Len was 52 when he developed acute angina and was treated with percutaneous angioplasty. He had an uneventful course and returned to his work as a manager in a large company. He had always been an anxious man and a worrier. His worry increased greatly after he was diagnosed with heart disease. His wife consulted their family physician, saying she feared he was going to “worry himself to death.”

There’s quite a lot of evidence that now shows that depression is an independent risk factor for adverse outcomes in people with heart disease. What about anxiety? Recently, a large prospective study (the Heart and Soul Study) looked at Generalized Anxiety Disorder (GAD in the DSM IV) in a cohort of 1,015 heart patients (Archives of General Psychiatry, 2010; 67 [No.7]:750-8). Heart patients in the study had extensive baseline cardiac measurements as well as a psychiatric diagnostic interview. They were followed for six years for the following outcomes: MI, primary stroke, heart failure, TIA or death.

Of the 1,015 patients, 106 met DSM IV criteria for Generalized Anxiety Disorder in the previous year at entry into the study. There were 371 cardiovascular events in the cohort during the six years of follow-up: the age-adjusted annual rate of cardiovascular events was 9.6% in the group of people with GAD and 6.6% in the group without GAD. The research team looked for possible confounding mediators such as male sex, comorbid conditions, smoking, activity level, antidepressant drug use, CRP level, etc. Comorbid Major Depression didn’t change the effect size for GAD significantly. The researchers concluded that their data showed that having GAD was associated with a 74% greater rate of cardiovascular events after adjusting for multiple other variables.

This study was significant because of the careful diagnosis of GAD — other studies had relied solely on self-report — and the depth of other data, including biological parameters, which allowed careful examination of many possible confounding variables. The authors noted that in previous research they had concluded that most of the increased risk of poor cardiovascular outcomes associated with Major Depression could be explained by associated poor health behaviours. They could find no such explanation in their cohort of anxious cardiac patients.

Nasty cocktail

Major Depression and Generalized Anxiety Disorder are often found together as comorbid conditions. In DSM IV they share four major symptoms: restlessness or agitation, fatigue, problems concentrating, and disturbed sleep. Many clinicians feel that patients often fluctuate between the two disorders, at times meeting diagnostic criteria for one and later the other. There are population studies that have found that these two disorders co-exist (are comorbid) up to 80% of the time. This high degree of overlap has led some researchers to propose that the two disorders be folded into a more integrated category of “distress disorder” in DSM V.

What does this mean for your patient? It’s now well established that the presence of significant anxiety in a depressed person is associated with greater difficulty getting the depression to respond to treatment (see the STAR*D Study). There is data supporting the safe use of two antidepressants to treat depression in heart patients — sertraline and citalopram. There’s no data for the use of antidepressants to treat GAD in heart patients; several SSRI antidepressants, however, have been shown to be effective in Generalized Anxiety Disorder (though not in a heart disease population). We don’t know whether treating GAD in heart patients can modify the elevated risk of coronary events, but given the apparent cost/benefit ratio, it would seem worth trying. GAD can also be effectively treated with psychotherapy; those who are willing to undertake it may well benefit, though there’s even less data available about such treatment in heart patients.

Lonely hearts

Earlier work on heart patients found an association of poorer outcomes in those who were less socially connected and integrated, leading some researchers to conclude that people can die of a lonely heart. This also led to other work looking at strengthening bonds of love as a way to improve outcomes. This work remains preliminary — we have little understanding of the biology of any of these associations. The Heart and Soul researchers looked at 24-hour urinary cortisol and heart beat variability (found previously to be associated with poor outcomes in depressed cardiac patients) but found nothing definitive. The mechanism connecting GAD to cardiovascular events is not yet clear. Catecholamine surges may still be a possibility — the researchers noted that 24-hour measures may not catch surges that could play a significant role.

As for our patient Len, he agreed to a trial of sertraline. He said that he was aware that his anxiety had peaked because he was facing the possibility of death for the first time. He was open to exploring the emotions that had been stirred up in himself and accepted a referral for psychotherapy. The last we heard he was stable and doing well.