Men who are depressed have higher levels of inflammatory markers associated with coronary heart disease than men who are not, according to a study reported in Circulation: Journal of the American Heart Association.
Some observational studies have linked depression with heart disease, which includes angina, non-fatal and fatal heart attacks, but the mechanism underlying the association is unknown.
Lead author Jean P. Empana, M.D., M.P.H., D.H., in the epidemiology department at Paul Brousse Hospital in Villejuif, France, said, “This is the first study investigating the respective contributions to coronary heart disease (CHD) of depression and inflammatory markers. Previous reports investigating the association between depression and individual inflammatory markers have produced conflicting results. In this study, we investigated a wide range of inflammatory markers.”
Researchers used data from the PRIME Study, a prospective study evaluating coronary heart disease factors in healthy middle-aged men in Ireland and France. They reviewed baseline blood samples of 304 men who developed heart disease within five years and 585 men who did not (controls). The men were healthy at baseline and were an average age of 55. Researchers noted levels of four inflammatory markers in their blood: C-reactive protein (CRP); fibrinogen; interleukin-6 (IL6); and adhesion cellular molecule -1 (ICAM-1).
The participants also answered questions evaluating negative perceptions of life, including statements such as, “I feel helpless.” The presence of depressive mood was defined as a depression score in the fourth quartile or higher at the baseline.
As expected, the average level of major cardiovascular risk factors and inflammatory markers were “significantly higher” in the men who developed heart disease than the controls. In addition, depressive mood was present in 28.3 percent of the cases versus 19.7 percent in the controls. Researchers noted a low but statistically significant correlation between depression score and IL6, CRP and ICAM-1, but not fibrinogen.
The average CRP level was 46 percent higher in men with depressive mood than in those without. Likewise, the average IL6 levels were 16 percent and ICAM-1 levels were 10 percent higher in depressed men.
Empana said this is the first study to find an association with ICAM-1 and depressive mood in a healthy population, suggesting that depressive mood is associated with endothelial dysfunction in a healthy (free of prior CHD) population.
This is of particular importance since endothelial dysfunction is thought to be one major step in the initiation of atherosclerosis. Endothelial dysfunction refers to change in the properties of the endothelium (part of the inner lining of the blood vessel) leading in particular to a procoagulant (instead of anticoagulant) activity and to the liberation in the blood flow of pro-inflammatory molecules. Endothelial dysfunction can be estimated indirectly by measuring circulating ICAM-1 levels, and more directly by evaluating the ability of the blood vessels to dilate in response to an increase in blood pressure. The causes of endothelial dysfunction are multiple and include endothelial injuries by smoking, hypertension, diabetes, or infectious agents.
One surprise of the study was that depressive mood was more frequent in French men than Irish men even though the incidence of heart disease is higher in Ireland. When analyzed by country, French men with the highest (4th quartile or higher) depression scores were 44 percent more likely to develop CHD than other French men with lower scores. Those in Belfast, Ireland, with the highest depression scores were 18 percent more likely to develop CHD than other Irish men. However, researchers noted that the sample size was too small to reliably detect whether these figures were statistically different.
After adjusting for other factors, men with depressive mood had about a 50 percent increase in the odds ratio of developing CHD within five years.
“There is an association between depression and CHD, but inflammation doesn’t seem to bridge the two as definitively as we may have expected,” Empana said.
The cause of the association between depressive disorders and inflammatory markers is largely unknown. For instance, depressive disorders can elevate concentrations of IL6 through hormones that can stimulate its release from adipose tissue. Alternatively, Interleukins might contribute to depressive disorders by stimulating hormones from central nervous structures that might be implicated in depression.
Co-authors are D. Henry Sykes, M.D.; Gerald Luc, M.D.; Irene Juhan-Vague, M.D., Ph.D.; Dominique Arveiler, M.D.; Jean Ferrieres, M.D., M.Sc.; Philippe Amouyel, M.D., Ph.D.; Annie Bingham, M.A.; Michele Montaye, M.D.; Jean Bernard Ruidavets, M.D.; Bernadette Haas, M.D.; Alun Evans, M.D.; Xavier Jouven, M.D., Ph.D.; and Pierre Ducimetiere, Ph.D.
