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Title: Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction

Authors:  Haffner SM, Lehto S, Ronnemaa T, et al

Reference: NEJM 1998;339:229-34

Reviewer: Max A Luna

Problem addressed; It is well known that diabetic populations have a higher incidence of coronary heart disease (CHD) and higher case fatality rate once they have CHD.

Purpose of study: To examine whether patients with diabetes who have not had myocardial infarctions should be treated as aggressively for cardiovascular risk factors as patients who have had myocardial infarctions.

Study design: This large prospective cohort compared the incidence of myocardial infraction among 1373 nondiabetic subjects with the incidence among 1059 diabetic subjects over a seven-year period.

Results: Type 2 diabetes was associated with older age, higher body-mass index, a greater prevalence of hypertension, higher triglyceride levels and lower levels of LDLc and HDLc.  In the overall population, prior myocardial infarction was associated with male sex, smoking, older age, hypertension, obesity, higher total and LDL cholesterol, higher tryglicerides and lower HDLc.

After seven years of follow-up the incidence of myocardial infarction among nondiabetic subjects was 18.8% in those with prior myocardial infarction (MI) and 3.5% in those without prior MI.  Among the diabetic subjects, the incidence of MI was 45% in those with prior MI and 20.2% in those without prior MI.

Table 1: Incidence of cardiovascular events during follow-up (percentages)

EVENT	NONDIABETIC PRIOR MI	SUBJECTS NO PRIOR MI	DIABETIC PRIOR MI	SUBJECTS NO PRIOR MI
FATAL OR NON FATAL MI	18.8	3.5*	45.0	20.2*
FATAL OR NON FATAL STROKE	7.2	1.9**	19.5	10.3*
DEATH FROM CARDIOVASCULAR CAUSE	15.9	2.1*	42.0	15.4*

*P < 0.001  **P < 0.01

Diabetic subjects without prior MI and nondiabetic subjects with prior MI had similar outcomes. After controlling for age, sex, LDLc, HDLc, triglycerides, smoking, and hypertension, the hazard ratio for cardiovascular mortality between these two groups was not significantly different.  (Hazard Ratio 1.2 95% CI 0.6-2.4)

Discussion: After controlling for the relevant variables, the data indicates that the type II diabetic patients without prior MI and nondiabetic patients with prior MI have similar cardiovascular outcome.  The case fatality rate for first myocardial infarction is higher in diabetic than nondiabetic patients (45% men and 39% in women with diabetes, 38% men and 25% in women without diabetes).  This population would not have the chance to benefit from secondary prevention therapies, indicating that aggressive risk factor reduction should be offered to prevent the first myocardial infarction.

Comments: Given the high price of statins, the appropriate risk reduction for diabetes may be not be affordable for many developing countries. A heart healthy diet will always be the first strategy to implement.

It was particularly interesting that this study did not report the percentage of subjects that were lost to follow-up.  There was no systematic follow-up of subjects in this cohort.  For this reason, we ignore whether the subjects with history of MI had more aggressive coronary preventive therapy, which may account for the outcome. Nevertheless, the diabetic group may have had closer follow-up due to the nature of their disease.  The direction of the potential bias due to this factor is not easily predicted.