By the end of the screening phase of the ADDITION study, 334 general practices (182 in Denmark, 49 in Cambridge, 24 in Leicester and 79 in the Netherlands) had screened 76,308 people (28,031 in Denmark, 24,654 in Cambridge, 5,740 in Leicester and 17,883 in the Netherlands). In total, 3,233 individuals with screen-detected diabetes were identified and a total of 3,057 individuals (1,533 in Denmark, 867 in Cambridge, 159 in Leicester and 498 in the Netherlands) were recruited to the ADDITION study. There were no significant differences in the characteristics of the 3,057 participants recruited to the trial compared with the 176 patients with screen-detected diabetes who were eligible but chose not to participate.
The baseline characteristics of the participants recruited to the trial including the risk factors for CHD are shown in Table 1. Across the centres significant differences were seen in the demographic characteristics of the participants, largely by virtue of differences in the underlying populations and the approach to screening. The Leicester population differed from the other three centres by having the youngest population (mean age = 57.2 years compared with 59.9 years in the other three groups, p < 0.001), the highest proportion of participants who were non-white (41.3 compared with 3.9% in the other groups, p < 0.001) and the highest proportion of people who were not employed (7.7 compared with 2.2% in the other centres, p < 0.01). The Danish population had the highest proportion of smokers (35% compared with 26% in the Netherlands, 18% in Cambridge and 16% in Leicester, p < 0.001) and also had the highest intake of alcohol units per week. The mean HbA1c was lower in the Danish population (6.8%) than in the other three centres (overall mean 7.3%, p < 0.001).
Anti-hypertensive, lipid-lowering and antiplatelet therapy
In the total study population 73% of the participants had a blood pressure greater than 140/90 mmHg and of these 58% had not been prescribed antihypertensive medication. Therefore, overall 42% of the cohort was hypertensive but not being treated. Even in the subpopulation of people already receiving antihypertensive therapy (Table 2) there was evident room for enhancement of blood pressure lowering, since the mean blood pressure level in this supposedly treated group was 151/86 mmHg. Indeed the blood pressure levels in the population receiving therapy were only marginally lower than those in the untreated group. In this group, 67% of people did not meet the treatment goal of a blood pressure of 140/90 showing the potential for intensified therapy or for behavioural modifications to enhance treatment adherence. Similarly, 70% of the cohort had a cholesterol level above 5.0 mmol/l. More women (75%) than men (65%, p < 0.001) were hypercholesterolaemic. Nearly all of these people with high cholesterol levels (91%) were not being treated with lipid-lowering pharmaceuticals. Overall 64% of the participants in the ADDITION trial had a total cholesterol level above 5 mmol/l at baseline but were not being treated. Among the people who were receiving lipid-lowering therapy (Table 3), there was evidence, as with blood pressure, that scope for intensifying therapy or enhancing adherence existed, since the mean cholesterol level in those receiving treatment was 4.9 mmol/l with a mean LDL-cholesterol of 2.8 mmol/l. Of these individuals, 41% were not meeting the treatment goal of a cholesterol level lower than 5 mmol/l. Of the total population 15% had aspirin treatment at inclusion.
The two UK centres had the highest proportion of people already on antihypertensive and lipid-lowering treatment at baseline. In Cambridge and Leicester 49 and 58% of the participants respectively were already on antihypertensive therapy compared with 32% in Denmark and 37% in the Netherlands (p < 0.001). The mean systolic BP was lower in the UK populations (145 mmHg) and in Denmark (151 mmHg) than among the Dutch (165 mmHg, p < 0.001). The mean diastolic blood pressure was significantly lower in the Cambridge population than in the other populations (83 mmHg compared with 89 mmHg in all other centres, p < 0.001). A similar pattern was seen for lipid-lowering therapy, which was being prescribed to 26 and 21% of the participants in Cambridge and Leicester respectively, compared with 9% in Denmark and 15% in the Netherlands (p < 0.001). The mean total cholesterol concentration was lowest in the Cambridge population compared with the other centres (5.3 mmol/l vs 5.6 mmol/l in all other centres, p < 0.001).
Table 4 shows the estimated absolute 10 year CHD risk by age-group and sex. In the whole group, the median 10 year risk was 16% (interquartile range 10–25%). The estimated risk for CHD was higher for men (median value = 21%; interquartile range: 15–30) than for women (11%; 7–16; p < 0.001), and the oldest age group had a significant higher risk than the younger groups (p < 0.001). We also observed minor differences in estimated risk between countries, with the Dutch population having the highest risk of developing CHD in the older age groups (p < 0.001). These high levels of estimated risk, together with the high mean level of baseline HbA1c plus the untreated hyperlipidaemia and hypertension, provide clear justification for examining the impact of intensified multifactorial therapy on this potentially modifiable risk.
As the UKPDS CHD risk score uses multiple factors, it is susceptible to missing data since all variables must be present for each individual for risk to be calculated. A full dataset was available for 83% of the total population. However, we investigated the effect of missing data on the overall median CHD risk by imputing missing variables in the remaining 17% of the population. As the results in Table 4 demonstrate, the median CHD risk estimates were unchanged when we included the values calculated using imputation. This suggests that the results are not biased by any specific characteristics of the individuals for whom some data were missing.