In a population-based primary care sample of patients with diabetes, major depression was associated with a significantly higher number of cardiovascular risk factors in the presence or absence of heart disease. In both groups, diabetic patients with major depression were significantly overrepresented among patients who had 3 or more cardiovascular risk factors. These patients with 3 or more risk factors presumably have the highest risk for development of either a new cardiovascular event or progression of CVD severity. Among diabetic patients without heart disease, depression was significantly associated with being a smoker, being obese (BMI ≥ 30 kg/m2), having an HbA1c level > 8.0%, and being less physically active. In patients with diabetes and evidence of heart disease, depression was significantly associated with obesity (BMI ≥ 30 kg/m2), lower exercise levels, and high triglyceride levels. Among diabetic patients with heart disease, the percentage of patients who smoked was lower, perhaps because a cardiovascular event motivated these patients to quit smoking.
This is the first study we are aware of that describes the association of major depression with a large number of cardiac risk factors in patients with predominantly type 2 diabetes. The results are similar to findings from a recent community-based study that reported the association of depression with multiple cardiac risk factors and cardiac mortality in a study of 93,676 women (age 50 to 79).33
This large community study reported that depressive symptoms were associated with a higher risk of smoking, having a BMI > 27.3, being sedentary, and having hypertension, diabetes, and high cholesterol.
In the Pittsburgh Epidemiology of Diabetes Complications Study, researchers found a longitudinal relationship between depression and later development of CVD among patients with type 1 diabetes.8
These researchers also found that this relationship appeared to be, in part, explained by the association of depression with potential mediators such as insulin resistance, autonomic dysregulation (based on increased heart rate and decreased heart rate variability), markers of inflammation, smoking, and complications associated with diabetes such as microalbuminuria.8
Our finding of a greater rate of smoking in patients with major depression and diabetes without CVD supports these findings. Whereas in bivariate analyses, increased microalbuminuria levels were significantly associated with major depression in the diabetic group without CVD, this association disappeared after controlling for covariates.
Our data also suggest that in patients with depression and diabetes, behavioral mediators such as smoking, obesity, sedentary lifestyle, and glycemic control may contribute to the increased risk of heart disease that has been found in longitudinal studies in depressed versus nondepressed patients with diabetes. Several of these behavioral mediators, including sedentary lifestyle and obesity (as well as both diabetes and depression), have also been found to be related to higher C-reactive protein levels, an inflammatory risk factor for coronary artery disease.34
Research has consistently demonstrated that major depression is more common in women than in men.35
Patients with diabetes are no exception.36
These findings may partially explain why improved biomedical prevention and treatment of heart disease has decreased mortality in men, but not in women.37
An important research question is whether interventions that improve accuracy of diagnosis and quality of treatment of depression along with behavioral treatment of risk factors would improve cardiac morbidity and mortality in patients with diabetes, especially women. The higher rate of obesity, smoking, and triglyceride levels in patients with depression, diabetes, and heart disease found in this study may also contribute to the increased risk of mortality in patients with diabetes and a history of heart disease that has been found in prior studies.38,39
Although our data is cross-sectional, limiting our ability to ascertain whether depression or the cardiac risk factors came first, longitudinal studies have shown that depression earlier in life raises the risk of both obesity11,12
Several studies have also found that depression is associated with an increased risk of sedentary lifestyle among adults.13,14
Moreover, recent data suggest that depression is associated with less success in quitting smoking over a decade of adult life,41
higher dropout rates in exercise rehabilitation programs of patients with heart disease,42
as well as higher dropout from weight loss programs in patients with diabetes.43
Major depression has also been found to be associated with decreased adherence to oral hypoglycemic medications in patients with type 2 diabetes44
and to aspirin in patients with CVD.45
These data suggest that intervention programs aimed at decreasing the rates of obesity, smoking, and sedentary lifestyle and improving adherence to medication among patients with both diabetes and heart disease may need to address the high rate of depression in these patients, especially patients with multiple risk factors.
Biological studies have also found that both major depression and diabetes have been shown to be independently associated with increased platelet adhesiveness and exaggerated aggregation,17,18,46,47
increased markers of inflammatory response such as C-reactive protein,19,48
and endothelial dysfunction.49,50
When major depression is comorbid with diabetes, there may be additive risk from these the behavioral mediators (i.e., smoking, obesity, lack of exercise, and poor glycemic control) and biologic factors that are associated with heart disease.
Strengths of the study include the large population-based sample of patients with type 2 diabetes observed in naturalistic care in a large primary care system. However, the use of naturalistic laboratory data limited obtaining timely measurement of lipids and markers of microalbuminuria. Using automated data to ascertain the presence or absence of heart disease may also contain misclassifications. The cross-sectional design of the study also precludes explanations of causality. For instance, we cannot be certain whether depression preceded lack of exercise and the development of heart disease or whether having heart disease led to depression and associated inactivity. Other limitations include lack of physiologic measures such as markers of inflammation and autonomic nervous system regulation. A final limitation is that our analyses did not control for medical comorbidity (there were no differences in medical comorbidity in the depressed vs nondepressed patients without evidence of heart disease) because our comorbidity measure overlapped with outcome variables such as hypertension, hyperlipidemia, and kidney disease.