CardioExchange Archive

In a recent Journal of the American College of Cardiology study, Ye et al explored whether behavioral mechanisms (i.e., alcohol use, smoking, physical inactivity, and medication non-adherence) explain the association between depressive symptoms and myocardial infarction (MI) or death in individuals with coronary heart disease (CHD) enrolled in the REGARDS (REason for Geographic and Racial Differences in Stroke) study. The authors confirmed that elevated depressive symptoms are associated with an increased risk of MI or death, and that, of the behavioral mechanisms assessed, smoking and physical inactivity were the most substantial contributors. CardioExchange’s Dr. John Ryan discusses these findings with the study’s Senior Author, Dr. Monika Safford.

Ryan: Dr. Safford, why did you feel it was important to study the role of behavioral mechanisms in depression and CHD? And why did you choose alcohol use, smoking, physical inactivity, and medication non-adherence? Do you think there are other behavioral mechanisms that play a role?

Safford: Given the well-described association between depressive symptoms and CHD outcomes, we wanted to better understand the mechanisms that may lead to this observation. Understanding these mechanisms points the way to new directions for treating this vulnerable population. The four behavioral mechanisms we chose — alcohol use, smoking, physical activity, and medication non-adherence — all had plausible associations with both depression and CHD and were available in the national, population-based biracial REGARDS cohort study, which was an exciting setting for the study. However, although these four pathways are very important, the situation is likely more complex, and there are probably other important behavioral mechanisms that we were not able to study, including being unable or unwilling to follow up with physicians. Nevertheless, this study is a good first step to better understanding the relationship between depression and CHD outcomes.

Ryan: Do you now think that depression does not have an independent effect on CV risk and only exerts an effect as it is mediated through these risk factors?

Safford: Our results on smoking and physical activity are consistent with findings from the Heart and Soul Study and the Cardiovascular Health Study, so we think these two factors definitely do play a large role in explaining the association between depression and cardiac risk. However, we must be careful when we interpret these results and attribute causality. For instance, are depressed individuals less likely to exercise and are therefore at higher risk for cardiac events, or is it that individuals who don’t exercise are more likely to be depressed, which then confers higher risk? Both scenarios can lead to the results we have shown. In the most rigorous sense of the term, to claim mediation would require us to show that one precedes the other, for which we would need assessments at additional time points. To make the picture even more complex, the causal pathways may also differ between individuals, and these individual variations may be part of the reason why it has  been so difficult to identify successful strategies to treat depression that also reduce cardiac risk in this patient population. Finally, we should note that in our analysis, although the independent effect of depressive symptoms was no longer statistically significant after accounting for behavioral mechanisms, our bootstrap analysis showed that the behavioral mechanisms only explained 36.9% of the overall effect with a fairly wide confidence interval, suggesting that additional risk factors that we did not have available play a role, and that there may be considerable variability in these unmeasured effects.

Ryan: Do CV specialists need to screen for depression? Or should we focus on risk factors, acknowledging that treating depression is good in its own right, but can be left to the primary care provider?

Safford: From the patient’s perspective, depression has a huge impact on quality of life.  Depression is also very common in patients with CHD, so it definitely warrants screening and treatment from that perspective alone. We think our study supports a holistic approach that recognizes that risk factors such as physical inactivity and smoking may be especially prevalent in CHD patients with depressive symptoms, and that it is important to address these problems.  Guidelines such as the AHA Science Advisory on depression and CHD call for CV specialists to screen for depression and provide appropriate referral, which is certainly a reasonable approach given how closely CV specialists often follow CHD patients, though the level of evidence for this recommendation is still mostly expert opinion. We think what is ultimately needed is a more robust evidence base for team-based, collaborative approaches that are now emerging (see Katon WJ et al, N Engl J Med 2010 and Davidson KW et al, Arch Intern Med 2010) to effectively and efficiently treat depression, and in which CV specialists play a prominent role.