Diabetes care needs evidence based interventions to reduce risk of vascular diseaseBMJ 2000; 320 doi: https://doi.org/10.1136/bmj.320.7249.1554 (Published 10 June 2000) Cite this as: BMJ 2000;320:1554
Individual risk factors in isolation are poor predictors of risk
- Christopher D Byrne, professor, endocrinology and metabolism (, )
- Sarah H Wild, lecturer, public health medicine ()
- University of Southampton, School of Medicine, Southampton General Hospital, Southampton SO16 6YD
- Health Care Research Unit, University of Southampton, School of Medicine
The absolute risk of a first myocardial infarction is influenced by factors that include age, sex, blood pressure, the total concentration of high density lipoproteins, the cholesterol ratio, and diabetes.1 The prevalence of diabetes increases with age, and having the disease removes the protective effect of female sex against cardiovascular disease. Diabetes is commonly associated with hypertension, and an unfavourable lipid pattern combined with these factors contributes to the increase in the relative risk of myocardial infarction. In people with type 2 diabetes the risk of myocardial infarction is between two and six times higher than that of the general population.
The initial threshold for using lipid lowering treatment for the primary prevention of myocardial infarction as recommended by European and British guidelines is 2% and 3% risk per year, respectively.1 2 This is similar to the average risk of recurrence of a myocardial infarction.3 4 People who have had a first myocardial infarction are considered to be at a sufficiently high risk to be eligible for secondary prevention with lipid lowering treatment,1 whereas many people who have never had a myocardial infarction have a risk well below the threshold. In contrast, people with diabetes and a single other cardiovascular risk factor may have a risk of a first myocardial infarction that is above this threshold.5 For example, in men 60 years old who have diabetes and hypertension the absolute risk of a first myocardial infarction is predicted to be >3% per year.1 Thus, the primary prevention of coronary heart disease in people with diabetes approximates to the secondary prevention of coronary heart disease in people with normal glucose tolerance. To predict the risk in people with type 2 diabetes, assessment tables such as those provided in the joint British guidelines should be used.1
How does evidence suggest that we should intervene to reduce the impact of cardiovascular disease in people with diabetes? The benefits of controlling their weight, stopping smoking, increasing their physical activity, and eating a Mediterranean diet have not been shown for people with diabetes. Large randomised controlled trials support the use of aspirin, angiotensin converting enzyme inhibitors, and lipid lowering agents (either statins or fibrates) in people with a high absolute risk of coronary heart disease.3 4 6–9 Extrapolating from the limited evidence suggests that these treatments are likely to be effective in people with diabetes if their absolute risk of myocardial infarction is >3% per year.
What is the evidence that tight control of plasma glucose concentrations or blood pressure attenuates the impact of vascular complications in type 2 diabetes? The results of the United Kingdom prospective diabetes study provide some evidence that tight control of blood glucose (HbA1c 7%) reduces the risk of myocardial infarction (P=0.052) but not of stroke (P=0.52).10 Tight control of blood pressure (to <150/85 mm Hg) reduced the risk of ischaemic stroke (P=0.013) but had little impact on the risk of myocardial infarction (P=0.13).11 When combined with the evidence from the hypertension optimal treatment trial, a target blood pressure of 130/80 and an HbA1c value of 7% seem to be desirable among people with diabetes in whom the absolute risk of myocardial infarction is >3% per year.1 12
Evidence from large randomised controlled trials shows that treating people with statins reduces the relative risk of myocardial infarction by about 30% regardless of the absolute risk of cardiovascular disease at baseline. Importantly, treatment also improves survival, reducing the relative risk of all cause mortality by 20-30% over 5 years of follow up. Although the number of people with diabetes in these trials was small, it seems that the benefit of statin treatment is similar among people with and without diabetes.3 4 6 The benefits of treatment occur in all subgroups regardless of baseline concentrations of cholesterol.3 Thus, decisions to treat patients with statins should not be based solely on concentrations of total cholesterol or low density lipoprotein cholesterol but on a person's absolute risk of a vascular event. This is particularly relevant with people with type 2 diabetes because the primary lipid abnormality associated with diabetes involves the metabolism of triglycerides and high density lipoproteins, and people with diabetes often have normal plasma concentrations of cholesterol.
Additional evidence is required to assess the effectiveness of fibrates in people with diabetes. However, a secondary prevention trial, the Veterans Administration high density lipoprotein intervention trial (a randomised controlled trial), showed a 25% reduction in the risk of vascular events in a subgroup of men with diabetes who were treated with gemfibrozil (P=0.05). This result was consistent with a 22% overall reduction in risk of vascular events for all participants in the trial who were treated (P=0.006).7
A further, potentially important intervention to reduce cardiovascular risk among people with diabetes was recently reported from the subset of people with diabetes in the heart outcomes prevention evaluation study.13 A total of 3577 men aged 55 years or older with diabetes and an additional cardiovascular risk factor were treated with either 10 mg ramipril (an angiotensin converting enzyme inhibitor) or placebo. Men were excluded if they had heart failure, a reduced ejection fraction, or proteinuria. Active treatment reduced the risk of stroke by 33% (P=0.007) and myocardial infarction by 22% (P=0.01).13 It is highly unlikely that this benefit was due to reductions in blood pressure because the mean reductions (systolic/diastolic) were 2/3 mm Hg in the ramipril group and 1/2 mm Hg in the placebo group. Adjustment for these differences in blood pressure did not alter the results.
People with type 2 diabetes have a markedly increased risk of myocardial infarction and stroke compared with the general population. It is not appropriate to base treatment decisions on concepts of primary versus secondary prevention or on the presence of individual cardiovascular risk factors viewed in isolation. Emphasis should be put on treating people with therapies of proven benefit in whom the overall risk of myocardial infarction is assessed as being 3% per year. This approach is likely to be more cost effective than treating individual risk factors in people who are at a lower absolute risk for cardiovascular disease. The potential benefits for the future health of many people with type 2 diabetes could be considerable.
Christopher D Byrne has received speaking and consultation fees from the pharmaceutical industry.