Our study compared different criteria for the classification of AGR in patients with CAD and without previously known glucometabolic disturbances. The major finding was that an evaluation of glucometabolic status based on fasting glycaemia only, even after applying the most recent ADA criterion, would have misclassified 41% of the patients. Moreover, an algorithm based on easily available clinical and laboratory data was much too imprecise to be of practical value.
Our survey of a large number of people with a wide range of acute or stable CAD gives a good representation of patients seen in all‐day clinical practice. To our knowledge, it represents one of the largest populations of patients with coronary heart disease and no previous glucose disturbances, in whom both FPG and post‐challenge glycaemia were tested.15
Overall prevalence of glucose disturbances
Our data confirm the observation by Norhammar et al3
that previously unknown AGR is common in patients with acute myocardial infarction and extend it, revealing a similar proportion of newly discovered AGR among patients with stable CAD. Studies on the actual prevalence of subclinical hyperglycaemia in patients with CAD rarely include an OGTT. A similar proportion of 18% of cases with unknown diabetes was disclosed by OGTT in patients scheduled for coronary angiography,16
whereas the 19% prevalence of raised FPG (
6.1 mmol/l) in our cohort matches the 20% found in the Bezafibrate Infarction Prevention Study.17
The glucose disturbances seem to be twice as common in patients with CAD as in the general population.2,15,18
The frequency of FPG in the diabetic range (
7.0 mmol/l) among patients with CAD was not much different from that in the general population in the DECODE Study (5% and 4%), whereas the 2‐h post‐load hyperglycaemia (
11.1 mmol/l) was much more common (16% and 4%, respectively; fig 2). The overall prevalence of IFG, as defined by the WHO (
6.1 mmol/l) or ADA 2004 (
5.6 mmol/l) criteria, was found in 15% and 31% in the present cohort, respectively, which corresponds to reports from the Inter99, Paris Prospective or the NHANES populations. The prevalence of IGT did, however, differ strikingly, with 36% among surveyed patients with CAD compared with 13%, 12% and 8% in the above‐mentioned populations.18
The inter‐relation between IGT and future cardiovascular mortality and morbidity compared with IFG was first shown by the Funagata Diabetes Study.19
Abnormal glucose tolerance was an independent determinant of long‐term outcome in patients treated with coronary angioplasty.20
Recently, the Glucose Tolerance in Patients with Acute Myocardial Infarction Study showed that newly detected abnormal glucose tolerance in patients with an acute myocardial infarction is a strong prognostic predictor during long‐term follow‐up.5
The importance of an early and appropriate recognition of the glucometabolic state in patients with CAD is underlined by its effect on the clinical course and thereby patient management. It is possible to interfere with the decline of glucose homoeostasis and prevent patients with IGT from progressing to diabetes mellitus using lifestyle or pharmacological interventions.21,22
Awareness of the actual glucometabolic state in patients with CAD should contribute to a more aggressive risk factor control.23
That metabolically active treatment modalities may improve the prognosis of patients with cardiovascular disease and AGR is indicated by the Study To Prevent NIDDM24
and the PROspective pioglitAzone Clinical Trial In macroVascular Events trials.25
The use of both FPG and post‐challenge glycaemia for patient evaluation enabled a comparison of the different classification modalities, with FPG strongly encouraged over an OGTT by ADA.7,8
The degree of disagreement between ADA and WHO criteria was the same whether patients entered the cardiology centres on acute or elective basis. Even if the reproducibility of FPG is higher than that of the 2‐h post‐challenge levels, the reproducibility of recognising newly diagnosed diabetes was virtually identical for the ADA and WHO criteria, 77% and 74%, respectively.26,27
Moreover, weighted κ, expressing the chance‐corrected proportional agreement between the outcome of OGTT and classification not based on postprandial glycaemia, was relatively low.
If only FPG had been used for glucometabolic evaluation, 45% of patients with diabetes shown by an OGTT and 73% with IGT would have remained undiagnosed according to the ADA 1997 criteria.7
Applying the updated ADA criteria,8
these proportions would have been lower, but still substantial, at 29% and 57%, respectively. The overall concordance between IFG (ADA) and IGT (WHO) increased from 5% to 11% by changing the definition of normal FPG from <6.1 to <5.6 mmol/l. Despite this improvement, glucose disturbances would have remained undetected in 21% of all patients with an isolated IGT (fig 2). A new category of patients with FPG concentrations between 5.6 and 6.1 mmol/l, comprising 8% of all patients, would have been classified as prediabetic, creating a potential problem, as their risk of developing diabetes and cardiovascular complications remains unknown. Accordingly, the ADA 2004 criterion evokes concerns by logistic and medical reasons.28,29
Moreover, 2‐h post‐load glycaemia was shown to be a more sensitive predictor for cardiovascular outcomes than FPG.19,29,30
The prognostic potential of the new ADA criterion should therefore be further evaluated before it is generally adopted as an appropriate assessment tool for glucometabolic evaluation of patients with CAD.
Classification without OGTT
Several routine measurements were reported in the survey records, enabling a test of their feasibility for estimation of the glucometabolic state. The best potential predictors were HDL‐C, waist circumference and HbA1c, which were included in the statistical models adjusted for age. Considering a misclassification rate of 44%, the ordinal logistic regression model was not helpful. Thus, an OGTT is still required for appropriate glucometabolic characterisation.
The prospective recruitment of patients seen at a large number of European cardiology centres was an advantage, mirroring all‐day practice. Adherence to the volunteer protocol was, however, incomplete, with 1495 eligible patients having not undergone an OGTT and having a somewhat restricted availability of HbA1c samples. The main reason was that ethical permits to perform an OGTT were not issued in some countries. Another but considerably less prevalent reason was technical obstacles experienced in the cardiology care setting for these not‐as‐routine experienced measures. Finally, some patients did not undergo an OGTT because of overt fasting hyperglycaemia that was considered sufficient to establish the diagnosis of diabetes (n
84; 7.3%). Overall, the patients who did not undergo an OGTT were somewhat older and more often women. They had a higher waist circumference, higher HbA1c values and were more often diagnosed with heart failure (table 2). Any of these features indicate an increased likelihood for having diabetes or impaired glucose regulation. Thus, we can assume that if OGTT would have been tested in all eligible patients, the overall prevalence of AGR would, if anything, be higher than that reported in 1867 patients in whom OGTT was performed. This does not constitute any major concern for the present results, as it is unlikely that diagnostic accuracy would have been different in patients who were not tested.
Ninety six per cent of the population studied was of Caucasian ethnicity. Thus, the results may not apply directly to people of other origins, in particular Asian or Black populations, in whom the prevalence of diabetes is known to be higher.