ATHEROSCLEROSIS UPDATE
ATHEROSCLEROSE: LE POINT Canadian Atherosclerosis Society / Societe canadienne d'atherosclerose
Apolipoproteins and risk of coronary heart disease Philip W. Connelly, PhD
It is well established that measurement of apolipoprotein levels is valuable in atherosclerosis research; indeed, without such measurements, future studies are unlikely to yield new information.' Total plasma apolipoprotein A-I (apo A-I), total plasma apolipoprotein B (apo B) and lipoprotein (a) have been most consistently shown to discriminate between patients with disease and matched controls.2-6 Also, Brown and colleagues' recently reported the usefulness of classifying patients on the basis of apo B levels. Through the efforts of the International Federation of Clinical Chemistry's Committee on Apolipoproteins calibration of the assays for apo A-I and B has progressed significantly,3 and secondary reference material has been prepared and validated for both. In addition, the European Bureau of Reference will soon release primary standard grade material for apo A-I and B.3 Automated systems are available for measuring their concentrations, and, with appropriate supplementary reagents, rapid and cost-effective techniques such as nephelometry can accurately measure the levels even in samples with very high concentrations of triglycerides. Biologic and analytic variation is likely to be the most important factor determining the relative practicality of measuring lipid and apolipoprotein levels to determine risk. For example, people with a 5% biologic coefficient of variation in the cholesterol level who were tested by a laboratory with a 2.4% analytic coefficient of variation would require five measurements at separate times to define the true value with 95% confidence.4 If the same people had a biologic coefficient of variation of 7.3% in another variable and were tested by a laboratory with a 1.3% analytic coefficient of variation nine measurements would be required. People with a 5.5% biologic
coefficient of variation in the level of high-density lipoprotein cholesterol who were tested by a laboratory with a 2.5% analytic coefficient of variation would require six measurements. Those with a 4.7% biologic coefficient of variation in the level of apo A-I who were tested by a laboratory with a 1.2% analytic coefficient of variation would require four measurements. The predictive power of apolipoprotein levels as risk factors is not yet known, but studies are under way.5 Thus, although the debate over the need to measure the levels is vigorous,26 many of the criticisms have been addressed, and the answers to others are on the horizon. As these data become available, clinicians will acquire the basis for using the apolipoproteins to complement both the assessment of traditional risk factors and the management of affected patients.
References 1. Brown G, Albers JJ, Fischer LD et al: Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med 1990; 323: 1289-1298 2. Sniderman AD, Silberberg J: Is it time to measure apolipoprotein B? Arteriosclerosis 1990; 10: 665-667 3. Dati F: Standardization of commercial assays for serum apo A-I and apo B: a consensus procedure for the production of calibration materials. Scand J Clin Lab Invest 1990; 50 (suppl 198): 73-79 4. Ford RP: Essential data derived from biological variation for establishment and use of lipid analyses. Ann Clin Biochem 1989; 26: 281-285 5. ARIC Working Group: The Atherosclerosis Risk in Communities (ARIC) study: design and objectives. Am J Epidemiol 1989; 129: 687-702 6. Vega GL, Grundy SM: Does measurement of apolipoprotein B have a place in cholesterol management? Arteriosclerosis 1990; 10: 668-671
Dr. Connelly is an assistant professor in the departments ofMedicine, Biochemistry and Clinical Biochemistry at the University of Toronto, Toronto, Ont. The opinions expressed in this article are his and not necessarily those ofthe Canadian Atherosclerosis Society. Reprint requests to: Dr. Philip W. Connelly, Director, Lipid Research Laboratory, St. Michael's Hospital, 30 Bond St., Toronto, ON M5B 1 W8 -
For prescribing information see page 1335
CAN MED ASSOC J 1991; 144 (10)
1277
ATHEROSCLEROSE: LE POINT Canadian Atherosclerosis Society / Societe canadienne d'atherosclerose
Apolipoproteins and risk of coronary heart disease Philip W. Connelly, PhD
It is well established that measurement of apolipoprotein levels is valuable in atherosclerosis research; indeed, without such measurements, future studies are unlikely to yield new information.' Total plasma apolipoprotein A-I (apo A-I), total plasma apolipoprotein B (apo B) and lipoprotein (a) have been most consistently shown to discriminate between patients with disease and matched controls.2-6 Also, Brown and colleagues' recently reported the usefulness of classifying patients on the basis of apo B levels. Through the efforts of the International Federation of Clinical Chemistry's Committee on Apolipoproteins calibration of the assays for apo A-I and B has progressed significantly,3 and secondary reference material has been prepared and validated for both. In addition, the European Bureau of Reference will soon release primary standard grade material for apo A-I and B.3 Automated systems are available for measuring their concentrations, and, with appropriate supplementary reagents, rapid and cost-effective techniques such as nephelometry can accurately measure the levels even in samples with very high concentrations of triglycerides. Biologic and analytic variation is likely to be the most important factor determining the relative practicality of measuring lipid and apolipoprotein levels to determine risk. For example, people with a 5% biologic coefficient of variation in the cholesterol level who were tested by a laboratory with a 2.4% analytic coefficient of variation would require five measurements at separate times to define the true value with 95% confidence.4 If the same people had a biologic coefficient of variation of 7.3% in another variable and were tested by a laboratory with a 1.3% analytic coefficient of variation nine measurements would be required. People with a 5.5% biologic
coefficient of variation in the level of high-density lipoprotein cholesterol who were tested by a laboratory with a 2.5% analytic coefficient of variation would require six measurements. Those with a 4.7% biologic coefficient of variation in the level of apo A-I who were tested by a laboratory with a 1.2% analytic coefficient of variation would require four measurements. The predictive power of apolipoprotein levels as risk factors is not yet known, but studies are under way.5 Thus, although the debate over the need to measure the levels is vigorous,26 many of the criticisms have been addressed, and the answers to others are on the horizon. As these data become available, clinicians will acquire the basis for using the apolipoproteins to complement both the assessment of traditional risk factors and the management of affected patients.
References 1. Brown G, Albers JJ, Fischer LD et al: Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med 1990; 323: 1289-1298 2. Sniderman AD, Silberberg J: Is it time to measure apolipoprotein B? Arteriosclerosis 1990; 10: 665-667 3. Dati F: Standardization of commercial assays for serum apo A-I and apo B: a consensus procedure for the production of calibration materials. Scand J Clin Lab Invest 1990; 50 (suppl 198): 73-79 4. Ford RP: Essential data derived from biological variation for establishment and use of lipid analyses. Ann Clin Biochem 1989; 26: 281-285 5. ARIC Working Group: The Atherosclerosis Risk in Communities (ARIC) study: design and objectives. Am J Epidemiol 1989; 129: 687-702 6. Vega GL, Grundy SM: Does measurement of apolipoprotein B have a place in cholesterol management? Arteriosclerosis 1990; 10: 668-671
Dr. Connelly is an assistant professor in the departments ofMedicine, Biochemistry and Clinical Biochemistry at the University of Toronto, Toronto, Ont. The opinions expressed in this article are his and not necessarily those ofthe Canadian Atherosclerosis Society. Reprint requests to: Dr. Philip W. Connelly, Director, Lipid Research Laboratory, St. Michael's Hospital, 30 Bond St., Toronto, ON M5B 1 W8 -
For prescribing information see page 1335
CAN MED ASSOC J 1991; 144 (10)
1277
