Cardiovascular disease (CVD) is the world’s biggest killer. From strokes and heart attacks to peripheral arterial disease, CVD includes all diseases that affect the heart and arteries. The WHO estimates that CVD causes over 42.5% of all deaths annually (“Cardiovascular diseases,” 2024), while countless others live with life-altering disabilities. 

While many of us now know that we can exercise regularly and limit processed foods to protect our heart and blood vessels, mental health is often overlooked in conversations about CVD. Research dating back to 1985 has shown that people with depression are less likely to recover from CVDs (Rabins et al., 1985). More recent studies show that these conditions are highly likely to coexist (Hare et al., 2014), and that symptoms of depression are associated with an increased risk of cardiovascular disease and vice versa (Barefoot and Schroll, 1996; Harshfield et al., 2020). A key area of exploration is the role of inflammation – the body’s response to injury and infection – and how it bridges the brain and the body. 

The brain used to be considered an “immune-privileged” organ – because of its vital importance, it is shielded from the potential damage that inflammation may cause. However, we now know that this immune status is not absolute. While immune cells from the rest of the body do not normally enter the brain, specialized brain immune cells respond to inflammatory stimuli from the rest of the body through multiple chemical and nervous pathways (Dantzer et al., 2008). These pathways often involve cytokines, which are chemical messengers produced by cells to cause and manage immune responses. In this way, the brain constantly monitors immune activity happening elsewhere in the body, enabling it to coordinate “sickness behaviors” (Dantzer et al., 2008)” – the persistent fatigue, irritability, poor appetite, and disrupted cognition that are all too familiar to anybody who has ever been ill. 

The similarity between these “sickness behaviors” and clinical depression is striking. Both feature social withdrawal, decreased reactivity to reward, and a range of cognitive, behavioral and social symptoms (Dantzer et al., 2008). While most people recover from transient illnesses without long-term effects on mental health, prolonged or excessive inflammation may cause these symptoms to evolve into clinical depression. A classic example is that new or relapsing depression is a common and well-documented side effect of treatment with interferon-alpha (Raison et al., 2005), a powerful cytokine used to boost the immune system to fight hepatitis C and some cancers. 

Notably, a constant state of low-grade inflammation is a hallmark of CVD (“Inflammation, Atherosclerosis, and Coronary Artery Disease | New England Journal of Medicine,” 2005.). The main cause of CVD, atherosclerosis, involves the buildup of plaques in the walls of the arteries. Immune cells within these plaques are persistently activated to produce inflammatory cytokines, causing systemwide effects that ultimately act on the brain. Additionally, patients who have suffered a heart attack or stroke are frequently found to have increased levels of cytokines and other inflammatory chemicals in their blood (Aukrust et al., 1999; Folyovich et al., 2014; Lindahl et al., 2000; Wilhelmsen et al., 1984), which could help explain why many people with cardiovascular disease experience depressive symptoms that go beyond the emotional impact of a debilitating medical event. 

This relationship between depression and cardiovascular disease may go both ways. Inflammation is also a major contributor to the development of heart disease, hence why smokers and diabetics are at increased risk of various cardiovascular problems. Inflammation alters the physical properties of inner linings of vessel walls (Henein et al., 2022), making them more prone to accumulating fatty deposits and attracting inflammatory immune cells. These processes hasten plaque formation and atherosclerosis. 

Interestingly, depression is also a state of constant, low-grade inflammation. This chronic inflammation arises from multiple places. Psychological stressors like exams, job stress, and childhood trauma, which often precede depression, stimulate the production of pro-inflammatory cytokines while decreasing levels of anti-inflammatory cytokines (Berk et al., 2013). People with depression are also much more likely to smoke (Lasser et al., 2000) and less likely to be physically active (Roshanaei-Moghaddam et al., 2009). Combined, these factors contribute to the widespread inflammation seen in depression that may contribute to cardiovascular disease progression. 

While inflammation is amongst the most studied mechanisms that connect the two conditions, the relationship between CVD and depression is shaped by a range of environmental, molecular, and even genetic factors. Ultimately, the link between mental and cardiovascular health reflects the complex interconnection between physical and psychological processes. 

As we celebrate Mental Health Awareness Week, the complex relationship between mind and body is a timely reminder that mental and physical health are integrally related. We must care for our mind with the same commitment that we give to our physical body. Our brains deserve the same attention that we would give to any other organ – as research shows, listening to your mind might just save your heart. 

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