Dysglycemia: A Key Cardiovascular Risk Factor

Hertzel C. Gerstein; Sarah E. Capes

doi:10.1055/s-2002-32040

Seminars in Vascular Medicine, Table of Contents

Semin Vasc Med 2002; 2(2): 165-174
DOI: 10.1055/s-2002-32040

Dysglycemia: A Key Cardiovascular Risk Factor

Hertzel C. Gerstein, Sarah E. Capes

¹Department of Medicine and the Division of Endocrinology and Metabolism, McMaster University, Hamilton, Ontario, Canada

Abstract

ABSTRACT

Although diabetes is a strong independent risk factor for cardiovascular events, this risk is not confined to glucose levels above the diagnostic threshold for diabetes. Rather, there is now a growing consensus that the risk of cardiovascular events rises progressively as the fasting and postprandial glucose levels rise from the clearly normal range right into the diabetes range. Hence, dysglycemia (i.e., any elevated fasting or glucose level) is a progressive, continuous risk factor for cardiovascular events. In this respect it resembles every other well-established and progressive cardiovascular risk factor, such as age, LDL cholesterol, systolic and diastolic blood pressure, degree of smoking, albumin excretion, and body mass index. Whether or not strategies designed to normalize glucose levels in people with either diabetes or lesser degrees of dysglycemia will also reduce cardiovascular risk remains to be established. The results of several large international trials of glucose lowering in dysglycemic individuals should clarify the cardiovascular benefits of such an approach within the next few years.

KEYWORDS

Dysglycemia - cardiovascular events - risk factor - clinical trials

Full Text

References

REFERENCES

1 Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care . 1997; 20 1183-1197
2 Alberti K G, Zimmet P Z. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation [comments]. Diabet Med . 1998; 15 539-553
3 Stamler J, Vaccaro O, Neaton J D, Wentworth D. Diabetes, other risk factors, and 12-year cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care . 1993; 16 434-444
4 Chen Y T, Vaccarino V, Williams C S, Butler J, Berkman L F, Krumholz H M. Risk factors for heart failure in the elderly: a prospective community-based study. Am J Med . 1999; 106 605-612
5 Kannel W B, McGee D L. Diabetes and cardiovascular disease. The Framingham Study. JAMA . 1979; 241 2035-2038
6 Fuller J H, Shipley M J, Rose G, Jarrett R J, Keen H. Mortality from coronary heart disease and stroke in relation to degree of glycemia: the Whitehall Study. Br Med J Clin Research Ed . 1983; 287 867-870
7 Barrett-Connor E, Cohn B A, Wingard D L, Edelstein S L. Why is diabetes mellitus a stronger risk factor for fatal ischemic heart disease in women than in men?. <~>The Rancho Bernardo Study. JAMA . 1991; 265 627-631
8 Goldbourt U, Yaari S, Medalie J H. Factors predictive of long-term coronary heart disease mortality among 10,059 male Israeli civil servants and municipal employees. A 23-year mortality follow-up in the Israeli Ischemic Heart Disease Study. Cardiology . 1993; 82 100-121
9 Manson J E, Coldlitz G A, Stampfer M J. A prospective study of maturity-onset diabetes mellitus and risk of coronary heart disease and stroke in women. Arch Int Med . 1991; 151 1141-1147
10 Morrish N J, Stevens L K, Fuller J H, Keen H, Jarrett R J. Incidence of macrovascular disease in diabetes mellitus: the London follow-up to the WHO multinational study of vascular disease in diabetics. Diabetologia . 1991; 34 584-589
11 ETDRS Investigators. Aspirin effects on mortality and morbidity in patients with diabetes mellitus. Early treatment of diabetic retinopathy study report 14. JAMA . 1992; 266 1292-1300
12 Damsgaard E M, Froland A, Jorgensen O D, Mogensen C E. Eight- to nine-year mortality in known non-insulin dependent diabetes and controls. Kidney Int . 1992; 42 731-735
13 Neil A, Hawkins M, Potok M, Thorogood M, Cohen D A, Mann J. A prospective population-based study of microalbuminuria as a predictor of mortality in NIDDM. Diabetes Care . 1993; 16 996-1003
14 Wei M, Gaskill S P, Haffner S M, Stern M P. Effects of diabetes and level of glycemia on all-cause and cardiovascular mortality. The San Antonio Heart Study. Diabetes Care . 1998; 21 1167-1172
15 Miettinen H, Lehto S, Salomaa V. Impact of diabetes on mortality after the first myocardial infarction. Diabetes Care . 1998; 21 69-75
16 Haffner S M, Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. New Engl J Med . 1998; 339 229-234
17 Turner R C, Millns H, Neil H AW. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: UKPDS 23. BMJ . 1998; 316 823-828
18 Hadden D R, Patterson C C, Atkinson A B. Macrovascular disease and hyperglycemia: 10-year survival analysis in type 2 diabetes mellitus: the Belfast Diet Study. Diabet Med . 1997; 14 663-672
19 Kuller L H, Velentgas P, Barzilay J, Beauchamp N J, O'Leary D H, Savage P J. Diabetes mellitus: subclinical cardiovascular disease and risk of incident cardiovascular disease and all-cause mortality. Arterioscler Thromb Vasc Biol . 2000; 20 823-829
20 Malmberg K, Yusuf S, Gerstein H C. Impact of diabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction: results of the OASIS (Organization to Assess Strategies for Ischemic Syndromes) registry. Circulation . 2000; 102 1014-1019
21 Stratton I M, Adler A I, Neil H A. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ . 2000; 321 405-412
22 Reed D, Yano K. Predictors of arteriographically defined coronary stenosis in the Honolulu Heart Program. Comparisons of cohort and arteriography series analyses. Am J Epidemiol . 1991; 134 111-122
23 Ledru F, Ducimetiere P, Battaglia S. New diagnostic criteria for diabetes and coronary artery disease: insights from an angiographic study. J Am Coll Cardiol . 2001; 37 1543-1550
24 Bonora E, Kiechl S, Oberhollenzer F. Impaired glucose tolerance, type II diabetes mellitus and carotid atherosclerosis: prospective results from the Bruneck Study. Diabetologia . 2000; 43 156-164
25 McGill Jr C H, McMahan C A, Malcom G T, Oalmann M C, Strong J P. Relation of glycohemoglobin and adiposity to atherosclerosis in youth. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. Arterioscler Thromb Vasc Biol . 1995; 15 431-440
26 Vitelli L L, Shahar E, Heiss G. Glycosylated hemoglobin level and carotid intimal-medial thickening in nondiabetic individuals. The Atherosclerosis Risk in Communities Study. Diabetes Care . 1997; 20 1454-1458
27 Glucose tolerance and moGlucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria. The DECODE study group. European Diabetes Epidemiology Group.. Diabetes epidemiology: collaborative analysis of diagnostic criteria in Europe. Lancet . 1999; 354 617-621
28 Saydah S H, Loria C M, Eberhardt M S, Brancati F L. Subclinical states of glucose intolerance risk of death in the U.S. Diabetes Care . 2001; 24 447-453
29 Delode Study Group. Glucose tolerance cardiovascular mortality: comparison of fasting 2-hour diagnostic criteria. Arch Intern Med . 2001; 161 397-405
30 Balkau B, Shipley M, Jarrett R J. High blood glucose concentration is a risk factor for mortality in middle-aged nondiabetic men. Diabetes Care . 1998; 21 360-367
31 Gerstein H C, Mann J FE, Yi Q. Albuminuria risk of cardiovascular events death, and heart failure in diabetic nondiabetic individuals. JAMA . 2001; 286 421-426
32 Bjornholt J V, Erikssen G, Aaser E. Fasting blood glucose: an underestimated risk factor for cardiovascular death. Results from a 22-year follow-up of healthy nondiabetic men. Diabetes Care . 1999; 22 45-49
33 Balkau B, Bertrais S, Ducimetiere P, Eschwege E. Is there a glycemic threshold for mortality risk?. Diabetes Care . 1999; 22 696-699
34 Khaw K T, Wareham N, Luben R. Glycated haemoglobin diabetes, and mortality in men in Norfolk cohort of European Prospective Investigation of Cancer Nutrition (EPIC-Norfolk). BMJ . 2001; 322 15
35 Neaton J D, Wentworth D, and the MRFIT Research Group. Serum cholesterol blood pressure cigarette smoking death from coronary heart disease. Overall findings differences by age for 316,099 white men. Arch Int Med . 1992; 152 56-64
36 Avignon A, Radauceanu A, Monnier L. Nonfasting plasma glucose is a better marker of diabetic control than fasting plasma glucose in type 2 diabetes. Diabetes Care . 1997; 20 1822-1826
37 de Vegt F, Dekker J M, Ruhe H G. Hyperglycaemia is associated with all-cause cardiovascular mortality in the Hoorn population: the Hoorn Study. Diabetologia . 1999; 42 926-931
38 Barzilay J I, Spiekerman C F, Wahl P W. Cardiovascular disease in older adults with glucose disorders: comparison of American Diabetes Association criteria for diabetes mellitus with WHO criteria [comments]. Lancet . 1999; 354 622-625
39 Capes S E, Hunt D, Malmberg K, Gerstein H C. Stress hyperglycaemia increased risk of death after myocardial infarction in patients with without diabetes: a systematic overview. Lancet . 2000; 355 773-778
40 Haller H. Postprandial glucose vascular disease. Diabet Med . 1997; S50-S56
41 Brownlee M, Cerami A, Vlassara H. Advanced glycosylation end products in tissue the biochemical basis of diabetic complications. N Engl J Med . 1988; 318 1315-1321
42 Schiekofer S, Balletshofer B, Andrassy M, Bierhaus A, Nawroth P P. Endothelial dysfunction in diabetes mellitus. Semin Thromb Hemost . 2000; 26 503-511
43 Ginsberg H N. Insulin resistance cardiovascular disease. J Clin Invest . 2000; 106 453-458
44 McFarlane S I, Banerji M, Sowers J R. Insulin resistance cardiovascular disease. J Clin Endocrinol Metab . 2001; 86 713-718
45 Timar O, Sestier F, Levy E. Metabolic syndrome X: a review. Can J Cardiol . 2000; 16 779-789
46 Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med . 1993; 329 977-986
47 Lawson M, Gerstein H C, Tsui E, Zinman B. Effect of intensive therapy on early macrovascular disease in young individuals with type 1 diabetes. A systematic review meta-analysis. Diabetes Care . 1999; B35-B39
48 United Kingdom Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet . 1998; 352 837-853
49 Gerstein H C, Malmberg K, Capes S, Yusuf S. Cardiovascular diseases. In: Gerstein HC Haynes RB eds. Evidence-Based Diabetes Care Hamilton Ontario: BC Decker Inc 2001 : 488-514
50 Malmberg K, Ryden L, Efendic S. Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): effects on mortality at 1 year. J Am Coll Cardiol . 1995; 26 57-65
51 Malmberg K. Prospective randomised study of intensive insulin treatment on long-term survival after acute myocardial infarction in patients with diabetes mellitus. DIGAMI (Diabetes Mellitus Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group [comments]. BMJ . 1997; 314 1512-1515
52 Fath-Ordoubadi F, Beatt K J. Glucose-insulin-potassium therapy for treatment of acute myocardial infarction: an overview of randomized placebo-controlled trials [comments]. Circulation . 1997; 96 1152-1156
53 The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor ramipril, on cardiovascular events in high-risk patients. New Engl J Med . 2000; 342 145-153
54 Hansson L, Lindholm L H, Niskanen L. Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial [comments]. Lancet . 1999; 353(9153) 611-616
55 Freeman D J, Norrie J, Sattar N. Pravastatin the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study. Circulation . 2001; 103 357-362
56 Coutinho M, Gerstein H C, Wang Y, Yusuf S. The relationship between glucose incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. Diabetes Care . 1999; 22 233-240
57 Gall M-A, Borch-Johnsen K, Hougaard P, Nielsen F S, Parving H-H. Albuminuria poor glycemic control predict mortality in NIDDM. Diabetes . 1995; 44 1303-1309
58 Agewall S, Wikstrand J, Ljungman S, Fagerberg B, and the Risk Factor Intervention Study Group. Usefulness of microalbuminuria in predicting cardiovascular mortality in treated hypertensive men with without diabetes mellitus. Am J Cardiol . 1997; 80 164-169
59 Moss S E, Klein R, Klein B EK, Meuer S M. The association of glycemia cause-specific mortality in a diabetic population. Arch Intern Med . 1994; 154 2473-2479
60 Fu C C, Chang C J, Tseng C H. Development of macrovascular diseases in NIDDM patients in northern Taiwan. A 4-year follow-up study. Diabetes Care . 1993; 16 137-143
61 Simons L A, Friedlander Y, McCallum J, Simons J. Fasting plasma glucose in non-diabetic elderly women predicts increased all-causes mortality coronary heart disease risk. Aust N Z J Med . 2000; 30 41-47