The Metabolic Syndrome and Vascular Disease

  • Aresh J. Anwar
  • Anthony H. Barnett
  • Sudhesh Kumar
Part of the Contemporary Cardiology book series (CONCARD)


The concept of the metabolic syndrome is perhaps the most significant development in the management of cardiovascular disease in the last 10 years. Previously, physicians had often treated coexisting diabetes, hypertension, or dyslipidemia as separate diseases, without considering the impact of treatment for one on the other. Avogaro and Creapaldi (1) first described the syndrome over 40 years ago. The importance of the concept for everyday clinical practice was only highlighted in 1988, however, when Gerald Reaven (2) drew attention to a constellation of features associated with coronary heart disease (Table 1). In view of the rather limited understanding of the nature of the association of these features at that time, Reaven used the term syndrome X (3). He also suggested that insulin resistance played a central etiologic role in providing a link between these components.


Insulin Resistance Coronary Heart Disease Metabolic Syndrome Coronary Heart Disease Mortality United Kingdom Prospective Diabetes Study 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Avogaro P, Creapaldi G. Essential hyperlipiemia, obesity and diabetes (abstract) Diabetologia 1965; 1:137.Google Scholar
  2. 2.
    Reaven GM. Banting Lecture 1988: role of insulin resistance in human disease. Diabetes 1988;37: 1595–1607.PubMedGoogle Scholar
  3. 3.
    Laws A, Reaven GM. Insulin resistance and risk factors for coronary heart disease. Baillieres Clin Endocrinol Metab. 1994;7:1063–1078.Google Scholar
  4. 4.
    Haffner SM, Mietinen H. Insulin resistance: implications for type II diabetes mellitus and coronary heart disease. Am J Med 1997;103:152–159.PubMedGoogle Scholar
  5. 5.
    Ferranini E, Haffner SM, Mitchell BD, Stern MP. Hyperinsulinaemia: the key feature of a cardiovascular and metabolic syndrome. Diabetologia 1991;34:416–422.Google Scholar
  6. 6.
    Berenson GS, Srinivasan SR, Bao W, Newman WP, Tracy RE, Wattigney WA. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. N Engl J Med 1998;338:1650–1656.PubMedGoogle Scholar
  7. 7.
    Bao W, Srinivasan SR, Wattigney WA, Berenson GS. Persistence of multiple cardiovascular risk clustering related to syndrome X from childhood to young adulthood: the Bogalusa Heart Study. Arch Intern Med 1994;154:1842–1847.PubMedGoogle Scholar
  8. 8.
    Hodge AM, Zimmet P. The epidemiology of obesity. Baillieres Clin Endocrinol Metab 1994;8:577–599.PubMedGoogle Scholar
  9. 9.
    McKeigue PM, Shah B, Maramot MG. Relation of central obesity and insulin resistance with high diabetes prevalence and cardiovascular risk in South Asians. Lancet 1991;337:382–386.PubMedGoogle Scholar
  10. 10.
    Neel JV. Diabetes mellitus: a thrifty genotype rendered detrimental by “progress”? Am J Hum Genet 1962;14:353–362.PubMedGoogle Scholar
  11. 11.
    Wendorf M, Goldfine ID. Archaeology of NIDDM: excavation of the thrifty genotype. Diabetes 1991; 40:161–165.PubMedGoogle Scholar
  12. 12.
    Reaven GM. Hypothesis: muscle insulin resistance is the (“not so”) thrifty genotype. Diabetologia 1998;41:482–484.PubMedGoogle Scholar
  13. 13.
    Owen OE, Felig P, Morgan AP, Wahren J, Cahill GF Jr. Liver and kidney metabolism during prolonged starvation. J Clin Invest 1969;48:574–583.PubMedGoogle Scholar
  14. 14.
    Owen OE, Morgan AP, Kemo HG, Sullivan JM, Herrara MG, Cahill GF Jr. Brain metabolism during prolonged starvation. J Clin Invest 1967;46:1589–1595.PubMedGoogle Scholar
  15. 15.
    Barker DJP. Intra-uterine origins of cardiovascular and obstructive lung disease in adult life. JR Coll Phys Lond 1991;25:129–133.Google Scholar
  16. 16.
    Barker DJP, Hales CN, Fall CH, Osmond C, Phipps K, Clark PM. Type 2 (non-insulin dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced foetal growth. Diabetologia 1993;36:62–67.PubMedGoogle Scholar
  17. 17.
    McCance DR, Pettitt DJ, Hanson RL, Jacobson LTH, Knowle WC, Bennett PH. Birth weight and noninsulin dependent diabetes: “thrifty genotype,” “thrifty phenotype” or “ surviving small baby genotype.” BMJ 1994;308:942–945.PubMedGoogle Scholar
  18. 18.
    Valdez R, Athens MA, Thompson GH, Bradshaw BS, Stern MP. Birth weight and adult outcomes in a diethnic population in the USA. Diabetologia 1994;37:674–631Google Scholar
  19. 19.
    Lithell HO, McKeigue PM, Berglund L, Mohsen R, Lithell U-B, Leon DA. Relation of size at birth to non-insulin dependent diabetes and insulin concentrations in men aged 50–60 years. BMJ 1996;312: 406–410.PubMedGoogle Scholar
  20. 20.
    Poulsen P, Vaag AA, Kyvik KO, et al. Low birth weight is associated with NIDDM in discordant monozygotic and dizygotic twin pairs. Diabetologia 1997;40:439–446.PubMedGoogle Scholar
  21. 21.
    Stern MP. Diabetes and cardiovascular disease: the “common soil” hypothesis. Diabetes 1995;44:369–374.PubMedGoogle Scholar
  22. 22.
    Stern M. The insulin resistance syndrome. In: Alberti KGMM, Zimmet P, DeFronzo R, Keen H, eds. International Textbook of Diabetes Mellitus. John Wiley and Sons, London, UK, 1997, pp. 255–283.Google Scholar
  23. 23.
    Hansen BC, Bodkin HL. Heterogeneity of insulin responses: phases leading to type II(non-insulin dependent) diabetes mellitus in the rhesus monkey. Diabetologia 1986;29:713–719.PubMedGoogle Scholar
  24. 24.
    Zimmet P. Kelly West Lecture 1991. Challenges in diabetes epidemiology-from west to the rest. Diabetes Care 1992;15:2:232–252.PubMedGoogle Scholar
  25. 25.
    Zimmet P, Dowse G, Bennet P. Hyperinsulinaemia is a predictor of non-insulin dependent diabetes mellitus. Diabetes Metab 1991;17:101–108.Google Scholar
  26. 26.
    Petit DJ, Moll PP, Kottke BA. Insulin resistance in apparently healthy children (abstract). Diabetes 1990;339(Suppl 1):75A.Google Scholar
  27. 27.
    White K, Gracy M, Schumacher L, Spargo R, Kretchmer N. Hyperinsulinaemia and impaired glucose tolerance in young Australian Aborigines. Lancet 1990;2:735.Google Scholar
  28. 28.
    Stout RW. Insulin and atheroma. Diabetes Care 1990;13:631–654.PubMedGoogle Scholar
  29. 29.
    Duff GL, McMillan GC. The effect of alloxan diabetes on experimental cholesterol atherosclerosis in the rabbit. I. The inhibition of experimental cholesterol atherosclerosis in alloxan diabetes. II. The effect of alloxan diabetes on the retrogression of experimental cholesterol atherosclerosis. J Exp Med 1949; 89:611–629.Google Scholar
  30. 30.
    McGill HC Jr, Holman RL. The influence of alloxan diabetes on cholesterol atheromatosis in the rabbit. Proc Soc Exp Biol Med 1954;72:72–73.Google Scholar
  31. 31.
    Duff GL, Brechin DJH, Findelstein WE. The effect of alloxan diabetes on experimental cholesterol atherosclerosis in the rabbit. IV. The effect of insulin therapy on the inhibition of atherosclerosis in the alloxan-diabetic rabbit. J Exp Med 1954;100:371–380.PubMedGoogle Scholar
  32. 32.
    Norddestgaard BG, Zilversmit DB. Hyperglycaemia in normotriglyceridemic, hypercholestrolemic insulin treated diabetic rabbits does not accelerate atherogenesis. Atherosclerosis 1988;72:37–47.Google Scholar
  33. 33.
    Cruz AB Jr, Amatuzio DS, Grande F, Hay LJ. Effect of intraarterial insulin on tissue cholesterol and fatty acids in alloxan-diabetic dogs. Circ Res 1961;9:39–43.PubMedGoogle Scholar
  34. 34.
    Pfeilfle B, Ditschuneit H. Effect of insulin on growth of cultured arterial smooth muscle cells. Diabetologia 1981;20:155–158.Google Scholar
  35. 35.
    Krone W, Naegele H, Behnke B, Greten H. Opposite effects of insulin and catecholamines on LDLreceptor activity in human mononuclear leukocytes. Diabetes 1988;37:1386–1391.PubMedGoogle Scholar
  36. 36.
    Oppenheimer MJ, Sundquist K, Bierman EL. Down regulation of high density lipoprotein receptor in human fibroblasts by insulin and IGF-1. Diabetes 1989;38:117–122.PubMedGoogle Scholar
  37. 37.
    Elliot TG, Viberti G. Relationship between insulin resistance and the risk for coronary heart disease in diabetes mellitus and the general population: a critical appraisal. Baillieres Clin Endocrinol Metab 1993;7:1079–1103.Google Scholar
  38. 38.
    Duciemetiere P, Eschwege E, Papoz L, Richard JL, Claude JR. Relationship of plasma insulin levels to the incidence of myocardial infarction and coronary heart disease mortality in a middle aged population. Diabetologia 1980;19:205–210.Google Scholar
  39. 39.
    Eschwege E, Richard JL, Thibult N, et al. Coronary heart disease mortality in relation to diabetes, blood glucose and plasma insulin levels: the Paris Prospective Study, ten years later. Horm Metab Res 1985; 15(Suppl):41–46.Google Scholar
  40. 40.
    Fontbonne A, Charles MA, Thibult N, et al. Hyperinsulinaemia as a predictor of coronary heart disease mortality in a healthy population: the Paris Prospective Study 15 year follow up. Diabetologia 1991;34: 356–361.PubMedGoogle Scholar
  41. 41.
    Pyorala K. Relationship of glucose tolerance and plasma insulin to the incidence of coronary heart disease: results from two population studies in Finland. Diabetes Care 1979;2:121–141.Google Scholar
  42. 42.
    Pyorala K, Savolainen E, Kaukola S, Haapakoski J. Plasma insulin as coronary heart disease risk factor: relationship to other risk factors and predictive value during 9.5 year follow-up of the Helsinki Policeman Study population. Acta Med Scad 1985;70(Suppl):35–52.Google Scholar
  43. 43.
    Despres JP, Lamarche B, Mauriege P, et al. Hyperinsulinaemia as an independent risk factor for ischaemic heart disease. N Engl J Med 1996;334:952–957.PubMedGoogle Scholar
  44. 44.
    Hargreaves AD, Logan RL, Elton RA, Buchanan KD, Oliver MF, Riemersma RA. Glucose tolerance, plasma insulin, HDL cholesterol and obesity: 12-year follow-up and development of coronary heart disease in Edinburgh men. Atherosclerosis 1992;94:61–69.PubMedGoogle Scholar
  45. 45.
    Welin L, Eriksson H, Larsson B, Ohlson LO, Svardsudd K, Tibblin G. Hyperinsulinaemia is not a major coronary risk factor in elderly men. The study of men born in 1913. Diabetologia 1992;35:766–770.Google Scholar
  46. 46.
    Welborn TA, Wearne K. Coronary heart disease incidence and cardiovascular mortality in Busselton with reference to glucose and insulin concentration. Diabetes Care 1979;21:154–160.Google Scholar
  47. 47.
    Cullen K, Stenhouse NS, Wearne KL, Welborne TA. Multiple regression analysis of risk factors for cardiovascular disease and cancer mortality in Busselton, Western Australia 3 year study. J Chron Dis 1983;36:371–377.PubMedGoogle Scholar
  48. 48.
    Ferrara A, Barrett-Connor EL, Edelstein SL. Hyperinsulinaemia does not increase the risk of fatal cardiovascular disease in elderly men or women without diabetes: the Rancho Bernardo Study, 1984–1991. Am J Epidemiol 1994;140:857–869.PubMedGoogle Scholar
  49. 49.
    Nattrass M. Managing diabetes after myocardial infarction. BMJ 1997;314:1497.PubMedGoogle Scholar
  50. 50.
    Malmberg K for the DIGAMI Study Group. Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. BMJ 1997;314:1512–1515.Google Scholar
  51. 51.
    UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulponylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;12:837–853.Google Scholar
  52. 52.
    Nathan D. Some answers, more controversy, from UKPDS. Lancet 1998;352:832–833.PubMedGoogle Scholar
  53. 53.
    Welborn TA, Breckenbridge A, Rubenstein AH, Dollery CT, Fraser TR. Serum insulin in essential hypertension and in peripheral vascular disease. Lancet 1996;I:1336–1337.Google Scholar
  54. 54.
    Modan M, Hallin H, Almog S, et al. Hyperinsulinaemia:a link between hypertension, obesity and glucose intolerance. J Clin Invest 1985;75:809–817.PubMedGoogle Scholar
  55. 55.
    Saad MF, Lillioja S, Nyomba BI, et al. Racial differences in the relation between blood pressure and insulin resistance. N Engl J Med 1991;324:733–739.PubMedGoogle Scholar
  56. 56.
    Falkner B, Hulman S, Tannenbaum J, Kushner H. Insulin resistance and blood pressure in young black men. Hypertension 1990;16:706–711.PubMedGoogle Scholar
  57. 57.
    Collins VR, Dowse GK, Finch CFG, Zimmet PZ. An inconsistent relationship between insulin and blood pressure in three Pacific island populations. J Clin Epidemiol 1990;43:1369–1378.PubMedGoogle Scholar
  58. 58.
    Landsberg L, Krieger DR. Obesity, metabolism and the sympathetic nervous system. Am J Hyperten 1989;2:125S–132S.Google Scholar
  59. 59.
    Rocchini AP, Moorehead C, DeRemer S, Goodfriend TL, Ball DL. Hyperinsulinaemia and the aldosterone and pressor responses to angiotensin. II. Hypertension 1990;15:861–866.PubMedGoogle Scholar
  60. 60.
    Ward KD, Sparrow D, Landsberg L, Young JB, Weiss ST. The influence of obesity, insulin and the sympathetic nervous system activity on blood pressure. Clin Res 1993;41:168A.Google Scholar
  61. 61.
    DeFronzo RA, Ferrannini E. Insulin resistance: a multifaceted syndrome responsible for MDDM, obesity, hypertension, dyslipidaemia and atherosclerotic cardiovascular disease. Diabetes Care 1991;14:173–194.PubMedGoogle Scholar
  62. 62.
    Laing C-S, Doherty JU, Faillace R, et al. Insulin infusion in conscious dogs: effects on systemic and coronary haemodynamics, regional blood flows and plasma catecholamines. J Clin Invest 1982;69: 1321–1336.Google Scholar
  63. 63.
    Laakso M, Edelman SV, Brechtel G, Baron AD. Decreased effects of insulin to stimulate skeletal muscle blood flow in obese man: a novel mechanism for insulin resistance. J Clin Invest 1990;85:1844–1852.PubMedGoogle Scholar
  64. 64.
    Creagar MA, Liang C-S, Coffman JD. Beta-adrenergic-mediated vasodilator response to insulin in the human forearm. J Pharmacol Exp Ther 1985;235:709–714.Google Scholar
  65. 65.
    Anderson EA, Hoffman RP, Balon TW, Sinkey CA, Mark AL. Hyperinsulinaemia produces both sympathetic neural activation and vasodilation in normal humans. J Clin Invest 1991;87:2246–2252.PubMedGoogle Scholar
  66. 66.
    Berne C, Fagius J, Pollare T, Hjemdahl P. The sympathetic response to euglycamic hyperinsulinaemia. Diabetologia 1992;35:873–879.PubMedGoogle Scholar
  67. 67.
    Garrow J. Importance of obesity. BMJ 1991;303:704–706.PubMedGoogle Scholar
  68. 68.
    Kissebah AH, Krakower GR. Regional adiposity and morbidity. Physiol Rev 1994;74:761–809.PubMedGoogle Scholar
  69. 69.
    Lew EA, Garfinkel L. Variations in mortality by weight among 750,000 men and women. J Chron Dis 1974;32:563–576.Google Scholar
  70. 70.
    Build Study. 1979. Society of Actuaries and Association of Life Insurance Medical Directors, Chicago, 1980.Google Scholar
  71. 71.
    Willett WC, Manson JE, Stampfer MJ, et al. Weight, weight change and coronary heart disease in women. JAMA 1995:27:1461–1465.Google Scholar
  72. 72.
    Royal College of Physicians. Obesity. JR Coll Physicians Lond 1983;17:3–58.Google Scholar
  73. 73.
    Colditz GA, Willett WC, Rotnitzky A, Manson JE. Weight gain as risk factor for clinical diabetes mellitus in women. Ann Intern Med 1995;122:481–486.PubMedGoogle Scholar
  74. 74.
    Jung RT. Obesity as a disease. Br Med Bull 1997;35:307–321.Google Scholar
  75. 75.
    Vague J. The degree of masculine differentiation of obesities, a factor determining predisposition to diabetes, atherosclerosis, gout and uric calculous disease. Am J Clin Nutr 1956;4:20–34.PubMedGoogle Scholar
  76. 76.
    Larsson B. Svardsudd K. Welin L. Wilhelmsen L. Bjorntorp P. Tibblin G. Abdominal adipose tissue distribution, obesity, and risk of cardiovascular disease and death: 12 year follow up of participants in the study of men born in 1913. BMJ 1984;288:1401–1404.PubMedGoogle Scholar
  77. 77.
    Bengtsson C. Bjorkelund C. Lapidus L. Lissner L. Association of serum lipid concentration and obesity with mortality in women. 20 year follow up of participants in the prospective population study in Gothenburg Sweden. BMJ 1993;307:1385–1388.PubMedGoogle Scholar
  78. 78.
    Stokes J, Garrison RJ, Kannek WB. The independent association of various indices of obesity to the 22 year incidence of coronary heart disease: the Framingham Heart Study. In: Vague J, Bjorntorp P, Guy-Grand B, Rebuffe-Scrive M, Vague P, eds. Proceedings of the International Symposium on the Metabolic Complications of Human Obesities. Marseilles, France, 1985, pp. 49–57.Google Scholar
  79. 79.
    Arner P. Regional adipocity in man. J Endocrinol 1997;155:191–192.PubMedGoogle Scholar
  80. 80.
    Bujalska IJ, Kumar S, Stewart PM. Does central obesity reflect Cushing’s disease of the omentum. Lancet 1998,349:1210–1213.Google Scholar
  81. 81.
    Ludvil B, Nolan JJ, Bolago J, Sacks D, Olefsky J. Effects of obesity on insulin resistance in normal subjects and patients with NIDDM. Diabetes 1995,44:1121–1125.Google Scholar
  82. 82.
    Campbell PJ, Gerich JE. Impact of obesity on insulin action in volunteers with normal glucose tolerance: demonstration of threshold for the adverse effects of obesity. J Clin Endocrinol Metab 1990,70: 1114–1118.PubMedGoogle Scholar
  83. 83.
    Swinburn BA, Nyomba BL, Saad MF, et al. Insulin resistances associated with lower rates of weight gain in Pima Indians. J Clin Invest 1991,88:168–173.PubMedGoogle Scholar
  84. 84.
    Odeleeye OE, de Courten M, Ravussin E. Insulin resistance as a predictor of body weight gain in 5–10 year old Pima Indians. Diabetes 1995;44(Suppl 1):7a.Google Scholar
  85. 85.
    Bjorntorp P, Portal adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis 1990;42:493–496.Google Scholar
  86. 86.
    Durrington PN, Newton RS, Weinstein DB, Steinberg D. Effects of insulin and glucose on VLDL triglyceride secretion by cultured rat hepatocytes. J Clin Invest 1982;70:63–73.PubMedGoogle Scholar
  87. 87.
    Jackson TW, Salhanick AI, Elvoson J, Deichman ML, Amaatruda JM. Insulin regulates apolipoprotein B turnover and phosphorylation in rat hepatocytes. J Clin Invest 1990;86:1746–1751.PubMedGoogle Scholar
  88. 88.
    Coleman DL. Effects of parabiosis of obese with diabetes and normal mice. Diabetologia 1973;9: 294–298.PubMedGoogle Scholar
  89. 89.
    Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994;372:425–432.PubMedGoogle Scholar
  90. 90.
    Halaas JL, Gajiwala KS, Maffei M, et al. Weight reducing effects of the plasma protein encoded by the obese gene. Science1995;269:543–546.Google Scholar
  91. 91.
    Stephens TW, Basinski M, Bristow PK, et al. The role of neuropeptide Y in the antiobesity action of the obese gene product. Nature 1995;377:530–532.PubMedGoogle Scholar
  92. 92.
    Erickson JC, Clegg KE, Palmiter RD. Attenuation of the obesity syndrome of ob/ob mice by loss of neuropeptide Y. S cience1996; 274: 1704 – 1707.Google Scholar
  93. 93.
    Shimabukuro M, Koyama K, Chen G, et al. Direct antidiabetic effect of leptin through triglyceride depletion of tissues. Proc Natl Acad Sci USA 1997; 94: 4637 – 4641.PubMedGoogle Scholar
  94. 94.
    Muller G, Ertl J, Gerl M, Preibisch G. Leptin impairs metabolic actions of insulin in isolated rat adipocytes. J Biol Chem 1997;272:10, 585–10, 593.Google Scholar
  95. 95.
    Zimmet P, Hodge A, Nicholson M, et al. Serum leptin concentration, obesity and insulin resistance in Western Samoans: cross-sectional study. BMJ 1996; 313: 965 – 969.PubMedGoogle Scholar
  96. 96.
    Larsson H, Elmstahl S, Ahren B. Plasma leptin levels correlate to islet function independently of body fat in post-menopausal women. Diabetes 1996; 45: 1580 – 1584.PubMedGoogle Scholar
  97. 97.
    Damani S, Gabriel M, Khan A, Boyadjian R, Kamadar V, Saad M. Adiposity and insulinaemis determine plasma leptin concentration (abstract). Diabetes 1996; 45 (Suppl 1): 41A.Google Scholar
  98. 98.
    Ramanchandran A, Snehalatha C,Vijay V, Satayavani K, Latha E, Haffner SM. Plasma leptin in non-diabetic Asian Indians. Association with abdominal obesity. Diabetes Med 1997; 14: 937 – 941.Google Scholar
  99. 99.
    Carmeliet P, Schoonjans L, Kieckens L, et al. Physiological consequences of loss of plasminogen activator gene function in mice. Nature 1994; 368: 419 – 424.PubMedGoogle Scholar
  100. 100.
    Carmeliet P, Bouche A, De Clercq C, et al. Biological effects of disruption of the tissue-type plasminogen activator and plasminogen activator inhibitor-1 genes in mice. Ann NY Acad Sci 1995; 748: 367 – 382.PubMedGoogle Scholar
  101. 101.
    Erickson LA, Fici Gj, Lund JE, Boyle TP, Polites HG, Marotti KR. Development of venous occlusions in mice transgenic for the PAI-1 gene. Nature 1990; 346: 74 – 76.PubMedGoogle Scholar
  102. 102.
    Schneiderman J, Sawdey MS, Keeton MR, et al. Increased type 1 plasminogen activator inhibitor gene expression in atherosclerotic human arteries. Proc Natl Acad Sci USA 1992; 89: 6998 – 7002.PubMedGoogle Scholar
  103. 103.
    Eliasson M, Evrin PE, Lundblad D. Fibrinogen and fibrinolytic variables in relation to anthropometry, lipids and blood pressure. The Northern Sweden MONICA Study. J Clin Epidemiol 1994; 47: 513 – 524.PubMedGoogle Scholar
  104. 104.
    Sundell IB, Nilsson TK, Ranby M, Hallmans G, Hellsten G. Fibrinolytic variables are related to age, sex, blood pressure, and body build measurements: a cross-sectional study in Norsjo, Sweden. J Clin Epidemiol 1989; 42: 719 – 723.PubMedGoogle Scholar
  105. 105.
    Juhan-Vague I, Alessi MC. PAI-1, obesity, insulin resistance and risk of cardiovascular events. Thromb Haemost 1997; 78: 656 – 660.PubMedGoogle Scholar
  106. 106.
    Eliasson M, Evrin PE, Lundblad D. Fibrinogen and fibrinolytic variables in relation to anthropometry, lipids and blood pressure. The Northern Sweden MONICA Study. J Clin Epidemiol 1994; 47: 513 – 524.PubMedGoogle Scholar
  107. 107.
    Sundell IB, Dahlgren S, Ranby M, Lundin E, Stenling R, Nilsson TK. Reduction of elevated plasminogen activator inhibitor levels during modest weight loss. Fibrinolysis 1989; 3: 51 – 53.Google Scholar
  108. 108.
    Gray RP, Panahloo A, Mohamed-Ali V, Patterson DL, Yudkin JS. Proinsulin-like molecules and plasminogen activator inhibitor typel (PAI-1) activity in diabetic subjects with and without myocardial infarction. Atherosclerosis 1997; 130: 171 – 178.PubMedGoogle Scholar
  109. 109.
    Thompson SG, Kienast J, Pyke SDM, Haverkate F, van de Loo JCW. Haemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. N Engl J Med 1995; 332: 635.PubMedGoogle Scholar
  110. 110.
    Coley WB. The treatment of malignant tumours by repeated inoculations of erysipelas; with a report of ten original cases. Clin Orthop 1991; 262: 3 - 11.PubMedGoogle Scholar
  111. 111.
    Old LJ. Tumour necrosis factor (TNF). Science 1985; 230: 630 - 632.PubMedGoogle Scholar
  112. 112.
    Argiles JM, Lopez-Soriano J, Busquets S, Lopez-Soriano FJ. Journey from cachexia to obesity by TNF. FASEB J 1997; 11: 743 - 751.PubMedGoogle Scholar
  113. 113.
    Hotamisligil GS, Peraldi P, Spiegelman BM. The molecular link between obesity and diabetes. Curr Opin Endocrinol Diabetes 1996, 3: 16 - 23.Google Scholar
  114. 114.
    Despres JP. Lipoprotein metabolism in visceral obesity. Int J Obesity 1991; 2: 5 - 15.Google Scholar
  115. 115.
    Gaziano JM. When should heart disease prevention begin? N Engl J Med 1998; 338: 1690 - 1691.PubMedGoogle Scholar
  116. 116.
    De Fronzo RA, Varzilai N, Simonson DC. Mechanism of metformin action in obese and lean non-insulin dependent diabetic subjects. J Clin Endocrinol Metab1991; 73: 1294 - 1301.Google Scholar
  117. 117.
    Vague P, Juhan-Vague I, Alessi MC, Badier C, Valadier J. Metformin decreases the high plasminogen activator inhibition capacity, plasma insulin and triglyceride levels in non diabetic obese subjects. Thromb Haemost 1987; 57: 326 - 328.PubMedGoogle Scholar
  118. 118.
    Wood D. European and American recommendations for coronary heart disease prevention. Eur Heart J 1998;19(Suppl A):Al2–A19.Google Scholar
  119. 119.
    Jones AF, Game FL. Cardiovascular risk assessment. Mod Hypertems Manage 1999; 1: 10 – 13.Google Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Aresh J. Anwar
  • Anthony H. Barnett
  • Sudhesh Kumar

There are no affiliations available

Personalised recommendations