Depression can exacerbate cardiovascular disease (CVD), and CVD can exacerbate depression (Figure). Thus, effectively treating depression enhances heart disease treatment, particularly if psychiatrists and medical physicians collaborate in providing patient care.
This article describes a patient with risk factors for heart disease, illustrates the physiologic pathways that link depression and CVD, and offers clinical tips to help you improve outcomes for patients with both disorders.
Case report: Trying to ‘get going’
Mr. D, age 51, presents with vegetative symptoms and a personal and family history of CVD, depression, and substance abuse disorders. He was born in a small town in Kentucky and raised in Louisville’s poorest neighborhood. After his mother died at age 42 of “hardening of the arteries,” his father started drinking more, working less, and “never really got going again.”
Figure Neuroendocrine pathways by which depression may cause or promote CVD
Box
The depression-CVD connection
Among patients with a recent myocardial infarction (MI), as many as two-thirds report depressive symptoms.1 Major depression has been reported in:
- 16% to 22% of patients hospitalized post-MI,2,3 compared with 5% in the general population and 10% in the primary care population4
- 15% of patients with unstable angina5 and 20% of patients undergoing coronary artery bypass (CABG) surgery.6
Among the annual 1.5 million Americans who have an acute MI or unstable angina, 40% develop depression immediately thereafter. These 600,000 depressed patients are three times more likely to die within 6 months, compared with post-MI patients who are not depressed.7
Mr. D worked 20 years as a construction contractor, often running several work crews at once. At age 41, he slid into a depressive episode after his second divorce. He struggled with low energy, disturbed sleep, hopelessness, and increased smoking and drinking for 1 year, but he did not seek help.
Two years later, he suffered an inferior wall transmural myocardial infarction. His CVD risk factors included family history of early heart disease, smoking for 32 years, and elevated low-density lipoprotein (LDL) cholesterol. After subsequent episodes of unstable angina, stents were placed in two coronary arteries. Though his cardiologist cleared him to return to work, he felt able to work only part-time and erratically.
During a visit to their family doctor several years later, Mr. D’s wife suggested that her husband might be depressed. Reluctantly, Mr. D consulted a psychiatrist.
The psychiatrist diagnosed major depressive disorder and prescribed sertraline, 50 mg/d. Within 2 months, Mr. D’s symptoms had dropped by 50% on a symptom severity measure. He did not refill his prescription, however, because of concerns about sexual side effects. Two months later he was hospitalized for another episode of unstable angina. His depression had returned within 1 month of stopping sertraline.
The psychiatrist switched him to citalopram, 20 mg/d, and carefully monitored depressive symptoms, side effects, and medication adherence. Aside from talking with the psychiatrist for a half-hour in his family doctor’s office every few weeks, Mr. D refused to undergo psychotherapy. He eventually achieved depression remission with a combination of citalopram, 20 mg/d, and nefazodone, 200 mg/d.
Depression-CVD connection
As in Mr. D’s case, depression and CVD commonly occur together, often with serious consequences (Box). 1-7 The association between depression and CVD is not limited to depression’s effect on existing disease, however. Depression often precedes coronary disease by about 30 years—suggesting possible cause and effect. Two systematic reviews8,9 found that depression increased CVD risk by 64%.
Seven well-controlled studies5-7,10-13 compared the relative effect of depression on the cardiovascular system with that of established CVD predictors. All seven found depression’s independent effect to be significant and comparable to or greater than that of ejection fraction, previous MI history, or number of vessels with >50% narrowing.
Comorbid depression and CVD usually persists months or years,14 and most studies indicate a dose-response relationship; the more severe the depression, the greater the risk for CVD to develop or progress.8,15
The link between depression treatment and CVD risk has not been well-studied. The only randomized, controlled trial found that cognitive therapy for depression did not significantly reduce cardiac events among patients with known CVD.16
Possible mechanisms
Depression’s effect on CVD. How does depression affect CVD development and progression? Both behavioral and biological pathways may be involved.17 The behavioral pathway proposes that depression triggers behaviors—such as smoking, overeating, and sedentary lifestyles—that increase the risk of developing or worsening CVD. The biological pathway proposes that neuroendocrine changes during depression accelerate CVD development.
About one-half of persons with major depression exhibit hypothalamic-pituitary-adrenal (HPA) axis dysregulation, with excessive secretion of corticotropin releasing factor (CRF) and chronically elevated cortisol.18 This HPA dysregulation is related to defective negative feedback at the paraventricular nucleus of the hypothalamus. Chronic HPA axis dysregulation promotes vascular inflammation, and several studies have reported C-reactive protein elevation and cytokine changes in patients with major depression.19,20