Abstract
We investigated the relationship between apolipoprotein E (apoE) polymorphism and cardiovascular responses to experimentally induced mental stress. Mental stress was induced in 28 healthy 16-year-old boys with a series of stressors (e.g., mental arithmetic, Stroop Color-Word Interference Test). Heart rate (HR), finger blood volume, and skin conductance level were recorded continuously during the task performance. We found that boys with apoE3/2 or apoE3/3 showed marginally significantly greater HR reactivity and significantly greater task levels of HR and HR variability (HRV) during the mental stress than subjects with apoE4/2, apoE4/3, or apoE4/4. In addition, E4/2, E4/3, and E4/4 subjects manifested a distinct stress-related decrease in HRV relative to baseline values while E3/2 and E3/3 subjects showed a slight increase. The results suggests that apoE polymorphism is associated with cardiovascular responsivity to mental stress in adolescent boys.
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REFERENCES
Åkerblom, H. K., Uhari, M., Pesonen, E., Dahl, M., Kaprio, E. A., Nuutinen, E. M., Pietikäinen, M., Salo, M. K., Aromaa, A., Kannas, L., Keltikangas-Järvinen, L., Kuusela, V., Räsänen, L., Rönnemaa, T., Knip, M., Telama, R., Valimaki, I., Pyörälä, K., and Viikari, J. (1991). Cardiovascular risk in young Finns. Ann. Med. 23: 35–40.
Alpert, B. S., and Wilson, D. K. (1992). Stress reactivity in childhood and adolescence. In Turner, J. R., Sherwood, A., and Light, K. C. (eds.), Individual Differences in Cardiovascular Response to Stress, Plenum Press, New York, pp. 187–201.
Berenson, G. S., Wattigney, W. A., Tracy, R. E., Newman, W. P., Srinivasan, S. R., Webber, L. S., Dalferes, E. R., and Strong, J. P. (1992). Atherosclerosis of the aorta and coronary arteries and cardiovascular risk factors in persons aged 6 to 30 years and studied at necropsy (the Bogalusa Heart Study). Am. J. Cardiol. 70: 851–858.
Boyles, J. K., Pitas, R. E., Wilson, E., Mahley, R. W., and Taylor, J. M. (1985). Apolipoprotein E associated with astrocytic glia of the central nervous system and with nonmyelinating glia of the peripheral nervous system. J. Clin. Invest. 76: 1501–1513.
Burker, E. J., Fredrikson, M., Rifai, M., Siegel, W., and Blumenthal, J. A. (1994). Serum lipids, neuroendocrine, and cardiovascular responses to stress in men and women with mild hypertension. Behav. Med. 19: 155–161.
Cacioppo, J. T. (1994). Social neuroscience: Autonomic, neuroendocrine, and immune responses to stress. Psychophysiology 31: 113–128.
Clarkson, T. B., Kaplan, J. R., Adams, M. R., and Manuck, S. B. (1987). Psychosocial influences on the pathogenesis of atherosclerosis among nonhuman primates. Circulation 76(Suppl. 1): I-29–I-40.
Cohen, J. (1988). Statistical Power Analysis for the Behavioral Sciences, 2nd ed., Erlbaum, Hillsdale, NJ.
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., and Pericakvance, M. A. (1993). Gene dose of apolipoprotein-E type-4 allele and the risk of Alzheimer's disease in late onset families. Science 261: 921–923.
Crutcher, K. A., Clay, M. A., Scott, S. A., Tian, X., Tolar, M., and Harmony, J. A. K. (1994). Neurite degeneration elicited by apolipoprotein E peptides. Exp. Neurol. 130: 120–126.
Dahlström, S., Viikari, J., Akerblom, H. K., Solakivi-Jaakkola, T., Uhari, M., DahI, M., Lähde, P.-L., Pesonen, E., Pietikäinen, M., Suoninen, P., and Louhivuori, K. (1985). Atherosclerosis precursors in Finnish children and adolescents. II. Height, weight, body mass index, and skinfolds and their correlation to metabolic variables. Acta Paediatr. Scand. Suppl. 318: 65–78.
Dallongeville, J., Lussier-Cacan, S., and Davignon, J. (1992). Modulation of plasma triglyceride levels by apoE phenotypes: A meta-analysis. J. Lipid Res. 33: 447–454.
Davignon, J., Gregg, R. E., and Sing, C. F. (1988). Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis 8: 1–21.
Donald, J. A., Wallis, S. C., Kessling, A., Tippett, P., Robson, E. B., Ball, S., Davies, K. E., Scambler, P., Berg, K., and Heiberg, A. (1985). Linkage relationships of the gene for apolipoprotein CII with loci on chromosome 19. Hum. Genet. 69: 39–43.
Edelberg, R. (1967). Electrical properties of the skin. In Brown, C. C. (ed.), Methods in Psychophysiology, Williams & Wilkins, Baltimore, pp. 1–53.
Elshourbagy, N. A., Liao, W. S., Mahley, R. W., and Taylor, J. M. (1985). Apolipoprotein E mRNA is abundant in the brain and adrenals, as well as in the liver, and is present in other peripheral tissues of rats and marmosets. Proc. Natl. Acad. Sci. USA 82: 203–207.
Fredrikson, M., Lundberg, U., and Tuomisto M. (1991). Serum lipid levels and cardiovascular reactivity. J. Psychophysiology 5: 89–96.
Grossman, P., Brinkman, A., and DeVries, J. (1992). Cardiac autonomic mechanisms associated with borderline hypertension under varying behavioral demands: Evidence for attenuated parasympathetic tone but not for enhanced beta-adrenergic activity. Psychophysiology 29: 698–711.
Hayano, J., Sakakibara, Y., Yamada, M., Ohte, N., Fujinami, T., Yokoyama, K., Watanabe, Y., and Takata, K. (1990). Decreased magnitude of heart rate spectral components in coronary artery disease. Circulation 81: 1217–1224.
Hayano, J., Sakakibara, Y., Yamada, A., Yamada, M., Mukai, S., Fujinami, T., Yokoyama, K., Watanabe, Y., and Takata, K. (1991). Accuracy of assessment of cardiac vagal tone by heart rate variability in normal subjects. Am. J. Cardiol. 67: 199–204.
Hewitt, J. K., and Turner, J. R. (1995). Behavior genetic studies of cardiovascular responses to stress. In Turner, J. R., Cardon, L. R., and Hewitt, J. K. (eds.), Behavior Genetic Approaches in Behavioral Medicine. Perspectives on Individual Differences, Plenum Press, New York, pp. 87–103.
Hixson, J. E. (1991). Apolipoprotein E polymorphisms affect atherosclerosis in young males. Arterioscler. Thromb. 11: 1237–1244.
Houston, B. K. (1992). Personality characteristics, reactivity, and cardiovascular disease. In Turner, J. R., Sherwood, A., and Light, K. C. (eds.), Individual Differences in Cardiovascular Response to Stress, Plenum Press, New York, pp. 103–123.
Ignatius, M. J., Shooter, E. M., Pitas, R. E., and Mahley, R. W. (1987). Lipoprotein uptake by neuronal growth cones in vitro. Science 236: 959–962.
Jorgensen, R., Nash, J., Lasser, N., Hymowitz, N., and Langer, A. (1988). Heart rate acceleration and its relationship to total serum cholesterol, triglycerides, and blood pressure reactivity in men with mild hypertension. Psychophysiology 25: 39–44.
Keltikangas-Järvinen, L., Räikkönen, K., and Lehtimäki, T. (1993). Dependence between apolipoprotein E phenotypes and temperament in children, adolescents, and young adults. Psychosom. Med. 55: 155–163.
Keys, A., Taylor, H. L., Blackburn, H., Brozek, J., Anderson, J. T., and Simonson, E. (1971). Mortality and coronary heart disease among men studied for 23 years. Arch. Intern. Med. 128: 201–214.
Lehtimäki, T., Moilanen, T., Viikari, J., Åkerblom, H. K., Ehnholm, C., Rönnemaa, T., Marniemi, J., Dahlen, G., and Nikkari, T. (1990). Apolipoprotein E phenotypes in Finnish youths: A cross-sectional and 6-year follow-up study. J. Lipid Res. 31: 487–495.
Lehtimäki, T., Porkka, K., Viikari, J., Ehnholm, C., Åkerblom, H. K., and Nikkari, T. (1994). Apolipoprotein E phenotypes and serum lipids in newborns and 3-year-old children: The Cardiovascular Risk in Young Finns Study. Pediatrics 94: 489–493.
Luc, G., Bard, J.-M., Arveiler, D., Evans, A., Cambou, J.-P., Bingham, A., Amouyel, P., Schaffer, P., Ruidavets, J.-B., Cambien, F., Fruchart, J.-C., and Ducimetiere, P. (1994). Impact of apolipoprotein E polymorphism on lipoproteins and risk of myocardial infarction. The ECTIM study. Arterioscler. Thromb. 14: 1617–1624.
Manuck, S. B., Kaplan, J. R., Adams, M. R., and Clarkson, T. B. (1989a). Behaviorally elicited heart rate reactivity and atherosclerosis in female Cynomologus monkeys (Macaca fascicularis). Psychosom. Med. 51: 306–318.
Manuck, S. B., Muldoon, M. F., Kaplan, J. R., Adams, M. R., and Polefrone, J. M. (1989b). Coronary artery atherosclerosis and cardiac response to stress in cynomolgus monkeys. In Siegman, A. W., and Dembroski, T. M. (eds.), In search of coronary-prone behavior: Beyond Type A, Erlbaum, Hillsdale, NJ, pp. 207–227.
Moller, J. H., Taubert, K. A., Allen, H. D., Clark, E. B., and Lauer, R. M. (1994). Cardiovascular health and disease in children: Current status. Circulation 89: 923–930.
Mortimer, B.-C., Redgrave, T. G., Spangler, E. A., Verstuyft, J. G., and Rubin, E. M. (1994). Effect of human apoE4 on the clearance of chylomicron-like lipid emulsions and atherogenesis in transgenic mice. Arterioscler. Thromb. 14: 1542–1552.
Pitas, R. E., Boyles, J. K., Lee, S. H., Hui, D., and Weisgraber, K. H. (1987). Lipoproteins and their receptors in the central nervous system. Characterization of the lipoproteins in cerebrospinal fluid and identification of apolipoprotein B,E(LDL) receptors in the brain. J. Biol. Chem. 262: 14352–14360.
Plomin, R. (1995). Genes and behaviour. Ann. Med. 27: 503–505.
Porges, S. W., and Byrne, E. A. (1992). Research methods for measurement of heart rate and respiration. Biol. Psychol. 34: 93–130.
Reyland, M. E., and Williams, D. L. (1991). Suppression of cAMP-mediated signal transduction in mouse adrenocortical cells which express apolipoprotein E. J. Biol. Chem. 266: 21099–21104.
Rose, R. J. (1992). Genes, stress, and cardiovascular reactivity. In Turner, J.R., Sherwood, A., and Light, K.C. (eds.), Individual differences in cardiovascular response to stress, Plenum Press, New York, pp. 87–102.
Rozanski, A., Bairey, C. N., Krantz, D. S., Friedman, J., Resser, K., Morell, M., Hilton-Chalfen, S., Hestrin, L., Bietendorf, J., and Berman, D. S. (1988). Mental stress and the induction of silent myocardial ischemia in patients with coronary artery disease. N. Engl. J. Med. 318: 1005–1012.
Rozanski, A., Krantz, D.S., and Bairey, C.N. (1991). Ventricular responses to mental stress testing in patients with coronary artery disease: Pathophysiological implications. Circulation 83(Suppl. 2):.II-137–II-144.
Rönnemaa, T., Knip, M., Lautala, P., Vükari, J., Uhari, M., Leino, A., Kaprio, E. A., Salo, M. K., Dahl, M., Nuutinen, E. M., Pesonen, E., Pietikäinen, M., and Åkerblom, H. K. (1991). Serum insulin and other cardiovascular risk indicators in children, adolescents and young adults. Ann. Med. 23: 67–72.
Salo, M. K., Rantanen, R., Huupponen, T., Lehtimäki, T., and Jokela, H. (1993). Apolipoprotein E phenotypes and plasma lipids in diabetic children and adolescents. Eur. J. Pediatr. 152: 564–568.
Stein, P. K., Bosner, M. S., Kleiger, R. E., and Conger, B. M. (1994). Heart rate variability: A measure of cardiac autonomic tone. Am. Heart J. 127: 1376–1381.
Stengård, J. H., Zerba, K. E., Pekkanen, J., Ehnholm, C., Nissinen, A., and Sin C. F. (1995). Apolipoprotein E polymorphism predicts death from coronary heart disease in a longitudinal study of elderly Finnish men. Circulation 91: 265–269.
Straznicky, N. E., Louis, W. J., McGrade, P., and Howes, L. G. (1993). The effects of dietary lipid modification on blood pressure, cardiovascular reactivity and sympathetic activity in man. J. Hypertens. 11: 427–437.
Uhari, M., Nuutinen, M., Turtinen, J., Pokka, T., Kuusela, V., Åkerblom, H. K., Dahl, M., Kaprio, E. A., Pesonen, E., Pietikäinen, M., Salo, M. K., and Vükari, J. (1991). Blood pressure in children, adolescents and young adults. Ann. Med. 23: 47–51.
Utermann, G. (1987). Apolipoprotein E polymorphism in health and disease. Am. Heart J. 113: 433–440.
Utermann, G., Hees, M., and Steinmetz, A. (1977). Polymorphism of apolipoprotein E and occurrence of dysbetalipoproteinemia in man. Nature 269: 604–607.
Utermann, G., Langenbeck, U., Beisiegel, U., and Weber, W. (1980). Genetics of the apolipoprotein E system in man. Am. J. Hum. Genet. 32: 339–347.
Viikari, J., Rönnemaa, T., Seppänen, A., Marniemi, J., Porkka, K., Rasanen, L., Uhari, M., Salo, M. K., Kaprio, E. A., Nuutinen, E. M., Pesonen, E., Pietikäinen, M., Dahl, M., and Åkerblom, H. K. (1991). Serum lipids and lipoproteins in children, adolescents and young adults in 1980–1986. Ann. Med. 23: 53–59.
Zannis, V. I., Just, P. W., and Breslow, J. L. (1981). Human apolipoprotein E isoprotein subclasses are genetically determined. Am. J. Hum. Genet. 33:11–24.
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Ravaja, N., Räikkönen, K., Lyytinen, H. et al. Apolipoprotein E Phenotypes and Cardiovascular Responses to Experimentally Induced Mental Stress in Adolescent Boys. J Behav Med 20, 571–587 (1997). https://doi.org/10.1023/A:1025518524884
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DOI: https://doi.org/10.1023/A:1025518524884