Depression Harder on the Hearts of Younger Women

Pauline Anderson

June 18, 2014

Depression appears to be particularly harmful to the heart in younger women, new research suggests.

A study conducted by investigators at Emory University in Atlanta, Georgia, showed that more than 25% of women aged 55 years and younger who underwent coronary angiography and who were depressed were much more likely to die of heart disease, suffer a myocardial infarction (MI), or require revascularization.

The results should heighten awareness among both psychiatrists and heart specialists that young women may be especially susceptible to the cardiovascular consequences of depression.

"For cardiologists, one of the applications of this research is that depression should be included in the routine list of risk factors discussed with patients along with, for example, smoking and diabetes," lead author Amit J. Shah, MD, told Medscape Medical News.

"For psychiatrists, it would probably be best to recommend healthy eating and a healthy lifestyle, to remind patients not to forget about the heart, because it's a risk factor, and to just be a little more aggressive from a prevention perspective."

The study was published online June 18 in the Journal of the American Heart Association.

Highest Risk in Youngest Women

The analysis included 3237 participants in the Emory Cardiovascular Biobank, who were enrolled before undergoing elective or emergent coronary angiography.

Researchers assessed depressive symptoms in patients using the 9-question Primary Cary Evaluation of Mental Disorders Brief Patient Health Questionnaire (PHQ-9). They categorized depression as moderate to severe (10 or more points out of 27 on the PHQ-9) and none to mild (less than 10 points).

The youngest female group (up to age 55 years) had the highest prevalence of moderate to severe depression (27%), whereas men aged 65 years and older had the lowest (19%).

Dr. Amit Shah

Reviewers who were masked to depression status and other patient data assessed coronary angiographies. Patients were categorized as having coronary artery disease (CAD) or not having CAD.

Follow-up examinations were conducted 2 and 5 years after enrollment. The median follow-up time was 2.9 years.

The study's primary outcome was all-cause death. The secondary endpoint was major adverse cardiovascular events (MACE), which for this study occurred if a patient died, was hospitalized for an MI, or received new revascularization procedures (percutaneous coronary intervention [PCI] or coronary artery bypass surgery [CABG]).

Researchers compared characteristics of depression in 6 subgroups stratified by age ― up to age 55; 56 to 64; and 65 and older ― and sex. With some exceptions, the moderately to severely depressed group showed a greater prevalence of cardiovascular risk factors and comorbidities than those without depression or with mild depression.

There were significant differences in history of PCI and CABG as well as in the decision to perform stenting for women aged 55 years or younger and not in other subgroups.

Although there was no association between depressive symptoms and CAD in the total sample, there was significant heterogeneity across age and sex. Depressive symptoms were associated with CAD only in women 55 and younger; each 1-point increase in PHQ-9 score was associated with 1.07 increased odds (95% confidence interval [CI], 1.02 - 1.13) of CAD.

Demographics, cardiovascular risk factors, and reason for coronary angiography did not explain the association.

When the researchers excluded acute MI cases and examined only elective cases, the results were similar to those of the whole group. In women aged 55 and younger, the adjusted OR of CAD for each PHQ-9 point increase was 1.07 (95% CI, 1.01 - 1.12). The interaction between case urgency and depression was not significant (P = .41).

The researchers performed a number of other statistical tests to assess the relationship between depression and CAD. When depression was used as a predictor of CAD, moderate to severe depression was associated with an increase in odds of CAD in the younger women only, with adjusted OR of 2.02 (95% CI, 1.03 - 3.97).

Stratified by age, depressive symptoms had the highest adjusted hazard ratio (HR) of death and MACE (1.08 and 1.06, respectively) in the youngest women, with the HRs for women decreasing as the age category increased.

Head Scratcher

Physicians are "scratching their heads" over how to handle the issue of heart-related risks in young women with depression, especially because "there aren't necessarily any slam-dunk treatments" for depression, said Dr. Shah.

"It's hard to tell what the best next direction is other than trying to figure out why this is happening, just from the pathophysiology perspective."

There are several possibilities. One is that the link between CAD and depression is genetic; one previous study showed that in women but not men, there was an association between depression and a haplotype of a leukotriene gene that is involved in inflammation.

Neurologic variations could be a cause, too. "There may be core differences in the structure of the brain between women and men, which may affect reactivity to stress, with women possibly having a heightened physiological stress response," said Dr. Shah.

The authors point out that early life trauma, which is a risk factor for depression, is known to exacerbate the cortisol response caused by acute stress in young women. They note that emerging data suggest that stress reduction customized to women could be helpful in reducing risks.

A heightened stress response may lead to metabolic disorders and obesity. Behavioral factors such as sedentary lifestyle and smoking may also play a role in the heart-brain connection.

Another possibility is that young women become depressed in response to a diagnosis of CAD. "We have to take seriously how much of this is dominated by women who have known coronary disease and have a difficult time coping with it," said Dr. Shah.

There may be a "snowball" effect in the "spiral down" from having depression and then having CAD, or having CAD and then having depression, said Dr. Shah. "Probably a lot of different things are happening at the same time; as people get more depressed, they're less likely to take medications, less likely to see a doctor, and over time, things can deteriorate pretty quickly."

Ischemic heart disease is the most common cause of death in women, so reducing the risk and consequences of depression in young women may have significant public health impact, say the authors. In 2008, the American Heart Association (AHA) issued a scientific statement recommending that depression be considered a formal risk factor, in addition to diabetes and hypertension.

Missing the Boat

Commenting on the study, Suzanne Steinbaum, MD, director, Women's Heart Health, Heart and Vascular Institute, Lenox Hill Hospital, New York City, and a spokesperson for the AHA, said that "more than anything else, it sheds a very, very, clear light on how significant depression is."

A lot of women "blow off their symptoms," so by the time they get to a doctor, it might be too late or they do not do as well, said Dr. Steinbaum. "Women just don't get diagnosed as quickly as men."

"What is so compelling about this particular study is that it's in this population of younger women and is specifically looking at heart attacks in young women, and discusses why the outcomes are worse. That question has not been addressed in this way until now."

Heart disease is the number one killer of women, and according to Dr. Steinbaum, stress and inflammation play a big role in raising risk in this population.

"If we don't look at one of the biggest inflammatory generators, which is depression and other psychosocial issues, we are missing the boat."

She agreed that there needs to be a "collaborative effort" between cardiologists and psychiatrists. More psychiatrists should send their depressed patients to a cardiologist for screening, she said.

The study was supported by the National Institutes of Health, the National Center for Advancing Translational Sciences of the National Institutes of Health, and the Emory Heart and Vascular Institute. The authors have disclosed no relevant financial relationships. Dr. Steinbaum is author of Dr. Suzanne Steinbaum's Heart Book: Every Woman's Guide to a Heart-Healthy Life.

J Am Heart Assoc. Published online June 18, 2014. Full article


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