The Gender Specific Impact of Diabetes and Myocardial Infarction at Baseline and During Follow-Up on Mortality From All Causes and Coronary Heart Disease

abstract & commentary

By Jonathan Abrams, MD
Professor of Medicine, Division of Cardiology, University of New Mexico, Albuquerque
Dr. Abrams serves on the speaker’s bureau for Merck, Pfizer, and Parke-Davis.

Synopsis: In order to reduce CVD mortality, more active management and prevention of diabetes is needed.

Source: Hu G, et al. The Gender-Specific Impact of Diabetes and Myocardial Infarction at Baseline and During Follow-Up on Mortality From All Causes and Coronary Heart Disease. J Am Coll Cardiol. 2005;45:1413-1418.

It is well known that the presence of type 2 diabetes is a lethal risk factor for cardiovascular disease (CVD) and, particularly, coronary heart disease (CHD). Mortality from heart attack, need for requiring revascularization procedures, or the development of congestive heart failure all carry a major increased risk of 2-4-fold when compared to non diabetics, particularly in women.

Recently, the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) and the American Diabetes Association designated type 2 diabetes as a coronary risk equivalent (ie, adult type 2 diabetics who have not had an overt CVD event should be considered as having occult CAD). Thus, all CHD risk factors should be treated aggressively. For instance, the target for LDL cholesterol in an adult type 2 diabetic is < 100 mg/dL.

Many guidelines also suggest using an angiotensin-converting enzyme inhibitor in diabetics. The Heart Protection Study (HOPE) and Collaborative Atorvastatin Diabetes Study (CARDS) confirm that a standard dose of a statin drug given to type 2 diabetics not selected for hyperlipidemia results in a considerable reduction in morbidity and mortality over 3 to 5 years.

A special advisory from the NCEP-ATP III in 2004 encourages treatment of high-risk individuals who have CAD or a high burden of CAD risk factors to a target LDL cholesterol as low as 70-80 mg/dL. Many adult diabetics fit into this high-risk classification, whether or not they have had a prior cardiovascular event.

A recent publication from Finland examined the impact of baseline diabetes and/or myocardial infarction (MI) on 7000 patients followed for a mean of 12 years.1 The goal of the study was to compare the magnitude, CVD risk, and total mortality for diabetics or non-diabetics with a history of MI at baseline, as well as in subjects who developed diabetes or an MI during follow-up (incidental diabetes or MI).

The patients were all from Finland and represented 6 population surveys carried out between 1972 and 1997. A random sample of 7% of the population comprised the study cohort, stratified by gender and age. Two related cohorts were examined: a baseline group of individuals who had prior diabetes or MI (n = 2416), as well as a group of individuals with incidental diabetes or MI (n = 4315). Specific CVD and CAD rates, as well as total mortality were calculated and standardized for 10-year age intervals. The cohorts were examined to determine whether disease status impacted mortality to the same degree in men and women.

Results: Compared to men who had diabetes at baseline, those with a prior MI had a higher mortality from CAD, CVD, and all causes. However, women with a prior MI had a lower risk of death during follow-up from CAD, CVD, and total mortality, compared to women who had diabetes but no MI at baseline. Men and women with both diabetes and MI at entry had the highest risk of death from CAD and CVD. For those individuals who developed diabetes or MI during the follow-up (incident diabetes or MI), followed for a mean of 8 years, the findings differed. Men and women who developed an MI during the observational period had a higher adjusted mortality rate of over 2-fold, compared to those who developed diabetes but no MI during the follow-up period; there was no gender difference in CAD, CVD, and all cause mortality in this population. As with the cohort who had either diabetes or MI at baseline, men and women with both incident diabetes and MI had the highest risk of CAD and mortality.

To summarize, men with a prior MI at baseline had worse survival than men with prior diabetes; the reverse was true in women, with prior diabetes associated with a worse survival than those with a prior MI history. Men and women with an incident MI (eg, on study) had a worse prognosis compared to those with incident diabetes during follow-up.

Hu and colleagues refer to a number of published studies addressing some of these issues and, particularly, gender differences in various outcomes, including CAD mortality in individuals with diabetes without prior infarction. The best known study, by Haffner and colleagues, also from Finland, is quite familiar to many, showing equivalent death rates in individuals with a prior MI at entry over the 7-year follow-up period, when compared to those who had no MI but were diabetic at entry.2 However, not all studies have corroborated these data.

A Framingham analysis also demonstrated that diabetic women had a greater risk for CHD death than those with prior MI, but in men the opposite was true, with prior MI imparting greater risk than diabetes.3 The striking feature in the present report is that "women with prior MI at baseline had a markedly lower risk of CHD and total mortality, compared with women with prior diabetes at baseline," whereas women with an incident MI had a greater risk of death, compared with those with incident diabetes.

Haffner et al suggest that these gender differences may, in part, be dependent on the duration of the disease and, as such, diabetes or an MI may result in differential risk for subsequent events. They note that among patients with an acute MI, risk is highest immediately following the heart attack, with stabilization over time; however, in diabetics, risk appears to be cumulative and increases with duration of the disease. Haffner et al confirm that the data support the well-known observations that type 2 diabetes eliminates the approximate 10-year protection that women have from developing clinical CVD, compared to men.

Haffner et al conclude, "In order to reduce CVD mortality, more active management and prevention of diabetes is needed." They also suggest that differential treatment strategies may be appropriate between men and women depending on MI or diabetic status.

Commentary

This is an interesting study and is important because of the large number of individuals followed over a long period of time. Perusal of the multi-variate survival curves is particularly useful in demonstrating the differential risk. Thus in men, a prior MI imparts greater risk for subsequent CAD and CVD than type 2 diabetes, similar to incident diabetes or MI in men. However, for women, having prior diabetes manifests a greater risk than a prior MI, while having an incident MI carries a worse survival prognosis than those with incident diabetes.

For all cohorts, the combination of diabetes and a prior MI resulted in the most lethal outcomes. Although discussion of the various cohort subgroups is somewhat confusing, the take-home message seems to be clear: Diabetics, as well as individuals with clinical CAD and no diabetes, deserve vigorous preventive therapies, including lifestyle approaches (weight-loss, exercise), as well as a pharmacologic cocktail that should include aspirin, a statin, and an ace inhibitor. This mandate is particularly important in women with no known CAD. Furthermore, aggressive therapy of hyperglycemia is important in patients with type 2 diabetes with or without a prior MI. While glucose control has yet to be proven to have a large impact on survival in diabetes, considerable evidence supports such an approach.

References

1. Hu G, et al. The Gender-Specific Impact of Diabetes and Myocardial Infarction at Baseline and During Follow-Up on Mortality From All Causes and Coronary Heart Disease. J Am Coll Cardiol. 2005;45:1413-1418.

2. Haffner SM, 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;339:229-234.

3. Natarajan S, et al. Sex Differences in Risk for Coronary Heart Disease Mortality Associated with Diabetes and Established Coronary Heart Disease. Arch Intern Med. 2003;163:1735-1740.