You are leaving Medscape Education
Cancel Continue
Log in to save activities Your saved activities will show here so that you can easily access them whenever you're ready. Log in here CME & Education Log in to keep track of your credits.


Lack of Exercise, Other Bad Behaviors Explain Link Between Depression and CVD, Study Suggests

  • Authors: News Author: Shelley Wood
    CME Author: Désirée Lie, MD, MSEd
  • CME/CE Released: 11/26/2008
  • Valid for credit through: 11/26/2009
Start Activity

Target Audience and Goal Statement

This article is intended for primary care clinicians, cardiologists, psychiatrists, and other specialists who care for patients at risk for depression or cardiovascular disease.

The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care.

Upon completion of this activity, participants will be able to:

  1. Describe the association between depressive symptoms and cardiovascular disease risk.
  2. Identify the behavioral factor explaining the association between depressive symptoms and cardiovascular disease events.


As an organization accredited by the ACCME, Medscape, LLC requires everyone who is in a position to control the content of an education activity to disclose all relevant financial relationships with any commercial interest. The ACCME defines "relevant financial relationships" as financial relationships in any amount, occurring within the past 12 months, including financial relationships of a spouse or life partner, that could create a conflict of interest.

Medscape, LLC encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.


  • Shelley Wood

    Shelley Wood is a journalist for, part of the WebMD Professional Network. She has been with since 2000, and specializes in interventional cardiology. She studied literature at McGill University and the University of Cape Town and received her graduate degree in journalism from the University of British Columbia, specializing in health reporting. She can be reached at [email protected]


    Disclosure: Shelley Wood has disclosed no relevant financial relationships.


  • Brande Nicole Martin

    Brande Nicole Martin is the News CME editor for Medscape Medical News.


    Disclosure: Brande Nicole Martin has disclosed no relevant financial information.


  • Laurie E. Scudder, MS, NP-C

    Nurse Planner, Medscape; Adjunct Assistant Professor, School of Health Sciences, George Washington University, Washington, DC; Curriculum Coordinator, Nurse Practitioner Alternatives, Inc., Ellicott City; Nurse Practitioner, Baltimore City School-Based Health Centers, Baltimore, Maryland


    Disclosure: Laurie Scudder, MS, NP-C, has disclosed no relevant financial information.

CME Author(s)

  • Désirée Lie, MD, MSEd

    Clinical Professor, Family Medicine, University of California, Orange; Director, Division of Faculty Development, UCI Medical Center, Orange, California


    Disclosure: Désirée Lie, MD, MSEd, has disclosed no relevant financial relationships.

Accreditation Statements

    For Physicians

  • Medscape, LLC is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

    Medscape, LLC designates this educational activity for a maximum of 0.25 AMA PRA Category 1 Credit(s)™ . Physicians should only claim credit commensurate with the extent of their participation in the activity. Medscape Medical News has been reviewed and is acceptable for up to 350 Prescribed credits by the American Academy of Family Physicians. AAFP accreditation begins 09/01/08. Term of approval is for 1 year from this date. This activity is approved for 0.25 Prescribed credits. Credit may be claimed for 1 year from the date of this activity.

    Note: Total credit is subject to change based on topic selection and article length.

    AAFP Accreditation Questions

    Contact This Provider

    For Nurses

  • Medscape is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation.

    Awarded 0.25 contact hour(s) of continuing nursing education for RNs and APNs; None of these credits is in the area of pharmacology.

    Contact This Provider

For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]

Instructions for Participation and Credit

There are no fees for participating in or receiving credit for this online educational activity. For information on applicability and acceptance of continuing education credit for this activity, please consult your professional licensing board.

This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page.

Follow these steps to earn CME/CE credit*:

  1. Read the target audience, learning objectives, and author disclosures.
  2. Study the educational content online or printed out.
  3. Online, choose the best answer to each test question. To receive a certificate, you must receive a passing score as designated at the top of the test. Medscape encourages you to complete the Activity Evaluation to provide feedback for future programming.
You may now view or print the certificate from your CME/CE Tracker. You may print the certificate but you cannot alter it. Credits will be tallied in your CME/CE Tracker and archived for 5 years; at any point within this time period you can print out the tally as well as the certificates by accessing "Edit Your Profile" at the top of your Medscape homepage.

*The credit that you receive is based on your user profile.


Lack of Exercise, Other Bad Behaviors Explain Link Between Depression and CVD, Study Suggests

Authors: News Author: Shelley Wood CME Author: Désirée Lie, MD, MSEdFaculty and Disclosures

CME/CE Released: 11/26/2008

Valid for credit through: 11/26/2009


From Heartwire — a professional news service of WebMD

November 26, 2008 — Researchers who set out to pick apart the bonds that link depression and cardiovascular disease (CVD) say that health behaviors and not complex biological processes largely account for the increased risk of cardiac events in people with depression [1]. Physical inactivity, in particular, likely accounts for the bulk of the risk, Dr Mary A Whooley (VA Medical Center, San Francisco, CA) and colleagues write in the November 26, 2008 issue of the Journal of the American Medical Association.

The Heart and Soul Study looked at over 1000 people with stable coronary heart disease, followed for almost five years, measuring depressive symptoms at baseline in relation to subsequent heart failure, myocardial infarction (MI), stroke, transient ischemic attack, or death.

Whooley explained to heartwire that while depression has long been known to increase the risk of heart disease, the candidate mechanisms had not previously been. "There's been a lot of interest in physiological consequences of depression, like elevated norepinephrine, elevated cortisol, low heart-rate variability, and platelet activation, but there hasn't been as much focus on the behavioral mediators, although they certainly have been suggested by previous studies. Surprisingly, we found that the fancy physiological mediators really were not explaining the association and that it seemed to be all about health behaviors."

According to Whooley, depressed patients were less likely to take their medications as prescribed, less likely to exercise, and more likely to smoke. "And after you accounted for those health behaviors, the association between depression and CVD went away. So we concluded that link between depression and heart disease is largely explained by these health behaviors."

Good, but challenging news

As with other studies, Whooley et al's analysis showed a clear link between depression and cardiovascular (CV) events. Of the 341 events that occurred over the 4876 person-years of follow-up, the age-adjusted rate of events was 10% among the 199 individuals with depressive symptoms and only 6.7% among the 818 subjects without depressive symptoms (p=0.002). That translated into a 31% increased risk of cardiovascular events in depressed subjects, after adjustment for comorbidities and disease severity.

If biological mediators were factored into the analysis—things like use of antidepressant drugs, heart-rate variability, levels of serotonin and omega-3s, or 24-hour excretion of norepinephrine and cortisol—the effect size for depressive symptoms on cardiovascular events did not substantially change. However, when behavioral factors such as adherence to medication, smoking status, and most strikingly physical activity were factored in, the association between depressive symptoms and cardiovascular events was no longer statistically significant.

"This is good news in that these are modifiable and it's cheap to get people to exercise and to take their medications; the more challenging news is that it's very hard to change behaviors," Whooley commented. "We can't just give people a medication that will magically lower their norepinephrine or cortisol, we have to start behavioral interventions, and those are notoriously difficult."

Whooley also acknowledged that it doesn't matter whether patients first grew depressed due to lack of physical exercise or stopped exercising when they became depressed. "Very likely it's a vicious cycle and the association is bidirectional," she said. "In our opinion, it doesn't really matter whether it's the chicken or the egg because the bottom line is the same—if you increase exercise in these patients, you're going to reduce their risk of heart disease. But the thing to remember about depressed patients is that they are that much less motivated to do things, so it takes extra effort to get them to exercise, take their medications, and stop smoking."

The Heart and Soul results may help explain the failure of a number of high-profile trials looking at whether use of antidepressant medication in depressed subjects could improve cardiovascular outcomes. Whooley et al's results "open up another potential intervention," she said. Indeed, the Understanding Prognostic Benefits of Exercise and Antidepressant Therapy (UPBEAT) study, still under way, is comparing antidepressants with an exercise intervention in improving cardiovascular risk factors. "It won't be looking at whether we can actually prevent events, but rather changes in inflammation and things like that. But it is the next step in the right direction," Whooley said.

Her group is also continuing to investigate the association between physical activity level and heart disease in depressed subjects, with the ultimate aim of developing an intervention that might be able to reduce the risk of events in people with cardiovascular disease.


  1. Whooley MA, de Jonge P, Vittinghoff E, et al. Depressive symptoms, health behaviors, and risk of cardiovascular events in patients with coronary heart disease. JAMA 2008;300:2379-2388.

The complete contents of Heartwire , a professional news service of WebMD, can be found at, a Web site for cardiovascular healthcare professionals.

Clinical Context

Depression is recognized as a risk factor for CVD and for recurrent adverse CV events, including heart failure and MI. However, the mechanism of this association is not clear and could involve lack of exercise, poor medication adherence, underlying cardiac disease severity, or other factors.

This is a multicenter prospective cohort study of patients with underlying stable CVD to examine the association between depressive symptoms and risk for CV events.

Study Highlights

  • Included were adults with at least 1 of the following: history of MI, angiographic evidence of at least a 50% stenosis in 1 or more coronary vessels, history of revascularization, or exercise ischemia by treadmill testing.
  • 1024 participants were enrolled from public health clinics, university, and veteran's medical centers from 1 US region.
  • At baseline, participants were interviewed and received blood tests, psychiatric questionnaire, echocardiogram, treadmill test, and 24-hour electrocardiogram and a urine collection was taken.
  • Depressive symptoms were screened by using the 9-item Patient Health Questionnaire, a self-report instrument measuring the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for depression.
  • Items were scored from 0 for no symptoms within 2 weeks to a score of 3 for daily symptoms within the past 2 weeks.
  • The presence of major depressive disorder was ascertained by the computerized Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, interview schedule.
  • Behavioral mediators were assessed including smoking, alcohol consumption, physical activity, use of antidepressants, and medication adherence.
  • The exercise treadmill Bruce protocol was used to assess physical fitness.
  • Annual telephone interviews were conducted with participants or proxies, and death certificates were used to confirm diagnosis at death.
  • Outcomes were heart failure, MI, stroke, transient ischemic attack, or death.
  • Mean age was 63 and 68 years. More than 75% of participants were white, more than 80% were high school graduates, and mean body mass index was 29 kg/m2.
  • Of 1017 participants analyzed, 19.6% had depressive symptoms (Patient Health Questionnaire score of 10 or higher).
  • Those with depressive symptoms were younger and less likely to be men, more likely to smoke, to be less physically active, to be less adherent to medications, and to have a higher body mass index.
  • Depressive symptoms were associated with greater antidepressant use.
  • 341 CV events occurred over 4876 person-years of follow-up with a mean of 4.8 years follow-up.
  • The age-adjusted annual rate of CV events was 10% among those with depressive symptoms and 6.7% among those without depressive symptoms, with an HR of 1.50 (P = .002).
  • Adjustment for physical activity was associated with a 31.7% reduction in the strength of the association.
  • Once physical inactivity was accounted for, the HR was no longer significant for the association between depression and CVD (HR, 0.96; P = .79).
  • Physical inactivity as a factor was associated with a 44% greater rate of CV events (HR, 1.44; P = .002).
  • The association between depressive symptoms and CV events was not significantly altered after adjusting for other comorbidities, cardiac disease severity, use of antidepressants, heart rate variability, and excretion of cortisol and norepinephrine.
  • There was a dose-response association between depressive symptoms and CV events, with increasing score associated with 15% increase in risk (HR, 1.12; P = .02).
  • Adjustment for smoking and nonadherence reduced the size of the association to an HR of 1.09.
  • The authors concluded that there was likely a bidirectional association between depression and physical inactivity and both contributed to the risk for CV events.

Pearls for Practice

  • In patients with underlying CV disease, depressive symptoms are associated with increased risk for CV events.
  • The association between depression and CV risk is dose-dependent and largely accounted for by physical inactivity.


  • Print