(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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|
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 H A W Neil, V Seagroatt, D J Betteridge, M P Cooper, P N Durrington, J P Miller, M Seed, R P Naoumova, G R Thompson, R Huxley, et al. Established and emerging coronary risk factors in patients with heterozygous familial hypercholesterolaemia Heart, December 1, 2004; 90(12): 1431 - 1437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Berglund and R. Ramakrishnan Lipoprotein(a): An Elusive Cardiovascular Risk Factor Arterioscler. Thromb. Vasc. Biol., December 1, 2004; 24(12): 2219 - 2226. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
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|
|
|
|
|
|
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|