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CVD and mental health disorders: Link established, more research needed
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Evidence continues to accumulate on the link between CVD and mental health disorders. Some studies have demonstrated that patients with depression, anxiety, bipolar disorder and schizophrenia are more likely to develop atherosclerosis and CVD later in life than those without these conditions. Other research suggests that patients with CVD are more likely to have depression than those without CVD.
Despite these associations, there is tremendous uncertainty about the mechanisms underlying the link between CVD and mental health disorders, and questions remain about the role of the cardiology community in addressing it.
In an interview with Cardiology Today, Sharonne N. Hayes, MD, FACC, FAHA, said mental health disorders “are risk factors for CVD, or certainly associated with CVD.
“It is difficult to determine the extent of the association because the research has not been strong in that regard. Some of this has to do with the fact that cardiologists have been relatively slow to make that connection and to acknowledge the heart–mind connection,” said Hayes, founder of the Women’s Heart Clinic and the Office of Diversity and Inclusion and professor of medicine and cardiovascular diseases at Mayo Clinic.
Predisposition in youth
This topic came to the forefront earlier this year, when the American Heart Association published a scientific statement declaring that major depressive disorder and bipolar disorder predispose youth to accelerated atherosclerosis and early CVD.
“The overall objective of this statement is to increase awareness and recognition of [major depressive disorder] and [bipolar disorder] among youth as moderate-risk conditions for early CVD,” the statement’s authors wrote.
Credit: Mayo Clinic; printed with permission.
Among other things, the panel, chaired by Benjamin I. Goldstein, MD, PhD, a child-adolescent psychiatrist at Sunnybrook Health Sciences Centre, Toronto, and the University of Toronto, cited evidence from two observational, population-based studies showing that major depressive disorder, anxiety, bipolar disorder and suicide attempts in children and young adults were associated with premature CVD or related deaths; epidemiological studies that have demonstrated a link between depressive symptoms regardless of severity and increased carotid intima-media thickness; and small studies linking major depressive disorder in adolescents and young adults to impaired endothelial function. Youth with depressive disorder or bipolar disorder have an elevated prevalence of traditional CVD risk factors, including obesity, diabetes and insulin resistance, dyslipidemia and hypertension, according to the AHA statement.
Other research has identified pathophysiological processes common to mood disorders and CVD, including inflammation, oxidative stress and autonomic dysfunction, as well as behavioral and environmental CVD risk factors that are disproportionately observed in youth with mood disorders, such as early maltreatment, sleep disturbance, sedentary lifestyle, poor nutrition, smoking and substance abuse.
Further, certain medications used to treat mental health disorders appear to have adverse cardiac effects, according to the statement. Examples include tricyclic antidepressants and autonomic dysfunction; lithium and anticonvulsant drugs and weight gain; and certain antipsychotic drugs and adverse consequences for components of the metabolic syndrome.
Most of the research on this link concerns depression, according to Hayes. An exacerbating factor is that “individuals with depression are less likely to be adherent to medications, to attend cardiac rehabilitation, to exercise and to eat well. If you are depressed, the last thing you want to do is get out and take a healthy walk,” she said.
However, despite the research cited in the recent AHA statement, some question the available data. Steven E. Nissen, MD, FACC, chairman of the Robert and Suzanne Tomsich department of cardiovascular medicine at Cleveland Clinic’s Sydell and Arnold Miller Family Heart and Vascular Institute, told Cardiology Today that the data cited in the statement are not conclusive enough to act on. “The AHA was premature in coming to such a conclusion,” he said. “These are just not reliable data.”
Hayes noted that “aside from a few, the general cardiology community has not been looking at this for a long time, but there have been epidemiologic data for decades showing that all of these psychiatric disorders, including anxiety, are associated with increased risk for CV events.”
Mechanistic studies have been few and far between. But a recent genomic study conducted by Hans W. Moises, PhD, from the molecular genetics laboratory of the department of psychiatry at Kiel University Hospital, Germany, and colleagues concluded that “schizophrenia is probably a mild adult vascular-ischemic and postischemic repair disorder” and “might be caused by the cerebral analog of microvascular angina.” This finding could have implications for the connection between schizophrenia and CVD.
Moises and investigators observed that schizophrenia-related genes had a significant overrepresentation of genes known to be involved in vascular function, vasoregulation, shear stress, cerebral ischemia, neurodevelopment and postischemic repair.
Nature of relationship uncertain
Cardiologists and psychiatrists interviewed by Cardiology Today said it is difficult to pinpoint why mental health disorders and CVD might be connected because most of the data come from epidemiological studies, and many different factors appear to be in play.
“Like many epidemiological associations, we don’t have solid data. So the problem is that there are many unmeasured confounders,” said Nissen, a member of the Cardiology Today Editorial Board. “If you have disease, you may be more likely to be depressed than if you don’t have disease. If you have risk factors that limit your quality of life, you may be more depressed. A question that comes up is whether it’s depression per se or simply the associations that go with depression? There isn’t a reliable way to figure it out.”
Mark A. Frye, MD, professor of psychiatry at Mayo Clinic and director of the Mayo Clinic Depression Center, said, “There clearly is evidence to suggest that mood disorders are risk factors for subsequent cardiac events,” but there are many hypotheses as to why that might be the case.
“One hypothesis to further study is whether there is something about the underlying biology of the mood disorders that is similar to the underlying biology of cardiac disease, and does one predispose to the other?” he said. “Another part of that may be ... how we treat depression, or the comorbidity patterns we see with depression — high rates of smoking, increased weight gain related to a change in diet related to depression that might predispose to elevated cholesterol levels — or that some of the medications we prescribe can have weight gain as a side effect.”
A significant connection appears to be obesity, Peter F. Cohn, MD, emeritus chief of cardiology and professor of medicine at Stony Brook University, said in an interview.
“The link with many of [the proposed mechanisms] is obesity,” he said. “In my experience, adults with major depressive disorders don’t eat properly and are sedentary, and both of these factors lead to obesity. In addition, metabolic syndrome, which is built around hyperglycemia leading to frank diabetes, is also frequently observed in patients with depression. Of course, anything that causes increased lipids or BP is a factor. There seems to be a well-thought-out evidence pathway to show that this link occurs.”
Allan S. Jaffe, MD, FACC, FAHA, FESC, told Cardiology Today: “There are a variety of pathophysiological mechanisms that can be suggested that might be relevant. We know, for example, that depression is associated with excessive amounts of catecholamines in the central nervous system. We know that arrhythmias can come from the central nervous system, and that strokes can evoke reflex changes in the heart directly.”
Complicating matters is “a lack of coordinated care for these individuals. Getting people into the appropriate programs is sometimes a task. There clearly is a need for a more integrated way of dealing with these individuals in terms of their long-term CV health,” said Jaffe, professor of medicine, cardiology, laboratory medicine and pathology at Mayo Clinic.
CVD as risk factor for depression
On the other hand, there also is evidence that CVD may elevate risk for depression.
“It has been estimated that 20% to 25% of individuals after a cardiac event, particularly MI, will demonstrate depressive symptoms. These symptoms may be short-lived and not require treatment, but they are definitely associated,” Hayes said. “What we know is that the association is durable; in fact, we’ve been able to identify individuals who are more likely to have depression that doesn’t remit after MI,” including those with prior depression and women.
A link in that direction is evident for depression, but not schizophrenia or bipolar disorder, according to Cohn, a Cardiology Today Editorial Board member. “These are genetic problems that are not environmentally induced the way that depression could be,” he said.
Nissen said he believes that there is adequate evidence that “situational depression” does occur in patients who have CVD. “If you have a disorder that limits your quality of life, you may well become more depressed. That’s true whether it be cancer, heart disease, diabetes or anything else.”
Ongoing research is evaluating whether there are any biological factors involved in MI that predispose an individual to depression, according to Frye. Additionally, “New medicines that are being used to treat the cardiac condition may have fatigue and depressed mood as side effects,” he said. “Most likely, a patient is going to be encouraged and counseled on how to make lifestyle changes to reduce risk for another MI, and transitioning to these lifestyles can be challenging for some patients.”
Implications for cardiologists
Given that associations between mental health disorders and CVD are known, but the mechanisms behind them are not, a question remains as to how cardiologists can manage these risks.
“The first thing that cardiologists need to do is to take ownership for this important risk factor for their patients,” Hayes said. She noted that a good strategy is “adopting this as part of the history ... and then taking that into account as we assess and determine the level and intensity of treating risk factors.”
“The way we’re moving toward — although this isn’t codified in current guidelines — is that if someone has a prior or current history of depression or anxiety and they are on the border of initiating treatment for hypertension or hyperlipidemia, that might sway us to be more aggressive in managing those risk factors. I personally use it often as an add-on risk factor.”
Frye said the cardiologist should not be expected to manage his or her patients’ psychological health, but there are simple ways to assess patient mood and take that into account while determining how to treat a CV condition.
“One example is a patient-rated score where they are asked to track their mood, called the PHQ-9,” he said. “It’s in the public domain. General internal medicine practices and most cardiology practices can easily integrate this into their private practice. It is an excellent way to quickly get a sense of whether your cardiac patient is struggling with depression or your CV rehabilitation patient is not making progress you think is appropriate. They might have depression that is contributing to the lack of therapeutic outcome.”
Optimally, Frye said, a cardiologist would operate as part of an integrated team with psychiatrists and other health care professionals who manage mental health disorders and/or CV conditions.
“When you are part of a team, you can learn tools and techniques to screen for depression in your cardiac clinics,” he said. “Conversely, when cardiac patients are asked to be seen [by a psychiatrist], we can have access to our cardiovascular colleagues and know that they are tracking important cardiac milestones for them.”
Jaffe and others said patients with a cardiac condition and a mental health disorder can especially benefit from cardiac rehabilitation.
“These individuals will probably need more supportive care to [manage their risk factors],” said Jaffe, a member of the Cardiology Today Editorial Board. “It’s one of the reasons why many people have advocated ... that these sorts of things should be linked to cardiac rehab. But it’s difficult to get these people to go to cardiac rehab. In my opinion, what will be necessary is a commitment to dealing with these patients and their unique challenges, as opposed to trying to mainstream them into a central paradigm.”
If there are certain therapies that work particularly well for improving CV outcomes specifically in those with mental health disorders, they unfortunately have not yet been uncovered.
Several studies have examined whether treating depressive symptoms leads to better CV outcomes; however, none of those studies have yielded positive results, experts said. Notably, in the ENRICHD trial, Jaffe and colleagues randomly assigned patients with MI and major/minor depression to usual medical care or a cognitive behavioral therapy intervention. Although the cognitive behavioral therapy group had improved psychosocial outcomes compared with controls, the rate of event-free survival at a mean follow-up of 29 months was similar.
“Some people, particularly cardiologists, took away that if treating depression doesn’t reduce the risk for MI, then we don’t need to treat it,” Hayes said. “That certainly should not have been the take away and, in fact, was not the conclusion of the trial. The proactive message is that we need to assess and identify individuals at higher risk for depression and anxiety after a cardiac event; we need to follow them to make sure that if they have early depressive symptoms, that the symptoms resolve, and then refer for further treatment if they do not.”
However, according to Nissen, current evidence does not support treating patients with mental health disorders differently than patients without mental health disorders. “I would not do anything different with those patients, from a point of view of prevention,” he said. “We have good algorithms for predicting risk. I happen to like the Reynolds Risk Score; I treat the conventional risk factors, and I don’t modify that based on the presence or absence of psychological conditions.”
Early intervention
It is less clear what cardiologists can do to help manage the relationship between mental health disorders and atherosclerosis or CVD in youth. Except for patients with congenital heart disease or familial hypercholesterolemia, cardiologists rarely see children, adolescents or young adults in their practices.
“This is where lifestyle and primordial prevention is key: getting younger individuals to exercise and have healthy eating patterns and monitoring their standard risk factors,” Hayes said. “We also need to identify [medication side effects] as a risk factor and be even more proactive in these young folks’ lifestyles.”
It is important for cardiologists to convey to pediatricians that their patients with mental health disorders may be at future risk for CVD, she said.
For Cohn, the relationship between mental health disorders and future CV risk is another reason to make strong efforts to prevent obesity in youth. “Obesity is an epidemic in the United States, and it starts with young people,” he said. “My advice to pediatricians is: Don’t let these kids become obese. That’s easier said than done, though.”
To have an effect on youth, clinicians are going to have to make efforts to provide younger people with mental health disorders whatever help they need to manage their future CV risk factors, according to Jaffe. “Until we decide that we’re going to make this effort in some substantive way, it’s not likely to happen,” he said.
Future directions
Although many clues have emerged that mental health disorders and risk for atherosclerosis and CVD are linked in some way, it requires further research to determine how they are related and how they can be optimally treated.
“Perhaps one of the most important issues is to try and tease out whether or not one could get good compliance with health behaviors, and whether that is the predominant mechanism,” Jaffe said. “There is also a need to figure out what are the most effective treatments. Many of the treatments [for mental health disorders] actually make heart disease worse. So the question would be whether there are opportunities to develop better approaches that would be not only more efficacious but less apt to cause toxicity.”
A multidisciplinary group at Mayo Clinic is investigating whether there is a similar underlying biology to mood disorders and how cardiac disease develops, according to Frye. “Our way of approaching this is looking at a younger group of people who have mood disorders, but do not yet have cardiac disease,” he said. “We also need to better understand and design more effective pharmacotherapies and structured psychotherapies to address symptoms in primary care and in CV care for these patients.”
However, Hayes said, progress is most likely to happen once cardiologists and their patients no longer see mental health disorders as a stigma.
“We need to acknowledge it. Mental health issues still have a huge stigma among providers,” she said. “Patients find this to be such a stigma that if they are profoundly depressed or have other issues, the act of suggesting a referral ... for treatment of this can be taken negatively. We have to have a broader toolkit to have that conversation. We need to figure out how to address these important issues without turning off our patients.” – by Erik Swain
- References:
- Goldstein BI, et al. Circulation. 2015;doi:10.1161/CIR.0000000000000229.
- Moises HW, et al. Transl Psychiatry. 2015;doi:10.1038/tp.2015.103.
- Writing Committee for the ENRICHD Investigators. JAMA. 2003;doi:10.1001/jama.289.23.3106.
- For more information:
- Peter F. Cohn, MD, can be reached at 200 Motor Parkway, Hauppauge, NY 11788; email: peter.cohn@stonybrook.edu.
- Mark A. Frye, MD, can be reached at Division of Psychiatry, Mayo Clinic, 200 First St. SW, Rochester, MN 55902; email: frye.mark@mayo.edu.
- Sharonne N. Hayes, MD, FACC, FAHA, can be reached at Division of Cardiology, Mayo Clinic, 200 First St. SW, Rochester, MN 55902; email: hayes.sharonne@mayo.edu.
- Allan S. Jaffe, MD, FACC, FAHA, FESC, can be reached at Division of Cardiology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905; email: jaffe.allan@mayo.edu.
- Steven E. Nissen, MD, FACC, can be reached at Cleveland Clinic Main Campus, Mail Code J2-3, 9500 Euclid Ave., Cleveland, OH 44195; email: nissens@ccf.org.
Disclosures: Frye reports receiving grant support from AssureRx, Janssen Research and Development, Myriad and Pfizer, and consulting for Janssen Research and Development, Mitsubishi Tanabe Pharma Corp., Myriad, Neuralstem, Sunovion, Supernus and Teva, all for work unrelated to CVD. Jaffe reports consulting for Novartis and for most of the major diagnostics companies, predominantly related to biomarkers. Cohn, Hayes and Nissen report no relevant financial disclosures.