Do mood disorders in teens increase CVD risk?

Teenagers who suffer from mood disorders are more likely than their peers to experience some level of cardiovascular disease (CVD) as they enter adulthood, according to a new scientific statement from the American Heart Association (AHA).

The statement, published in Circulation, adds major depressive disorder (MDD) and bipolar disorder (BP) to a list of conditions associated with an increased risk of CVD, and aims to bring light to adolescent trends toward later CVD risks in the MDD and BD populations, allowing for earlier intervention and preventive strategies.

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“Pediatricians are accustomed to having greater vigilance for cardiovascular risk factors among teens were specific medical conditions, such as juvenile inflammatory arthritis,” says lead author Benjamin I. Goldstein, MD, PhD, chair of the AHA Atherosclerosis, Hypertension and Obesity in Youth Committee of the Council on Cardiovascular Disease in the Young.

“What's new here is that teens with mood disorders should henceforth be approached with similarly increased vigilance, as reflected in increased screening for cardiovascular risk factors and intervening to modify those risk factors at lower thresholds than for the general teenage population,” Goldstein says. “Because managing mood disorders in and of themselves requires time of pediatricians, there may be a need for longer and/or more office visits to allow for adequate attention to both mental and physical health.”

Not much is known about the connection between CVD prevalence and adolescents with mood disorders, other than that it exists. Multiple potential pathways linking mood disorders and CVD are present, says Goldstein.

“Although the link between mood disorders and CVD exceeds what can be explained, traditional CVD risk factors such as obesity and hypertension, specifically targeting those traditional CVD risk factors, is in my view the highest yield and best justified strategy at this time,” he says.

Goldstein says mood disorders are not rare cases in pediatric practice by any means, and pediatricians must realize the tremendous opportunity they have to prevent accumulated CVD risk factors in these populations.

Prevalence

Major depressive disorder and BP collectively affect about 10% of the US adolescent population, and pediatricians are on the front line in recognizing and beginning treatment for these conditions.

Cardiovascular disease is the leading cause of death in patients with BD, AHA notes, and mortality rates are higher in individuals with BD than in the general population. The second most common cause of death in BD is malignancy, yet prevalence among BD patients appears no different than in the general population.

The prevalence of CVD in BP patients does not appear tied to medication regimens, either, since excess and premature CVD has been documented in BD patients for more than 70 years-prior to the use of mood stabilizers and antipsychotic drugs.

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Adults patients with BD have a 5-fold increased risk of CVD that appears 14 years sooner than their general population peers-and half of those patients never received any pharmacological treatment for BD. Additionally, prevalence of CVD in BP patients is twice as great as for adults with MDD.

Altogether, MDD and BD present a 10-times higher risk than all the previously identified moderate-risk conditions combined. Early identification and intervention in adolescent cases of MDD and BP could have a profound impact on the development of CVD as they age, according to the statement. To achieve success on this front, AHA recommends improved CVD risk factor screening, prevention, and screening at an earlier age for patients with MDD or BD.

Risk factors and comorbidities

The AHA warns that there is compelling evidence that excessive and premature CVD is present in adults with MDD and BD. Cardiovascular disease in adults with MDD or BD are 3 times higher than in adults with mood disorders, and the CVD struck on average of 7.5 years earlier, according to AHA.

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The increased risk is tied to the hypothalamic-pituitary-adrenal axis and sympathomedullary hyperactivity, increased platelet reactivity, reduced heart rate variability, vascular inflammation, oxidative stress, and endothelial dysfunction-all likely set in motion by lifestyle choices brought on through the mood disorders, according to AHA. There is also evidence that depression and CVD share genetic pathways, says AHA, as well as a familial nature link. The AHA believes there is also a link to the shared calcium channels implicated in the pathophysiology of both BD and CVD.

“The magnitude of increased risk for CVD in adulthood is substantial, most likely because of a combination of factors that include direct effects of MDD and BD through shared pathophysiological processes (eg, inflammation), direct effects of mood disorder symptoms (eg, sleep disruption), indirect effects of mood disorder symptoms (eg, smoking, suboptimal nutrition and physical activity), and accumulation of excessive traditional CVD risk factors,” according to AHA’s new statement. “Importantly, there is evidence of clustering of risk factors (eg, smoking, hypertension, obesity, suboptimal nutrition or physical activity) among people, including teenagers, with MDD and BD. As a result, although MDD and BD warrant inclusion among tier II moderate-risk conditions overall, careful assessment is warranted to additionally identify those patients with risk factor clustering (≥2 risk factors), for whom a tier I high-risk designation would apply.”

Through previous studies, AHA reveals that adolescents with MDD and BD are at higher risk for several CVD manifestations such as accelerated atherosclerosis, premature cardiovascular mortality, and increased ischemic heart disease (IHD) mortality. The mortality risk of IHD was shown in previous studies to be 13% among males and 65% among females, according to AHA. Additionally, increased carotid artery-media thickness (CIMT) has been linked to depressive symptoms, and one of the earliest signs of CVD risk is impaired endothelial function. In previous studies, young adults with no cardiovascular risk factors and not history of taking antidepressant medications were also found to have several markers of atherosclerosis.

A higher prevalence of concurrent factors of CVD is also present in the MDD and BD populations, according to AHA. Pediatric obesity was linked to metabolic syndrome (MetS) or medication regimens in MDD and BD populations, and there is evidence of associations between depressive symptoms and diabetes mellitus in adolescents. Young adults with BD also are at a higher risk of developing dyslipidemia compared with the general population, says AHA.

Hypertension also was found to be significantly more prevalent in adults with MDD and BD, and it occurs at younger ages than in the general population. Inflammation may play a role, as well, with depressed adolescents displaying higher levels of proinflammatory cytokines than the general population. Other issues increasing cardiovascular risks in MDD and BD populations include increased oxidative stress markers, autonomic dysfunction, as well as behavioral and environmental factors including early maltreatment and poor lifestyle.

According to AHA, children who are maltreated in their early years are more prone to developing depression, as well as dysregulation of the hypothalamic-pituitary-adrenal axis, higher levels of C-reactive protein, and more signs of cardiometabolic risk through early and middle adulthood. Studies also uncovered a significantly higher prevalence of MetS and low-grade inflammation in adults that were exposed to childhood maltreatment, and they faced higher lifetime rates of stroke and myocardial infarction.

Sleep is another factor, with depressed adolescents experiencing short rapid eye movement cycles, more frequent nighttime arousals, and circadian phase shifts-which are also associated with CIMT, increased inflammation, and poor cardiovascular outcomes.

Major depressive disorder and BD populations are more likely to have sedentary lifestyles, poor nutrition, and substance abuse, according to AHA, which are additional risk factors for CVD.

Some of the medications aimed at improving MDD and BD may also be to blame, according to AHA. There are associations between autonomic dysfunction and antidepressants, and between lithium/anticonvulsant drugs and weight gain. However, AHA notes that the evidence that these medications increase CVD risk or mortality is lacking. The statement also notes that in spite of associations between medications for mood disorders and CVD risk factors, many of the studies conducted utilize a vast number of participants who are not or have not ever received any medications for MDD or BD.

Management

The first step to managing the increased risk of CVD in MDD and BP adolescent populations is diagnosis and concurrent assessment of other CVD risk factors such as family history of CVD, risk behaviors like smoking, and elevated blood pressure. Patients with at least 2 additional risk factors other than MDD or BP should be considered at high risk for CVD, according to AHA. Those with less than 2 risk factors may be placed in the moderate risk category.

More research is needed to better understand the pathophysiology of CVD risk in populations with MDD and BD, as well as the impact of other psychiatric disorders, says AHA.

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“Future studies should therefore ascertain both diagnoses and symptoms and should examine whether the severity, persistence, and recurrence of symptoms impacts CVD risk,” says AHA. “There is an unrealized opportunity to increase our knowledge on this topic by incorporating CVD-related measures in studies of teenagers with MDD and BD.”

Additionally, AHA says it’s currently unclear as to whether treatment of MDD and BD at an early age can reduce CVD risks.

The AHA recommends a “transformational change” in the management of MDD and BD to better incorporate CVD risk assessment and management.

“There is preliminary evidence that integrating cardiovascular risk assessment and management in the treatment of adults with MDD and BD may have salutary effects both on CVD risk and on psychiatric outcomes,” AHA notes.

Pediatricians, primary care providers, psychiatrists, parents, payers, and policy makers also should have a role in working to improve the CVD risk in MDD and BD populations, says AHA, and collaborative efforts are critical pending the development of additional evidence-based guidelines for these populations.