Lipid and apolipoprotein predictors of atherosclerosis in youth: apolipoprotein concentrations do not materially improve prediction of arterial lesions in PDAY subjects. The PDAY Research Group.

We compared serum lipid and apolipoprotein predictors of atherosclerosis in cases from the multicenter study, Pathobiological Determinants of Atherosclerosis in Youth (PDAY). The lipid measures included HDL cholesterol (HDL-C) and non-HDL-C, and the apolipoprotein measures included concentrations of apoA1, apoB, and Lp(a), and sizes of the apo(a) proteins. We tested whether the apolipoprotein measures predicted atherosclerotic lesions as well as the more traditional lipid measures. We estimated extent of lesions as fatty streaks or raised lesions (fibrous plaques, complicated or calcified lesions) in 3 sites: thoracic aorta, abdominal aorta, and right coronary artery. Neither apoA1 nor apoB measures were as strongly or consistently correlated with extent of lesions as the corresponding lipid measure (HDL-C and non-HDL-C, respectively). Beyond the basic model that included sex, age, race, smoking status, hypertension, and the lipid measures, apoA1 and apoB added only an average 1.3% increased explanatory ability to the model, whereas HDL-C plus non-HDL-C added an average 2.5%. The results suggest that the traditional lipid measures are more useful than apolipoprotein measures for detecting young persons at high risk of precocious atherosclerosis. Because of large racial differences, the two Lp(a)-related measures, Lp(a) concentrations and apo(a) size, were evaluated in blacks and whites separately. Under these circumstances, neither of the Lp(a)-related measures was strongly or consistently correlated with extent of lesions.

[1]  E. Chen,et al.  cDNA sequence of human apolipoprotein(a) is homologous to plasminogen , 1987, Nature.

[2]  A. Sniderman,et al.  Is it time to measure apolipoprotein B? , 1990, Arteriosclerosis.

[3]  J. Deslypere,et al.  Discriminative value of lipids and apoproteins in coronary heart disease. , 1982, Atherosclerosis.

[4]  P. Ridker,et al.  A prospective study of lipoprotein(a) and the risk of myocardial infarction. , 1993, JAMA.

[5]  J. Fruchart,et al.  HDL heterogeneity and atherosclerosis. , 1996, Critical reviews in clinical laboratory sciences.

[6]  G. Manis,et al.  Hereditary and dietary effects on apolipoprotein[a] isoforms and Lp[a] in baboons. , 1989, Journal of lipid research.

[7]  F. Kronenberg,et al.  Association of serum lipoprotein(a) levels and apolipoprotein(a) size polymorphism with target-organ damage in arterial hypertension. , 1997, JAMA.

[8]  J. Lee,et al.  A single point mutation (Trp72-->Arg) in human apo(a) kringle 4-37 associated with a lysine binding defect in Lp(a). , 1994, Biochimica et biophysica acta.

[9]  J. Gofman,et al.  Lipoproteins, coronary heart disease, and atherosclerosis. , 1954, Physiological reviews.

[10]  M. Moore Fasting insulin and apolipoprotein B levels and low density lipoprotein particle size as risk factors for ischemic heart disease. , 1998, Journal of insurance medicine.

[11]  J. J. Thompson,et al.  Human lipoprotein(a) quantified by 'capture' ELISA. , 1991, Annals of clinical and laboratory science.

[12]  L. Sundblad,et al.  Immunochemical Determination of ß-Lipoproteins , 1969 .

[13]  D. Ruppert,et al.  Transformation and Weighting in Regression , 1988 .

[14]  M. Burstein,et al.  Sur un dosage rapide du cholesterol lié aux α-et aux β-lipoprotéines du sérum , 1960 .

[15]  E. Boerwinkle,et al.  Apo(a) isoforms predict risk for coronary heart disease. A study in six populations. , 1992, Arteriosclerosis and thrombosis : a journal of vascular biology.

[16]  J. Glanville Post-mortem Serum Cholesterol Levels , 1960, British medical journal.

[17]  J. Cornhill,et al.  Relation of a postmortem renal index of hypertension to atherosclerosis and coronary artery size in young men and women. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[18]  P. Barter,et al.  High-density lipoproteins and coronary heart disease. , 1991, Journal of cardiovascular risk.

[19]  F. Kronenberg,et al.  Lipoprotein(a) in health and disease. , 1996, Critical reviews in clinical laboratory sciences.

[20]  P. Wilson,et al.  Plasma lipoprotein and apolipoprotein levels in Taipei and Framingham. , 1993, Arteriosclerosis and thrombosis : a journal of vascular biology.

[21]  L. Wilkins Natural history of aortic and coronary atherosclerotic lesions in youth. Findings from the PDAY Study. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. , 1993, Arteriosclerosis and thrombosis : a journal of vascular biology.

[22]  M. Schroll,et al.  Apolipoprotein(a) isoforms and coronary heart disease in men: a nested case-control study. , 1997, Atherosclerosis.

[23]  J. Strong,et al.  Lipoproteins and apolipoproteins in postmortem serum. , 1988, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[24]  K. Cianflone,et al.  Measurement of apoproteins: time to improve the diagnosis and treatment of the atherogenic dyslipoproteinemias. , 1996, Clinical chemistry.

[25]  L. Solberg,et al.  Selected methodologic aspects of the International Atherosclerosis Project. , 1968, Laboratory investigation; a journal of technical methods and pathology.

[26]  B. Bouma,et al.  Lysine-Binding Heterogeneity of Lp(a): Consequences for Fibrin Binding and Inhibition of Plasminogen Activation , 1992, Thrombosis and Haemostasis.

[27]  D. Rainwater Stability of apolipoprotein(a) isoform phenotype to postmortem conditions. , 1999, Clinica chimica acta; international journal of clinical chemistry.

[28]  K. Hajjar,et al.  The role of lipoprotein(a) in atherogenesis and thrombosis. , 1996, Annual review of medicine.

[29]  S M Grundy,et al.  Small LDL, atherogenic dyslipidemia, and the metabolic syndrome. , 1997, Circulation.

[30]  D. Rader,et al.  Quantitation of Plasma Apolipoproteins in the Primary and Secondary Prevention of Coronary Artery Disease , 1994, Annals of Internal Medicine.

[31]  D. Jacobs,et al.  Distribution of lipoproteins and apolipoproteins in young adults The CARDIA Study. , 1989, Arteriosclerosis.

[32]  Relationship of atherosclerosis in young men to serum lipoprotein cholesterol concentrations and smoking. A preliminary report from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. , 1990, JAMA.

[33]  P. Alaupovic Apoliproproteins and lipoproteins. , 1971, Atherosclerosis.

[34]  S. Haffner,et al.  Insulin and 2-hour glucose levels are inversely related to Lp(a) concentrations controlled for LPA genotype. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[35]  D. Mittelman,et al.  A System for the Separation of the Components of Human Blood: Quantitative Procedures for the Separation of the Protein Components of Human Plasma1a,b,c , 1950 .

[36]  J. Huttunen,et al.  Lipoprotein (a) and coronary heart disease risk: a nested case-control study of the Helsinki Heart Study participants. , 1991, Atherosclerosis.

[37]  C. Kammerer,et al.  Lipoprotein Lp(a): effects of allelic variation at the LPA locus. , 1998, The Journal of experimental zoology.

[38]  W. Kohr,et al.  Partial amino acid sequence of apolipoprotein(a) shows that it is homologous to plasminogen. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[39]  V. Armstrong,et al.  The association between serum Lp(a) concentrations and angiographically assessed coronary atherosclerosis. Dependence on serum LDL levels. , 1986, Atherosclerosis.

[40]  A. Zinsmeister,et al.  Apolipoprotein A-I as a marker of angiographically assessed coronary-artery disease. , 1983, The New England journal of medicine.

[41]  J. J. Thompson,et al.  Identification of a mouse monoclonal antibody, LHLP-1, specific for human Lp(a). , 1985, Journal of lipid research.

[42]  G. Cazzolato,et al.  Are Apolipoproteins Better Discriminators than Lipids for Atherosclerosis , 1979 .

[43]  O. Klezovitch,et al.  Evidence that the fibrinogen binding domain of Apo(a) is outside the lysine binding site of kringle IV-10: a study involving naturally occurring lysine binding defective lipoprotein(a) phenotypes. , 1996, The Journal of clinical investigation.

[44]  J. Strong,et al.  Effects of serum lipoproteins and smoking on atherosclerosis in young men and women. The PDAY Research Group. Pathobiological Determinants of Atherosclerosis in Youth. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[45]  D. Rainwater Genetic basis for multimodal relationship between apolipoprotein (a) size and lipoprotein (a) concentration in Mexican-Americans. , 1995, Atherosclerosis.

[46]  P. Fu,et al.  Enzymatic determination of total serum cholesterol. , 1974, Clinical chemistry.

[47]  S. Grundy,et al.  Does measurement of apolipoprotein B have a place in cholesterol management? , 1990, Arteriosclerosis.

[48]  T. Venetta,et al.  Quantification of lipoprotein(a) particles containing various apolipoprotein(a) isoforms by a monoclonal anti-apo(a) capture antibody and a polyclonal anti-apolipoprotein B detection antibody sandwich enzyme immunoassay. , 1993, Clinical chemistry.

[49]  P. Roheim,et al.  Optimization and Characterization of Capture ELISA Methodology for Lp(a) Lipoprotein Quantification , 1992, Annals of clinical biochemistry.

[50]  F. Kronenberg,et al.  Lipoprotein(a) in stored plasma samples and the ravages of time. Why epidemiological studies might fail. , 1996, Arteriosclerosis, thrombosis, and vascular biology.

[51]  J. Strong,et al.  Relation of glycohemoglobin and adiposity to atherosclerosis in youth. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. , 1995, Arteriosclerosis, thrombosis, and vascular biology.

[52]  S. Hunt,et al.  Lipoprotein(a) interactions with lipid and nonlipid risk factors in early familial coronary artery disease. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[53]  N. Wald,et al.  Apolipoproteins and ischaemic heart disease: implications for screening , 1994, The Lancet.

[54]  C. Kammerer,et al.  Characterization of the genetic elements controlling lipoprotein(a) concentrations in Mexican Americans. Evidence for at least three controlling elements linked to LPA, the locus encoding apolipoprotein(a). , 1997, Atherosclerosis.

[55]  P. Harpel,et al.  Lipoprotein(a), Plasmin Modulation, and Atherogenesis , 1995, Thrombosis and Haemostasis.

[56]  C. M. Carpenter,et al.  A simple method for quantitation of serum beta-lipoproteins by means of the immunocrit. , 1961, American journal of clinical pathology.

[57]  H. Kunkel,et al.  Lipoprotein patterns of serum obtained by zone electrophoresis. , 1952, The Journal of clinical investigation.

[58]  N. Draper,et al.  Applied Regression Analysis , 1967 .

[59]  J. Strong,et al.  Relation of a postmortem renal index of hypertension to atherosclerosis in youth. The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. , 1995, Arteriosclerosis, thrombosis, and vascular biology.

[60]  A. Sniderman,et al.  Apoproteins B and A-I and coronary artery disease in humans. , 1984, Arteriosclerosis.

[61]  J. Enticknap Lipids in cadaver sera after fatal heart attacks , 1961, Journal of clinical pathology.

[62]  N. Draper,et al.  Applied Regression Analysis , 1966 .

[63]  A. Zinsmeister,et al.  Apolipoproteins and coronary artery disease. , 1986, Mayo Clinic proceedings.

[64]  F. Kronenberg,et al.  Apolipoprotein(a) kringle IV repeat number predicts risk for coronary heart disease. , 1996, Arteriosclerosis, thrombosis, and vascular biology.

[65]  A. Sharrett,et al.  Associations of lipoprotein cholesterols, apolipoproteins A-I and B, and triglycerides with carotid atherosclerosis and coronary heart disease. The Atherosclerosis Risk in Communities (ARIC) Study. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[66]  J. Coresh,et al.  Small, dense low-density lipoprotein particles and coronary heart disease risk: A clear association with uncertain implications. , 1996, JAMA.

[67]  C. Kang,et al.  Lipoprotein(a) isoforms display differences in affinity for plasminogen-like binding to human mononuclear cells. , 1997, Arteriosclerosis, thrombosis, and vascular biology.