Diabetes as a CHD equivalent

Dr VC Kuppuswamy and Dr Sandeep Gupta consider the case for more aggressive risk assessment.

Risk for CVD is two- to four-fold higher among patietns with diabetes

Cardiovascular disease (including CHD, peripheral vascular disease and cerebrovascular disease) is the cause of death in about 80 per cent of patients with type-2 diabetes.1

The association between type-2 diabetes and CVD is well established. The risk for CVD is two- to four-fold higher among patients with diabetes than in non-diabetic patients.

Furthermore, the risk of death from CHD in patients with diabetes may match that of patients who have had an MI.2 This raises the question of whether diabetes mellitus should be treated as 'CHD equivalent' and whether patients should be treated as aggressively as if they had CHD.

Aggressive cholesterol reduction
The plasma total and LDL cholesterol level is a strong predictor of the risk of cardiovascular events in patients with diabetes and in patients with CHD.

The high-risk status of these groups of patients and their need for more aggressive lipid-lowering therapy has been recognised by the US National Cholesterol Education Program.

Consequently, the third report of the National Cholesterol Education Program recommended lower goals for LDL in patients with CHD or diabetes.3

However, there is a lack of consensus about how aggressively to treat LDL in patients with diabetes because individual risk factors in isolation are poor predictors of risk and calculated absolute risk of MI in a patient with diabetes may be the best option to guide therapy.4

Therefore treating every patient with diabetes - about 2.3 million people in the UK - with a statin may not be a clinical or cost-effective option. Perhaps prescribing a statin in diabetic patients with an absolute risk of >3 per cent for MI per year may be a way forward.

A CHD equivalent?
The National Cholesterol Education Program has called for the recognition of diabetes mellitus as CHD equivalent, but this is still being debated. One way to assess whether patients with diabetes and those who already have clinical CHD have a similar risk of cardiovascular events is to compare the risk of such events in diabetic patients with and without prior CHD with that in non-diabetic patients with and without prior CHD.

One study, which examined seven-year incidence of cardiovascular events among 890 patients with diabetes who had no history of MI and 69 patients without diabetes who had previously had MI, reported the risk of death from CHD as not significantly different between the two groups.5

An important weakness of this study was the lack of power to detect differences between the two groups.

A cross-sectional study in Scotland comparing 1,155 patients with type-2 diabetes with 1,347 who had had an MI in the preceding eight years showed adjusted relative risk for death from all causes to be 2.27 (95% CI 1.82-2.83) for patients who had had MI compared with those with diabetes.6

The cohort study of the same trial, comparing 3,477 patients of all ages with newly diagnosed type-2 diabetes with 7,414 patients who had just had MI, showed that patients who had just had MI had a higher risk of death from all causes, cardio-vascular death and hospital admission for MI.

This study demonstrates that patients with type-2 diabetes do not share the same heightened risk of death that is observed in patients with established CHD.

Therefore clinicians should be cautious about basing treatment decisions on individual risk factors for CVD and should be guided by overall risk score for developing CHD in a patient.

Stroke-related mortality
The Women's Pooling Project evaluated 24,343 women with no previous CVD. The main endpoints were death caused by total stroke, non-haemorrhagic stroke and haemorrhagic stroke by race, age and cholesterol quintile.

The study showed that cholesterol is a risk factor for non-haemorrhagic stroke death in women <55 years of age and is more strongly associated with mortality in black women <55 years of age than in white women. This highlights the fact that strategies for stroke prevention should consider the long-term consequences of risk factors, including elevated cholesterol in relatively young women.7

It is not certain whether one risk factor carries more weight than others in the development of CVD and whether it is prudent to base therapeutic decisions on the presence or absence of a single risk factor and whether such a strategy would be cost-effective. In that context, the question whether diabetes mellitus is equivalent to CHD remains.

In this case, it is best to follow the national guidelines. NICE guidelines for diabetes mellitus recommend that preventive strategies to reduce cardiovascular risk in diabetic patients should be based on overall cardiovascular risk scoring.8

However, the guideline does suggest a more aggressive role for lipid reduction, stating that every patient with diabetes >40 years old should receive a generic statin at the starting dosage.

Furthermore, although the CVD mortality rate has recently decreased in patients with diabetes, a higher risk for CVD remains a major problem for these patients.9 This is of particular relevance in the UK, with the increase in the number of elderly patients with diabetes, ethnic minority populations with high rates of diabetes and CHD, and the success of methods to reduce microvascular complications.

  • Dr Kuppuswamy is specialist registrar in cardiology, Basildon Cardiothoracic Centre, Basildon & Thurrock University Hospital NHS Foundation Trust, Essex; Dr Gupta is consultant cardiologist, Whipps Cross University Hospital and St Bartholomew's Hospital, London References

1. 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: 434-44.

2. Haffner S M, Lehto S, Ronnemaa T et al. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998; 339: 229-43.

3. 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) final report. Circulation 2002; 106(25): 3140-1.

4. Byrne C D, Wild S H. Diabetes care needs evidence based interventions to reduce risk of vascular disease. BMJ 2000; 320: 1554-5.

5. Haffner S M, Lehto S, Ronnemaa T et al. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998; 339: 229-43.

6. Evans J M, Wang J, Morris A D. Comparison of cardiovascular risk between patients with type 2 diabetes and those who had had a myocardial infarction: cross sectional and cohort studies. BMJ 2002; 324: 939-42 (erratum BMJ 2002; 324: 1357).

7. Horenstein R B, Smith D E, Mosca L. Cholesterol predicts stroke mortality in the Women's Pooling Project. Stroke 2002; 33: 1863-8.

8. NICE. Type 2 diabetes: the management of type 2 diabetes (update). CG66. London, NICE, May 2008.

9. Wetterhall S F, Olson D R, DeStefano F et al. Trends in diabetes and diabetic compli-cations, 1980-1987. Diabetes Care 1992; 15: 960-7.

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