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From syndrome X to cardiometabolic risk: clinical and public health implications

  • Jean-Pierre Després (a1) (a2) (a3)


Although the first description of a syndrome defined by the co-existence of atherogenic and diabetogenic metabolic abnormalities is debated in the literature, it was Gerald Reaven who proposed, in his landmark 1988 Banting award lecture, that a significant proportion of individuals (with diabetes or not) were characterised by insulin resistance causing prejudice to cardiovascular health. However, Reaven was influenced by seminal observations made more than 50 years earlier by Himsworth who proposed that there were two forms of diabetes (insulin resistant v. insulin sensitive). Reaven went further in proposing the theory that insulin resistance was the most prevalent cause of CVD associated with metabolic abnormalities that he named syndrome X. Because there was a syndrome X documented in cardiology, the term evolved to insulin resistance syndrome. As Reaven could also find insulin-resistant individuals in non-obese subjects, he did not include obesity as a feature of syndrome X. Imaging studies then revealed that excess adipose tissue in the abdominal cavity, a condition described as visceral obesity, was the form of overweight/obesity associated with insulin resistance and its related abnormalities. As obesity risk assessment and management remain largely based on body weight (BMI) and weight loss, it is proposed that our clinical approaches and public health messages should be revisited. First, patients should be educated about the importance of monitoring their waistline as a crude index of abdominal adiposity. Secondly, public health approaches focussing on ‘lifestyle vital signs’ including achieving healthy waistlines rather than healthy body weights should be developed.


Corresponding author

Corresponding author: Jean-Pierre Després, email


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1.N. C. D. Risk Factor Collaboration (2016) Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants. Lancet 387, 13771396.
2.N. C. D. Risk Factor Collaboration (2016) Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4·4 million participants. Lancet 387, 15131530.
3.Gonzalez-Muniesa, P, Martinez-Gonzalez, MA, Hu, FB et al. (2017) Obesity. Nat Rev Dis Primers 3, 17034.
4.Wen, CP & Wu, X (2012) Stressing harms of physical inactivity to promote exercise. Lancet 380, 192193.
5.Hruby, A, Manson, JE, Qi, L et al. . (2016) Determinants and consequences of obesity. Am J Public Health 106, 16561662.
6.Mozaffarian, D (2016) Dietary and policy priorities for cardiovascular disease, diabetes, and obesity: a comprehensive review. Circulation 133, 187225.
7.Fries, JF (1980) Aging, natural death, and the compression of morbidity. N Engl J Med 303, 130135.
8.Mozaffarian, D (2011) Achieving cardiovascular health: a bleak outlook or tremendous potential? J Am Coll Cardiol 57, 16971699.
9.Reaven, GM (1988) Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 37, 15951607.
10.Reaven, GM (2011) Insulin resistance: the link between obesity and cardiovascular disease. Med Clin North Am 95, 875892.
11.Himsworth, HP (1936) Diabetes mellitus: Its differentiation into insulin-sensitive and insulin-insensitive types. Lancet 227, 127130.
12.Tokunaga, K, Matsuzawa, Y, Ishikawa, K et al. (1983) A novel technique for the determination of body fat by computed tomography. Int J Obes 7, 437445.
13.Lemieux, S, Prud'homme, D, Bouchard, C et al. (1993) Sex differences in the relation of visceral adipose tissue accumulation to total body fatness. Am J Clin Nutr 58, 463467.
14.Kvist, H, Chowdhury, B, Grangard, U et al. (1988) Total and visceral adipose-tissue volumes derived from measurements with computed tomography in adult men and women: predictive equations. Am J Clin Nutr 48, 13511361.
15.Després, JP, Moorjani, S, Lupien, PJ et al. (1990) Regional distribution of body fat, plasma lipoproteins, and cardiovascular disease. Arteriosclerosis 10, 497511.
16.Després, JP (1993) Abdominal obesity as important component of insulin-resistance syndrome. Nutrition 9, 452459.
17.Després, JP, Lemieux, I, Bergeron, J et al. (2008) Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk. Arterioscler Thromb Vasc Biol 28, 10391049.
18.Després, JP (2012) Body fat distribution and risk of cardiovascular disease: an update. Circulation 126, 13011313.
19.Tchernof, A & Després, JP (2013) Pathophysiology of human visceral obesity: an update. Physiol Rev 93, 359404.
20.Després, JP & Lemieux, I (2006) Abdominal obesity and metabolic syndrome. Nature 444, 881887.
21.Shah, RV, Murthy, VL, Abbasi, SA et al. (2014) Visceral adiposity and the risk of metabolic syndrome across body mass index: the MESA Study. JACC Cardiovasc Imaging 7, 12211235.
22.Matsuzawa, Y (2008) The role of fat topology in the risk of disease. Int J Obes (Lond) 32, Suppl. 7, S83S92.
23.Neeland, IJ, Poirier, P & Després, JP (2018) Cardiovascular and metabolic heterogeneity of obesity: clinical challenges and implications for management. Circulation 137, 13911406.
24.Smith, U (2015) Abdominal obesity: a marker of ectopic fat accumulation. J Clin Invest 125, 17901792.
25.Neeland, IJ, Turer, AT, Ayers, CR et al. (2015) Body fat distribution and incident cardiovascular disease in obese adults. J Am Coll Cardiol 65, 21502151.
26.Klein, S, Fontana, L, Young, VL et al. (2004) Absence of an effect of liposuction on insulin action and risk factors for coronary heart disease. N Engl J Med 350, 25492557.
27.Cheng, TO (2007) Cardiac syndrome X versus metabolic syndrome X. Int J Cardiol 119, 137138.
28.Kemp, HG Jr (1973) Left ventricular function in patients with the anginal syndrome and normal coronary arteriograms. Am J Cardiol 32, 375376.
29.Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2001) Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 285, 24862497.
30.Lemieux, I, Pascot, A, Couillard, C et al. (2000) Hypertriglyceridemic waist. A marker of the atherogenic metabolic triad (hyperinsulinemia, hyperapolipoprotein B, small, dense LDL) in men? Circulation 102, 179184.
31.Galassi, A, Reynolds, K & He, J (2006) Metabolic syndrome and risk of cardiovascular disease: a meta-analysis. Am J Med 119, 812819.
32.Gami, AS, Witt, BJ, Howard, DE et al. (2007) Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies. J Am Coll Cardiol 49, 403414.
33.Gale, EA (2005) The myth of the metabolic syndrome. Diabetologia 48, 16791683.
34.Kahn, R, Buse, J, Ferrannini, E et al. (2005) The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 28, 22892304.
35.Després, JP, Cartier, A, Côté, M et al. (2008) The concept of cardiometabolic risk: bridging the fields of diabetology and cardiology. Ann Med 40, 514523.
36.Lemieux, I, Poirier, P, Bergeron, J et al. (2007) Hypertriglyceridemic waist: a useful screening phenotype in preventive cardiology? Can J Cardiol 23, Suppl. B, 23B31B.
37.Reaven, GM (2005) The metabolic syndrome: requiescat in pace. Clin Chem 51, 931938.
38.Reaven, GM (2006) The metabolic syndrome: is this diagnosis necessary? Am J Clin Nutr 83, 12371247.
39.Reaven, GM (2011) The metabolic syndrome: time to get off the merry-go-round? J Intern Med 269, 127136.
40.Després, JP (2018) The Reaven syndrome: a tribute to a giant. Nat Rev Endocrinol 14, 319320.
41.D'Agostino, RB Sr, Vasan, RS, Pencina, MJ et al. (2008) General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation 117, 743753.
42.Assmann, G, Schulte, H, Cullen, P et al. (2007) Assessing risk of myocardial infarction and stroke: new data from the Prospective Cardiovascular Munster (PROCAM) study. Eur J Clin Invest 37, 925932.
43.Conroy, RM, Pyorala, K, Fitzgerald, AP et al. (2003) Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J 24, 9871003.
44.Després, JP, Poirier, P, Bergeron, J et al. (2008) From individual risk factors to the metabolic syndrome to global cardiometabolic risk. Eur Heart J 10, Suppl. B, B24B33.
45.Britton, KA & Fox, CS (2011) Ectopic fat depots and cardiovascular disease. Circulation 124, e837e841.
46.Morelli, M, Gaggini, M, Daniele, G et al. (2013) Ectopic fat: the true culprit linking obesity and cardiovascular disease? Thromb Haemost 110, 651660.
47.Karpe, F & Pinnick, KE (2015) Biology of upper-body and lower-body adipose tissue – link to whole-body phenotypes. Nat Rev Endocrinol 11, 90100.
48.Hardy, T, Oakley, F, Anstee, QM et al. (2016) Nonalcoholic fatty liver disease: Pathogenesis and disease spectrum. Annu Rev Pathol 11, 451496.
49.Byrne, CD & Targher, G (2015) NAFLD: a multisystem disease. J Hepatol 62, Suppl. 1, S47S64.
50.Fabbrini, E, Sullivan, S & Klein, S (2010) Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications. Hepatology 51, 679689.
51.Lim, S, Taskinen, MR & Boren, J (2019) Crosstalk between nonalcoholic fatty liver disease and cardiometabolic syndrome. Obes Rev 20, 599611.
52.Smith, JD, Borel, AL, Nazare, JA et al. (2012) Visceral adipose tissue indicates the severity of cardiometabolic risk in patients with and without type 2 diabetes: results from the INSPIRE ME IAA study. J Clin Endocrinol Metab 97, 15171525.
53.Baillot, A, Nazare, JA, Borel, AL et al. (2018) Visceral adipose tissue vs. liver fat as drivers of cardiometabolic risk: The INSPIRE ME IAA Study.
54.Alexander, CM, Landsman, PB, Teutsch, SM et al. (2003) NCEP-defined metabolic syndrome, diabetes, and prevalence of coronary heart disease among NHANES III participants age 50 years and older. Diabetes 52, 12101214.
55.Lavie, CJ, De Schutter, A & Milani, RV (2015) Healthy obese versus unhealthy lean: the obesity paradox. Nat Rev Endocrinol 11, 5562.
56.Després, JP (2012) What is ‘metabolically healthy obesity’?: from epidemiology to pathophysiological insights. J Clin Endocrinol Metab 97, 22832285.
57.Kramer, CK, Zinman, B & Retnakaran, R (2013) Are metabolically healthy overweight and obesity benign conditions?: a systematic review and meta-analysis. Ann Intern Med 159, 758769.
58.Rao, S, Pandey, A, Garg, S et al. (2019) Effect of exercise and pharmacological interventions on visceral adiposity: a systematic review and meta-analysis of long-term randomized controlled trials. Mayo Clin Proc 94, 211224.
59.Gepner, Y, Shelef, I, Schwarzfuchs, D et al. (2018) Effect of distinct lifestyle interventions on mobilization of fat storage pools: CENTRAL Magnetic Resonance Imaging Randomized Controlled Trial. Circulation 137, 11431157.
60.Ross, R & Bradshaw, AJ (2009) The future of obesity reduction: beyond weight loss. Nat Rev Endocrinol 5, 319325.
61.Davidson, LE, Hudson, R, Kilpatrick, K et al. (2009) Effects of exercise modality on insulin resistance and functional limitation in older adults: a randomized controlled trial. Arch Intern Med 169, 122131.
62.Després, JP (2015) Obesity and cardiovascular disease: weight loss is not the only target. Can J Cardiol 31, 216222.
63.Tuomilehto, J, Lindstrom, J, Eriksson, JG et al. (2001) Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 344, 13431350.
64.Knowler, WC, Barrett-Connor, E, Fowler, SE et al. (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346, 393403.
65.Borel, AL, Nazare, JA, Baillot, A et al. (2017) Cardiometabolic risk improvement in response to a 3-yr lifestyle modification program in men: contribution of improved cardiorespiratory fitness vs. weight loss. Am J Physiol Endocrinol Metab 312, E273E281.
66.Lévesque, V, Vallières, M, Poirier, P et al. (2015) Targeting abdominal adiposity and cardiorespiratory fitness in the workplace. Med Sci Sports Exerc 47, 13421350.
67.Lévesque, V, Poirier, P, Després, JP et al. (2015) Assessing and targeting key lifestyle cardiovascular risk factors at the workplace: effect on hemoglobin A1c levels. Ann Med 47, 605614.
68.Lévesque, V, Poirier, P, Després, JP et al. (2017) Relation between a simple lifestyle risk score and established biological risk factors for cardiovascular disease. Am J Cardiol 120, 19391946.
69.Kodama, S, Saito, K, Tanaka, S et al. (2009) Cardiorespiratory fitness as a quantitative predictor of all-cause mortality and cardiovascular events in healthy men and women: a meta-analysis. JAMA 301, 20242035.
70.Myers, J (2014) New American Heart Association/American College of Cardiology guidelines on cardiovascular risk: when will fitness get the recognition it deserves? Mayo Clin Proc 89, 722726.
71.Ross, R, Blair, SN, Arena, R et al. (2016) Importance of assessing cardiorespiratory fitness in clinical practice: a case for fitness as a clinical vital sign: a scientific statement from the American Heart Association. Circulation 134, e653e699.



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