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Quantitation of Plasma Apolipoproteins in the Primary and Secondary Prevention of Coronary Artery Disease

Daniel J. Rader, MD; Jeffrey M. Hoeg, MD; and H. Bryan Brewer, MD
[+] Article and Author Information

From the Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. Requests for Reprints: Daniel Rader, MD, Institute for Human Gene Therapy, University of Pennsylvania Medical Center, 601 Maloney, 3400 Spruce Street, Philadelphia, PA 19104. Acknowledgments: The authors thank Loan Kusterbeck and Donna James for secretarial assistance.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1994;120(12):1012-1025. doi:10.7326/0003-4819-120-12-199406150-00008
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Purpose: To review current knowledge of apolipoprotein quantitation used in the clinical management of persons with or at risk for the development of premature coronary artery disease.

Data Sources: The English-language literature was analyzed using MEDLINE (1975 to 1993) with key words “apolipoproteins,” “quantitation,” and “coronary artery disease.” Article bibliographies were also reviewed to obtain additional references.

Study Selection: Published, peer-reviewed retrospective and prospective studies relevant to the association of plasma apolipoprotein levels with coronary artery disease in humans.

Data Synthesis: Most studies concerned apolipoprotein A-I (apo A-I), apolipoprotein B (apo B), and lipoprotein(a) (Lp[a]). In retrospective cross-sectional studies, apo A-I levels were not substantially more predictive of coronary artery disease than were high-density lipoprotein (HDL) cholesterol levels. In contrast, levels of apo B and Lp(a) were often more strongly associated with coronary artery disease than were traditional lipid measurements. In studies of the relation between apolipoprotein levels in children and premature coronary artery disease in their parents, Lp(a) levels, but not apo A-I and apo B levels, were consistently predictive of familial coronary artery disease. Prospective studies have yielded variable results for all three apolipoproteins. Low apo A-I levels were consistently associated with coronary artery disease in six prospective studies but were not more predictive than HDL levels. Apolipoprotein B levels were strongly associated with coronary artery disease in four of five prospective studies but were more predictive of coronary artery disease than were total cholesterol levels in only two of the four studies. Lipoprotein(a) levels were strongly associated with coronary artery disease in five of seven prospective studies but were not associated in two of the four largest studies.

Conclusions: Too few large prospective studies of apolipoprotein quantitation using validated assay methods, both in general unselected populations and in subgroups of persons with premature coronary artery disease or family histories of premature coronary artery disease, are available to make definitive recommendations concerning clinical utility. The data do not support use of apolipoprotein quantitation as a screening tool to predict coronary artery disease risk in the general population. However, the data suggest that quantitation of apo B and Lp(a) may be indicated in subgroups of persons with premature coronary artery disease or with family histories of premature coronary artery disease. In these persons, an increased apo B or Lp(a) level or both could be a clinical indication for more aggressive treatment of low-density lipoprotein cholesterol.

Figures

Grahic Jump Location
Figure 1.
Schematic diagram of lipoprotein metabolism.

HDL = high-density lipoproteins; IDL = intermediate-density lipoproteins; LDL = low-density lipoproteins; VLDL = very low-density lipoproteins.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Algorithm to quantitate lipids and apolipoproteins in patients with coronary artery disease.

apo = apolipoprotein; CAD = coronary artery disease; HDL = high-density lipoprotein; LDL = low-density lipoprotein; Lp(a) = lipoprotein(a).

Grahic Jump Location
Grahic Jump Location
Figure 3.
Algorithm to quantitate lipids and apolipoproteins in patients with a family history of premature coronary artery disease.

apo = apolipoprotein; CAD = coronary artery disease; HDL = high-density lipoprotein; LDL = low-density lipoprotein; Lp(a) = lipoprotein(a).

Grahic Jump Location

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