Clinical Context

Depression is a common diagnosis after myocardial infarction (MI). A systematic review and meta-analysis by Doyle and colleagues reports that 20% of patients develop major depression after MI, and up to 31% of patients have symptoms of depression post-MI.^[1]

Symptoms of depression are more common among women compared with men overall, but Doyle and colleagues were interested in sex-based differences in the prevalence of depression after MI. They also analyzed the effects of depression on rates of mortality among women and men. Their results were published in the May 2015 issue of Psychosomatic Medicine.

The researchers assessed individual data from more than 10,000 patients with a history of MI who participated in a total of 16 prospective studies that evaluated depression. A total of 36% of women and 29% of men had elevated levels of depression. Although depression was associated with higher rates of mortality in both sexes, depression was associated with a greater risk for mortality among men.

The current study analyzes sex-based differences regarding depressive symptoms and self-reported health status in the setting of peripheral artery disease (PAD).

Study Synopsis and Perspective

Women with PAD are almost twice as likely as their male counterparts to have depression, and all patients with PAD with depression have a much worse 1-year recovery path than those without depression, results of a new study show.

The findings highlight the importance of screening patients who have PAD for depression, study author Kim G. Smolderen, PhD, a clinical health psychologist and codirector of the Vascular Medicine Outcomes Research Program, Yale University School of Medicine, New Haven, Connecticut, told Medscape Medical News.

"Depression may be a significant problem that may prevent physicians from getting the treatment results they were aiming for," Dr Smolderen said.

To maximize outcomes, clinicians should "spend time detecting" depression and linking patients to the appropriate "holistic care," she said.

The study was published online August 12 in the Journal of the American Heart Association.^[2]

PAD, a narrowing of the peripheral arteries primarily of the legs, affects more than 8 million Americans. In patients who have multiple atherosclerotic risk factors, including smoking and diabetes mellitus, the prevalence of PAD can be as high as 30%.

Although women are at least as likely as men to develop PAD, they may experience worse functional impairment. Aside from cardiovascular risk management, PAD treatments focus on relieving symptoms and improving quality of life through medications, exercise, or invasive treatments, said Dr Smolderen.

Depression Disadvantage

Having depression puts patients with PAD at a disadvantage, she said. "If it's not treated or recognized, this might complicate their recovery from PAD or their rehabilitation process."

But depression in patients with PAD is often "not on people's radar," she said. "As we think about treating PAD, we think about treating the legs and not the whole person."

It is been unclear to what extent depressive symptoms may be associated with a worse health recovery for patients with PAD and whether women are affected differently than men.

This new prospective observational study included 1243 adult patients at 16 vascular specialty clinics in the United States, the Netherlands, and Australia. Participants were enrolled in the Patient-Centered Outcomes Related to Treatment Practices in Peripheral Artery Disease Investigating Trajectories (PORTRAIT) registry.

Eligible patients had to have a Doppler resting ankle-brachial index (ABI) of 0.90 or less or a significant decrease in postexercise ankle pressure of 20 mm Hg or more. They also had to have new-onset or recent exacerbation of exertional leg symptoms, regardless of whether symptoms were typical (buttock, thigh, hip, or calf pain; numbness or discomfort inhibiting the ability to walk distances) or atypical.

The mean age of the patients was 67.6 years, and 38% were women. Most (72.1%) were White.

Fewer women than men in the study were married (44.4% vs 68.1%; P < .001) or employed (17.5% vs 27.4%; P < .001). Women were more likely to be sedentary (51.6% vs 34.2%; P < .001) and to avoid care because of cost (16.8% vs 12.5%; P = .035).

Compared with men, women had lower mean ABI values (0.65 vs 0.67; P = .045), and they were more likely to present with atypical and bilateral symptoms.

Researchers determined health status at baseline and at 3, 6, and 12 months, using the 20-item multidimensional Peripheral Artery Questionnaire (PAQ), which measures 6 relevant domains: physical function, symptoms, symptom stability, social limitations, treatment satisfaction, and quality of life. Scores range from 0 to 100, and higher scores indicate better functioning.

They also used the generic EQ-5D Visual Analogue Scale (EQ-5D VAS), which assesses overall health status. Scores range from 0 to 100, with 0 indicating worst and 100 indicating best.

Common Tool

Investigators assessed depressive symptoms at baseline and at 3 months using the 8-item Patient Health Questionnaire (PHQ-8). Scores range from 0 to 27. PHQ-8 scores lower than 5 indicate no depressive symptoms, scores from 5 to 9 indicate mild symptoms, and scores of 10 or higher indicate moderate to severe depressive symptoms.

The PHQ-8 is a "very commonly used screening tool," although a high score does not necessarily mean the patient meets Diagnostic and Statistical Manual of Mental Disorders criteria for depression, which would require additional testing and evaluation, said Dr Smolderen.

About 16% of the overall cohort had moderate to severe depressive symptoms, according to the PHQ-8. Rates were much higher in women than in men (21.1% vs 12.9%; P < .001). Mean PHQ-8 scores at baseline were 5.6 in women vs 4.2 in men.

The depression rate among women in the study is about on par with that among women in general, although in some studies, it is as high as 1 in 3, said Dr Smolderen. Such high rates are also "seen across the cardiovascular disease spectrum," she added.

Of those with clinically relevant depressive symptoms, almost half of women and one third of men in the study were receiving some form of treatment for depression.

In both men and women, patients with depressive symptoms were more likely to be younger, to avoid care because of cost, and to be sedentary compared with their counterparts without depressive symptoms. Both men and women with depression were less likely to be married compared with those without depression.

All patients with depressive symptoms (PHQ-8, ≥10) at baseline had consistently lower unadjusted PAQ health status scores than those without these symptoms (mean differences ranged from 17.8 to 26.9). Mean differences in the EQ-5D VAS between depressed and nondepressed patients varied from 12.3 to 19.5.

The researchers reconstructed a 1-year health status trajectory as to whether or not patients reported depressive symptoms when diagnosed with PAD.

After adjusting for age, country, race, avoidance of care because of cost, education, ABI, exacerbation of symptoms, bilateral disease, smoking, diabetes, coronary artery disease, and sleep apnea, patients with depressive symptoms had lower PAQ scores than nondepressed patients at baseline (adjusted mean score, 25.4 vs 46.7; P < .0001) and at 12 months (adjusted mean score, 50.0 vs 66.1; P < .0001).

Discrepancy Sustained

The "20-something discrepancy" in scores at the start of the study was sustained over time, said Dr Smolderen. "You never see such large differences for treatment effects, so it's really clinically meaningful," she said.

She noted that the effect was as large for men as for women. "Regardless of whether you were a woman or a man dealing with depression you were affected as much; the difference was that women had twice the rate of depression," she said.

Results for the analysis of EQ-5D VAS scores over time largely mirrored the PAQ results.

Loneliness and poverty might help explain why women with cardiovascular disease are more vulnerable to depression. In this study, only about a third (34.7%) of women with clinically relevant depression were married (compared with 56.6% of men), and more women than men with depression avoided care because of cost (32.0% vs 23.0%).

It is unknown whether biological differences specific to PAD explain the sex differences in the study. However, female participants had more bilateral disease than male participants as well as lower mean ABI, which the authors note indicates more advanced disease.

Patients with depression may be more vulnerable to cardiovascular disease in general because of increased platelet reactivity, inflammation, and endothelial dysfunction, said Dr Smolderen.

Being depressed may have major implications for the success of rehabilitation and functioning over time for patients with PAD. "Since PAD management relies heavily on making lifestyle changes, people are not going to be able to successfully make those changes if depression is a significant problem," said Dr Smolderen.

"Treating these patients more holistically and addressing their depression concerns up front is key, but to do so, you have to have a care pathway in place, with linkage to accessible mental health care."

The study focused on patients treated at vascular specialty clinics, so the findings may not extend to the general PAD population, the authors note. The emphasis on depressive symptoms excludes other mental health concerns such as anxiety or stress, say the authors. They note that unmeasured clinical factors could have contributed to depressive symptoms.

Novel Study

Commenting for Medscape Medical News, Khendi White Solaru, MD, from the Division of Cardiovascular Medicine, University Hospitals, Harrington Heart and Vascular Institute, and assistant professor, Case Western Reserve University, Cleveland, Ohio, found the study "very interesting."

"What was novel about this study is that the authors found that both women and men who had depressive symptoms were more likely to have PAD symptoms and poorer quality of life" and "were less likely to have improvement in these symptoms 1 year later than those without depressive symptoms."

Because PAD adversely affects quality of life, "we need to screen our patients with PAD for depression, as these patients may be at high risk for functional impairment," said Dr Solaru.

She noted potential study limitations. The measurement of both depressive symptoms and PAD symptoms was based on subjective surveys, and the follow-up period of the study was only 1 year.

"This may not be enough time to measure impact of health status after depression has resolved," she said.

Dr Solaru added that she welcomes more research on depression in this patient population. "This is an underrecognized disease and one with profound implications on quality of life as well as overall cardiovascular health," she said.

The study was partially funded through a Patient-Centered Outcomes Research Institute award. Dr Smolderen is supported by an unrestricted research grant from Terumo and is a consultant for Optum Labs LLC. Dr Solaru has disclosed no relevant financial relationships.

J Am Heart Assoc. Published online August 12, 2020.

Clinical Implications

• A previous meta-analysis found that symptoms of depression were more common among women than men after MI. Although depression was associated with higher rates of mortality in both sexes, depression was associated with a greater risk for mortality among men.
• The current study confirms that women with PAD have more depression symptoms compared with men, and they also reported worse health status. Depression was found to account for 19% of the difference in self-perceived health status in comparing women and men.
• Implications for the Healthcare Team: The healthcare team should routinely assess patients, especially women, with PAD for depression and initiate treatment or referral as appropriate. Communication at team meetings of individual patient care needs requires the team to assess and manage individuals with PAD for symptoms of depression.

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