumb, A. S. Wierzbicki, P. H. Sonksen, D. L. Russell-Jones, and A. M. Umpleby Effects of Growth Hormone (GH) Replacement Therapy on Low-Density Lipoprotein Apolipoprotein B100 Kinetics in Adult Patients with GH Deficiency: A Stable Isotope Study J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1801 - 1807. [Abstract] [Full Text] [PDF]
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S. E. Humphries, P. M. Ridker, and P. J. Talmud Genetic Testing for Cardiovascular Disease Susceptibility: A Useful Clinical Management Tool or Possible Misinformation? Arterioscler Thromb Vasc Biol, April 1, 2004; 24(4): 628 - 636. [Abstract] [Full Text] [PDF]
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P. Muntner, L. L. Hamm, J. W. Kusek, J. Chen, P. K. Whelton, and J. He The Prevalence of Nontraditional Risk Factors for Coronary Heart Disease in Patients with Chronic Kidney Disease Ann Intern Med, January 6, 2004; 140(1): 9 - 17. [Abstract] [Full Text] [PDF]
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M. Trovati and F. Cavalot Optimization of Hypolipidemic and Antiplatelet Treatment in the Diabetic Patient with Renal Disease J. Am. Soc. Nephrol., January 1, 2004; 15(90010): S12 - 20. [Abstract] [Full Text]
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N. Sattar, D. W. McCarey, H. Capell, and I. B. McInnes Explaining How "High-Grade" Systemic Inflammation Accelerates Vascular Risk in Rheumatoid Arthritis Circulation, December 16, 2003; 108(24): 2957 - 2963. [Abstract] [Full Text] [PDF]
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S. M. Marcovina, M. L. Koschinsky, J. J. Albers, and S. Skarlatos Report of the National Heart, Lung, and Blood Institute Workshop on Lipoprotein(a) and Cardiovascular Disease: Recent Advances and Future Directions Clin. Chem., November 1, 2003; 49(11): 1785 - 1796. [Abstract] [Full Text] [PDF]
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T. Huby, V. Afzal, C. Doucet, R. M. Lawn, E. L. Gong, M. J. Chapman, J. Thillet, and E. M. Rubin Regulation of the Expression of the Apolipoprotein(a) Gene: Evidence for a Regulatory Role of the 5' Distal Apolipoprotein(a) Transcription Control Region Enhancer in Yeast Artificial Chromosome Transgenic Mice Arterioscler Thromb Vasc Biol, September 1, 2003; 23(9): 1633 - 1639. [Abstract] [Full Text] [PDF]
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D. G. Hackam and S. S. Anand Emerging Risk Factors for Atherosclerotic Vascular Disease: A Critical Review of the Evidence JAMA, August 20, 2003; 290(7): 932 - 940. [Abstract] [Full Text] [PDF]
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S van Wissen, T J Smilde, M D Trip, T. de Boo, J J P Kastelein, and A F H Stalenhoef Long term statin treatment reduces lipoprotein(a) concentrations in heterozygous familial hypercholesterolaemia Heart, August 1, 2003; 89(8): 893 - 896. [Abstract] [Full Text] [PDF]
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R. A. Barkley, A. C. Brown, C. L. Hanis, S. L. Kardia, S. T. Turner, and E. Boerwinkle Lack of genetic linkage evidence for a trans-acting factor having a large effect on plasma lipoprotein[a] levels in African Americans J. Lipid Res., July 1, 2003; 44(7): 1301 - 1305. [Abstract] [Full Text] [PDF]
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M. Miller Niacin as a Component of Combination Therapy for Dyslipidemia Mayo Clin. Proc., June 1, 2003; 78(6): 735 - 742. [Abstract] [PDF]
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S. R. Holmer, C. Hengstenberg, H.-G. Kraft, B. Mayer, M. Poll, S. Kurzinger, M. Fischer, H. Lowel, G. Klein, G. A.J. Riegger, et al. Association of Polymorphisms of the Apolipoprotein(a) Gene With Lipoprotein(a) Levels and Myocardial Infarction Circulation, February 11, 2003; 107(5): 696 - 701. [Abstract] [Full Text] [PDF]
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C. Gazzaruso, A. Garzaniti, S. Giordanetti, C. Falcone, E. De Amici, D. Geroldi, and P. Fratino Assessment of Asymptomatic Coronary Artery Disease in Apparently Uncomplicated Type 2 Diabetic Patients: A role for lipoprotein(a) and apolipoprotein(a) polymorphism Diabetes Care, August 1, 2002; 25(8): 1418 - 1424. [Abstract] [Full Text] [PDF]
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